Massenspektrometrie von Lösungen und Vorrichtung dafür

Mikrofluidische Glykananalyse

Es werden Mikrofluideinheiten und -verfahren zum Analysieren der Glykanprofile von Glykoproteinen bereitgestellt. Einige Ausführungsformen der Mikrofluideinheiten weisen eine Deglykosylierungs-Säule zum Abspalten der Glykane, wahlweise eine Reinigungssäule zum Entfernen der Proteine, eine Trap-Säule zum Anreichern der Glykane und eine Trennsäule zum Trennen der Glykane auf. Die Mikrofluideinheiten und -verfahren verbessern die Geschwindigkeit und das Auflösungsvermögen der Glykananalyse beträchtlich.

Verfahren und Vorrichtung zur Schnittstellenbildung zwischen Flüssigchromatographie oder superkritischer Chromatographie und einem Massenspektrometer (LC-SFC/MS)

Massenspektrometerinterfacegehäuse

Vorrichtung (100) zum Durchführen chemischer Analysen, wobei die Vorrichtung (100) umfasst: ein Massenspektrometriemodul (130) und ein Interfacemodul (120) in Kommunikation mit einem Eingang des Massenspektrometriemoduls (130), um Material, das eine Probeenthält, dem Massenspektrometriemodul (130) zuzuführen, wobei das Interfacemodul (120) umfasst: ein Behältnis (121), das eine Kammer (121A) definiert und eine Öffnung, um auf Komponenten zugreifen zu können, die in der Kammer (121A) angeordnet sind, eine Tür (122), um die Öffnung zu blockieren, wenn sich die Tür (122) in einer geschlossenen Position befindet, und um Zugriff auf die Kammer (121A) zu ermöglichen, wenn sich die Tür in einer geöffneten Position befindet, ein Dichtungselement (124) zum Anordnen zwischen der Tür (122) und dem Behältnis (121), um das Behältnis (121) abzudichten, wenn sich die Tür (122) in der geschlossenen Position befindet, wobei das Dichtungselement (124) einen modifizierten O-Ring umfasst, wobei der modifizierte ...

Ionisierung desorbierter Analytmoleküle bei Atmosphärendruck

Verfahren zur Ionisierung von Analytmolekülen nahe Atmosphärendruck, dadurch gekennzeichnet, dass mit einer Elektrosprüheinrichtung ein Sprühnebel erzeugt wird und die Analytmoleküle von einem festen Träger desorbiert werden, wobei die desorbierten Analytmoleküle in der Nähe des Sprühnebels erzeugt werden oder in die Nähe des Sprühnebels gebracht werden und durch protonierende und deprotonierende Substanzen des Sprühnebels ionisiert werden.

Integrated system for liquid separation and electrospray ionization

Method and apparatus for providing a substance for the analysis of isotope ratios

In-source reduction of biomolecules and their analysis by ION mobility MS/MS

Integrated system for liqiod separation and electrospray ionization

Mass-spectrometer interface housing

Probe adaptor assembly

An apparatus (Fig. 6, 200) suitable for connecting an ionisation probe assembly (110) to a mass and/or ion mobility spectrometer comprising an attachment member 122 for releasably attaching, screw fitting 231, a probe assembly (110) to the apparatus (200). A cap 240 for enclosing the attachment member 122 is provided which is configurable to enclose the attachment member 122 when a probe assembly (110) is attached to the apparatus. The cap 240 also has an aperture 241 through which at least a portion of the probe assembly 118 can pass. A device, such as a ball bearing 242, is used to close the aperture 241 when the cap 240 encloses the attachment member 122 and when no probe assembly (110) is attached to the apparatus. This prevents contact with the attachment member 122 when the probe assembly (110) is not attached to the apparatus (200) and the cap 240 is closed.

In-source reduction of biomolecules and their analysis by ION mobility MS/MS

Integrated nanospray system

SYSTEM FOR THE TRANSPORT OF MICROSCOPIC LIQUID QUANTITIES

ATMOSPHERIC PRESSURE ION INTERFACE FOR A MASS SPECTROMETER

METHOD FOR THE CONNECTION OF A CAPILLARY WITH A MICRO FLUID DEVICE

Apparatus for efficient liquid chromatography/mass spectrometry processing

Method and instrument for automated analysis of fluid-based processing systems

SYSTEMS AND METHODS FOR HIGH-THROUGHPUT MICROFLUIDIC SAMPLE ANALYSIS

PNEUMATICALLY ASSISTED ELECTROSPRAY DEVICE WITH ALTERNATING PRESSURE GRADIENTS FOR MASS SPECTROMETRY

An apparatus for producing gas-phase ions from a sample compound in a carrier liquid. The electrospray needle (or capillary) (100) of the present invention includes a central metal tube (102) which carries the liquid containing the sample compound. The central tube (102) is surrounded by a plurality of tubes (104) which transport a nebulizing gas. The nebulizing gas tubes are placed symmetrically around the outside of the liquid containing tube. The nebulizer of the present invention produces a symmetric, non-annular gas flow which has variations in pressure around the circumference of the central tube. The pressure variations of the nebulizing gas flow produce additional shear forces on the liquid emerging from the central tube. This assists in forming a uniform electrospray of droplets from the liquid at lower nebulizing gas flow rates, thereby reducing the disadvantageous effects of the higber gas flow rates used in the art. The symmetric arrangement of the nebulizing gas tube provides ...

STRUCTURAL UNITS THAT DEFINE FLUIDIC FUNCTIONS

A microfluidic device that comprises several microchannel structures in which there are an inlet port, an outlet port and therebetween a substructure comprising a fluidic function. The device has an axis of symmetry around which the microchannel structures are arranged as two or more concentric annular zones. for an inlet port and an outlet port of the same microchannel structure the inlet port is typically closer to the axis of symmetry than the outlet port. Each microchannel structure comprises a substructure that can retain liquid while the disc is spun around the axis and/or the inlet ports are positioned separate from the paths waste liquid leaving open waste outlet ports will follow across the surface of the disc when it is spun. For the microchannel structures of an annular zones the corresponding substructures are at essentially at the same radial distance while corresponding substructures in microchannel structures of different annular zones are at different radial distances. The ...

CONDUCTIVE POLYMER COATED NANO-ELECTROSPRAY EMITTER

The present invention relates to a nanospray emitter (10) including an emitter body (12) which includes a fluid inlet (14), an outlet orifice (16), and a passage (18) communicating between the fluid inlet and outlet orifice; and an electrically conductive polymer coating (19) on at least a portion of the emitter body. Also disclosed are a nano-electrospray device including the nanospray emitter of the present invention, a method for making a nanospray emitter of the present invention, a method of forming a nanospray using the nanospray emitter of the present invention, and a method of analyzing a solution using the nanospray emitter of the present invention.

FINGERPRINTING OF COMPLEX HYDROCARBON CONTAINING MIXTURES

The invention provides a method of analysing a complex hydrocarbon-containing mixture, the method comprising the steps of: obtaining a liquid sample of the complex hydrocarbon-containing mixture; injecting the sample into a liquid carrier flowing to a mass spectrometer, wherein the mass spectrometer is set so as to ionise molecules in the sample without causing fragmentation thereof; recording a mass spectrum for ions obtained from the sample; and using the mass spectrum to obtain fingerprint of the mixture. In one embodiment, two or more mass spectra are recorded and are combined to obtain a fingerprint of the mixture.

A METHOD OF AND APPARATUS FOR IONIZING AN ANALYTE AND ION SOURCE PROBE FOR USE THEREWITH

A device for electrospray ionization comprises two gas sources, or an arc jet of gas, provide second and third flows, of a gas, and include heaters for heating the second and third flows. The second and third flows intersect with the first flow at a selected mixing region, to promote turbulent mixing of the first, second and third flows, the first, second and third directions being different from one another, and each of the second and third directions being selected to provide each of the second and third flows with a velocity component in the first direction and a velocity component towards the axis of the capillary tube, thereby to promote entrainment of the heated gas in the spray, with the heated gas acting to assist the evaporation of the droplets to release ions therefrom. At least some of the ions produced from the droplets are drawn through the orifice for analysis.

CHARACTERIZATION OF REACTION VARIABLES

A microscale method for the characterization of one or more reaction variables that influence the formation or dissociation of an affinity complex comprising a ligand and a binder, which have mutual affinity for each other. The method is characterized in comprising the steps of: (i) providing a microfluidic device comprising a microchannel structures that are under a common flow control, each microchannel structure comprising a reaction microactivity; (ii) performing essentially in parallel an experiment in each of two or more of the plurality of microchannel structures, the experiment in these two or more microchannel structures comprising either a) formation of an immobilized form of the complex and retaining under flow conditions said form within the reaction microactivity, or b) dissociating, preferably under flow condition, an immobilized form of the complex which has been included in the microfluidic device provided in step (i), at least one reaction variable varies or is uncharacterized ...

A SYSTEM AND METHOD FOR HIGH THROUGHPUT SAMPLE PREPARATION AND ANALYSIS USING COLUMN CHROMATOGRAPHY

A system and method high throughput sample preparation and analysis using column chromatography. Each port in a plurality of ports has a port input that interfaces with a first fluid source and a port output. A fluidic circuit is coupled to each port output and to a second fluid source, the fluidic circuit for controlling fluid flow from the plurality of ports and the second fluid source. The fluidic circuit is also coupled to a plurality of chromatography columns. An interface to an analyzer receives output from at least one of the plurality of chromatography columns. The plurality of chromatography columns is moved relative to the analyzer via a translation stage, such that sample output from one of the plurality of chromatography columns can be selectively presented to the analyzer.

A SYSTEM AND METHOD FOR HIGH THROUGHPUT PROCESSING OF DROPLETS

A method for high throughput processing of a plurality of droplets. The droplets are dispensed onto a moving surface (1) and delayed in a delay line (11) in which the droplets hang from the moving surface for at least a specified minimum period of time. A laminate (6) may be spooled onto the moving surface (1) and each droplet may be dispensed onto the laminate (6). At least one operation is performed on each droplet from the group of operations consisting of mixing, diluting, concentration, heating, cooling, humidifying, filtering, and analyzing. The laminate (6) may then, in certain embodiments, be spooled off the moving surface (1), processed, and reused.

PARALLEL FLUID ELECTROSPRAY MASS SPECTROMETER

A method of analyzing each of a plurality of fluid samples (11-16), comprising, simultaneously spraying a plurality fluid samples (11-16) from electrospray needle array (20) towards mass spectrometer (50); positioning blocking device (40) to block all but one (32-34) of fluid samples (31-34) from reaching mass spectrometer (50); moving electrospray needle array (20) and blocking device (40) relative to one another to permit at least two of the plurality of fluid samples (31, 32) to reach mass spectrometer (50) one at a time; and analyzing the mass spectrum of fluid samples (31, 32, 33, 34) sequentially reaching mass spectrometer (50). A system for analyzing the composition of each of a plurality of fluid samples (31-34), comprising, mass spectrometer (50); multi-head electrospray needle array (20) for spraying fluid samples (31-34) towards mass spectrometer (50); and blocking device (40) positioned between electrospray needle array (20) and mass spectrometer (50), blocking device (40) dimensioned ...

SOFTWARE FOR MICROFLUIDIC SYSTEMS INTERFACING WITH MASS SPECTROMETRY

Methods, devices, and systems for improving the quality of electrospray ionization mass spectrometer (ESI-MS) data are described, as are methods, devices, and systems for achieving improved correlation between chemical separation data and mass spectrometry data.

TRIPLE QUADRUPOLE MASS SPECTROMETERS CONFIGURED TO DETECT MRM TRANSITIONS OF PESTICIDE RESIDUES

This disclosure provides quantitative, rapid, and reliable LCMS/MS methods for analyzing panels of pesticides and mycotoxins in various samples, including very hydrophobic and chlorinated compounds normally analyzed on a GCMS/MS system. The methods can be carried out using a single instrument and can detect and quantify levels of the pesticides and mycotoxins that are well below action limits specified by U.S. states (e.g., California) and other countries (e.g., Canada) for these compounds in cannabis products.

METHODS FOR DETECTING CHROMOGRANIN A BY MASS SPECTROMETRY

Provided are methods for detecting chromogranin A by mass spectrometry. In another aspect, provided herein are methods for quantitating chromogranin A by mass spectrometry. In another aspect, provided herein are methods for prognosis of or measuring the size of neuroendocrine tumors by mass spectrometry.

ONLINE CHROMATOGRAPHY AND ELECTROSPRAY IONIZATION MASS SPECTROMETER

Methods and system for protein characterization using online chromatography and electrospray ionization mass spectrometry are provided.

SYSTEM AND METHOD OF PRECONCENTRATING ANALYTES IN A MICROFLUIDIC DEVICE

A method and system for preconcentrating analytes at a microvalve in a microfluidic device (1600) is disclosed. The system includes a sample channel (1610) loaded with a sample solution. The sample channel (1610) includes a semi-permeable membrane microvalve (1630). An electric potential is applied at or across the microvalve (1630) to preconcentrate the sample solution when the microvalve is closed. Sample solution is subsequently injected into the separation channel (1640,2105). A tapered capillary end (2110) is inserted into the separation channel (2105). Also disclosed are methods including pretreatments of the device or valve for preconcentration of the analytes. For preconcentration of anionic analytes, the device is baked. For preconcentration of the cationic analytes, the surface of the membrane microvalve (1630) is coated with a polycationic coating, and the device is baked.

METHOD OF DETECTING BLOOD PLASMA AMYGDALIN AFTER ADMINISTRATION OF FUZHENG HUAYU(FZHY)

A method of detecting blood plasma amygdalin after administration of Fuzheng Huayu (FZHY) is disclosed. The method includes: (1) adding 2-5 mol/L phosphoric acid to plasma of a mammal administered FZHY and mixing the solution of plasma-phosphoric acid (1:2-3, v/v), applying the solution to a Waters Oasis HLB small column activated by methanol and water; after leaching by water and 80-100% methanol and eluting by 0.2-1% ammonia-methanol, drying and enriching the eluent at 25-30 °C; and redissolving with mobile phase; (2) UPLC/MS measuring wherein the UPLC condition comprises an Acquity UPLC BEH C18, 2.1 x 100 mm chromatographic column, mobile phase A comprising water-acetonitrile-formic acid at a ratio (v/v/v) of 95:5:0.1, and mobile phase B comprising acetonitrile-formic acid at a ratio (v/v) of 100:0.1; and the MS condition comprises an electric spraying ion source (ESI), detecting with positive ion mode and scanning at the range of m/z 150-800. The method can be used for pharmacokinetics ...

METHODS FOR SCREENING COMPOUND LIBRARIES

Disclosed are methods for screening compound libraries using frontal chromatography in combination with mass spectrometry to identify and rank those members of the library that bind to a target receptor. Methods are also disclose d which permit a compound library to be rapidly screened to determine if any members of the library have a higher affinity for the target receptor relative to a pre-selecte d indicator compound.

METHOD FOR RELEASING AND LABELLING 0-GLYCANS

The application describes a one-pot process for releasing and labelling O-glycans from glycoproteins, thereby facilitating analysis via LC-ESI-MS-MS. The process comprises contacting the glycoprotein with an amine, eg. methylamine, dimethylamine, or ammonia, NH3 in the presence of a labelling agent, especially l-phenyl-3-methyl-5-pyrazolone (PMP,- CAS Reg. No. 89-25-8), l-naphthyl-3-methyl-5-pyrazolone (NMP) or 1- (4-methoxy)phenyl-3-methyl-5-pyrazolone (PMPMP, CAS Reg. No. 60798-06-3).

CHROMATOGRAPHY APPARATUS HAVING DIFFUSION-BONDED AND SURFACE-MODIFIED COMPONENTS

A microfluidic device for separating a sample by chromatography includes diffusion bonded metallic sheets joined together to create a hermetically sealed interface between each adjacent metallic sheet without the introduction of a secondary material. Enclosed within the diffusion bonded sheets is a separation channel accessible by at least one of an inlet or an outlet. The separation channel is packed with micrometer-sized particles serving as a stationary phase in a chromatographic separation. Wetted surfaces of the separation channel include a coating of an organic material at least one monolayer thick.

SAMPLE COMPONENT TRAPPING, RELEASE, AND SEPARATION WITH MEMBRANE ASSEMBLIES INTERFACED TO ELECTROSPRAY MASS SPECTROMETRY

The invention provides a method and apparatus for trapping, releasing and/or separating sample components in solution passing through a channel with or without packing material present by passing ion current through the channel driven by an electric field. A portion of the ion current comprises cation and/or anion species generated from second solution flows separated from the sample solution flow path by semipermeable membranes. Cation and/or Anion ion species generated in the second solution flow regions are transferred into the sample solution flow path through ion selective semipermeable membranes. Ion current moving along the sample solution flow path is controlled by varying the composition of the second solutions and/or changing the voltage between membrane sections for a given sample solution composition. The sample composition may also be varied separately or in parallel to enhance trapping, release and/or separation efficiency and range. The invention when interfaced to an Atmospheric ...

INTEGRATED SYSTEM FOR LIQUID SEPARATION AND ELECTROSPRAY IONIZATION

The present invention relates to an integrated system for liquid separation, such as LC, CE, affinity chromatography, and ion exchange chromatography. The invention relates to a specialized protection means for protecting a fragile electrospray needle when not in use. The integrated system for liquid separation and electrospray ionization comprises: a separation column; an electrospray emitter connected with the separation column; a retractable protective sleeve for covering and supporting the electrospray emitter along at least a portion of its axis; and a resilient member biasing the protective sleeve towards an extended position wherein the protective sleeve covers a tip of the electrospray emitter. In one embodiment, the system also comprises a specialised electrical contact means for applying voltage to the electrospray needle.

UNIFORM PATTERNING FOR DEEP REACTIVE ION ETCHING

A method for improving the etch uniformity of features (21) of a device and etch profiles for devices made, for example, by deep reactive ion etching, by patterning sacrificial features or devices adjacent target features or devices. The method for providing etch depth uniformity for plasma etching, includes adding sacrificial features to a substrate containing a plurality of target features, etching the sacrificial and target features and separating the substrate into a plurality of pieces, wherein at least one piece contains at least one target feature.

CHARGED DROPLET SPRAYERS

Charged droplet spray is formed from a solution with all or a portion of the charged droplet spray current generated from reduction or oxidation (redox) reactions occurring on surfaces removed from the first or sample solution flow path. In one embodiment of the invention, two solution flow channels are separated by a semipermeable membrane. A first or sample solution flowing through the first solution flow channel exchanges cation or anion charged species through the semipermeable membrane with a second solution or gas flowing through the second flow channel. Charge exchange is driven by the electric field applied at the charged droplet sprayer sample solution outlet. Redox reactions occur at an electrode surface in contact with the second solution. The invention increases the control and range of the Electrospray ionization process during ES/MS operation. Alternative embodiments of the invention provide for conducting redox reactions on conductive surfaces removed from the first or sample ...

METHODS FOR SEPARATION AND DETECTION OF KETOSTEROIDS AND OTHER CARBONYL-CONTAINING COMPOUNDS

Methods for enhancing detection by mass spectroscopy (MS) and/or chromatographic separability of carbonyl-containing compounds such as steroids are disclosed. Reaction of a carbonyl compound with a sulfonhydrazide compound provides a sulfonhydrazone with enhanced ionization efficiency during the electrospray ionization process. In a particularly disclosed embodiment, derivatization of catechol estrogens with p-toluenesulfonhydrazide enhances both detection by atmospheric pressure ionization-MS (API-MS), such as electron spray ionization-MS (ESI-MS) and separation by liquid chromatography (such as HPLC) under reverse phase conditions. In yet other embodiments, the sulfonhydrazone is further reacted with a sulfonyl halide under alkaline conditions to derivatize hydroxyl groups in the compound. Prior formation of the sulfonhydrazide derivative protects the carbonyl bond of the compound during subsequent alkaline reaction with the sulfonyl halide.

MULTI COLUMN CHROMATOGRAPHY SYSTEM

The present invention relates to a method and apparatus for chromatographically analyzing each of a plurality of samples in detector, comprising an autosampler to contain a plurality of samples for chromatographic analysis and a plurality of chromatographic systems, each system comprising one or more pumps and one or more chromatography columns. A detector is included for detecting compounds in the samples from each of the chromatography systems along with a valve positioned between the detector and the plurality of chromatography systems, the valve permitting each sample to reach the detector in sequence. A computer control device is included which adjusts the introduction of samples from the autosampler into the plurality of chromatography systems as well as the position of the valve to sequentially separate and deliver compounds within the samples to the detector.

Integrated monolithic microfabricated electrospray and liquid chromatography system and method

An electrospray device, a liquid chromatography device and an electrospray-liquid chromatography system are disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray. The liquid chromatography device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow; a cover substrate bonded to the separation substrate to enclose the reservoir and the separation channel adjacent the cover substrate ...

Sample injection system

One embodiment of the invention provides a sample injection system including a vacuum source, a conduit in communication with the vacuum source, a fluid sensor configured to detect the presence of the fluid in the conduit, a sample loop in communication with the conduit; and a sipper in communication with the sample loop.

MASS SPECTROMETER

A mass spectrometer which comprises an ion source for ionizing a sample and a mass analyzing region for introducing the thus formed ions into a vacuum and mass analyzing the ions, the ion source being provided with a spray ion source comprising a heatable capillary working at least under the atmospheric pressure, the center axis of the capillary being aligned along the center of an aperture for withdrawing the ions and the tip end of the capillary being positioned close to the aperture ionizes a sample from a liquid chromatograph by both atmospheric pressure ionization mode and a thermospray ionization mode and mass analyze the ions, thereby obtaining more exact analytical information on the sample.

System and method for desorbing and detecting an analyte sorbed on a solid phase microextraction device

Disclosed herein is a system for desorbing and detecting an analyte sorbed on a solid phase microextraction (SPME) device. The system includes a desorption chamber sized to accept the SPME device while defining a void volume of less than about 50 μL; a flow injector in fluid connection with the desorption chamber, the desorption chamber and the flow injector being fluidly connected by at least a flow-insulating fluid connector; a solvent source in fluid connection with the flow injector; and a fluid switch that: in a desorption position, allows the solvent to be sprayed from the flow injector while flow-insulating any desorption solution in the desorption chamber, and in an detecting position, turns off the solvent source while maintaining the fluid connection between the flow injector and the desorption chamber, transferring the desorption solution through the flow-insulating fluid connector to the flow injector as a substantially undiluted plug of liquid.

Microfluidic system

A dual-side field-emission display has one cathode plate and two anode plates. The cathode plate has two opposite surfaces, and each surface has a cathode conductive layer and an electron emission layer formed thereon. The anode plates are disposed at two opposing sides of the cathode plate. Each of the anode plates has an anode conductive layer and a phosphor layer.

Integrated electrospray ionization emitter and detection cell for parallel measurements by fluorescence and mass spectrometry

An integrated mass spectrometer electrospray emitter and fluorescence detector allows improved volumetric measurements of separate components from a liquid chromatography column by improving correlation between the readings of these instruments and reducing dead volume and sample size requirements.

MASS SPECTROMETER AND MASS SPECTROMETRY METHOD

The degree of ion dissociation which occurs within a first intermediate vacuum chamber (212) maintained at a comparatively low degree of vacuum depends not only on the amount of energy of the ion but also on the size and other properties of the ion. Accordingly, a predetermined optimum level of DC bias voltage is applied to an ion guide (24) so as to create, within the first intermediate vacuum chamber (212), a DC electric field which barely induces the dissociation of an ion originating from a target compound in a sample while promoting the dissociation of an ion originating from a foreign substance which will form a noise signal in the observation of the target compound. The optimum DC bias voltage is previously determined by creating extracted ion chromatograms based on data collected under various DC bias voltages and evaluating the SN ratio using the chromatograms. Consequently, the accuracy and sensitivity of the quantitative determination is improved as compared to a conventional ...

IMPACT IONISATION SPRAY OR ELECTROSPRAY IONISATION ION SOURCE

An impact ionisation spray or electrospray ionisation ion source comprising a nebuliser () having a first conduit () for providing a liquid sample and a second conduit () for providing a nebulisation gas in order to nebulise the liquid sample is disclosed. The first conduit () and second conduit () are of unitary construction with each other and may be made from glass. The ion source can provide a consistent and/or predictable spray profile for the nebulised sample. 1. An impactor spray or electrospray ionisation ion source comprising:a nebuliser having a first conduit for providing a liquid sample and a second conduit for providing a nebulisation gas in order to nebulise the liquid sample, wherein the first conduit and second conduit are of unitary construction with each other.2. An ion source as claimed in claim 1 , wherein an outlet of the first conduit has a substantially circular cross-sectional profile and/or an outlet of the second conduit has a substantially circular cross-sectional profile.3. An ion source as claimed in claim 1 , wherein an outlet of the second conduit surrounds or circumferentially encloses a single first conduit.4. An ion source as claimed in claim 1 , wherein outlets of the first conduit and second conduit are substantially concentric and/or coterminous.5. An ion source as claimed in claim 1 , wherein the nebuliser is formed of a blown material.6. An ion source as claimed in claim 1 , wherein the nebuliser is formed of a moulded material.7. An ion source as claimed in claim 1 , wherein the nebuliser is formed of glass.8. An ion source as claimed in claim 1 , wherein the nebuliser is formed of a ceramic claim 1 , plastics or polymer material.9. An ion source as claimed in claim 1 , wherein the nebuliser is formed of a substantially non-metallic and/or substantially non-ferrous and/or substantially non-conductive material.10. An ion source as claimed in claim 1 , further comprising a liner conduit within the first conduit claim 1 , wherein ...

PRESSURE DRIVEN FLUIDIC INJECTION FOR CHEMICAL SEPARATIONS

Methods, systems and devices that allow independently applied pressures to a BGE reservoir and a sample reservoir for pressure-driven injection that can inject a discrete sample plug into a separation channel that does not require voltage applied to the sample reservoir and can allow for in-channel focusing methods to be used. The methods, systems and devices are particularly suitable for use with a mass spectrometer. 1providing a microfluidic device with at least one separation channel in fluid communication with a background electrolyte (BGE) reservoir, a waste reservoir connected to the separation channel through a waste channel, and a sample reservoir connected to the separation channel through a sample channel;injecting a fluid sample from the sample reservoir into the at least one separation channel by concurrently applying pressurized gas to the BGE reservoir, the sample reservoir and optionally the waste reservoir;delivering fluid from the BGE reservoir into the at least one separation channel to define a plug of the sample in the at least one separation channel by reducing a gas pressure in the sample reservoir, so that a gas pressure in the BGE reservoir is greater than the gas pressure in the sample reservoir;electrophoretically separating an analyte component of the sample from other sample components in the at least one separation channel by generating an axial electric field within the separation channel; andperforming at least one of:(a) electrospraying the separated analyte component from at least one emitter in fluid communication with the at least one separation channel; and(b) measuring an electrical signal corresponding to the separated analyte component in or emerging from the separation channel.. A method of sample processing, comprising: This application is a continuation of U.S. patent application Ser. No. 15/570,505, filed Oct. 30, 2017, which is a 35 U.S.C. § 371 national phase application of International Application Serial No. PCT/US2016/ ...

LIQUID CHROMATOGRAPH

A liquid chromatograph that ionizes a sample eluted from a column using an ionization probe connected to the column and analyzes the sample using an ion analyzer , the liquid chromatograph includes: a column oven in which the column is accommodated; and a guide mechanism that is provided inside the column oven , permits the column to move in a predetermined direction following movement of the ionization probe , and regulates movement in other directions. 1. A liquid chromatograph configured to ionize a sample eluted from a column using an ionization probe connected to the column and to analyze the sample using an ion analyzer , the liquid chromatograph comprising:a) a column oven in which the column is accommodated; andb) a guide mechanism provided inside the column oven, and configured to allow the column to move in a predetermined direction following movement of the ionization probe, to restrict movement in other directions.2. The liquid chromatograph according to claim 1 , wherein the guide mechanism includes a column holder configured to hold the column and a recess that is formed in the column oven and is longer than an outer diameter of the column holder in the predetermined direction.3. The liquid chromatograph according to claim 2 , further comprising an ionization probe fixture fixed to the ionization probe claim 2 ,wherein the column holder comprises:a column fixture fixed to the column; anda movement restricting tool configured to allow the column fixture to advance in an axial direction of the column while restricting the column or the column fixture and the ionization probe or the ionization probe fixture such that flow paths of the column and the ionization probe are matched with each other, and restrict the ionization probe fixture such that the ionization probe fixture does not retreat beyond a predetermined position in an axial direction of the ionization probe.4. The liquid chromatograph according to claim 3 , wherein the column fixture is fixed to ...

Characterization of reaction variables

A microscale method for the characterization of one or more reaction variables that influence the formation or dissociation of an affinity complex comprising a ligand and a binder, which have mutual affinity for each other. The method is characterized in comprising the steps of: (i) providing a microfluidic device comprising a microchannel structures that are under a common flow control, each microchannel structure comprising a reaction microactivity; (ii) performing essentially in parallel an experiment in each of two or more of the plurality of microchannel structures, the experiment in these two or more microchannel structures comprising either a) formation of an immobilized form of the complex and retaining under flow conditions said form within the reaction microactivity, or b) dissociating, preferably under flow condition, an immobilized form of the complex which has been included in the microfluidic device provided in step (i), at least one reaction variable varies or is uncharacterized ...

MASS SPECTROMETRY CONTROL DEVICE, MASS SPECTROMETRY DEVICE, MASS SPECTROMETRY METHOD AND PROGRAM

A mass spectrometry control device includes a deriver that derives, based on a set of allergens that are detectable without being distinguished from one another among a plurality of allergens to be detected and data that indicates a plurality of peptides produced by subjecting each allergen to a cleavage process, first peptides produced in common when the plurality of allergens included in the set are subjected to the cleavage process and at least one of parameters for detecting the first peptides, and a setter that sets a condition of mass spectrometry to detect at least one of the first peptides.

Method and device for interfacing liquid chromatography or supercritical fluid chromatography with a mass spectrometer (LC-SFC/MS)

METHOD AND APPARATUS FOR IMPROVING ELECTROSPRAY IONIZATION OF SOLUTE SPECIES

СПОСОБ ИДЕНТИФИКАЦИИ ВЕЩЕСТВ С ИСПОЛЬЗОВАНИЕМ МАСС-СПЕКТРОМЕТРА

Группа изобретений относится к идентификации химических соединений с применением хромато-масс-спектрометра. Раскрыт способ идентификации химического соединения, включающий следующие стадии: вводят растворенное в полярном растворителе химическое соединение в хроматограф, после чего после выхода с колонки хроматографа соединение поступает в совмещенный с хроматографом источник электроспрей ионизации; подают электрическое напряжение на иглу, распыляя раствор химического соединения в спрей заряженных капель для ионизации, при этом заряженные капли, образованные химическим соединением, попадают в один из выходов нагреваемого переходного тройника, образующего Т-образное соединение с вакуумной частью масс-спектрометра и с камерой, содержащей дейтерирующий агент; определяют молекулярную массу химического соединения, а также массу его фрагментов при заданном режиме фрагментации в масс-спектрометре; повторяют указанные стадии, используя определяемое химическое соединение, модифицированное путем изотопного ...

METHODE ZUR VERBINDUNG EINER KAPILLARE MIT EINER MIKROFLUIDVORRICHTUNG

Verfahren zur Quantifizierung von Polypeptiden mittels Massenspektrometrie

Verfahren zur Identifizierung eines Polypeptids in einer Probe, das umfasst (i) Behandeln einer Probe, in der ein Insulin vermutet wird, mit einer Base, (ii) Extrahieren einer ersten Fraktion der behandelten Probe mittels Festphasenextraktion unter Verwendung eines Mixmodus- oder polymerem Umkehrphasenmediums und eines ersten, säurehaltigen Lösungsmittels, (iii) Trennen einer Komponente der ersten Fraktion mittels Flüssigchromatographie unter Verwendung einer chromatographischen Oberfläche mit einer hydrophoben Oberflächengruppe und einem oder mehreren ionisierbaren Modifikatoren, und eines zweiten säurehaltigen Lösungsmittels, und (iv) Analysieren der Komponente der ersten Fraktion mittels Massenspektroskopie, wodurch das Polypeptid, wenn vorhanden, mithilfe eines Signals identifiziert wird, das einem Sequenzfragment-Ion des Polypeptids entspricht, beinhalten. Das Signal kann einem in einem ersten Quadrupol ausgewählten intakten mehrfach geladenen Vorstufenfragment und seinem entsprechenden ...

Integriertes System zur Flüssigkeitstrennung und Elektrospray-Ionisation

Integriertes System zur flüssigen Trennung und Elektrosprayionisierung, umfassend:- eine Trennsäule (1);- ein Elektrosprayemitter (2), verbunden mit der Trennsäule (1); und- eine rückschiebbaren Schutzhülse (8) zum Bedecken und/oder Stützen des Elektrosprayemitters (2) entlang wenigstens einem Teil seiner Achse, wobei die Schutzhülse (8) verschiebbar um den Elektrosprayemitter montiert ist; worin die rückschiebbare Schutzhülse (8) in eine herausgefahrene Position bewegbar ist und worin eine Spitze des Elektrosprayemitters durch die Schutzhülse (8) bedeckt ist und worin ein Rückstellelement (10) bereitgestellt wird, um die Schutzhülse (8) in die herausgefahrene Position zu bringen, wobei sie die Spitze des Elektrosprayemitters bedeckt,worindie Schutzhülse (8) in einer äußeren Hülle (7) eingeschlossen ist und darin beweglich ist,die äußere Hülle (7) eine elektrisch leitende Hülle ist,die elektrisch leitende Hülle (7) für die Insertion in einen Halter, der einen Hochspannungskontaktpunkt aufweist ...

Integriertes Nanospray-System

Eine integrierte Baugruppe zur Nanospray-Ionisierung umfassend einen Nanospray-Emitter; einen Drucktastenschlitten mit einem Tastenelement, das durch eine Bohrung in der Baugruppe hervorragt; einen integrierten Hochspannungskontaktstift; eine Bohrung in der Baugruppe für das reversible Herausragen des Nanospray-Emitters und einen Druckmechanismus zum Drücken und Zurückziehen, bei dem der Bereich der Vorwärtsbewegung des Emitters nicht vom Bewegungsumfang der Taste abhängig ist, und bei Betätigung des Tastenelements und des Federelements zum Zurückziehen des Nanospray-Emitters, der Nanospray-Emitter nach vorne gedrückt wird, um einen elektrischen Kontakt herzustellen, und beim Loslassen sich die Taste zurückzieht und den elektrischen Kontakt unterbricht.

Microfluidic device for electrospraying

Secondary electrospray ionization at reduced pressure

A ring shaped counter electrode to improve beam stability and compound sensitivity on a ceramic tile type microfluidic device

Method and device for mass spectrometry

This device for mass spectrometry is equipped with a liquid specimen supply part which sends a liquid specimen sandwiched between bubbles, an ion source part which ionizes the specimen, and a mass spectrometry part in which the ions generated in the ion source part are separated in accordance with mass and detected. The device is characterized in that the ion source part is configured so as to include a liquid supply tube (305) which is for transporting a specimen from the liquid specimen supply part, a degassing/liquid retention part (307) in which bubbles (302) are removed, a spraying part (306) which ionizes the specimen, and a high-voltage power supply part (309) which applies a high voltage to the spraying part (306). The device is further characterized in that after removing the bubbles (302) (308), a Taylor cone is formed from the resultant pre-solution (303), and the specimen is ionized thereafter. Thus, the ionization of an intended specimen is stabilized, and the measurement reproducibility ...

Methods for quantifying polypeptides using mass spectrometry

Combined electrospray/particle beam liquid chromatography/mass spectrometer

Probe assembly connector

Fluidic separation devices and methods with reduced sample broadening

Probe adaptor assembly

Probe adaptor assembly

Method and device for mass spectrometry

Electrospraying method for mass spectrometric analysis

DIELECTRIC FILM

LCMS technology and its uses

Isotyping immunoglobulins using accurate molecular mass

This document relates to methods for detecting and quantifying heavy and light chains of immunoglobulin using mass spectrometry techniques.

AUTOMATED ON-LINE EVAPORATING LIGHT SCATTERING DETECTION TO QUANTIFY ISOLATED FLUID SAMPLE COMPOUNDS IN MICROTITER PLATE FORMAT

Single pass methods and systems for measuring the total masses of individual compounds present in fluid samples in real time, and particularly for fluid samples prepared in microtiter plate format are provided. Individual compounds are isolated by fluid separation column (14). Portions of the individual compounds isolated by column (14) are analyzed by mass spectrometer (16), which determines their concentration on the basis of their molecular weights, and an evaporative light scattering detector (24), (which determines the total masses of each of the isolated compounds passing therethrough). Total collected masses of the individual compounds are calculated by determining the amount and portion of the isolated compounds diverted into evaporative light scattering detector (24) during a period of fraction collection.

A METHODS AND INTERFACES FOR SINGLE AND MULTIDIMENTIONAL SEPARATIONS FOR CHARACTERIZATION AND/OR IDENTIFICATION OF MOLECULES BY MASS SPECTROMETRY

INTEGRATED MONOLITHIC MICROFABRICATED ELECTROSPRAY AND LIQUID CHROMATOGRAPHY SYSTEM AND METHOD

An electrospray device (100), a liquid chromatography device and an electrospray-liquid chromatography system are disclosed. The electrospray device (100) includes a substrate (102) defining a channel (104) between an entrance orifice (106) on an injection surface (108) and an exit orifice on an ejection surface (112), a nozzle (110) defined by a portion recessed (114) from the ejection surface (112) surrounding the exit orifice, and an electrode for application of an electric potential to the substrate (102) to optimize and generate an electrospray. The exit orifice of the liquid chromatography device may be homogeneously interfaced with the entrance orifice (106) of the electrospray device (100) to form an integrated single system.

DIFFERENTIAL PHAGE CAPTURE PROTEOMICS

Disclosed herein are methods for identifying, isolating and comparing proteins and other biomolecules differing between two complex biological samples using affinity chromatography and phage display techniques.

DETECTION OF BLOOD PLASMA DANSHENSU AND SALVIANOLIC ACID B OF DISSIPATING BLOOD STASIS BOTANICAL

A detection method of blood plasma danshensu and salvianolic acid B of di ssipating blood stasis botanical is disclosed. The method includes: (1) pret reating mammalian plasma sample: applying the plasma with medicine to small column of Waters Oasis HLB activated by methanol and water; after leaching a nd eluting, drying and enriching the eluent; after redissolving with mobile phase, measuring by UPLC/MS; (2) UPLC/MS measuring: UPLC condition: chromato graphic column: Acquity UPLC BEH C18, 2.1´100mm, mobile phase A: water-aceto nitrile-formic acid 95:5:0.1 v/v/v, mobile phase B: acetonitrile-formic acid 100:0.1 v/v; MS condition: electric spraying ion source(ESI), detecting wit h negative ion mode, scanning at the range of m/z 150-800. The method can be used for pharmacokinetics study of danshensu and salvianolic acid B in diss ipating blood stasis botanical.

INTEGRATED NANOSPRAY SYSTEM

Integrated nanospray ionization package, comprising a nanospray emitter, a push button carriage with button element projecting through a bore in said package, an integral high voltage contact pin, a bore in said package for reversible protrusion of the nanospray emitter, a push-and-retract spring mechanism in which the range of forward motion of the emitter is not dependent on range of travel of the said button, and then upon actuation of said button element and spring element for retraction of said nanospray emitter, said nanospray emitter is pushed forward to establish electrical contact, and upon release of said button retracts and breaks the electrical contact.

METHOD AND APPARATUS FOR FOCUSING IONS IN VISCOUS FLOW JET EXPANSION REGION OF AN ELECTROSPRAY APPARATUS

An electrospray ion source having a capillary tube for directing ions from an ionizing region to an analyzing region where it forms a gas jet with ions which expands and a tube lens cooperating with said capillary for forcing ions to the center of said jet.

MICROSCALE FLUID HANDLING SYSTEM

A microscale fluid handling system (10) that permits the efficient transfer of nanoliter to picoliter quantities of a fluid sample from the spatially concentrated environment of a microfabricated chip to "off-chip" analytical or collection devices (23) for further off-chip sample manipulation and analysis is disclosed. The fluid handling system (10) is fabricated in the form of one or more channels (12), in any suitable format, provided in a microchip body or substrate of silica, polymer or other suitable non-conductive material, or of stainless steel, noble metal, silicon or other suitable conductive or semiconductive material. The microchip fluid handling system (10) includes one or more exit ports (16) integral with the end of one or more of the channels (12) for consecutive or simultaneous off-chip analysis or collection of the sample. The exit port or ports (16) may be configured, for example, as an electrospray interface for transfer of a fluid sample to a mass spectrometer (23).

ELECTROSPRAY DEVICE FOR MASS SPECTROMETER

An electrospray apparatus employing multiple electrospray needles mounted in a circular arrangement sequentially delivers multiple sample streams to a mass spectrometer for analysis. One electrospray device includes an electrospray chamber, a rotatable needle supporting plate, a plurality of electrospray needles mounted on the plate, and a charger for applying a charge to droplets delivered to the electrospray chamber by the needles. Another electrospray device includes an electrospray chamber, a plurality of electrospray needles arranged in a circular arrangement, a charger, and a rotatable member for delivering gas phase ions from one needle at a time to the mass spectrometer. The rotatable electrospray apparatus provides fast repetitive analysis of simultaneously operating chromatography columns or other sample streams with a single mass spectrometer.

Method for improving stability in simultaneous detection of 10 kinds of gibberellin

DEVICE AND METHOD FOR THE SYNTHESIS OF INTERMEDIATES OF A CHEMICAL ENTITY SPECIES ELECTROCHEMICALLY

SYSTEM AND METHOD FOR DETECTING AND QUANTIFYING BY MASS SPECTROMETRY AND BY ACTIVATING MOLECULAR SPECIES IONISED

La présente invention concerne un système et un procédé de spectrométrie de masse, comprenant les étapes suivantes : a. ionisation d'un analyte pour former un ion précurseur (A) ayant un ratio masse sur charge (m/z), où m représente la masse et z le nombre de charge électrique; b. activation de l'ion précurseur (A) par interaction avec un faisceau d'espèces neutres, d'ions, d'électrons ou de photons, ayant une énergie choisie en fonction des propriétés physico-chimiques de l'ion précurseur, ladite activation étant adaptée pour produire un ion-produit (B, C) ayant la même masse m que ledit ion précurseur (A) et un nombre de charge électrique z' tel que z' est un nombre entier non nul différent de z, z' étant de préférence choisi parmi z+1, z+2, z+3, z-1, z-2, z-3, l'ion-produit étant formé par ionisation, détachement d'électrons, capture ou transfert d'électrons sans fragmentation ; c. séparation de l'ion-produit (B, C, E, F) ayant un ratio masse sur charge (m/z') prédéterminé ; d. détection ...

Lipid biomarker composition for diagnosing of cancer and uses thereof

LCMS TECHNOLOGY AND ITS USES

INTEGRATED NANOSPRAY SYSTEM

Integrated nanospray ionization package, comprising a nanospray emitter, a push button carriage with button element projecting through a bore in said package, an integral high voltage contact pin, a bore in said package for reversible protrusion of the nanospray emitter, a push-and-retract spring mechanism in which the range of forward motion of the emitter is not dependent on range of travel of the said button, and then upon actuation of said button element and spring element for retraction of said nanospray emitter, said nanospray emitter is pushed forward to establish electrical contact, and upon release of said button retracts and breaks the electrical contact.

SELF-CONTAINED CAPILLARY ELECTROPHORESIS SYSTEM FOR INTERFACING WITH MASS SPECTROMETRY

A complete capillary electrophoresis (CE) system that is capable of providing a continuous flow of effluent at the exit of the flow-through outlet vial is provided. A self- contained capillary electrophoresis system with a flow-through outlet vial for interfacing with mass spectrometry includes a capillary having an upstream inlet end and a downstream terminus end; an electrically conductive hollow needle having an inner wall defining an internal tapered chamber, the internal tapered chamber dimensioned and configured to slidably accept the terminus end of the capillary, the capillary longitudinally inserted into and mounted within the internal tapered chamber to a distance whereby the terminus end of the capillary abuts the inner wall of the needle at the taper; and wherein a micro-reservoir is formed between the terminus end of the capillary and the downstream exit orifice.

TANDEM QUADRUPOLE MASS SPECTROMETER

A process condition parameter storage unit (51) for a control unit (50) is provided with a dwell time calculation table (51a) indicating the correspondence between CID gas pressure in a collision cell (31) and dwell time for data collection. In the table (51a), the dwell time increases with higher CID gas pressure. When execution of MRM measurement mode is instructed, the control unit (50) determines the dwell time according to the CID gas pressure at that time, and controls a data collecting unit (41) so as to integrate detection signals from an ion detector (34) during the dwell time and obtain an integrated value. When the CID gas pressure of the collision cell (31) is high, ion deceleration is conspicuous and the increase in ionic strength is slow, but when the dwell time is longer, the impact of the slow increase on the integrated value is relatively mitigated and the precision of the integratedvalue is improved. Thus, quantification precision can be improved.

METHOD FOR THE REDUCTION OF A DATA RECORD

Disclosed is a computer method for reducing a data record comprising N (n+1) -tuples (x1a, x2a, ..., xna, ya), wherein a=1,2, ..., N while n amounts to at least 2. Said method encompasses the following steps: a) a first cumulative data record is created by adding up the y-values of the tuples; b) a second cumulative data record is created by replacing the added y-values of the tuples with the sums of the y-values of the tuples whose x2-values lie within an interval around the x2-value of the original tuple of the first cumulative data record; c) a threshold value is determined for the y-values; d) the y-values of the nth cumulative data record are compared to the respective threshold value; e) a reduced data record is generated by removing all tuples whose respective y-value in the nth cumulative data record from step b) or c) does not exceed the threshold value, from the data record that is to be reduced.

MASS SPECTROMETRY OF PROSTAGLANDINS

A liquid chromatography-electrospray ionization mass spectrometry method is capable of separating and identifying different prostaglandin isomers, including PGD2 and PGE2. Unlike traditional as chromatography methods, little sample preparation and no derivatization are required. The chromatography is performed under acidic conditions that are optimal for separating the isomers. A basic sheath flow liquid is added to the chromatographic eluent, resulting in high ionization efficiency when the electrospray ionization is performed in negative ion mode. Additionally, by altering the energy at which the ionization is performed, tandem mass spectra of the two isomers can be made to differ as a result of the different relative energies of the two isomers.

PH GRADIENT ION EXCHANGE LC-MS AND MASS COMPATIBLE BUFFERS

A system for pH gradient ion exchange LC-MS and methods of using such system are described. A buffer system for pH gradient LC-MS that are compatible with a mass spectrometer and methods of using such buffer system are also disclosed.

Combined electrospray/particle beam liquid chromatography/mass spectrometer

A liquid chromatography-mass spectrometry system that can be configured as either a particle beam or an electrospray interface is provided. The device incorporates structural elements that are common to both interfaces thereby eliminating the need to have two completely separate ES and PB LC/MS systems. The LC/MS device according to the present invention generally comprises a momentum separator, nozzle housing, mass spectrometer, and a vacuum subsystem. A mass spectrometer housing encloses a quadrupole mass analyzer. When used in the ES mode, and ES source module is coupled into the inventive device. Similarly, when used in the PB mode, a PB source module is coupled into the inventive device along with a separate source PB probe. The mass analyzer chamber can accommodate a particle beam source probe for generating ions from analyte particles. In either mode, the modules can consist of commercially available interfaces modified for use with the inventive device.

DETERMINATION OF CONCENTRATIONS AND AMOUNTS OF PERFLUOROALKYL SUBSTANCES BY LC/MS/MS

A method and system for injecting an unconcentrated sample into a receiving LC/MS/MS system that is configured to determine a concentration of one or more PFAS analytes within the unconcentrated sample, wherein the LC/MS/MS includes ESI. The unconcentrated sample is subjected to the following ESI conditions: i) a probe gas temperature of approximately 120° C. to approximately 180° C.; ii) a sheath gas heater setting of approximately 250° C. to approximately 400° C.; and iii) a sheath gas flow of approximately 8 L/min to approximately 12 L/min. The unconcentrated sample's concentration and/or an injected amount of the one or more PFAS analytes is determined.

Method and System for Analysing a Dose Formulation of a Metered Dose Device

One aspect of the invention features a method of analyzing dose metered devices by spraying an aerosol from a metered dose device directly into a spray chamber of a mass spectrometer detector by firing a dose from a metered dose device, for example a pMDI, by depressing the pMDI in its actuator, which spraying step is optionally preceded by a step of priming the drug container of the metered dose device; ionizing the aerosol; and identifying and quantifying the content of the dose using the detector.

Method and Apparatus for Correlating Precursor and Product Ions in All-Ions Fragmentation Experiments

A method for matching precursor ions to product ions generated in a chromatography—mass spectrometry experiment comprises: choosing a time window defining a region of interest for precursor ion data and product ion data generated by the experiment; constructing a plurality of extracted ion chromatograms (XICs) for the precursor ion data and the product ion data within the region of interest; automatically detecting and characterizing chromatogram peaks within each XIC and automatically generating synthetic analytical fit peaks thereof; discarding a subset of the synthetic analytical peaks which do not satisfy noise reduction rules; performing a respective cross-correlation score calculation between each pair of synthetic analytical fit peaks; and recognizing matches between precursor ions and product ions based on the cross correlation scores.

Techniques for automated parameter adjustment using ion signal intensity feedback

Described are techniques for tuning parameters of a system. For one or more values of a distance, mass spectral analysis of a liquid analyte stream is performed. A corresponding ion signal intensity of a selected ion is obtained. The distance is measured from a first end of a first tube to a second end of a second tube which surrounds said first tube. Using a computing device, a current value of the distance is automatically adjusted in accordance with corresponding ion signal intensities obtained for the selected ion. Using a computing device, a desired value for the distance is automatically determined using the corresponding ion signal intensities. The desired value results in an ion signal intensity for the selected ion which is any of more than a threshold intensity and a maximum of ion signal intensities obtained by performing mass spectral analysis using different values for the distance.

HAZARDOUS SUBSTANCE ANALYZING SYSTEM

The following six methods included in a method package for hazardous substances in fiber products is stored beforehand in a method storage section (): simultaneous analysis method for specific aromatic amines, simultaneous analysis method for the first group of azo dyes, simultaneous analysis method for the second group of azo dyes, simultaneous analysis method for PFCs, simultaneous analysis method for AP, and simultaneous analysis method for APEO. Each analysis method includes analysis conditions and parameters which are suitable for a simultaneous analysis of a specific category of hazardous substances, e.g. azo dyes. An analysis condition setter () lists the six analysis methods on a display unit (), from which an operator selects one analysis method to be executed. The operator also prepares mobile phases and a column specified for each analysis method. An LC controller () and an MS controller () control each relevant section of the system according to the analysis conditions and parameters described in the selected analysis method, to analyze a sample prepared from a fiber product. By this analysis, a test for major hazardous substances in the fiber product can be performed. A test for a specific hazardous substance which the operator desires to detect can also be easily and efficiently performed. 1. A hazardous substance analyzing system for quantitatively analyzing hazardous substances contained in a sample by using an analyzing device , wherein:a liquid chromatograph mass spectrometer is used as the analyzing device, the liquid chromatograph mass spectrometer including a liquid chromatograph for temporally separating substances contained in a sample to be analyzed and a tandem mass spectrometer for ionizing the substances in the sample temporally separated by the liquid chromatograph and detecting product ions generated by dissociating a specific kind of ion among ions produced by ionization; andthe hazardous substance analyzing system includes: a1) a first ...

ISOTYPING IMMUNOGLOBULINS USING ACCURATE MOLECULAR MASS

This document relates to methods for detecting and quantifying heavy and light chains of immunoglobulin using mass spectrometry techniques. 1. A method for detecting immunoglobulin heavy chains in a sample , the method comprising:a) providing a biological sample comprising immunoglobulins, paired immunoglobulin heavy and light chains, or mixtures thereof;b) immunopurifying the sample, wherein the immunopurifying comprises using an antibody selected from the group consisting of an anti-human IgG antibody, an anti-human IgA antibody, an anti-human IgM antibody, an anti-human IgD antibody, an anti-human IgE antibody, and combinations thereof;c) subjecting the immunopurified sample to a decoupling step wherein immunoglobulin light chains are decoupled from immunoglobulin heavy chains; andd) subjecting the decoupled sample to a mass spectrometry technique to obtain a mass spectrum of the sample, said mass spectrum comprising one or more peaks corresponding to one or more intact immunoglobulin heavy chains in the sample; wherein said one or more peaks quantify the amount of the one or more intact immunoglobulin heavy chains in the sample.2. The method of claim 1 , wherein the antibody is a non-human antibody.3. The method of claim 2 , wherein the non-human antibody is at least one of a camelid antibody claim 2 , a cartilaginous fish antibody claim 2 , llama claim 2 , sheep claim 2 , goat claim 2 , or a mouse antibody.4. The method of claim 3 , wherein the antibody is a single domain antibody fragment (SDAF).5. The method of claim 4 , wherein the SDAF is derived from a camelid antibody claim 4 , a cartilaginous fish antibody claim 4 , llama claim 4 , a mouse antibody claim 4 , sheep claim 4 , goat claim 4 , or a human antibody.6. The method of claim 5 , wherein the SDAF is selected such that the mass spectrum generated in step c) for the single domain antibody fragment does not overlap with the mass spectrum generated in step c) for the immunoglobulin light chain or ...

C PEPTIDE DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques.

INTEGRATED ELECTROSPRAY EMITTER AND METHODS FOR MAKING SAME

An electrospray ionization emitter according to various aspects described herein can include an emitter body formed using fused silica. The emitter body can comprise a fluid conduit segment that includes a liquid connection end that has been coated with polyetheretherketone (PEEK) on at least one portion thereof. The liquid connection end can have a first outer diameter that is configured to be connected to a sample source to receive a sample liquid for ionization therefrom. The emitter body can further comprise an ionization discharge segment that is fluidly connected to the fluid conduit segment. The ionization discharge segment can have an ionization discharge end that is coated with a conductive material on at least one portion thereof and configured to have a second outer diameter that allows ionization of the liquid sample. 1. An electrospray ionization emitter comprising: a fluid conduit segment having a liquid connection end, the liquid connection end being coated with polyetheretherketone (PEEK) on at least one portion thereof and having a first outer diameter configured for connecting to a sample source and receiving a sample liquid for ionization therefrom; and', 'an ionization discharge segment fluidly connected to the fluid conduit segment, the ionization discharge segment having an ionization discharge end, the ionization discharge end being coated with a conductive material on at least one portion thereof and having a second outer diameter configured to allow ionization of the liquid sample, wherein the second outer diameter is smaller than the first outer diameter., 'an emitter body comprising fused silica, the emitter body comprising2. The electrospray ionization emitter of claim 1 , wherein the fluid conduit segment comprises a reinforcement coating on the at least one portion thereof claim 1 , the reinforcement coating being configured to facilitate coating of the at least one portion of the fluid conduit segment with PEEK.3. The electrospray ...

LIQUID SAMPLE INTRODUCTION SYSTEM FOR ION SOURCE AND ANALYSIS SYSTEM

A liquid sample introduction system for an ion source which ionizes a liquid sample by supplying the liquid sample to an ionization probe in an ion source and blowing an atomization-promoting gas at the liquid sample exiting from the tip of the ionization probe, the system including: a hermetically closable liquid sample container for holding a liquid sample; a liquid-supply-gas passage having one end connected to a point in a passage for an atomization-promoting gas leading to the ion source, and the other end connected to a space above a liquid level in the liquid sample container; a sample supply passage having one end connected to a space below the liquid level in the liquid sample container and the other end connected to the ionization probe; and a passage-switching unit in the sample supply passage for switching the sample supply passage between the communicating state and the closed state. 2. The liquid sample introduction system for an ion source according to claim 1 , further comprising a liquid-supply-gas pressure regulator for regulating a pressure of the gas flowing through the liquid-supply-gas passage.3. (canceled)4. The liquid sample introduction system for an ion source according to claim 1 , wherein one of the plurality of sub-ports is connected to an exit port of a liquid chromatograph.5. An analyzing system claim 1 , comprising:an ion analyzer for ionizing a target liquid sample after ionizing the liquid sample in an ionization chamber;{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the liquid sample introduction system for an ion source according to for ionizing a reference liquid sample in the ionization chamber; and'}a control unit for operating the liquid sample introduction system for an ion source so as to supply the reference liquid sample to the ionization probe during an execution of an analysis of an ion generated from the target liquid sample.6. The analyzing system according to claim 5 , wherein the control unit operates the liquid ...

QUANTITATIVE DETECTION METHOD FOR SNAKE VENOM THROMBIN-LIKE ENZYME (SVTLE)

The present invention relates to the technical field of chemical analysis and quantitative detection, in particular to a quantitative detection method for snake venom thrombin-like enzyme (SVTLE) from . The quantitative detection method for the SVTLE includes the following steps of taking a reference substance of marker peptide for the SVTLE from with an amino acid sequence of LDSPVSNSAHIAPLSLPSSAPSVGSVCR, and preparing a series of reference solutions with different concentrations; adding the reference solutions in test solutions respectively for enzymolysis, and then taking a supernatant after enzymolysis as a series of solutions to be detected; and adding the solutions to be detected in a liquid chromatogram-mass spectrometer, and then selecting a qualitative ion pair and a quantitative ion pair to detect contents of marker peptide in the solutions to be detected. 1. A quantitative detection method for snake venom thrombin-like enzyme (SVTLE) , comprising the following specific steps of:{'i': 'Agkistrodon halys pallas', '(1) taking a reference substance of a marker peptide for SVTLE from with an amino acid sequence of LDSPVSNSAHIAPLSLPSSAPSVGSVCR, and dissolving and diluting the reference substance to prepare a series of reference solutions with different concentrations;'}(2) taking a to-be-detected sample, and dissolving the to-be-detected sample to prepare a test solution;(3) taking the series of reference solutions with different concentrations in step (1), adding the test solutions in step (2) respectively for uniform mixing, conducting enzymolysis with trypsin, and then taking supernatants after enzymolysis as a series of solutions to be detected;(4) injecting the solutions to be detected in step (3) into a liquid chromatogram-mass spectrometer respectively, conducting multiple-reaction monitoring by adopting an electrospray positive ion mode, and conducting detection with tricharged 935.8→602.3 as a qualitative ion pair and tricharged 935.8→861.4 as a ...

Rapid Detection of Microbial Resistance to Lactam Antibiotics by LC-MS/MS

A rapid screening process is provided for identification of bacterial resistance to antibiotics by utilizing LC-MS/MS to quantitate concentrations of parent drugs and also detect hydrolysis products which result from beta-lactamase activity. The susceptibility testing is accomplished in time periods as short as 90 minutes, which includes incubation of bacteria with antibiotics and LC-MS/MS analysis. The antibiotics can be multiplexed for incubation with bacteria to minimize analysis time. 23 different strains of have been evaluated by this method including ATCC reference (3) as well as clinical isolates (20) and achieved complete concordance with traditional methods. To date the following antibiotics have been tested: penicillin, ampicillin, amoxicillin, cloxacillin, piperacillin/tazobactam, and cefotaxime. All incubations are conducted in the absence and presence of tazobactam which acts as a control. LC-MS/MS analysis was conducted on an AB SCIEX 3200 QTRAP system utilizing positive ion electrospray with MRM detection. 1. A system for detecting the resistance of a bacterial microbe to one or more antibiotic drugs , comprising:an incubation device configured to incubate a sample mixture of a bacterial microbe and one or more antibiotic drugs over a first time period, wherein initial concentrations of the one or more antibiotic drugs in the sample mixture is known;a separation device configured to separate the one or more antibiotic drugs from the incubated mixture over a second time period that follows the first time period;an ion source device configured to repeatedly transform the separated one or more antibiotic drugs into ions over the second time period;a tandem mass spectrometer configured to repeatedly select and fragment the ions of the one or more antibiotic drugs over the second time period, producing a plurality of product ion spectra for the one or more antibiotic drugs over the second time period; and calculate a chromatogram for product ions of the ...

REPLACEABLE EMITTER ASSEMBLY FOR INTERFACING A SEPARATION COLUMN TO A MASS SPECTROMETER

An electrospray emitter assembly for interfacing a separation column to a mass spectrometer is disclosed. An emitter capillary includes an inlet end and an outlet end. A fitting is coupled to the inlet end of the emitter, configured to be removably connected to the separation column. A stop with a defined through hole is integrated proximate the inlet end of the emitter to produce a path for liquid to flow from the separation column to the emitter via the through hole where a voltage is applied to the liquid entering the emitter. 1. An electrospray emitter assembly for interfacing a separation column to a mass spectrometer , comprising:a. an emitter capillary having an inlet end and an outlet end; andb. a fitting coupled to the inlet end of the emitter, configured to be removably connected to the separation column;wherein a stop with a defined through hole is integrated proximate the inlet end of the emitter to produce a path for liquid to flow from the separation column to the emitter via the through hole where a voltage is applied to the liquid entering the emitter.2. The emitter assembly of wherein the fitting is a female threaded end fitting.3. The emitter assembly of wherein the female threaded end fitting is configured for engagement with a plug type capillary fitting of the separation column.4. The emitter assembly of wherein the emitter capillary comprises a fused silica capillary claim 1 , a metal capillary claim 1 , a ceramic capillary claim 1 , or a glass capillary.5. The emitter assembly of wherein the separation column is removably connected via a transfer line with the emitter capillary through the fitting.6. The emitter assembly of wherein the separation column is a liquid chromatography (LC) column.7. The emitter assembly of wherein the integrated stop has a thickness of up to 1.0 mm.8. The emitter assembly of wherein the integrated stop has a thickness of between 100 μm to 300 μm.9. The emitter assembly of wherein the through hole in the stop has a ...

ISOTYPING IMMUNOGLOBULINS USING ACCURATE MOLECULAR MASS

This document relates to methods for detecting and quantifying heavy and light chains of immunoglobulin using mass spectrometry techniques. 1. A method for detecting immunoglobulin light chains , immunoglobulin heavy chains , or mixtures thereof in a sample , the method comprising:a) providing a sample comprising an immunoglobulin light chain, an immunoglobulin heavy chain, or mixtures thereof;b) immunopurifying the sample; andc) subjecting the immunopurified sample to a mass spectrometry technique to obtain a mass spectrum of the sample.2. The method of claim 1 , wherein immunopurifying comprises using an antibody selected from the group consisting of an anti-human IgG antibody claim 1 , an anti-human IgA antibody claim 1 , an anti-human IgM antibody claim 1 , an anti-human IgD antibody claim 1 , an anti-human IgE antibody claim 1 , an anti-human kappa antibody claim 1 , an anti-human lambda antibody claim 1 , and combinations thereof.3. The method of any one of - claim 1 , wherein the antibody is a non-human antibody.4. The method of any one of - claim 1 , wherein the non-human antibody is at least one of a camelid antibody claim 1 , a cartilaginous fish antibody claim 1 , llama claim 1 , sheep claim 1 , goat claim 1 , or a mouse antibody.5. The method of any one of - claim 1 , wherein the antibody is a single domain antibody fragment.6. The method of any one of - claim 1 , wherein the single domain antibody fragment (SDAF) is selected from the group consisting of an anti-human IgG SDAF claim 1 , an anti-human IgA SDAF claim 1 , an anti-human IgM SDAF claim 1 , an anti-human IgD SDAF claim 1 , an anti-human IgE SDAF claim 1 , an anti-human kappa SDAF claim 1 , an anti-human lambda SDAF claim 1 , and combinations thereof.7. The method of any one of - claim 1 , wherein the single domain antibody fragment is derived from a camelid antibody claim 1 , a cartilaginous fish antibody claim 1 , llama claim 1 , a mouse antibody claim 1 , sheep claim 1 , goat claim 1 , or a ...

MASS SPECTROMETRIC DETERMINATION OF EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID

The invention relates to the detection of DHA and EPA. In a particular aspect, the invention relates to methods for detecting DHA and EPA by mass spectrometry and kits for carrying out such methods. 1. A method for determining the amount of one or more omega-3 fatty acids in a sample by mass spectrometry , the method comprising:(i) ionizing said one or more omega-3 fatty acids from the sample to generate one or more ions detectable by mass spectrometry;(ii) determining the amount of said one or more omega-3 fatty acids ions by mass spectrometry; and(iii) relating the amount of DHA ions to the amount of one or more omega-3 fatty acids in the sample, wherein said one or more omega-3 fatty acids comprises docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA).2. The method of claim 1 , wherein said ionizing comprises atmospheric pressure chemical ionization (APCI).3. The method of claim 2 , wherein said APCI is in negative ionization mode.4. The method of claim 1 , wherein said ionizing comprises electrospray ionization (ESI).5. The method of claim 1 , wherein mass spectrometry comprises tandem mass spectrometry.6. The method of claim 1 , wherein said one or more ions comprise an ion with a mass to charge ratio (m/z) of 327.2±0.5.7. The method of claim 1 , wherein said one or more ions comprise an ion with a mass to charge ratio (m/z) of 301.2±0.5.8. The method of claim 1 , wherein said sample comprises human serum or plasma.9. The method of claim 1 , wherein said sample is subjected to a hydrolyzing agent prior to ionization.10. The method of claim 8 , wherein said hydrolyzing agent is an acid.11. The method of claim 1 , wherein said one or more omega-3 fatty acids is subjected to liquid/liquid extraction prior to ionization.12. The method of claim 1 , wherein said one or more omega-3 fatty acids is purified by liquid chromatography prior to ionization.13. The method of claim 12 , wherein said liquid chromatography comprises high performance liquid ...

METHODS FOR QUANTITATION OF INSULIN AND C-PEPTIDE

Methods are described for diagnosing or prognosing insulin resistance in diabetic and pre-diabetic patients, the method comprising determining the amount of insulin and C-peptide in a sample. Provided herein are mass spectrometric methods for detecting and quantifying insulin and C-peptide in a biological sample utilizing enrichment and/or purification methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for measuring insulin resistance in diabetic or pre-diabetic patients by mass spectrometry , the method comprising:(a) purifying a sample comprising insulin and C-peptide by liquid chromatography;(b) ionizing insulin and C-peptide by an ionization source under conditions suitable to generate one or more insulin and C-peptide ions detectable by mass spectrometry; and(c) determining the amount of one or more insulin and C-peptide ions by mass spectrometry,wherein the amount of the one or more ions determined is used to determine the amount of insulin and C-peptide in the sample.2. The method of claim 1 , wherein the method further comprises measuring creatinine levels.3. The method of claim 1 , wherein the method further comprises measuring body mass index (BMI).4. The method of claim 1 , wherein the method further comprises measuring triglyceride (TG) levels.5. The method of claim 1 , wherein the method further comprises measuring high density lipoprotein C (HDL-C) levels.6. The method of claim 1 , wherein the method further comprises measuring BMI claim 1 , TG claim 1 , and HDL-C levels.7. The method of claim 1 , wherein the method provides an insulin resistance score.8. The method of claim 1 , wherein the method provides a probability of developing insulin resistance.9. The method of claim 1 , wherein said biological sample comprises a plasma or serum sample.10. The method of claim 1 , wherein said ionization source is an electrospray (ESI) ionization source.11. The method of claim 1 , wherein ...

LIQUID CHROMATOGRAPH MASS SPECTROMETER

A liquid chromatograph mass spectrometer specifying a location where a flow path is clogged and recovering in a short time. The liquid chromatograph mass spectrometer includes a first flow path passing through a separation column, a second flow path not passing through the separation column, a mass spectrometry unit on the downstream side of the first and second flow paths and analyzes a sample that has passed through the first flow path, a first valve for connecting any one of the first and second flow paths to the mass spectrometry unit, and a controller for controlling driving of the first valve, connecting the first flow path to the mass spectrometric unit, comparing the measured value of the mass spectrometric unit with a predetermined threshold value, and connecting the second flow path to the mass spectrometry unit when it is determined to be abnormal. 2. The liquid chromatograph mass spectrometer according to claim 1 , wherein claim 1 , after driving the first valve claim 1 , the controller determines whether an ion source of the mass spectrometry unit is clogged based on the pressure of the second flow path measured by the pressure gauge.3. The liquid chromatograph mass spectrometer according to claim 2 , wherein claim 2 , when it is determined that clogging does not occur in the ion source of the mass spectrometry unit claim 2 , the controller determines that clogging occurs on a side of the separation column.4. The liquid chromatograph mass spectrometer according towherein the first liquid feed pump and the second liquid feed pump feed liquid at different pressures.5. The liquid chromatograph mass spectrometer according to claim 1 , further comprising:a plurality of the first flow paths;a plurality of the separation columns, each of which is provided in the plurality of the first flow paths; anda second valve that switches a flow path to any of the plurality of the first flow paths.6. The liquid chromatograph mass spectrometer according to claim 5 , ...

MASS SPECTROMETRY METHOD, MASS SPECTROMETRY , AND MASS SPECTROMETRIC DATA PROCESSING PROGRAM

In a mass spectrometric method of the invention, a mass spectrometer () is used having a mass separation unit () before and after a collision cell () for fragmenting ions. When a product ion corresponding to a precursor ion set for a sample is selected by performing product ion scan with respect to the precursor ion, an exclusion range of mass-to-charge ratios is set based on information on non-selection ions input by a user, and a product ion that satisfies a predefined criterion is selected within a range of mass-to-charge ratios excluding the exclusion range in a product ion spectrum. According to the mass spectrometric method of the invention, product ions suited for measurement on a target compound can be selected. 1. A mass spectrometric method , using a mass spectrometer haying a mass separation unit before and after a collision cell for fragmenting ions , for selecting a product ion corresponding to a precursor ion set for a sample by performing product ion scan with respect to the precursor ion , the method comprising:a) setting one or a plurality of mass-to-charge ratios based on information on non-selection ions input by a user; andb) selecting a product ion that satisfies a predefined criterion within a range excluding the one or plurality of mass-to-charge ratios in a product ion spectrum obtained by the product ion scan.2. The mass spectrometric method according to claim 1 , wherein the one or plurality of mass-to-charge ratios are set as a range haying a width.3. The mass spectrometric method according to claim 2 , wherein the width is determined in accordance with a command input by the user.4. The mass spectrometric method according to claim 1 , wherein a number of product ions are selected claim 1 , the number being indicated by the command input by the user.5. A mass spectrometer haying a mass separation unit before and after a collision cell for fragmenting ions claim 1 , the mass spectrometer being for selecting a product ion corresponding to a ...

CHROMATOGRAPHY APPARATUS HAVING DIFFUSION-BONDED AND SURFACE-MODIFIED COMPONENTS

A microfluidic device for separating a sample by chromatography includes diffusion bonded metallic sheets joined together to create a hermetically sealed interface between each adjacent metallic sheet without the introduction of a secondary material. Enclosed within the diffusion bonded sheets is a separation channel accessible by at least one of an inlet or an outlet. The separation channel is packed with micrometer-sized particles serving as a stationary phase in a chromatographic separation. Wetted surfaces of the separation channel include a coating of an organic material at least one monolayer thick. 1. A diffusion-bonded product manufactured comprising the steps of:supplying two or more substantially compositionally similar metal sheets with each having a flat major surface with no layer thereon to promote bonding; at least one of the two or more metal sheets including at least a portion of a microfluidic channel disposed therein;bringing the flat major surface of each of the two or more metal sheets into a contacting relationship with at least one of the two or more sheets thereby forming an interface and forming and enclosing the microfluidic channel at the interface between such sheets, the microfluidic channel having at least one entrance port and at least one exit port;heating the contacting sheets in a vacuum furnace or an inert-atmosphere furnace to a temperature substantially below melting temperature of such sheets;urging the contacting sheets together under a compressive stress while the sheets are being heated to bond the sheets together by causing grains of the two or more metal sheets to merge across the interface from one sheet to the other sheet;cooling the bonded two or more sheets to about room temperature; andapplying at least an organic coating to the microfluidic channel enclosed between the bonded two or more sheets through at least one of the at least one entrance port or the at least one exit port.2. The diffusion-bonded product of claim ...

CAPILLARY ELECTROPHORESIS-ELECTROSPRAY IONIZATION-MASS SPECTROMETRY SYSTEM

Aspects of the innovations presented herein relate to improved systems that in some embodiments perform capillary electrophoresis (CE) and CE in conjunction with electrospray ionization (ESI) as an input to a mass spectrometry system (MS). Some embodiments use a high voltage isolated CE power supply that is configured to float on the high voltage output of an ESI-MS power supply, with a protective resistance in the ESI-MS path, as well as DC/DC converter isolation and communication system isolation for the isolated CE power supply. Some embodiments additionally use a cartridge assembly integrating separation and conductive fluid capillaries with fluid cooling and protective retractable housings for the capillary end portions and for the ESI output. The protective housing may further be used with an adapter for interfacing with different MS systems. 1. An electrical circuit comprising:a first dc power supply having a first output and a first input;a first resistive electrical path connected to a ground that provides a first dc power supply return from the first output to the first input;a second dc power supply having a second output and a second input;a second resistive electrical path that provides a second dc power supply return from the second output to the second input, wherein the second resistive electrical path is isolated from the ground, and wherein the first output is electrically coupled with the second input;an isolated control circuit that is electrically coupled with the second dc power supply and is isolated from the ground, wherein the isolated control circuit is communicatively coupled with an interface board via a communication link, and wherein the communication link maintains isolation from the ground; anda DC/DC converter that provides isolated input power to the second dc power supply and the isolated control circuit.2. The electrical circuit of wherein the second resistive electrical path is electrically coupled to an electro-spray (ES) ...

SAMPLE INJECTION DEVICE

Provided herein is a sample injection method that enables efficient injection of a trace sample solution while reducing the measurement time. A sample solution is injected into a sample loop with air layers disposed on both sides of the sample solution, and the total amount of the sample solution, including the air layers, is injected into a detector. The start and the end of data collection are determined from the detection signal intensity changes that occur upon the air layers being injected into the detector, and the velocity of the flowing liquid is increased to reduce the measurement time. A washing solution is injected after the air layer to improve the washing efficiency and reduce the washing time. 1. A sample injection method for injecting a sample into a detector , using a sample loop , a container that contains a flowing solvent , a drawing section having a drawing pump , a flow path switching section that switches between (i) a first flow path joining the flowing solvent and the sample loop and a third flow path joining the sample loop and the detector and (ii) a second flow path joining the drawing section and the sample loop , and a liquid passing section having a passing pump coupled to the flow path switching section , the method comprising:switching the flow path switching section to the second flow path, to connect the drawing section including the drawing pump to the sample loop, to disconnect the passing pump from the sample loop, and to disconnect the sample loop from the detector;drawing the sample, using the drawing section with the drawing pump, into the sample loop with air layers disposed on both sides of the sample;switching the flow path switching section to the first flow path to connect the passing pump to the sample loop and the third flow path to connect the sample loop and the detector, and to disconnect the drawing section including the drawing pump from the sample loop; andpassing the flowing solvent from the container, using the ...

IONIZER AND MASS SPECTROMETER

An ionizer includes an ionization probe () provided with a capillary (), a metallic slender tube (), and a nebulizing gas pipe (). The ionization probe () is equipped to perform ESI-based ionization of components in a liquid sample. An electroconductive capillary () is disposed at a position forward in a flow direction of a nebulized flow of the liquid sample from the ionization probe (). A high voltage from a high voltage power supply () is applied to the electroconductive capillary () to induce corona discharge so that the components in the liquid sample are ionized by the APCI as well. At the time of tuning the ionizer, a standard sample solution is provided through the electroconductive capillary (), and a high voltage from the high voltage power supply () is applied to the electroconductive capillary () so that components in the standard sample solution are ionized by the ESI or due to an ion molecular reaction with solvent molecular ions produced in the ionization probe (). Thus, components in a standard sample can be ionized and subjected to mass spectrometry without pipe rearranging operations or without switch to and from different flow paths using a valve. 1. An ionizer , comprising:a nebulizer configured to eject a liquid sample into atmosphere at atmospheric pressure to form a nebulized flow of the liquid sample;an electroconductive capillary disposed at a position forward in a flow direction of the nebulized flow formed by the nebulizer;a liquid provider configured to provide a liquid through the electroconductive capillary; anda voltage application unit configured to apply a voltage to the electroconductive capillary.2. The ionizer according to claim 1 , wherein a nozzle configured to eject the liquid sample; and', 'a heater configured to dry the liquid sample ejected through the nozzle, and, 'the nebulizer includescomponents in the liquid sample are ionized by atmospheric pressure chemical ionization through corona discharge generated by the voltage ...

Pharmaceutical compositions comprising vanoxerine and antianginal compounds, and methods of administration of the same for treating episodes of cardiac arrhythmia, maintaining normal sinus rhythm, preventing recurrence of cardiac arrhythmia, and treatment of chronic cardiac arrhythmia in mammals

Disclosed embodiments are related to pharmaceutical compositions comprising vanoxerine and an antianginal compound and methods of administration of vanoxerine and an antianginal composition to maintain steady state pharmacological concentration levels in a mammal.

SYSTEM AND METHOD FOR DESORBING AND DETECTING AN ANALYTE SORBED ON A SOLID PHASE MICROEXTRACTION DEVICE

Disclosed herein is a system for desorbing and detecting an analyte sorbed on a solid phase microextraction (SPME) device. The system includes a desorption chamber sized to accept the SPME device while defining a void volume of less than about 50 μL; a flow injector in fluid connection with the desorption chamber, the desorption chamber and the flow injector being fluidly connected by at least a flow-insulating fluid connector; a solvent source in fluid connection with the flow injector; and a fluid switch that: in a desorption position, allows the solvent to be sprayed from the flow injector while flow-insulating any desorption solution in the desorption chamber, and in an detecting position, turns off the solvent source while maintaining the fluid connection between the flow injector and the desorption chamber, transferring the desorption solution through the flow-insulating fluid connector to the flow injector as a substantially undiluted plug of liquid. 1. A system for desorbing and detecting an analyte sorbed on a solid phase microextraction (SPME) device , the system comprising:a desorption chamber sized to accept the SPME device while defining a void volume of less than about 50 μL;a flow injector in fluid connection with the desorption chamber, the desorption chamber and the flow injector being fluidly connected by at least a flow-insulating fluid connector;a solvent source in fluid connection with the flow injector; and (a) in a desorption position, allows the solvent to be sprayed from the flow injector while flow-insulating any desorption solution in the desorption chamber, and', '(b) in an detecting position, isolates the solvent source from the flow injector by turning off the solvent flow while maintaining the fluid connection between the flow injector and the desorption chamber so as to transfer desorption solution in the desorption chamber through the flow-insulating fluid connector to the flow injector as a substantially undiluted plug of liquid., ' ...

TECHNIQUES FOR CHECKING STATE OF ANALYZERS

An automated method of monitoring a state of an analyzer is provided including a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream, including monitoring an electrospray ionization current of the ESI source and identifying a condition of multiple conditions of the analyzer based on the monitored ionization current of the ESI source, one of the conditions being a presence of a dead volume in a liquid chromatography stream of the analyzer downstream of an LC column of the LC stream. 1. An automated method of monitoring a state of an analyzer including a mass spectrometer (MS) with an electrospray ionization (ESI) source coupled to a liquid chromatography (LC) stream , the method comprising:monitoring an electrospray ionization current of the ESI source; andidentifying a condition of multiple conditions of the analyzer based on the monitored ionization current of the ESI source, wherein one of the conditions is a presence of a dead volume in a liquid chromatography stream of the analyzer downstream of an LC column of the LC stream.2. The method of claim 1 , further comprising monitoring one or more additional parameters including a pressure in a liquid chromatography (LC) stream of the analyzer claim 1 , wherein the identification of a condition is further based on the monitored additional parameters to distinguish the multiple conditions.3. The method of claim 1 , further comprising monitoring one or more additional parameters including one or more chromatographic features of a chromatogram of a liquid chromatography (LC) stream of the analyzer claim 1 , wherein the identification of a condition is further based on the monitored additional parameters to distinguish the multiple conditions.4. The method of claim 3 , wherein the chromatographic feature is selected from the list consisting of a peak width parameter claim 3 , a retention time parameter claim 3 , a peak height parameter claim 3 , a peak area ...

MASS SPECTROMETRY METHOD AND MASS SPECTROMETER

In a mass spectrometry method for performing a qualitative and/or quantitative determination of an analyte compound contained in a sample, using a mass chromatogram acquired for one or a plurality of ions selected as a reference ion from the ions produced from the analyte compound, the present method includes the steps of: setting one or a plurality of reference-ion candidates for each of the one or a plurality of reference ions; acquiring a mass chromatogram of the sample for each of the set reference-ion candidates; calculating a shape similarity between a peak appearing at a predetermined position on the mass chromatogram and a preset model peak; and designating, as the reference ion, a reference-ion candidate corresponding to a peak having the shape similarity equal to or higher than a predetermined value. 1. A mass spectrometry method for performing a qualitative and/or quantitative determination of an analyte compound contained in a sample , using a mass chromatogram acquired for one or a plurality of ions selected as a reference ion from ions produced from the analyte compound , the method comprising steps of:a) setting one or a plurality of reference-ion candidates for each of the one or a plurality of reference ions;b) acquiring a mass chromatogram of the sample for each of the set reference-ion candidates;c) calculating a shape similarity between a peak appearing at a predetermined position on the mass chromatogram and a model peak represented by a previously defined function; andd) designating, as the reference ion, a reference-ion candidate corresponding to a peak having the shape similarity equal to or higher than a predetermined value.2. The mass spectrometry method according to claim 1 , wherein the reference ion is a target ion and/or a qualifier ion.3. The mass spectrometry method according to claim 1 , wherein the reference ion is a combination of a precursor ion and a product ion.4. The mass spectrometry method according to claim 1 , wherein a ...

Method for Profiling Phytohormone Levels in Plant Tissue

The present invention provides a method for profiling phytohormone levels in plant tissue or tissue of other plastid containing organisms, i.e. a method for the simultaneous determination of a multitude of phytohormone levels in plant tissue or tissue of other plastid containing organisms, which method comprises the following steps: i. extraction of particulate tissue material of the plastid containing organism, in particulate tissue material of plants, with a liquid extractant, which is a mixture of at least one water miscible neutral organic solvent having from 1 to 3 carbon atoms and 1 heteroatom selected from O and N with water containing from 0.1 to 5% by weight, based on the extractant, of at least one acid, whereby a first liquid extract is obtained; ii. contacting the liquid extract obtained in step i. with a solid absorbent having a hydrophobically modified surface and removing the solid absorbent to obtain a second liquid extract; iii. evaporating the solvent from the second extract and then re-dissolving the obtained residue in a solvent mixture of at least one water miscible neutral organic solvent having from 1 to 3 carbon atoms and 1 heteroatom selected from O and N with water containing from 0.1 to 5% by weight, based on the solvent mixture, of at least one acid to obtain a reconstituted extract; iv. purification of the reconstituted extract by contacting it with a solid absorbent having a hydrophobically modified surface to obtain a purified reconstituted extract (eluate); and v. determining the relative concentrations of at least two, frequently at least 4, in particular at least 6, especially at least 8 or at least 10 phyto, e.g. from 2 to 60, frequently from 4 to 50, in particular from 6 to 45, especially from 8 to 40 or from 10 to 30 plant hormones (phytohormones) in the purified reconstituted extract obtained in step iv. by directly subjecting the purified reconstituted extract to an analyzing unit comprising a separation unit for separation the ...

INTEGRATED SAMPLE PROCESSING FOR ELECTROSPRAY IONIZATION DEVICES

Methods, systems and devices that generate differential axial transport in a fluidic device having at least one fluidic sample separation flow channel and at least one ESI emitter in communication with the at least one sample separation flow channel. In response to the generated differential axial transport, the at least one target analyte contained in a sample reservoir in communication with the sample separation channel is selectively transported to the at least one ESI emitter while inhibiting transport of contaminant materials contained in the sample reservoir toward the at least one ESI emitter thereby preferentially directing analyte molecules out of the at least one ESI emitter. The methods, systems and devices are particularly suitable for use with a mass spectrometer. 1. (canceled)2. A method , comprising:introducing a fluid comprising a target analyte and one or more non-target components in an electrolyte medium into a separation channel of a fluidic device, wherein the separation channel is in fluid communication with an emitter located in proximity to a first end of the separation channel;introducing further electrolyte medium into a background channel of the fluidic device, wherein the background channel is in fluid communication with the separation channel through a junction located in proximity to the emitter;maintaining the fluid in the separation channel at a first effective viscosity;maintaining the electrolyte medium in the background channel at a second effective viscosity different from the first effective viscosity; andselectively transporting the target analyte toward the first end of the separation channel.3. The method of claim 2 , wherein the second effective viscosity is smaller than the first effective viscosity.4. The method of claim 2 , wherein the first effective viscosity causes the fluid in the separation channel to have a first electroosmotic mobility in the separation channel claim 2 , the second effective viscosity causes the ...

SIMPLIFIED SOURCE CONTROL INTERFACE

A mass spectrometry system having a simplified control interface includes a processor and a memory. The memory includes instructions that when executed cause the processor to perform the steps of providing a user interface including a plurality of adjustment elements for adjusting at least one results effective parameter and at least one sample descriptive parameter; determining a plurality of instrument control parameters based on the at least one results effective parameter and the at least one sample descriptive parameter; and analyzing a sample while operating according to the plurality of instrument control parameters. 1. A mass spectrometry system having a simplified control interface , comprising:a processor; determining one or more instrument control parameters based upon equations relating a chromatographic liquid flow rate to the one or more instrument control parameters;', 'providing a user interface including a plurality of adjustment elements for adjusting at least one results effective parameter or at least one sample descriptive parameter;', 'adjusting the instrument control parameters based on an offset determined based on the at least one results effective parameter or the at least one sample descriptive parameter; and', 'analyzing a sample while operating according to the plurality of instrument control parameters., 'a memory including instructions that when executed cause the processor to perform the steps of2. The mass spectrometry system of wherein the number of the determined instrument control parameters is greater than the number of results effective parameters and sample descriptive parameters.3. The mass spectrometry system of wherein the at least one results effective parameter includes desired sensitivity.4. The mass spectrometry system of wherein the at least one sample descriptive parameter includes volatility of a sample solvent or stability of a target compound.5. The mass spectrometry system of wherein the instrument control ...

METHODS FOR QUANTITATION OF INSULIN AND C-PEPTIDE

Methods are described for diagnosing or prognosing insulin resistance in diabetic and pre-diabetic patients, the method comprising determining the amount of insulin and C-peptide in a sample. Provided herein are mass spectrometric methods for detecting and quantifying insulin and C-peptide in a biological sample utilizing enrichment and/or purification methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for measuring insulin resistance in diabetic or pre-diabetic patients , the method comprising:(a) subjecting insulin and C-peptide from a sample to an ionization source under conditions suitable to generate one or more insulin and C-peptide ions detectable by mass spectrometry; and(b) determining the amount of one or more insulin and C-peptide ions by mass spectrometry,wherein the amount of the one or more ions determined is used to determine the amount of insulin and C-peptide in the sample.2. The method of claim 1 , wherein the method further comprises measuring creatinine levels claim 1 , body mass index (BMI) claim 1 , triglyceride (TG) levels claim 1 , high density lipoprotein C (HDL-C) levels claim 1 , BMI claim 1 , TG claim 1 , or HDL-C levels.36.-. (canceled)7. The method of claim 1 , wherein the method provides an insulin resistance score or a probability of developing insulin resistance.8. (canceled)9. The method of claim 1 , wherein said biological sample comprises a plasma or serum sample.10. The method of claim 1 , wherein said ionization source is an electrospray (ESI) ionization source.11. The method of claim 1 , wherein said sample is subjected to acidic conditions or basic conditions prior to mass spectrometry.12. The method of claim 11 , wherein subjecting said sample to acidic conditions comprises subjecting said sample to formic acid.13. (canceled)14. The method of claim 11 , wherein subjecting said sample to basic conditions comprises subjecting said sample to trizma and/or ...

METHODS AND SYSTEMS FOR DIAGNOSING DISEASES

The present disclosure provided methods and systems for diagnosing diseases and monitoring their progression and therapeutic responses by detecting a presence or absence, or an increase or decrease, of one or more substances in a sample. 1100.-. (canceled)101. A microfluidic device , comprising:a fluid channel comprising an enrichment region and a separation region downstream of said enrichment region; andan emitter in fluid communication with said fluid channel,wherein said enrichment region is configured to (i) receive a solution comprising a plurality of biomarkers and (ii) concentrate said plurality of biomarkers to yield a concentrated solution comprising said plurality of biomarkers, andwherein said separation region is configured to (i) receive said concentrated solution comprising said plurality of biomarkers and (ii) separate said plurality of biomarkers.102. The microfluidic device of claim 101 , wherein said microfluidic device is monolithic.103. The microfluidic device of claim 101 , wherein said microfluidic device comprises a first substrate adjacent to a second substrate claim 101 , and wherein said emitter is disposed between said first substrate and said second substrate.104. The microfluidic device of claim 103 , wherein said first substrate or said second substrate comprises a semiconductor.105. The microfluidic device of claim 103 , wherein said fluid channel is disposed between said first substrate and said second substrate.106. The microfluidic device of claim 101 , wherein said enrichment region has a different dimension than said separation region.107. The microfluidic device of claim 101 , wherein said emitter comprises a nozzle.108. The microfluidic device of claim 107 , further comprising a base tube in fluid communication with said fluid channel claim 107 , wherein said nozzle extends from said base tube having a larger cross-sectional dimension than said nozzle.109. The microfluidic device of claim 107 , wherein said nozzle has a cross- ...

Use of vapor deposition coated flow paths for improved chromatography of metal interacting analytes

R1, R2, R3, R4, R5, and R6 are each independently selected from (C1-C6)alkoxy, —NH(C1-C6)alkyl, —N((C1-C6)alkyl)2, OH, ORA, and halo. RA represents a point of attachment to the interior surfaces of the fluidic system. At least one of R1, R2, R3, R4, R5, and R6 is ORA. X is (C1-C20)alkyl, —O[(CH2)2O]1-20—, —(C1-C10)[NH(CO)NH(C1-C10)]1-20-, or —(C1-C10)[alkylphenyl(C1-C10)alkyl]1-20-.

IONIZATION METHOD, IONIZATION APPARATUS, AND MASS ANALYSIS SYSTEM

In order to achieve an ionization method of high robustness with a small carry-over or less crosstalk, an ionization method is disclosed. A method includes the steps of: joining an ionization unit to a tube; sucking the sample from a sample container into a sample holder of the ionization unit to hold the sample; moving the ionization unit holding the sample to near the ionization unit using an ionization unit drive unit; and applying a voltage to the ionization unit using a power supply to ionize the sample by electrostatically spraying the sample from the holding unit. 1. An ionization method using an ionization unit having a sample holder configured to hold a sample , an ionization unit drive unit configured to drive the ionization unit , a power supply configured to apply a voltage to the ionization unit , and a sample suction tube , the method comprising the steps of:joining the ionization unit to the tube;sucking the sample from a sample container into a sample holder of the ionization unit to hold the sample;moving the ionization unit holding the sample to near a detecting unit using the ionization unit drive unit; andapplying a voltage to the ionization unit using the power supply to ionize the sample by electrostatically spraying the sample from the sample holder.23.-. (canceled)4. The ionization method according to claim 1 , further comprising the step of moving the sample container containing the sample to near the ionization unit.5. The ionization method according to claim 1 , further comprising the step of moving the ionization unit from near the detecting unit to discard the ionization unit using the ionization unit drive unit.6. The ionization method according to claim 1 , wherein:the ionization unit is an ionization needle including a metal capillary and a sample holding container having a tapered opening; andin the joining step, the opening of the sample holding container is joined to the tube.7. The ionization method according to claim 1 , wherein ...

Methods for detecting lacosamide by mass spectrometry

Provided are methods for determining the amount of lacosamide in a sample using mass spectrometry. The methods generally involve ionizing lacosamide in a sample and detecting and quantifying the amount of the ion to determine the amount of lacosamide in the sample.

POSITIONING OF A NEEDLE-LIKE COMPONENT IN A MASS SPECTROMETRY SYSTEM

A packaging for a needle-like component of a mass spectrometry (MS) system is provided. The packaging includes a receptacle configured for storing the needle-like component in a secured position inside the receptacle. The packaging further comprises an actuator configured to move the needle-like component from the secured position inside the receptacle to a mounting position in which the needle-like component projects out of the receptacle for mounting the needle-like component to the MS system. 1. A packaging for a needle-like component of a mass spectrometry (MS) system , comprising:a receptacle configured for storing the needle-like component in a secured position inside the receptacle;an actuator configured to move the needle-like component from the secured position inside the receptacle to a mounting position in which the needle-like component projects out of the receptacle for mounting the needle-like component to the MS system.2. The packaging of claim 1 , further comprising the needle-like component.3. The packaging of claim 1 , wherein the packaging further comprises a connector element configured to couple the packaging with the MS system.4. The packaging of claim 3 , wherein the connector element includes a fastening element.5. The packaging of claim 4 , wherein the fastening element is a thread claim 4 , a pin claim 4 , an interlock claim 4 , a key claim 4 , a shaped surface or another suitable fastening element to be coupled to a respective counterpart in the MS system to couple the packaging with the MS system.6. The packaging of claim 3 , wherein the connector element is configured to secure the packaging relative to the MS system.7. The packaging of claim 6 , wherein in a secured position of the packaging relative to the MS system the needle-like component is aligned at a predefined angle with a tube of a housing of the needle-like component of the MS system.8. The packaging of claim 1 , wherein the actuator is a pusher configured to push the needle- ...

Benchmark for lc-ms systems

The present invention relates to a method of monitoring performance of a liquid chromatography-mass spectrometry (LC-MS) system, comprising the steps of: (a) performing LC with a first buffer, said first buffer comprising a defined concentration of a first compound, said performing comprising a step of eluting; (b) subjecting the eluate of said LC to electro-spray ionization; and (c) determining the amount of said first compound in said eluate by means of MS, thereby monitoring said performance; wherein said first compound (i) has either no affinity or negligible affinity to the chromatographic matrix; and (ii) is detectable by MS.

Ionizer and mass spectrometer system

In the mass spectrometer system, a tip portion of a cylindrical portion ( 891 ) of a capillary ( 89 ) is coated with a coating material ( 892 ), the tip portion being an injection part for injecting a sample solution to an ionization section. Therefore, it is possible to suppress, by the coating material ( 892 ), the deformation of the capillary ( 89 ) when the sample solution is injected. In addition, it is possible to suppress the corrosion and the deformation of the capillary ( 89 ) by the coating material ( 892 ). As a result, the stability of the analysis operation in mass spectrometer system ( 1 ) can be improved.

Characterization of reaction variables

A microscale method for the characterization of one or more reaction variables that influence the formation or dissociation of an affinity complex comprising a ligand and a binder, which have mutual affinity for each other. The method is characterized in comprising the steps of: (i) providing a microfluidic device comprising a microchannel structures that are under a common flow control, each microchannel structure comprising a reaction microactivity; (ii) performing essentially in parallel an experiment in each of two or more of the plurality of microchannel structures, the experiment in these two or more microchannel structures comprising either a) formation of an immobilized form of the complex and retaining under flow conditions said form within the reaction microactivity, or b) dissociating, preferably under flow condition, an immobilized form of the complex which has been included in the microfluidic device provided in step (i), at least one reaction variable varies or is uncharacterized for said two or more microchannel structures while the remaining reaction variables are kept essentially constant; (iii) measuring the presentation of the complex in said reaction microactivity in said two or more microchannel structures; and (iv) characterizing said one or more reaction variables based on the values for presentation obtained in step (iii).

METHODS FOR DETECTING LACOSAMIDE BY MASS SPECTROMETRY

Provided are methods for determining the amount of lacosamide in a sample using mass spectrometry. The methods generally involve ionizing lacosamide in a sample and detecting and quantifying the amount of the ion to determine the amount of lacosamide in the sample. 1. A method for determining the amount of lacosamide in a sample , said method comprising:(i) purifying lacosamide from said sample by high performance liquid chromatography (HPLC);(ii) ionizing lacosamide and an internal standard to produce at least one lacosamide ion and at least one internal standard ion detectable by mass spectrometry, wherein the ions are fragmented with a collision energy of 35V;(iii) determining the amount of said at least one lacosamide ion and the amount of said at least one internal standard ion by mass spectrometry; and(iv) comparing the amount of said at least one lacosamide ion and the amount of said at least one internal standard ion to determine the amount of lacosamide in the sample;wherein said method has a lower limit of quantitation within the range of 20 μg/ml and 0.5 μg/ml, inclusive.2. The method of claim 1 , wherein said mass spectrometry is tandem mass spectrometry.3. The method of claim 1 , wherein said sample is a body fluid.4. The method of claim 1 , wherein said sample is plasma or serum.5. The method of claim 1 , wherein said internal standard is lacosamide-D3.6. The method of claim 1 , wherein said ionizing is conducted in positive ion mode. This application is a continuation of U.S. application Ser. No. 15/787,439, filed Oct. 18, 2017, which is a continuation of U.S. application Ser. No. 15/388,741, filed Dec. 22, 2016, now U.S. Pat. No. 9,823,227, which is a continuation of U.S. application Ser. No. 14/319,829, filed Jun. 30, 2014, now U.S. Pat. No. 9,530,635, which is a continuation of U.S. application Ser. No. 13/339,267, filed Dec. 28, 2011, now U.S. Pat. No. 8,779,355, each of which is incorporated by reference herein in its entirety.The invention ...

Methods of Multiplexing Sample Analysis by Mass Spectrometry

Provided herein are methods for multiplexed sample analysis by mass spectrometry. The methods may be performed without the need for chemical tagging. The methods also may include the analogous use of frequency modulation to multiplex mass spectrometric analysis, which may be referred to as frequency-modulated continuous flow analysis electrospray ionization mass spectrometry (FM-CFA-ESI-MS). 1. A method of analysis , the method comprising:providing a first liquid at a first flow rate that is varied at a first frequency, wherein the first liquid comprises at least one first analyte;providing a second liquid at a second flow rate that is varied at a second frequency, wherein the second liquid comprises at least one second analyte, and wherein the first frequency and the second frequency are different;combining the first liquid and the second liquid with a third liquid to form a combined liquid, wherein the third liquid has a time-dependent velocity effective to impart the combined liquid with a substantially constant flow rate;analyzing the combined liquid with a mass spectrometer to monitor one or more selected m/z ratios;collecting one or more reconstructed ion chromatograms for the one or more selected m/z ratios; andanalyzing the one or more reconstructed ion chromatograms to determine (i) which of the at least one first analyte, the at least one second analyte, or a combination thereof contributed to a signal, (ii) the relative concentration of the at least one first analyte, the at least one second analyte, or a combination thereof that contributed to the signal, or (iii) a combination thereof.2. The method of claim 1 , wherein the analyzing of the one or more reconstructed ion chromatograms comprises:subjecting the one or more reconstructed ion chromatograms to Fourier transform.3. The method of claim 1 , wherein the analyzing of the one or more reconstructed ion chromatograms reveals one or more time-dependent ion traces claim 1 , and the method further ...

ENHANCED SENSITIVITY OF DETECTION IN ELECTROSPRAY IONIZATION MASS SPECTROMETRY USING A POST-COLUMN MODIFIER AND A MICROFLUIDIC DEVICE

A microfluidic liquid chromatography-electrospray ionization (LC-ESI) device is provided for enhancing the sensitivity of mass spectrometric detection of an analyte in a sample. The device is designed to drive effective intermixing of an analytical flow stream exiting a chromatographic stationary phase and a post-column modifier reagent. The mixed flow stream thus obtained is used for generating an electrospray containing analyte ions. Also provided are methods for enhanced sensitivity of detection of an analyte in a sample. 1. A microfluidic liquid chromatography-electrospray ionization (LC-ESI) device for enhanced detection of an analyte in a sample , the device comprising:a first inlet port fluidly connected to an analytical fluid stream;a second inlet port in fluid communication with a pump for delivering a post-column modifier reagent;an ESI emitter, the emitter having a proximal end and a distal end and defining an emitter flow path therebetween, the proximal end including an interface portion adapted to receive and mix the eluate from an analytical microfluidic channel and the post-column modifier reagent to form a mixed flow stream, the distal end including a distal tip portion adapted to eject the mixed flow stream;an analytical microfluidic channel fluidly connected to the first inlet port and extending to the proximal end of the emitter; anda fluid delivery microfluidic channel fluidly connected to the second inlet port and extending to the proximal end of the emitter;wherein the interface portion comprises a longitudinally extending flow path adapted to receive the analytical flow stream from the analytical microfluidic channel; a laterally extending flow path disposed about the longitudinally extending flow path and adapted to receive the post-column modifier reagent, and a flow diversion device positioned therebetween, the flow diversion device being shaped to drive mixing of the eluate from the analytical microfluidic channel and the post-column ...

Systems and Methods for Ionization

A system for analyzing a sample includes a chromatographic device, an electrospray source, and a mass resolving device. The chromatographic device is configured to separate components of the sample as a function of retention time within a chromatographic column. The electrospray source is configured to direct a first portion of a flow from the chromatographic device via a waste outlet to a pressurized waste reservoir, direct a second portion of the flow to an electrospray ionization outlet to form a spray, and charge and desolvate the spray to form ions of the components of the sample. A flow rate of the second portion of the liquid flow is substantially determined by a pressure of the pressurized waste reservoir. The mass resolving device configured to receive the ions and characterize the mass-to-charge ratio of the ions. 1. A system for analyzing a sample comprising: direct a first portion of a flow from a chromatographic device via a waste outlet to a pressurized waste reservoir;', 'direct a second portion of the flow to an electrospray ionization outlet to form a spray, a flow rate of the second portion of the liquid flow is substantially determined by a pressure of the pressurized waste reservoir; and', 'charge and desolvate the spray to form ions of the components of the sample; and, 'an electrospray source configured to'} receive the ions; and', 'characterize the mass-to-charge ratio of the ions., 'a mass resolving device configured to2. The system of further comprising a chromatographic device configured to separate components of the sample as a function of retention time within a chromatographic column.3. The system of wherein the electrospray ionization outlet includes at least one electrospray emitter.4. The system of wherein the electrospray emitter includes a platinum wire to provide a high voltage to the second portion of the flow at the electrospray emitter.5. The system of wherein the at least one electrospray emitter includes an array of ...

INTEGRATED SAMPLE PROCESSING FOR ELECTROSPRAY IONIZATION DEVICES

Methods, systems and devices that generate differential axial transport in a fluidic device having at least one fluidic sample separation flow channel and at least one ESI emitter in communication with the at least one sample separation flow channel. In response to the generated differential axial transport, the at least one target analyte contained in a sample reservoir in communication with the sample separation channel is selectively transported to the at least one ESI emitter while inhibiting transport of contaminant materials contained in the sample reservoir toward the at least one ESI emitter thereby preferentially directing analyte molecules out of the at least one ESI emitter. The methods, systems and devices are particularly suitable for use with a mass spectrometer. 1generating differential axial transport in a fluidic device having at least one fluidic sample separation channel and at least one ESI emitter in communication with the at least one sample separation channel; andin response to the generated differential axial transport, selectively transporting at least one target analyte contained in a sample reservoir in communication with the sample separation channel to the at least one ESI emitter thereby inhibiting transport of contaminant materials contained in the sample reservoir.. A method of online sample processing for electrospray ionization (ESI), comprising: This application is a continuation of U.S. patent application Ser. No. 15/285,186, filed Oct. 4, 2016 (allowed), which is a continuation of U.S. patent application Ser. No. 14/402,278, filed Nov. 19, 2014, now U.S. Pat. No. 9,502,225, issued Nov. 22, 2016, which is a §371 National Stage Patent Application of PCT Application Serial Number PCT/US2013/044266, filed Jun. 5, 2013, which claims priority to and the benefit of U.S. Provisional Application Ser. No. 61/662,152, filed Jun. 20, 2012, the contents of which are hereby incorporated by reference as if recited in full herein.This invention ...

SIMPLIFIED SOURCE CONTROL INTERFACE

A mass spectrometry system having a simplified control interface includes a processor and a memory. The memory includes instructions that when executed cause the processor to perform the steps of providing a user interface including a plurality of adjustment elements for adjusting at least one results effective parameter and at least one sample descriptive parameter; determining a plurality of instrument control parameters based on the at least one results effective parameter and the at least one sample descriptive parameter; and analyzing a sample while operating according to the plurality of instrument control parameters. 1. A mass spectrometry system having a simplified control interface , comprising:a processor; determining one or more instrument control parameters based upon equations relating a chromatographic liquid flow rate to the one or more instrument control parameters;', 'providing a user interface including a plurality of adjustment elements for adjusting at least one results effective parameter or at least one sample descriptive parameter;', 'adjusting the instrument control parameters based on an offset determined based on the at least one results effective parameter or the at least one sample descriptive parameter; and', 'analyzing a sample while operating according to the plurality of instrument control parameters., 'a memory including instructions that when executed cause the processor to perform the steps of2. The mass spectrometry system of wherein the number of the determined instrument control parameters is greater than the number of results effective parameters and sample descriptive parameters.3. The mass spectrometry system of wherein the at least one results effective parameter includes desired sensitivity.4. The mass spectrometry system of wherein the at least one sample descriptive parameter includes volatility of a sample solvent or stability of a target compound.5. The mass spectrometry system of wherein the instrument control ...

Electrospray emitter assemblies for microfluidic chromatography apparatus

An apparatus for chemical separations includes a microfluidic substrate having an outlet aperture for outputting an eluent of a sample. An emitter assembly includes having a deformable end portion, an inlet near the deformable end portion to receive the sample eluent from the microfluidic substrate, and an electrically conductive outlet portion to emit a spray of the sample eluent. A force-applying unit applies a force to the emitter assembly that urges the deformable end portion into contact with the microfluidic substrate. The deformable end portion is more elastic than the microfluidic substrate so that the contact between the microfluidic substrate and the deformable end portion produces a substantially fluid-tight seal between the outlet aperture of the microfluidic substrate and the inlet of the emitter assembly.

INTEGRATED SAMPLE PROCESSING FOR ELECTROSPRAY IONIZATION DEVICES

Methods, systems and devices that generate differential axial transport in a fluidic device having at least one fluidic sample separation flow channel and at least one ESI emitter in communication with the at least one sample separation flow channel. In response to the generated differential axial transport, the at least one target analyte contained in a sample reservoir in communication with the sample separation channel is selectively transported to the at least one ESI emitter while inhibiting transport of contaminant materials contained in the sample reservoir toward the at least one ESI emitter thereby preferentially directing analyte molecules out of the at least one ESI emitter. The methods, systems and devices are particularly suitable for use with a mass spectrometer. 1generating differential axial transport in a fluidic device having at least one fluidic sample separation channel and at least one ESI emitter in communication with the at least one sample separation channel; andin response to the generated differential axial transport, selectively transporting at least one target analyte contained in a sample reservoir in communication with the sample separation channel to the at least one ESI emitter thereby inhibiting transport of contaminant materials contained in the sample reservoir.. A method of online sample processing for electrospray ionization (ESI), comprising: This application is a continuation of U.S. patent application Ser. No. 16/170,483, filed Oct. 25, 2018 (allowed), which is a continuation of U.S. patent application Ser. No. 15/810,648, filed Nov. 13, 2017, now U.S. Pat. No. 10,134,576, issued Nov. 20, 2018, which is a continuation of U.S. patent application Ser. No. 15/285,186, filed Oct. 4, 2016, now U.S. Pat. No. 9,818,594, issued Nov. 14, 2017, which is a continuation of U.S. patent application Ser. No. 14/402,278, filed Nov. 19, 2014, now U.S. Pat. No. 9,502,225, issued Nov. 22, 2016, which is a § 371 National Stage Patent Application ...

Electrospray Interface Device and Associated Methods

Apparatus, systems, and methods in accordance with various aspects of the applicant's teachings provide for improved interfaces for providing a sample flow from a sample conduit (e.g., an analytical conduit or capillary), including those used in sample separation techniques such as CE and HPLC, to an ESI source for ionization thereby. 1. A device for interfacing with an electrospray ionization source , comprising:a first conduit defining a first microchannel for fluid flow, the first microchannel having an entrance end for receiving a fluid sample containing one or more analytes of interest and an exit end for transmitting said fluid sample therefrom;a second conduit defining a second microchannel for fluid flow, the second microchannel having an entrance end for receiving the fluid sample transmitted from the exit end of the first microchannel and a discharge end for discharging said fluid sample into an ionization chamber of a mass spectrometer system, at least a portion of the second conduit comprising a porous surface, wherein the second conduit is coupled to the first conduit such that the exit end of the first microchannel is aligned with the microchannel of the second conduit so as to allow continuous fluid flow from the exit end of the first microchannel into the entrance end of the second microchannel;a housing at least partially surrounding the first and second conduit and defining a fluid chamber between an inner surface of the housing and the porous surface of the second conduit, the housing having at least one opening through which the second conduit extends from within the housing into the ionization chamber; andan electrode configured to be disposed in fluid contact with a conductive fluid contained within the fluid chamber, the electrode configured to be coupled to a power supply so as to provide an electrical current between the conductive fluid and the fluid sample within the second microchannel via the porous surface.2. The device of claim 1 , ...

Methods of analyzing crude oil

The invention generally relates to methods of analyzing crude oil. In certain embodiments, methods of the invention involve obtaining a crude oil sample, and subjecting the crude oil sample to mass spectrometry analysis. In certain embodiments, the method is performed without any sample pre-purification steps.

Ring Shaped Counter Electrode to Improve Beam Stability and Compound Sensitivity on a Ceramic Tile Type Microfluidic Device

An interface for a mass spectrometer is disclosed comprising a microfluidic substrate, tile or cartridge comprising a liquid chromatography separation column and an electrospray emitter . A counter electrode is arranged downstream of a tip of the electrospray emitter and is arranged and adapted to direct ions towards an atmospheric pressure interface or ion inlet aperture of a mass spectrometer. 1. An interface for a mass spectrometer comprising:a microfluidic substrate, tile or cartridge comprising a liquid chromatography separation column and an electrospray emitter; anda counter electrode arranged downstream from a tip of said electrospray emitter and arranged and adapted to direct ions towards an atmospheric pressure interface or ion inlet aperture of a mass spectrometer.2. An interface as claimed in claim 1 , wherein said counter electrode is arranged at a distance x mm downstream from said tip of said electrospray emitter claim 1 , wherein: (i) x is ≦10 mm claim 1 , ≦9 mm claim 1 , ≦8 mm claim 1 , ≦7 mm claim 1 , ≦6 mm claim 1 , ≦5 mm claim 1 , ≦4 mm claim 1 , ≦3 mm claim 1 , ≦2 mm or ≦1 mm; and/or (ii) x is >0 mm claim 1 , ≧0.5 mm claim 1 , ≧0.6 mm claim 1 , ≧0.7 mm claim 1 , ≧0.8 mm claim 1 , ≧0.9 mm or ≧1 mm.3. An interface as claimed in claim 1 , further comprising a voltage device arranged and adapted to apply a voltage to said electrospray emitter so as to maintain a potential difference between said electrospray emitter and said counter electrode claim 1 , wherein said potential difference between said electrospray emitter and said counter electrode results in the ionisation of droplets emitted from said electrospray emitter.4. An interface as claimed in claim 1 , wherein in use a liquid sample is passed through said liquid chromatography separation column at a flow rate <250 nL/min claim 1 , 250-500 nL/min claim 1 , 500-750 nL/min claim 1 , 750-1000 nL/min claim 1 , 1-2 μL/min claim 1 , 2-3 μL/min claim 1 , 3-4 μL/min claim 1 , 4-5 μL/min claim 1 , 5-6 ...

C PEPTIDE DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for determining the amount of C peptide in a sample by tandem mass spectrometry , the method comprising:(a) purifying a sample containing C peptide by high performance liquid chromatography (HPLC);(b) ionizing C peptide to generate one or more C peptide ions detectable by mass spectrometry;(c) determining the amount of one or more C peptide ions by tandem mass spectrometry, wherein the determined ions comprise a fragment ion with mass to charge ratio of 646.1±0.5;wherein the amount of ions determined in step (c) is related to the amount of a C peptide in said sample.2. The method of claim 1 , wherein said HPLC is 1-D HPLC.3. The method of claim 1 , wherein further comprising subjecting to solid phase extraction (SPE).4. The method of claim 3 , wherein said SPE and HPLC are conducted with on-line processing.5. The method of claim 1 , wherein said sample is from a human.6. The method of claim 1 , wherein said sample is plasma.7. The method of claim 1 , wherein said sample is serum.8. The method of claim 1 , wherein said mass spectrometry is high resolution/high accuracy mass spectrometry.9. The method of claim 8 , wherein said high resolution/high accuracy mass spectrometry is conducted at a FWHM of 10 claim 8 ,000 and a mass accuracy of 50 ppm.10. The method of claim 8 , wherein said high resolution/high accuracy mass spectrometer is a high resolution/high accuracy time-of-flight (TOF) mass spectrometer.11. The method of claim 1 , wherein the ionization is in positive ion mode. This application is a continuation of U.S. application Ser. No. 17/027,267, filed Sep. 21, 2020, now U.S. Pat. No. 11,346,845, which is a continuation of U.S. ...

Data Processing Device and Method for the Evaluation of Mass Spectrometry Data

A data processing device comprises a processor unit adapted to process a plurality of initial data vectors provided by a chromatograph and/or a mass spectrometer, the processing being carried out in one, two or more processing steps producing items of processed data, and a storage unit adapted to save and retrieve initial data vectors and/or items of processed data, in particular processed data vectors or identified compounds, and/or items of additional data, in particular properties of the sample introduced in the mass spectrometer. Each item of processed data and/or additional data is connected to at least one initial data vector, and wherein the processor unit is adapted to group, select and/or modify initial data vectors and/or items of processed data according to one or more items of additional data. 1. A data processing device , comprising a processor unit adapted to process a plurality of initial data vectors provided by a chromatograph and/or a mass spectrometer , the processing being carried out in one , two or more processing steps producing items of processed data , and a storage unit adapted to save and retrieve initial data vectors and/or items of processed data , in particular processed data vectors or identified compounds , and/or items of additional data , in particular properties of the sample introduced in the mass spectrometer , wherein each item of processed data and/or additional data is connected to at least one initial data vector , and wherein the processor unit is adapted to group , select and/or modify initial data vectors and/or items of processed data according to one or more items of additional data.2. The data processing device of claim 1 , wherein each initial data vector is assigned a unique identifier claim 1 , and wherein each item of processed data is connected to an item of processed data from a preceding processing step of the same initial data vector and/or directly to the initial data vector.3. The data processing device of ...

C PEPTIDE DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for determining the amount of C peptide in a sample by tandem mass spectrometry , the method comprising:(a) subjecting a sample suspected of containing C peptide to high performance liquid chromatography (HPLC) to obtain a fraction enriched in C peptide;(b) subjecting the enriched C peptide to an ionization source under conditions suitable to generate one or more C peptide ions detectable by mass spectrometry;(c) determining the amount of one or more C peptide ions by tandem mass spectrometry, wherein said determined ions comprise one or more fragment ions selected from the group of ions with mass to charge ratios consisting of 785.4±0.5 and 646.1±0.5;wherein the amount of ions determined in step (c) is related to the amount of a C peptide in said sample.2. The method of claim 1 , wherein said HPLC is 1-D HPLC.3. The method of claim 1 , wherein said ionization source is an electrospray (ESI) ionization source.4. The method of claim 1 , wherein further comprising subjecting to solid phase extraction (SPE).5. The method of claim 1 , wherein said sample comprises a biological sample.6. The method of claim 1 , wherein said sample is from a human.7. The method of claim 1 , wherein said sample comprises a body fluid sample.8. The method of claim 1 , wherein said sample comprises plasma or serum.9. A method for determining the amount of C peptide in a sample by tandem mass spectrometry claim 1 , the method comprising:(a) subjecting a sample suspected of containing C peptide to solid phase extraction (SPE) and 1-D high performance liquid chromatography (1-D HPLC) to obtain a fraction enriched in C peptide;(b) subjecting the fraction enriched C ...

Mobility Electrophoresis Separation Device, Operating Method Thereof, and Interface Between Liquid Chromatography and Mass Spectrometry

The present invention provides a mobility electrophoresis separation device, its operating method, and an interface between liquid chromatography and mass spectrometry. The mobility electrophoresis separation device comprises a separation capillary, a syringe pump for injecting a buffer solution, a syringe for injecting a sample solution, and two electrodes disposed apart from each other on either side of the separation capillary. A sample solution is injected by a syringe at a position of the capillary channel, and a buffer solution is injected into the capillary channel upstream the first position, and carries the sample solution to flow downstream. While the mixed liquid flows through the capillary, an electric field is applied in the direction of the flow. Different ions in the sample are thus separated in the flow due to their different velocities traveling in the flow. 1. A mobility electrophoresis separation device , comprising:a separating capillary comprising a first end and a second end, the first end of the separation capillary comprises an electrospray tip and the second end comprising a buffer solution injection end;a syringe pump connected to the buffer solution injection end;a syringe connected to the separation capillary at a position close to the syringe pump;a separation electrode, connected to the syringe pump, or connected to the separation capillary at a position close to the syringe pump; anda ground electrode, connected to the separation capillary at a position close to the electrospray tip.2. The mobility electrophoresis separation device according to claim 1 , wherein said mobility electrophoresis separation device further comprises:a first multi-way valve, through which the syringe pump and the syringe are connected to the separation capillary; anda second multi-way valve, through which the ground electrode is connected to the separation capillary.3. The mobility electrophoresis separation device according to claim 2 , wherein the ...

PRE-ASSEMBLED SEPARATION COLUMNS

There is provided an integrated system for liquid separation, such as LC, CE, affinity chromatography, and ion exchange chromatography, comprising a column and end-fittings embedded in a plastic material, such as a thermoplastic polymer. The system may further comprise an electrospray emitter directly connected with the outlet of the column, wherein a substantial part of the emitter is covered with the polymer material. There is also provided a method by which a separation column along with the accompanying end fittings for connection with adjacent liquid conduits is embedded in a polymer matrix. This configuration e.g. ensures that the factory-made, correct attachment of the fittings to the column is preserved (since the matrix prevents further user intervention, accidental or otherwise). Accordingly, the responsibility for the correct attachment of the fittings is shifted from the end user to the manufacturer. 1. An integrated separation column comprising end fittings and an electrospray emitter , wherein the separation column is connected directly or via a transferring conduit with the electrospray emitter through one of the end fittings , and said separation column , end fittings and electrospray emitter being embedded in a plastic material.2. The integrated separation column of claim 1 , wherein the electrospray emitter is either based on a glass capillary coated with electrically conductive material or a conductive metal.3. The integrated separation column of claim 2 , wherein the integrated separation column and electrospray emitter are embedded in the same plastic material.4. The integrated separation column of further comprising one of more of:RFID-tag, heating/cooling bars and thermo sensor, a high-voltage contact point for the electrospray emitter, counter electrode(s) with a geometry that benefits definition of the field lines around the electrospray emitter, and channels for gas flow embedded in the same plastic material.5. The integrated separation ...

METHODS FOR DETECTING LACOSAMIDE BY MASS SPECTROMETRY

Provided are methods for determining the amount of lacosamide in a sample using mass spectrometry. The methods generally involve ionizing lacosamide in a sample and detecting and quantifying the amount of the ion to determine the amount of lacosamide in the sample. 1. A method for determining the amount of lacosamide in a sample , said method comprising:(i) purifying lacosamide from said sample by high performance liquid chromatography (HPLC);(ii) ionizing lacosamide to produce at least two lacosamide fragment ions comprising a quantifier ion and a qualifier ion detectable by mass spectrometry;(iii) determining the amount of lacosamide by measuring the amount of a quantifier ion and confirming the identity of the lacosamide ion by detecting a qualifier ion by mass spectrometry.2. The method of claim 1 , wherein said quantifier ion has a mass/charge ratio of 91.0±0.5.3. The method of claim 1 , wherein said qualifier ion has a mass/charge ratio of 108.0±0.5.4. The method of claim 1 , wherein said mass spectrometry is tandem mass spectrometry.5. The method of claim 1 , wherein said sample is plasma.6. The method of claim 1 , wherein said sample is serum.7. The method of claim 1 , wherein said ionizing is by electrospray ionization.8. The method of claim 1 , wherein said ionizing is conducted in positive ion mode. This application is a continuation of U.S. application Ser. No. 16/927,769, filed Jul. 13, 2020, now U.S. Pat. No. 11,360,061, which is a continuation of U.S. application Ser. No. 16/715,823, filed Dec. 16, 2019, now U.S. Pat. No. 10,712,319, which is a continuation of U.S. application Ser. No. 15/787,439, filed Oct. 18, 2017, now U.S. Pat No. 10,509,016, which is a continuation of U.S. application Ser. No. 15/388,741, filed Dec. 22, 2016, now U.S. Pat. No. 9,823,227, which is a continuation of U.S. application Ser. No. 14/319,829, filed Jun. 30, 2014, now U.S. Pat. No. 9,530,635, which is a continuation of U.S. application Ser. No. 13/339,267, filed Dec. 28, ...

MASS SPECTROMETRY ASSAY METHOD FOR DETECTION AND QUANTITATION OF ORGANIC ACID METABOLITES

A method for determining in a sample, by mass spectrometry, the presence, absence, or amount of one or more analytes is described herein. The run time is less than six minutes. The method includes subjecting the sample to an ionization source under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the one or more analytes, wherein the one or more analytes are derivatized prior to ionization; measuring, in a single injection, by mass spectrometry, the amount of the one or more ions from each of the one or more analytes; and using the measured amount of the one or more ions to determine the amount of each of the one or more analytes in the sample. 130-. (canceled)31. A method for determining in a sample , by mass spectrometry , the presence , absence , or amount of one or more analytes selected from the group consisting of Acetic acid (C2) , Propionic acid (C3) , Butyric acid (C4) , Isobutyric acid (C4) , 2-Methyl-butyric acid (C5) , Isovaleric acid (C5) , Valeric acid (C5) , Caproic acid (Hexanoic acid , C6) , 3-Methylvaleric acid , 4-Methylvaleric acid (Isocaproic acid) , Lactic acid , Pyruvic acid , Fumaric acid , Succinic acid , Malic acid , alpha-Ketoglutaric acid , Aconitic acid , Citric acid , Isocitric acid , and combinations thereof , wherein the run time is less than six minutes , the method comprising:a) subjecting the sample to an ionization source under conditions suitable to produce one or more ions detectable by mass spectrometry from each of the one or more analytes, wherein the one or more analytes are derivatized prior to ionization;b) measuring, in a single injection, by mass spectrometry, the amount of the one or more ions from each of the one or more analytes; andc) using the measured amount of the one or more ions to determine the amount of each of the one or more analytes in the sample.32. The method of claim 31 , wherein pivalic acid interference is eliminated.33. The method of claim 31 , wherein the ...

IONIZATION PROBE CONNECTION JIG, LIQUID CHROMATOGRAPH, AND LIQUID CHROMATOGRAPH MASS SPECTROMETER

An ionization probe connection jig used to connect an outlet-side flow path of a column and an inlet-side flow path of an ionization probe in a liquid chromatograph, the ionization probe connection jig includes: a first element fixture fixed to a first element that is one of the column and the ionization probe ; a second element fixture fixed to a second element that is the other; and a movement regulating tool that permits the first element fixture to advance in an axial direction of the first element while regulating the first element or the first element fixture and the second element or the second element fixture such that flow paths of the first element and the second element are matched with each other, and regulates the second element fixture such that the second element fixture does not retreat beyond a predetermined position in a axial direction of the second element 1. An ionization probe connection jig used to connect an outlet-side flow path of a column and an inlet-side flow path of an ionization probe in a liquid chromatograph , the ionization probe connection jig comprising:a) a first element fixture fixed to a first element that is one of the column and the ionization probe;b) a second element fixture fixed to a second element that is the other of the column and the ionization probe; andc) a movement regulating tool configured to permit the first element fixture to advance in an axial direction of the first element and to restrict the second element fixture such that the second element fixture does not retreat beyond a predetermined position in an axial direction of the second element, while regulating the first element or the first element fixture and the second element or the second element fixture such that flow paths of the first element and the second element are aligned with each other.2. The ionization probe connection jig according to claim 1 , further comprisingd) a pressing mechanism configured to press the first element fixture so as to ...

MASS SPECTROMETRIC DETERMINATION OF EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID

The invention relates to the detection of DHA and EPA. In a particular aspect, the invention relates to methods for detecting DHA and EPA by mass spectrometry and kits for carrying out such methods. 1. A method for determining the amount of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) in a sample by mass spectrometry , the method comprising:(i) hydrolyzing the sample containing DHA and/or EPA with an acid;(ii) extracting DHA and/or EPA from the sample by liquid-liquid extraction;(iii) ionizing DHA and/or EPA from the sample to generate one or more ions detectable by mass spectrometry;(iv) determining the amount of DHA and/or EPA ions by mass spectrometry; and(v) relating the amount of DHA and/or EPA ions to the amount of DHA and/or EPA in the sample.2. The method of claim 1 , wherein said ionizing comprises atmospheric pressure chemical ionization (APCI).3. The method of claim 2 , wherein said APCI is in negative ionization mode.4. The method of claim 1 , wherein said ionizing comprises electrospray ionization (ESI).5. The method of claim 1 , wherein mass spectrometry comprises tandem mass spectrometry.6. The method of claim 1 , wherein mass spectrometry comprises single mass spectrometry.7. The method of claim 1 , wherein said one or more ions comprise an ion with a mass to charge ratio (m/z) of 327.2±0.5.8. The method of claim 1 , wherein said one or more ions comprise an ion with a mass to charge ratio (m/z) of 301.2±0.5.9. The method of claim 1 , wherein said sample comprises human serum or plasma.10. The method of claim 1 , wherein said acid is hydrochloric acid.11. The method of claim 1 , wherein said DHA and/or EPA is purified by liquid chromatography prior to ionization.12. The method of claim 11 , wherein said liquid chromatography comprises high performance liquid chromatography (HPLC).13. The method of claim 1 , wherein said method comprises determining the amount of an internal standard.14. The method of claim 13 , wherein said internal ...

DETECTION AND QUANTITATION OF GUANIDINOACETATE, CREATINE, AND CREATININE BY MASS SPECTROMETRY

Provided are methods for detecting or determining the amount of guanidinoacetate (GAA), creatine, and creatinine by mass spectrometry. 1. A method for detecting or determining the amount of guanidinoacetate (GAA) , creatine , and creatinine comprising:(a) purifying GAA, creatine, and creatinine in the sample;(b) ionizing GAA, creatine, and creatinine in the sample to produce one or more ion(s) of GAA, creatine, and creatinine;(c) detecting the ion(s) from step (b) by mass spectrometry;wherein the amount of the GAA, creatine, and creatinine ion(s) is related to the amount of GAA, creatine, and creatinine in the sample.2. The method of claim 1 , wherein said purifying comprises liquid chromatography.3. The method of claim 2 , wherein said liquid chromatography comprises high performance liquid chromatography (HPLC).4. The method of claim 1 , wherein said GAA claim 1 , creatine claim 1 , and creatinine are underivatized.5. The method of claim 1 , wherein said ionization comprises electrospray ionization (ESI).6. The method of claim 1 , wherein said ionization comprises ionizing in positive mode.7. The method of claim 1 , further comprising adding an internal standard.8. The method of claim 7 , wherein said internal standard is isotopically labeled.9. The method of claim 1 , wherein the sample is urine.10. The method of claim 1 , wherein the sample is serum.11. The method of claim 1 , wherein the limit of quantitation of the methods is less than or equal to 0.4 mg/L.12. The method of claim 1 , wherein the limit of quantitation of the methods is less than or equal to 0.3 mg/L.13. The method of claim 1 , wherein said ionizing comprises generating a guanidinoacetate (GAA) precursor ion with the mass/charge ratio of 118.1±0.5.14. The method of claim 13 , wherein the method further comprises generating one or more fragment ions with the mass/charge ratio of 72.1±0.5.15. The method of claim 1 , wherein said ionizing comprises generating a creatine precursor ion with the mass/ ...

USE OF GLYCAN AS BIOMARKERS FOR AUTOIMMUNE DISEASES

The present invention discloses a method of determining the presence of autoimmune disease with the use of glycan biomarkers. A method of improving the detection sensitivity of trace glycans from a mixture of glycans and a microfluidic chip therefor are also disclosed. 19-. (canceled)10. A microfluidic chip for enriching trace glycan from a mixture of glycans comprising an enrichment column that attaches to an analytical column , a first section that includes porous graphitized carbon;', 'a second section that connects to said first section and includes titanium dioxide; and', 'a third section that connects to said second section and includes porous graphitized carbon;, 'wherein said enrichment column enriches acidic glycans and includes'}wherein said analytical column includes porous graphitized carbon;wherein said first section and said third section of said enrichment column perform pre-enrichment of glycans to remove non-glycan constituents; said second section of said enrichment column performs enrichment of acidic glycans; and said analytical column performs chromatographic separation of glycans, such that detection sensitivity of low-abundance trace glycans is highly enhanced when a mixture of glycans runs through the microfluidic chip.11. The microfluidic chip of wherein said trace glycan is acidic glycan.12. The microfluidic chip of wherein said trace glycan is sulfated glycan.13. The microfluidic chip of wherein said trace glycan comprises a structure set forth in .14. A method of improving the detection sensitivity of trace glycan from a mixture of glycans comprising:a) loading a sample of said mixture of glycans onto an enrichment column;b) running said neutral glycans from step (a) onto an analytical column that performs chromatographic separation of glycans while said acidic glycans are retained on said enrichment column and 'wherein said enrichment column enriches acidic glycans while said analytical column performs chromatographic separation of ...

METHODS OF ANALYZING CRUDE OIL

The invention generally relates to methods of analyzing crude oil. In certain embodiments, methods of the invention involve obtaining a crude oil sample, and subjecting the crude oil sample to mass spectrometry analysis. In certain embodiments, the method is performed without any sample pre-purification steps. 120-. (canceled)21. A method for analyzing a crude oil sample for presence of a nitrogenous corrosion inhibitor , the method comprising:obtaining a crude oil sample from an oil pipeline, wherein the crude oil sample comprises a quaternary ammonium salt;introducing the crude oil sample to a porous paper substrate;applying solvent and voltage to the crude oil sample on the substrate to generate ions of the quaternary ammonium salt; andanalyzing the ions using a mass spectrometer to identify a nitrogenous corrosion inhibitor in the crude oil sample.22. The method according to claim 21 , wherein the mass spectrometer is selected from the group consisting of a bench-top mass spectrometer and a miniature mass spectrometer.23. The method according to claim 21 , wherein the method is performed without any intervening sample purification steps between the obtaining and introducing steps and between the introducing and applying steps.24. The method according to claim 23 , wherein the applying step is conducted without an external heat source.25. The method according to claim 21 , wherein the quaternary ammonium salt is selected from the group consisting of tetradodecylammonium bromide claim 21 , benzylhexadecyldimethylammonium chloride claim 21 , and a combination thereof.26. The method according to claim 21 , wherein the mass spectrometer is coupled with a discontinuous atmospheric pressure interface.27. The method according to claim 21 , wherein the solvent comprises a mixture of methanol and acetonitrile.28. The method according to claim 21 , wherein the porous substrate is paper.29. The method according to claim 28 , wherein the paper is filter paper.30. The method ...

Monitoring Liquid Chromatography Elution to Determine When to Perform a Lockmass Calibration

A method of mass spectrometry is disclosed that comprises acquiring mass spectral data during a single experimental run or acquisition of a mass spectrometer and determining a first time T during the single experimental run or acquisition for calibrating the mass spectrometer. The step of determining the first time T further comprises determining a time when the mass spectral data being acquired during the single experimental run or acquisition is equal to or below a threshold. The mass spectrometer is then calibrated by introducing calibrant or lockmass ions at the first time T. 1. A method of mass spectrometry comprising:acquiring mass spectral data during a single experimental run or acquisition of a mass spectrometer;determining a first time T during said single experimental run or acquisition for calibrating said mass spectrometer, wherein the step of determining further comprises determining a time when said mass spectral data being acquired during said single experimental run or acquisition is equal to or below a threshold; andcalibrating said mass spectrometer by introducing calibrant or lockmass ions at said first time T.2. A method as claimed in claim 1 , wherein said single experimental run or acquisition is carried out between a second time tand a third time t claim 1 , and wherein t Подробнее

METHOD FOR CHIRAL SEPARATION OF METHAMPHETAMINE AND AMPHATAMINE ENANTIOMERS

Methods for routine high throughput analysis with accurate results to determine the concentration of d- and/or l-isomers of methamphetamine and/or amphetamine in biological samples is provided. In some examples, the method includes mixing of a biological sample with an internal standard and diluting with a mobile phase, followed by eluting on a chiral stationary phase contained in a liquid chromatography column. The eluent obtained can then be analyzed using a mass analyzer for the presence of the analytes. 1. A method of detecting d- and/or l-enantiomers of methamphetamine and/or amphetamine in a biological sample from a subject , comprising:(a) preparing a sample for liquid chromatography by adding an internal standard into the biological sample;(b) subjecting the sample to liquid chromatography column comprising a chiral stationary phase; and(c) analyzing the eluent for the presence of said enantiomers using a mass analyzer.2. The method of claim 1 , further comprising centrifuging the sample after adding the internal standard.3. The method of claim 2 , further comprising diluting the sample after centrifuging the sample.4. The method of claim 1 , wherein the chiral stationary phase comprises macrocyclic glycopeptides.5. The method of claim 1 , wherein the biological sample is a bodily fluid selected from the group consisting of saliva claim 1 , sweat claim 1 , urine claim 1 , blood claim 1 , serum claim 1 , plasma claim 1 , spinal fluid claim 1 , and combinations thereof.6. The method of claim 1 , wherein the eluent is ionized prior to analyzing.7. The method of claim 6 , wherein the eluent is ionized via electrospray ionization technique.8. The method of claim 1 , wherein the mass analyzer is a quadrupole mass spectrometer.9. The method of claim 1 , wherein derivatization or extraction of the enantiomer by solid phase extraction is not performed. Drug abuse cases have been increasing in number and causing a serious social problem in recent years. Illicit drug ...

INTEGRATED SYSTEM FOR LIQUID SEPARATION AND ELECTROSPRAY IONIZATION

The present invention relates to an integrated system for liquid separation, such as LC, CE, affinity chromatography, and ion exchange chromatography. A preferred aspect relates to a specialised protection means for protecting the fragile electrospray needle when not in use. Another preferred aspect relates to a specialised electrical contact means for applying voltage to the electrospray needle. The invention comprises an integrated system for liquid separation and electrospray ionization comprising: a separation column; and an electrospray emitter connected with the separation column. In one aspect there is a retractable protective sleeve () for covering and supporting the electrospray emitter () along at least a portion of its axis. In another aspect there is an electrically conducting sheath surrounding the emitter and providing an electrical connection. 2. The integrated system of claim 1 , wherein the retractable protective sleeve is moveable to a retracted position wherein a tip of the electrospray emitter is uncovered.3. The integrated system according to claim 1 , wherein the protective sleeve is enclosed within and is moveable within an outer sheath.4. The integrated system according to claim 3 , wherein the outer sheath is an electrically conducting sheath.5. The integrated system according to claim 1 , wherein the separation column and electrospray emitter are embedded in a plastic material.6. The integrated system according to claim 1 , wherein the separation column is connected directly or via a transferring conduit with the electrospray emitter through one or more end fittings claim 1 , and said separation column claim 1 , end fittings and electrospray emitter are embedded in a plastic material.7. The integrated system according to claim 1 , wherein the separation column is an LC column.8. The integrated system according to claim 1 , wherein the separation column is coiled in a loop.9. The integrated system according to claim 1 , wherein the ...

Microfluidic Glycan Analysis

Microfluidic devices and methods for analyzing glycan profiles of glycoproteins are provided. Some embodiments of the devices comprise a deglycosylation column for cleaving glycans, an optional cleaning column for removing proteins, a trapping column for enriching glycans, and a separation column for resolving glycans. The devices and methods significantly improve the speed and sensitivity of glycan analysis. 2. The device of claim 1 , further comprising a cleaning column capable of binding proteins claim 1 , wherein the cleaning column is configured to be connectable to the deglycosylation column and/or the trapping column by the valve system.3. The device of claim 1 , wherein the enzyme is N-glycosidase F.4. The device of claim 1 , wherein the solid support in the deglycosylation column comprises beads or a monolithic medium.5. The device of claim 1 , wherein the separation column is a liquid chromatography column.6. The device of claim 1 , wherein the separation column is a capillary electrophoresis apparatus.7. The device of that comprises two layers claim 1 , wherein the deglycosylation column is in one layer claim 1 , and the trapping column and separation column are in the other layer.8. The device of that comprises three layers claim 2 , wherein the deglycosylation column is in a first layer claim 2 , the cleaning column is in a second layer claim 2 , and the trapping column and separation column are in a third layer.9. A system for analyzing a sample claim 1 , comprising the device of claim 1 , the switching element claim 1 , and a mass spectrometer.10. The system of claim 9 , wherein the mass spectrometer comprises an electrospray ion source.11. A method for analyzing the carbohydrate moieties of glycoproteins claim 9 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'applying a sample that may comprise glycoproteins to the device of ;'}digesting the glycoproteins in the deglycosylation column to result in cleaved carbohydrates;binding the ...

Simplified source control interface

A mass spectrometry system having a simplified control interface includes a processor and a memory. The memory includes instructions that when executed cause the processor to perform the steps of providing a user interface including a plurality of adjustment elements for adjusting at least one results effective parameter and at least one sample descriptive parameter; determining a plurality of instrument control parameters based on the at least one results effective parameter and the at least one sample descriptive parameter; and analyzing a sample while operating according to the plurality of instrument control parameters.

ELECTRODE ARRAY DEVICES AND METHODS

A plurality of electrodes may be arrayed to provide a lateral passage for analyte particles introduced off-axis, communicating with a central passage aligned with an outlet. 1. An electrode array having an upstream end and a downstream end , comprising:a plurality of electrode layers, each electrode layer comprising a plurality of electrodes disposed around a central aperture and spaced apart one from the other to provide an open inter-electrode space comprising the central aperture and at least one lateral gap contiguous with the central aperture and extending outward therefrom between adjacent electrodes;wherein the electrode layers are disposed in a stacked arrangement whereby the central apertures of the electrode layers are aligned to provide a central passage through the central apertures of a plurality of adjacent electrode layers and extending to the downstream end of the electrode array, and lateral gaps of the electrode layers are aligned to provide at least one lateral passage extending through the lateral gaps of a plurality of adjacent electrode layers and communicating with the central passage; andwherein the central aperture cross-section of successive electrode layers is decreasing in the downstream direction over at least a portion of the electrode array.2. An apparatus comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'an electrode array according to ;'}a direct current (DC) power supply controllable to apply DC potentials to electrodes of the electrode array in a gradient whereby the DC potential varies in the downstream direction; anda radio frequency (RF) power supply controllable to apply RF potentials to a plurality of electrodes in a plurality of electrode layers of the electrode array, whereby the RF potentials of opposing electrodes are in phase and the RF potentials of adjacent electrodes are of opposite phase.3. The electrode array of claim 1 , wherein the ratio of the central aperture cross-section of the electrode layer ...

SYSTEM AND METHOD OF ANALYSIS OF A PROTEIN USING LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY

The present disclosure pertains to method and system of characterizing a protein using an electrospray ionization source. 1. An electrospray ionization source , comprising:a container having a cap, wherein the cap has an inlet line port and an outlet line port;a sheath gas inlet line for providing a sheath gas to the inlet line port; anda modified desolvation gas outlet line capable of connecting the outlet line port to a sheath gas inlet of an electrospray ionization probe.2. The electrospray ionization source of claim 1 , wherein the container comprises an organic solvent and an additional chemical component.3. The electrospray ionization source of claim 2 , wherein the additional chemical component is an acid or a base.4. (canceled)5. The electrospray ionization source of claim 2 , wherein the organic solvent is acetonitrile.6. The electrospray ionization source of claim 3 , wherein the acid is trifluroacetic acid.7. The electrospray ionization source of claim 4 , wherein the base is triethylamine.8. The electrospray ionization source of claim 1 , wherein the electrospray ionization probe comprises an auxiliary gas inlet.910.-. (canceled)11. The electrospray ionization source of claim 8 , wherein the auxiliary gas inlet is supplied with an auxiliary gas.12. The electrospray ionization source of claim 1 , wherein the electrospray ionization probe comprises an electrospray emitter needle claim 1 , a sheath gas flow plumbing claim 1 , and an auxiliary gas flow plumbing.13. The electrospray ionization source of claim 12 , wherein the electrospray ionization probe is configured to direct flow in the sheath gas flow plumbing coaxially to the electrospray emitter needle.14. The electrospray ionization source of claim 12 , wherein the electrospray ionization probe is configured to direct the flow in the auxiliary gas flow plumbing coaxially to the electrospray emitter needle.15. (canceled)16. The electrospray ionization source of claim 1 , wherein the sheath gas inlet ...

Apparatus for Improved Immunosuppressant Drug Monitoring

A liquid chromatography/mass spectrometry system includes: a source of a first mobile phase solvent consisting essentially of water plus 10 mM ammonium formate plus 0.05% formic acid; a source of a second mobile phase solvent consisting essentially of methanol plus 10 mM ammonium formate plus 0.05% formic acid; a chromatography column comprising a length of 30 mm or less of a stationary phase comprising an 8-carbon alkyl chain material bonded to 2.6 μm diameter particles having solid silica cores surrounded by porous silica outer layers; an electrospray ion source of a mass spectrometer fluidically coupled to the chromatography column so as to generate ions therefrom; a mass analyzer of the mass spectrometer operable to quantitatively detect the ions; and a programmable processor electronically coupled to the mass analyzer and comprising instructions operable to determine, based on the ion detection, a concentration of everolimus, sirolimus, tacrolimus, or cyclosporin A. 1. A liquid chromatography/mass spectrometry system , comprising:a source of a first mobile phase solvent (MPA) consisting essentially of water plus 10 mM ammonium formate plus 0.05% formic acid;a source of a second mobile phase solvent (MPB) consisting essentially of methanol plus 10 mM ammonium formate plus 0.05% formic acid;a length of tubing operable to receive a liquid sample therein;a chromatography column comprising a length of 30 mm or less of a stationary phase comprising an 8-carbon alkyl chain material bonded to 2.6 μm diameter particles having solid silica cores surrounded by porous silica outer layers;a first and a second fluidic pump operable to respectively propel a first flow of the MPA solvent and a first flow of the MPB solvent through, in sequence, a first fluidic junction, the length of tubing and the chromatography column;a third and a fourth fluidic pump operable to respectively propel a second flow of the MPA solvent and a second flow of the MPB solvent through, in sequence, a ...

METHODS OF QUANTIFYING N2-(1-CARBOXYETHYL)-2'-DEOXY-GUANOSINE (CEDG) AND SYNTHESIS OF OLIGONUCLEOTIDES CONTAINING CEDG

Methods of quantifying N-carboxyethyl-2′-deoxyguanosine (CEdG) levels in biological samples and comparing those levels to known normal levels can diagnose a number of disorders, including diabetes and cancer. Methods can also determine whether therapies for disorders are effective by measuring CEdG levels before and after treatment. Measurement of CEdG levels occurs using liquid chromatography electrospray ionization tandem mass spectrometry. 1. A method of quantifying levels of N-carboxyethyl-2′-deoxyguanosine (CEdG) (R) and CEdG-R/10dG and CEdG (S) advanced glycation end products in a biological sample from a subject , comprising:{'sup': 15', '15', '15, 'sub': 5', '5', '5, 'performing a liquid chromatography electrospray ionizing tandem mass spectrometry assay (LC-ESI-MS/MS) on the biological sample using a stable isotope dilution comprising using an internal N-carboxyethyl-2′-deoxyguanosine (N-CEdG) standard comprising stereochemically pure N-CEdG (R) and stereochemically pure (S); and'}measuring the levels of CEdG (R) and CEdG (S) from the biological sample.2. The method of claim 1 , further comprising adding aminoguanidine and/or D-penicillamine to the biological sample prior to quantifying the levels of CEdG (R) and CEdG (S).3. The method of claim 1 , wherein the levels of CEdG (R) and CEdG (S) in the biological sample are compared to normal physiological levels of CEdG (R) and CEdG (S).4. The method of claim 1 , wherein the biological sample is a urine sample or a tissue sample.5. The method of claim 4 , wherein the tissue sample is a tumor tissue.6. The method of claim 5 , wherein the tumor tissue is a glycolytic cancer tumor tissue.7. The method of claim 6 , wherein the glycolytic cancer is breast claim 6 , kidney claim 6 , lung claim 6 , liver claim 6 , pancreas claim 6 , colon claim 6 , cervix claim 6 , or endometrial cancer.8. The method of claim 1 , wherein the internal standard comprises oligonucleotides containing stereochemically pure N-CEdG (R) and ...

QUANTITATION OF NAPHTHENIC ACIDS IN WATER AND CRUDE OIL

The present disclosure relates generally to processes for accurate quantitation of naphthenic acids in liquid samples. The method allows efficient identification as well as quantitation of NA species based on carbon number and ring structure, but requires no chemical modification or extraction of the sample allowing a rapid throughput. Reverse phase liquid chromatographic separation of the sample minimizes (or eliminates) matrix suppression effects to allow detection of all NAs present in various samples by mass spectroscopy with superior detection thresholds that are as much as 350-fold lower than conventional methods. 1. A process for quantitating one or more naphthenic acids in a liquid sample , comprising:a. Subjecting a portion of the liquid sample to reverse phase high performance liquid chromatography utilizing a chromatography column capable of separating molecules having a molecular weight of 2,000 or less to produce a chromatography effluent comprising at least partially separated naphthenic acids, each naphthenic comprising from 2 to 25 carbons;b. Directing the chromatography effluent to an electrospray ionization source to produce negatively charged naphthenic acid ions that are analyzed on a mass spectrometer to produce a raw mass spectrum; wherein the response factor is empirically-determined via measurement of the relative mass spectrum peak intensity of known quantities of carboxylic acid standards comprising between 2 and 25 carbons, the response factor being dependent upon the number of carbons in the carboxylic acid standards, the number of ring structures in the carboxylic acid standards, or both,', 'wherein the response factor corrects the signal magnitude of the one or more spectral peaks corresponding to the one or more naphthenic acids, thereby allowing more accurate quantitation of the one or more naphthenic acids in the liquid sample., 'c. Correcting the raw mass spectrum by multiplying the intensity of one or more spectral peaks ...

SYSTEMS FOR QUANTITATION OF NAPHTHENIC ACIDS IN WATER AND CRUDE OIL

The present disclosure relates generally to systems for accurate quantitation of naphthenic acids in liquid samples. The system allows efficient identification as well as quantitation of NA species based on carbon number and ring structure, but requires no chemical modification or extraction of the sample allowing a rapid throughput. Reverse phase liquid chromatographic separation of the sample minimizes (or eliminates) matrix suppression effects to allow detection of all NAs present in various samples by mass spectroscopy with superior detection thresholds that are as much as 350-fold lower than conventional systems. 1. A system for quantitating one or more naphthenic acids in a liquid sample , comprising:a. a reverse phase high performance liquid chromatography column configured to separate molecules having a molecular weight of 2,000 or less to produce a chromatography effluent comprising at least partially separated naphthenic acids comprising from 2 to 25 carbons;b. an electrospray ionization source connected to receive the at least partially separated naphthenic acids and produce negatively charged naphthenic acid ions;c. a mass spectrometer configured to detect the ratio of mass to charge for the negatively charged naphthenic acid ions within the sample mass spectrum and produce raw mass spectrum data comprising one or more spectral peaks representing a quantity of naphthenic acid; wherein the response factor is empirically-determined via measurement of the relative mass spectrum peak intensity of known quantities of carboxylic acid standards comprising between 2 and 25 carbons, the response factor being dependent upon the number of carbons in the carboxylic acid standards, the number of ring structures in the carboxylic acid standards, or both,', 'wherein the response factor corrects the signal magnitude of the one or more spectral peaks corresponding to the one or more naphthenic acids, thereby allowing more accurate quantitation of the one or more ...

C PEPTIDE DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for determining the amount of C peptide in a sample by tandem mass spectrometry , the method comprising:(a) subjecting a sample suspected of containing C peptide to high performance liquid chromatography (HPLC) to obtain a fraction enriched in C peptide;(b) subjecting the enriched C peptide to an ionization source under conditions suitable to generate one or more C peptide ions detectable by mass spectrometry;(c) determining the amount of one or more C peptide ions by tandem mass spectrometry, wherein said determined ions comprise a precursor ion with a mass to charge ratio of 1007.5±0.5 and one or more fragment ions selected from the group of ions with mass to charge ratios consisting of 927.6±0.5, 785.4±0.5, and 646.1±0.5;wherein the amount of ions determined in step (c) is related to the amount of a C peptide in said sample.2. The method of claim 1 , wherein said HPLC is 1-D HPLC.3. The method of claim 1 , wherein said ionization source is an electrospray (ESI) ionization source.4. The method of claim 1 , wherein the sample is subjected to solid phase extraction (SPE) prior to HPLC.5. The method of claim 4 , wherein said SPE and HPLC are conducted with on-line processing.6. The method of claim 1 , wherein said sample comprises a biological sample.7. The method of claim 1 , wherein said sample is from a human.8. The method of claim 1 , wherein said sample comprises a body fluid sample.9. The method of claim 1 , wherein said sample comprises plasma or serum.10. The method of claim 1 , wherein said one or more fragment ions comprise two or more fragment ions selected from the group consisting of 927.6±0.5 claim 1 , 785.4±0.5 claim 1 , ...

Process For The Characterization Of Glatiramer Acetate

The present invention is directed to process for characterization of Glatiramer acetate. The present invention further relates to process for characterization of Glatiramer acetate using size exclusion chromatography coupled with ultra performance liquid chromatography (SEC-UPLC) and high resolution mass spectrometry (HRMS). The present invention further provides statistical methods for characterizing and classifying Glatiramer acetate. 1. A process for characterizing of Glatiramer acetate , the process comprising:a. subjecting a sample of Glatiramer acetate to size exclusion chromatography (SEC);b. separating various fractions based on its size and subjecting the separated fractions through reverse phase chromatography to HRMS;c. processing of electrospray ionized ion masses and obtaining deconvoluted masses for checking mass distribution pattern of Glatiramer acetate; andd. characterizing the Glatiramer acetate using a statistical model.2. The process of claim 1 , wherein the size exclusion chromatography is coupled with ultra-performance liquid chromatography and UV detector (SEC-UPLC-UV).3. The process of claim 1 , wherein electrospray ionized masses data are generated by tandem mass spectrometric data such as ESI-QTOF.4. The process of claim 1 , wherein step (c) is performed using Unifi software version 1.8.2.169 from Waters.5. The process of claim 1 , wherein characterizing the Glatiramer acetate involves used of statistical models for the determination of mean mass claim 1 , standard deviations claim 1 , distribution curves claim 1 , +1 and −1 deviations and mass categorizations for characterization of Glatiramer acetate.6. A process for characterization of mixture of polypetides claim 1 , the process comprising using SEC-HRMS (Vion IMS-QTof) and statistical models for interpretations and illustrations wherein the mixture of polypetides consists of L-Alanine claim 1 , L-Tyrosine claim 1 , L-Lysine and L-Glutamic acid. The present invention is directed to ...

Platform for Native Liquid Chromatography-Mass Spectrometry

Disclosed are native liquid chromatography-mass spectrometry systems and methods of use. A native liquid chromatography-mass spectrometry system can include a liquid chromatography system capable of separating a sample; and an electrospray ionization mass spectrometry (ESI-MS) system in fluid communication with the liquid chromatography system, wherein the ESI-MS system comprises a multi-nozzle electrospray ionization emitter and a system for modifying a desolvation gas and a mass spectrometer, wherein the mass spectrometer is configured to receive ions and characterize mass to charge ratio of ions. 1. A native liquid chromatography-mass spectrometry system , comprising:a liquid chromatography system capable of separating a sample; andan electrospray ionization mass spectrometry (ESI-MS) system in fluid communication with the liquid chromatography system, wherein the ESI-MS system comprises a multi-nozzle electrospray ionization emitter, a system for modifying a desolvation gas, and a mass spectrometer, wherein the mass spectrometer is configured to receive ions and characterize mass to charge ratio of ions.2. The native liquid chromatography-mass spectrometry system of claim 1 , wherein the system for modifying a desolvation gas comprises a container having a cap and comprising an organic solvent and an additional chemical component comprising an acid or a base claim 1 , wherein the cap has an inlet line port and an outlet line port; a sheath gas inlet line for providing a sheath gas to the inlet line port; and a modified desolvation gas outlet line capable of connecting the modified desolvation gas outlet line port to the multi-nozzle electrospray ionization emitter.34-. (canceled)5. The native liquid chromatography-mass spectrometry system of claim 2 , wherein the acid is trifluoroacetic acid and wherein the base is triethylamine.67-. (canceled)8. The native liquid chromatography-mass spectrometry system of claim 2 , wherein the organic solvent is acetonitrile.9. ...

C PEPTIDE DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for determining the amount of C peptide in a sample by high resolution/high accuracy mass spectrometry , the method comprising:(a) subjecting a sample suspected of containing C peptide to solid phase extraction (SPE) to obtain a fraction enriched in C peptide;(b) subjecting the enriched C peptide to an ionization source under conditions suitable to generate one or more C peptide ions detectable by mass spectrometry;(c) determining the amount of one or more C peptide ions by high resolution/high accuracy mass spectrometry;wherein the amount of ions determined in step (c) is related to the amount of a C peptide in said sample.2. The method of claim 1 , wherein the sample is subjected to high performance liquid chromatography (HPLC) prior to ionization.3. The method of claim 1 , wherein said ionization source is an electrospray (ESI) ionization source.4. The method of claim 2 , wherein said SPE and HPLC are conducted with on-line processing.5. The method of claim 1 , wherein said sample comprises a biological sample.6. The method of claim 1 , wherein said sample is from a human.7. The method of claim 1 , wherein said sample comprises a body fluid sample.8. The method of claim 1 , wherein said sample comprises plasma or serum.9. The method of claim 1 , wherein said one or more ions detected in step (c) comprise a precursor ion with a mass to charge ratio (m/z) of about 1007.5±0.5.10. The method of claim 1 , wherein said one or more C peptide ions comprise two or more fragment ions selected from the group consisting of 927.6±0.5 claim 1 , 785.4±0.5 claim 1 , and 646.1±0.5.11. The method of claim 10 , wherein relating said ions determined in ...

IDENTIFICATION OF IMMUNOGLOBULINS USING MASS SPECTROMETRY

This document relates to materials and methods for identifying and/or quantifying immunoglobulins from a biological sample without pre-purification of the immunoglobulins prior to ionization and detection using mass spectrometry. For example, a monoclonal light chain from a monoclonal immunoglobulin may be observed using matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry after diluting a sample containing the monoclonal immunoglobulin with an aqueous buffer containing acid and a reducing agent then mixing the sample with alpha-cyano-4-hydroxycinnamic acid matrix (CHCA). In another example, an intact monoclonal immunoglobulin may be observed in a sample using MALDI-TOF mass spectrometry after diluting the sample containing the monoclonal immunoglobulin with water then mixing the sample with CHCA matrix. 1. A method for identifying and/or quantifying monoclonal and/or polyclonal immunoglobulins in a sample comprising the steps of:(i) providing a sample of blood, serum, plasma or cerebrospinal fluid containing an immunoglobulin from a subject;(ii) diluting the sample with water or an aqueous buffer to form a diluted sample;(iii) ionizing the diluted ample and detecting and optionally quantifying intact immunoglobulin or a light chain or a heavy chain of the immunoglobulin by mass spectrometry.2. A method according to wherein the sample is at least partially dried and is rehydrated with the water or aqueous buffer.3. A method according to claim 1 , wherein the immunoglobulin is not enriched prior to detecting and optionally quantifying the intact immunoglobulin or light chain or heavy chain by mass spectrometry.4. A method according to wherein the immunoglobulins are not enriched by affinity purification or size exclusion chromatography.5. A method according to claim 1 , wherein the mass spectrometry is liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS).6. A method according to claim 1 , wherein the diluted ...

HIGH SENSITIVITY ELECTROSPRAY INTERFACE

The invention provides a sheath-flow interface for producing electrospray from a capillary. The electrospray generated by the interface can be used as the source of ions for mass spectrometry. Electrokinetic flow in the interface can move a sheath liquid past the end of a capillary so as to mix with an analyte effluent discharged from the capillary. The sheath liquid and analyte mixture can be directed to an electrospray emitter to generate an electrospray. 1. A sheath-flow interface for producing electrospray from a capillary comprising:(a) a capillary configured to contain an analyte liquid, the capillary having an injection end configured to receive the analyte liquid and a distal end configured to expel analyte effluent, wherein the outer diameter of a segment of the distal end tapers to a reduced outer diameter within the range of about 20 μm to about 200 μm;(b) an electrospray emitter coaxially disposed surrounding at least the distal end of the capillary, the electrospray emitter having a distal end that is tapered to terminate at an opening, the opening being coaxially disposed in relation to the distal end of the capillary; and(c) a sheath liquid reservoir in liquid communication with an interior of the electrospray emitter, such that an electrically conductive sheath liquid can flow from the sheath liquid reservoir, through a connecting fixture intermediate the capillary and the electrospray emitter, across the distal end of the capillary, and through the opening at the distal end of the electrospray emitter;wherein the sheath liquid provides electrical contact between the capillary and the electrospray emitter, the sheath-flow interface is configured to produce a nanospray generated by electrokinetic flow of the sheath liquid mixed with the analyte effluent, and the electrokinetic flow is generated by an electric potential between the electrospray emitter and a target surface disposed adjacent, but not in physical contact with, the opening of the emitter. ...

Automated Adjustment of Capillary Voltage Based on the Elution Conditions to Retain Optimal Ionization Conditions

A method of Electrospray ionisation is disclosed comprising passing a sample liquid through a liquid chromatography column, monitoring a liquid chromatography back pressure and varying a voltage applied to an Electrospray ionisation source electrode in dependence upon said monitored liquid chromatography back pressure. 1. A method of Electrospray ionisation comprising:passing a sample liquid through a liquid chromatography column;monitoring a liquid chromatography back pressure; andvarying a voltage applied to an Electrospray ionisation source electrode in dependence upon said monitored liquid chromatography back pressure.2. A method as claimed claim 1 , wherein said voltage is applied to said Electrospray ionisation source electrode in order to ionise said sample liquid.3. A method as claimed in claim 1 , wherein said voltage is applied to a capillary of said Electrospray ionisation ion source claim 1 , wherein the application of said voltage to said capillary ionises said sample liquid passing through and emerging from said capillary.4. A method as claimed in claim 1 , further comprising:pre-determining, predicting or estimating a relationship between said monitored liquid chromatography back pressure and an optimal value of said voltage for ionising a sample; andvarying said voltage applied to said Electrospray ionisation source electrode in dependence upon said monitored liquid chromatography back pressure using said pre-determined, predicted or estimated relationship.5. A method as claimed in any preceding claim 1 , further comprising:determining a relationship between said monitored liquid chromatography back pressure and an optimal value of said voltage for ionising a sample during one or more initial liquid chromatography runs; andvarying said voltage applied to said Electrospray ionisation source electrode in dependence upon said monitored liquid chromatography back pressure using said determined relationship during one or more subsequent liquid ...

METHODS FOR DETECTING LACOSAMIDE BY MASS SPECTROMETRY

Provided are methods for determining the amount of lacosamide in a sample using mass spectrometry. The methods generally involve ionizing lacosamide in a sample and detecting and quantifying the amount of the ion to determine the amount of lacosamide in the sample. 1. A method for determining the amount of lacosamide in a sample , said method comprising:(i) subjecting the sample to protein precipitation;(ii) purifying lacosamide from said sample by high performance liquid chromatography (HPLC);(iii) ionizing lacosamide and an internal standard by electrospray ionization (ESI) to produce at least one lacosamide ion and at least one internal standard ion detectable by mass spectrometry;(iv) determining the amount of said at least one lacosamide ion and the amount of said at least one internal standard ion by mass spectrometry; and(v) comparing the amount of said at least one lacosamide ion and the amount of said at least one internal standard ion to determine the amount of lacosamide in the sample;wherein said method has a lower limit of quantitation within the range of 20 μg/ml and 0.5 μg/ml, inclusive.2. The method of claim 1 , wherein said mass spectrometry is tandem mass spectrometry.3. The method of claim 1 , wherein said sample is a body fluid.4. The method of claim 1 , wherein said sample is plasma or serum.5. The method of claim 1 , wherein said ionizing comprises generating a lacosamide precursor ion with a mass/charge ratio of 251.0±0.5 claim 1 , and generating one or more lacosamide fragment ions selected from the group consisting of ions with a mass/charge ratio of 91.0±0.5 and 108.0±0.5.6. The method of claim 1 , wherein said internal standard is lacosamide-D3.7. The method of claim 1 , wherein said ionizing comprises generating an internal standard precursor ion with a mass/charge ratio of 254.0±0.5 claim 1 , and generating an internal standard fragment ion with a mass/charge ratio of 91.0±0.5.8. The method of claim 1 , wherein said ionizing is conducted ...

METHOD OF USING CHEMICAL TAGS TO IMPROVE THE IDENTIFICATION, QUANTIFICATION AND SPATIAL LOCALIZATION OF COMPONENTS IN A SAMPLE

The present disclosure relates to a method for using chemical tags which have two or more sites for ionization to improve quantification and identification of components of interest from a complex mixture. This method relies on first selectively reacting one or more component in a sample with a chemical tag having two or more sites for ionization, followed by separation of components based on charge status, and finally characterization of each component to identify the same. Additionally disclosed are compounds useful as chemical tags in the disclosed methods. 1. A method of identifying components of a sample comprising:a) selectively reacting a component in the sample with a chemical tag which has two or more sites for ionization;b) separating the components using ion mobility spectrometry or capillary electrophoresis; andc) analyzing the sample to identify the components therein.2. The method of claim 1 , wherein the separation according to ion mobility spectrometry separates components based on the charge state of the component molecules.36-. (canceled)7. The method of claim 1 , wherein the sample is analyzed using an electrophoretic technique.810-. (canceled)11. The method of claim 1 , wherein the separation of the components in step b) is done using ion-mobility spectrometry (IM) and the analysis of the sample in step c) is done using MS.1213-. (canceled)14. The method of claim 1 , wherein the chemical tag contains a moiety which absorbs in the visible (VIS) spectrum or the infrared (IR) spectrum.1527-. (canceled)28. The method of claim 1 , further comprising calculating a collisional cross section (CCS) value of the ionized molecules claim 1 , wherein the collision cross section value assists in the identification of components in the sample.29. (canceled)30. The method of claim 1 , wherein the chemical tag comprises two or more functional groups which are readily ionizable claim 1 , each independently selected from amino claim 1 , carboxylic acid claim 1 , ...

Systems and Methods for Pesticide Detection

This disclosure provides quantitative, rapid, and reliable LC-MS/MS methods for analyzing panels of pesticides and mycotoxins in various samples, including very hydrophobic and chlorinated compounds normally analyzed on a GC-MS/MS system. The methods can be carried out using a single instrument and can detect and quantify levels of the pesticides and mycotoxins that are well below action limits specified by U.S. states (e.g., California) and other countries (e.g., Canada) for these compounds in cannabis products.

METHOD AND SYSTEM OF IDENTIFYING AND QUANTIFYING ANTIBODY FRAGMENTATION

Methods and system for identifying and quantifying antibody fragments and identifying the site of fragmentation on an antibody are provided herein. 1. A method for identification of a site of fragmentation of an antibody , said method comprising:contacting a sample including at least one fragment of the antibody to a chromatographic system having a mixed-mode size-exclusion chromatography resin with an additional functionality;washing said mixed-mode size-exclusion chromatography resin using a mobile phase to provide an eluent with the at least one fragment of the antibody;determining molecular weight data of the at least one fragment of the antibody in said eluent using a mass spectrometer; andcorrelating the molecular weight data of the at least one fragment of the antibody to data obtained from at least one known protein standard.2. The method of claim 1 , wherein the mobile phase has ammonium acetate claim 1 , ammonium bicarbonate claim 1 , or ammonium formate claim 1 , or combinations thereof.3. The method of claim 1 , wherein the mobile phase has a total concentration of less than about 600 mM of ammonium acetate and ammonium bicarbonate.4. The method of claim 1 , wherein the mobile phase has a flow rate of about 0.2 ml/min-about 0.4 ml/min.5. The method of claim 1 , wherein the amount of the sample loaded onto the mixed-mode size-exclusion chromatography resin is about 10 μg to about 100 μg.6. The method of claim 1 , wherein the antibody is a monoclonal antibody.7. The method of claim 1 , wherein the antibody is a bispecific antibody.8. The method of claim 1 , wherein the antibody is a therapeutic antibody.9. The method of claim 1 , wherein the mass spectrometer is coupled to the chromatographic system.10. The method of claim 1 , wherein the site of fragmentation of the antibody is in hinge region of the antibody.11. The method of claim 1 , wherein the site of fragmentation of the antibody is in a constant immunoglobulin domain.12. The method of claim 1 , ...

DIFLUOROACETIC ACID ION PAIRING REAGENT FOR HIGH SENSITIVITY, HIGH RESOLUTION LC-MS OF BIOMOLECULES

The present disclosure relates to the determination of analytes in a sample using chromatography. The present disclosure provides methods of separating an analyte from a sample. A mobile phase is flowed through a chromatography column. The mobile phase includes about 0.005% (v/v) to about 0.20% (v/v) difluoroacetic acid and less than about 100 ppb of any individual metal impurity. A sample including the analyte is injected into the mobile phase. The analyte is separated from the sample. 1. A method of separating an analyte from a sample , the method comprising:flowing a mobile phase through a chromatography column wherein the mobile phase comprises about 0.005% (v/v) to about 0.20% (v/v) difluoroacetic acid and less than about 100 ppb of any individual metal impurity;injecting a sample comprising the analyte into the mobile phase; andseparating the analyte from the sample.2. The method of claim 1 , wherein the chromatography column is a liquid chromatography column.3. The method of claim 1 , wherein the chromatography column is a reversed phase chromatography column.4. The method of claim 1 , wherein the chromatography column further comprises a stationary phase having a phenyl-based surface chemistry.5. The method of claim 4 , wherein the stationary phase is a superficially porous silica stationary phase bonded with phenyl moieties.6. The method of claim 4 , wherein the stationary phase is a fully porous silica stationary phase bonded with phenyl moieties.7. The method of claim 4 , wherein the stationary phase is an organosilica stationary phase bonded with phenyl moieties.8. The method of claim 1 , wherein the chromatography column further comprises a stationary phase having a polymeric polystyrene divinyl benzene surface chemistry.9. The method of claim 1 , wherein the mobile phase comprises less than about 50 ppb of any individual metal impurity.10. The method of claim 1 , wherein the mobile phase comprises less than about 20 ppb of any individual metal impurity ...

METHODS FOR QUANTIFYING POLYPEPTIDES USING MASS SPECTROMETRY

A method for identifying a polypeptide a specimen can include (i) treating a specimen suspected of including an insulin with a base; (ii) extracting a first fraction of the treated specimen by solid phase extraction using a mixed mode or polymeric reversed-phase media and a first solvent including an acid; (iii) separating a component of the first fraction by liquid chromatography using a chromatographic surface including a hydrophobic surface group and one or more ionizable modifiers, and a second solvent including an acid; and (iv) analyzing the component of the first fraction by mass spectroscopy, thereby identifying the polypeptide, if present, using a signal corresponding to a sequence fragment ion from the polypeptide. The signal can correspond to an intact multiply charged precursor fragment selected in a first quadrupole and its corresponding sequence fragment ion selected in a final quadrupole. 123-. (canceled)24. A method for identifying a polypeptide in a specimen , the method comprising:treating a specimen suspected of comprising an amount of a polypeptide with a base to form a treated specimen;extracting a first fraction of the treated specimen by solid phase extraction using a mixed mode or reversed-phase media and a first solvent comprising an acid;separating a component of the first fraction by liquid chromatography using a chromatographic surface comprising a hydrophobic surface group and one or more ionizable modifiers, and a second solvent comprising an acid, wherein the component of the first fraction comprises undigested polypeptide; andanalyzing the component of the first fraction by mass spectroscopy, thereby identifying the polypeptide, if present, using a signal corresponding to a sequence fragment ion from the polypeptide. This application is a continuation of U.S. utility application Ser. No. 14/395,952, filed on Oct. 14, 2014, and issued as U.S. Pat. No. 9,588,180 on Mar. 7, 2017. U.S. utility application Ser. No. 14/395,952 was a ...

Electrospray assisted capillary device for processing ultra low-volume samples

A spray-capillary device is configured to process ultra low-volume samples. The spray-capillary device includes a spray capillary that includes an inlet end and a discharge end. The spray capillary includes a porous section at the discharge end. A downstream connector provides an interface between the porous section of the spray capillary, a conductive fluid, and a high voltage electrical source. The application of voltage to the downstream connector causes electrospray ionization, which can be used to draw ultra law volume samples into the inlet end. A gas injection assembly can be used to increase the pressure on the inlet end of the spray capillary to encourage movement of the sample through the spray capillary. The spray-capillary device is well suited for providing ultra low samples to a mass spectrometer detection device.

Esi sprayer and ionizer

An ESI sprayer 211 configured to be used by being attached to a first hole 51 made in a housing 50 of an ionizer and a second hole 52 made at an end of the first hole 51, and the second hole 52 having an inner diameter smaller than that of the first hole 51, the second hole 52 having an end communicating with an ionization chamber 210, the ESI sprayer 211 includes: a first pipe 11 having an outer diameter smaller than an inner diameter of the first hole 51; a second pipe 12 having an outer diameter smaller than an inner diameter of the second hole 52; a pipe connecting jig 14 made of a conductive material and connecting end faces of the first pipe 11 and the second pipe 12 separated from each other; and a pipe protecting member 16 configured to be an extendable tubular body made of a conductive material and having an outer diameter smaller than the inner diameter of the first hole 51 and larger than the inner diameter of the second hole 52, the pipe protecting member 16 having one end fixed to the pipe connecting jig and being disposed so as to cover at least the end of the second pipe 52.

METHODS FOR QUANTIFYING POLYPEPTIDES USING MASS SPECTROMETRY

A method for identifying a polypeptide a specimen can include (i) treating a specimen suspected of including an insulin with a base; (ii) extracting a first fraction of the treated specimen by solid phase extraction using a mixed mode or polymeric reversed-phase media and a first solvent including an acid; (iii) separating a component of the first fraction by liquid chromatography using a chromatographic surface including a hydrophobic surface group and one or more ionizable modifiers, and a second solvent including an acid; and (iv) analyzing the component of the first fraction by mass spectroscopy, thereby identifying the polypeptide, if present, using a signal corresponding to a sequence fragment ion from the polypeptide. The signal can correspond to an intact multiply charged precursor fragment selected in a first quadrupole and its corresponding sequence fragment ion selected in a final quadrupole. 123.-. (canceled)24. A method for identifying a polypeptide in a specimen , the method comprising:treating a specimen comprising an amount of a polypeptide with a base to form a treated specimen;extracting a first fraction of the treated specimen by solid phase extraction using a mixed mode or reversed-phase media and a first solvent comprising an acid;separating a component of the first fraction by liquid chromatography using a chromatographic surface material comprising a hydrophobic surface group and one or more ionizable modifiers, and a second solvent comprising an acid, wherein the component of the first fraction comprises undigested polypeptide; andanalyzing the component of the first fraction by mass spectroscopy to identify the polypeptide in the specimen.25. The method of claim 24 , wherein the hydrophobic surface group comprises a carbon bonded phase.26. The method of claim 24 , wherein the hydrophobic surface group comprises an embedded polar group.27. The method of claim 24 , wherein liquid chromatography uses a chromatographic core material in addition ...

ONLINE CHROMATOGRAPHY AND ELECTROSPRAY IONIZATION MASS SPECTROMETER

Methods and system for protein characterization using online chromatography and electrospray ionization mass spectrometry are provided. 1. A method for characterizing an antibody-drug conjugate , said method comprising:contacting a sample including the antibody-drug conjugate to a chromatographic system having a size-exclusion chromatography resin;washing said size-exclusion chromatography resin using a mobile phase to provide an eluent including the antibody-drug conjugate; andcharacterizing the antibody-drug conjugate in said eluent using an electrospray ionization mass spectrometer under native conditions.2. The method of claim 1 , wherein the electrospray ionization mass spectrometer is coupled to the chromatographic system having the size-exclusion chromatography resin.3. The method of claim 1 , wherein the electrospray ionization mass spectrometer is a nano-electrospray ionization mass spectrometer.4. The method of claim 1 , wherein at least one three way-splitter is used to couple the electrospray ionization mass spectrometer to the chromatographic system having the size-exclusion chromatography resin.5. The method of claim 1 , wherein at least one three way-splitter is used to couple an ultraviolet detector to the chromatographic system having the size-exclusion chromatography resin.6. The method of claim 5 , wherein the eluent from washing the size-exclusion chromatography resin is introduced in the ultraviolet detector through the at least one three way-splitter at a flow rate of about 0.2 mL/min to about 0.4 mL/min.7. The method of claim 1 , wherein the mobile phase used to wash the size-exclusion chromatography resin comprises ammonium acetate.8. The method of claim 1 , wherein the mobile phase used to wash the size-exclusion chromatography resin comprises a volatile salt.9. The method of claim 1 , wherein the mobile phase used to wash the size-exclusion chromatography resin has a total concentration of about 100 mM.10. The method of claim 1 , wherein ...

Quantitation and Identification of Dimers In Co-Formulations

Methods and system for identification of dimer species using online chromatography and electrospray ionization mass spectrometry are provided. Also provided are methods and system for quantitation of heterodimer species using immunoprecipitation and liquid chromatography-mass spectrometry. 1. A method for identifying at least one dimer species , said method comprising:contacting a sample including the dimer species to a chromatographic system having a size-exclusion chromatography resin;washing said size-exclusion chromatography resin using a mobile phase to provide an eluent including the dimer species; andidentifying the dimer species in said eluent using an electrospray ionization mass spectrometer under native conditions.2. The method of claim 1 , wherein the electrospray ionization mass spectrometer is coupled online to the chromatographic system having the size-exclusion chromatography resin.3. The method of claim 1 , wherein the electrospray ionization mass spectrometer is a nano-electrospray ionization mass spectrometer.4. The method of claim 1 , wherein at least one splitter with at least three paths is used to allow fluid communication with the electrospray ionization mass spectrometer and the chromatographic system having the size-exclusion chromatography resin.5. The method of claim 1 , wherein at least one splitter with at least three paths is used to allow fluid communication between an ultraviolet detector to the chromatographic system having the size-exclusion chromatography resin.6. (canceled)7. (canceled)8. The method of claim 1 , wherein the mobile phase used to wash the size-exclusion chromatography resin comprises a volatile salt.9. (canceled)10. (canceled)11. (canceled)12. (canceled)13. The method of claim 1 , wherein the sample comprises at least two dimer species.14. The method of claim 1 , wherein the sample comprises a homodimer species.15. The method of claim 1 , wherein the sample comprises a heterodimer species.16. The method of claim 1 ...

MASS SPECTROMETRIC DETERMINATION OF EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID

The invention relates to the detection of DHA and EPA. In a particular aspect, the invention relates to methods for detecting DHA and EPA by mass spectrometry and kits for carrying out such methods. 1. A method for determining the amount of docosahexaenoic acid (DHA) in a sample by mass spectrometry , the method comprising:(i) ionizing DHA from the sample to generate one or more DHA ions detectable by mass spectrometry;(ii) determining the amount of said one or more DHA ions by mass spectrometry; and(iii) relating the amount of DHA ions to the amount of DHA in the sample.2. The method of claim 1 , wherein said ionizing comprises atmospheric pressure chemical ionization (APCI).3. The method of claim 2 , wherein said APCI is in negative ionization mode.4. The method of claim 1 , wherein said ionizing comprises electrospray ionization (ESI).5. The method of claim 1 , wherein mass spectrometry comprises tandem mass spectrometry.6. The method of claim 1 , wherein said one or more ions determined in step (ii) comprises an ion with a mass to charge ratio (m/z) of 327.2±0.5.7. The method of claim 1 , wherein said sample comprises human serum or plasma.8. The method of claim 1 , wherein said sample is subjected to a hydrolyzing agent prior to ionization.9. The method of claim 8 , wherein said hydrolyzing agent is an acid.10. The method of claim 1 , wherein DHA from said sample is subjected to liquid/liquid extraction prior to ionization.11. The method of claim 1 , wherein DHA from said sample is subjected to a liquid chromatography prior to ionization.12. The method of claim 11 , wherein said liquid chromatography comprises high performance liquid chromatography (HPLC).13. The method of claim 1 , wherein said method has a limit of detection for DHA in human serum at a concentration of about 5 μmol/L or less.14. The method of claim 1 , wherein said method comprises determining the amount of an internal standard.15. The method of claim 14 , wherein said internal standard is a ...

Liquid junction apparatus for electrospray ionization

The invention relates to a liquid junction apparatus for electrospray ionization in a mass spectrometer comprising an electrospray emitter, a capillary conduit assembly for conducting liquid to be electrosprayed, and a union comprising an electrically conductive material, in which the electrospray emitter and the capillary conduit assembly are accommodated in a bottom-sealing butt joint featuring low dead volume while retaining at least one of them pluggable and withdrawable. The liquid junction apparatus facilitates energizing the transmitted liquid to a predetermined voltage level at the liquid junction upstream of an actual emitter tip where electrospraying occurs, while retaining at least one of an electrospray emitter and a capillary conduit assembly pluggable into and withdrawable from a union that comprises a conductive material.

PRE-ASSEMBLED SEPARATION COLUMNS

There is provided an integrated system for liquid separation, such as LC, CE, affinity chromatography, and ion exchange chromatography, comprising a column and end-fittings embedded in a plastic material, such as a thermoplastic polymer. The system may further comprise an electrospray emitter directly connected with the outlet of the column, wherein a substantial part of the emitter is covered with the polymer material. There is also provided a method by which a separation column along with the accompanying end fittings for connection with adjacent liquid conduits is embedded in a polymer matrix. This configuration e.g. ensures that the factory-made, correct attachment of the fittings to the column is preserved (since the matrix prevents further user intervention, accidental or otherwise). Accordingly, the responsibility for the correct attachment of the fittings is shifted from the end user to the manufacturer. 1. (canceled)3. The integrated separation column of claim 2 , wherein the electrospray emitter is based on a glass capillary.4. The integrated separation column of claim 2 , wherein the plastic material is at least one of: a thermoplastic material claim 2 , polyetheretherketone (PEEK) claim 2 , fluoropolymer or duroplastic material or compound.5. The integrated separation column of claim 4 , wherein the plastic material is the thermoplastic material claim 4 , and the thermoplastic material comprises polyamide and/or polyurethane.6. The integrated separation column of claim 4 , wherein the plastic material is the fluoropolymer claim 4 , and the fluoropolymer comprises perfluoroamines (PFA) or fluorinated ethylene-propylene copolymer (FEP).7. The integrated separation column of claim 6 , wherein the plastic material is the duroplastic material or compound claim 6 , and the duroplastic material or compound comprises polyimide or liquid crystal polymers (LCP).8. The integrated separation column of further comprising an RFID-tag.9. The integrated separation ...

REPLACEABLE EMITTER ASSEMBLY FOR INTERFACING A SEPARATION COLUMN TO A MASS SPECTROMETER

An electrospray emitter assembly for interfacing a separation column to a mass spectrometer is disclosed. An emitter capillary includes an inlet end and an outlet end. A fitting is coupled to the inlet end of the emitter, configured to be removably connected to the separation column. A stop with a defined through hole is integrated proximate the inlet end of the emitter to produce a path for liquid to flow from the separation column to the emitter via the through hole where a voltage is applied to the liquid entering the emitter. 1. (canceled)2. An electrospray emitter assembly for interfacing a separation column to a mass spectrometer , comprising:a. an emitter capillary having an inlet end and an outlet end; andb. a fitting coupled to the inlet end of the emitter, configured to be removably connected to the separation column;wherein a stop with a defined through hole is integrated proximate the inlet end of the emitter to produce a path for liquid to flow from the separation column to the emitter via the through hole where a voltage is applied to the liquid entering the emitter.3. The emitter assembly of wherein the fitting is a female threaded end fitting.4. The emitter assembly of wherein the emitter capillary comprises a fused silica capillary claim 2 , a metal capillary claim 2 , a ceramic capillary claim 2 , or a glass capillary.5. The emitter assembly of wherein the separation column is removably connected via a transfer line with the emitter capillary through the fitting.6. The emitter assembly of wherein the integrated stop has a thickness of up to 1.0 mm.7. The emitter assembly of wherein the integrated stop has a thickness of between 100 μm to 300 μm.8. The emitter assembly of wherein the through hole in the stop has a diameter of between 3μm and 100 μm.9. The emitter assembly of further comprising a protective sleeve for covering and supporting the emitter.10. The emitter assembly of wherein the protective sleeve is slidably mounted around the emitter. ...

ION SOURCE

An object of the present invention is to improve the safety and stability of an ion source by making a temperature distribution of a heated gas uniform while ensuring heat insulating properties. The ion source according to the present invention includes a gas introduction port inside a probe holder that holds an ion probe. A heater that increases the temperature of a heated gas and the gas introduction port are connected by a plurality of pipes which extend along an extending direction of the ion probe and are independent of each other (see FIG. ). 1. An ion source , which ionizes a sample , comprising:a probe through which a solution containing the sample passes;a heated gas injection port which injects a heated gas that heats a substance injected from the probe;a heater which increases a temperature of the heated gas before the heated gas injection port injects the heated gas; anda gas introduction port which supplies the heated gas to the ion source,wherein the heater includes first and second heater gas inlets that receive the heated gas supplied from the gas introduction port to the ion source,the gas introduction port and the first heater gas inlet are connected by a first pipe extending along an extending direction of the probe,the gas introduction port and the second heater gas inlet are connected by a second pipe extending along the extending direction of the probe, andthe first pipe and the second pipe are configured as pipes having flow paths independent from each other.2. The ion source according to claim 1 , whereinthe heater is arranged so as to surround a partial region of an outer surface of the probe along the extending direction of the probe, andthe first pipe and the second pipe are arranged so as to extend along the extending direction of the probe in a space between the gas introduction port and the heater.3. The ion source according to claim 1 , whereinthe heater includes: a heat generator that generates heat; and a heat exchanger that ...

Compression Connection

A chromatography and fluidic device with connections capable of automated component changing, diagnostic leak and current sensing. The chromatography-electrospray device contains a chromatography column, a pre-column, a spray emitter, or other fluidic component imbedded within one or more inserts. The inserts are robotically placed in receiving hardware, and a “plug and play” compression fitting connection mechanism makes the fluidic seals in an automated fashion. A plurality of sensors capable of detecting leaks is situated in the device near leak-prone regions. The electrospray emitter has a current sensing electrode in proximity of the electrospray region, capable of detecting the electrospray current. In conjunction with an electronics system, these sensors allow for system and component diagnostics. The diagnostic information may then be used for manual or automated system repair. 123-. (canceled)24. A system for the automated compression connection of fluidic components comprising:receiving hardware comprising a conduit having an exit opening with a first mating surface of a compression connection and configured to align an insert placed therein;an interchangeable plug-and-play consumable insert configured for automated connection and comprising a conduit having an entry opening with a second mating surface of the compression connection;a drive force mechanism; andat least one mechanical support, wherein the drive force mechanism and the at least one mechanical support are each located in the receiving hardware, wherein the insert placed therein is disposed between the at least one mechanical support and the drive force mechanism, and wherein the drive force mechanism is configured to apply a substantially axial drive force opposed by the at least one mechanical support to align and compress the first and second mating surfaces together and create a leak-resistant seal at the compression connection between the insert and the receiving hardware, such that the ...

IONIZATION DEVICE

In order to implement a high-sensitivity mass spectrometry through an improvement in solvent removal efficiency during electrospray ionization and the like, an ionization device is provided with a light guide path which guides light from a light source to sample microparticles generated by a micronization device to irradiate the microparticles. A closest distance d between a spatial area in which the sample microparticles are present and a distal end of the light guide path is greater than or equal to 0.1 mm and less than or equal to 20 mm. A closest distance d between an area of light irradiation by the light guide path and any of a sample surface, a micronization device, and a sample holding unit that is the closest is greater than or equal to 0.01 mm and less than or equal to 10 mm. 1. An ionization device for ionization of a substance , the ionization device comprising:a sample holding unit that holds a sample including a target substance;a micronization device that turns the sample being held by the sample holding unit into sample microparticles;a light source; anda light guide path that guides light from the light source to the sample microparticles generated by the micronization device to irradiate the sample microparticles,whereina closest distance between a spatial area in which the sample microparticles are present and a distal end of the light guide path is greater than or equal to 0.1 mm and less than or equal to 20 mm, anda closest distance between an area of light irradiation by the light guide path and any of a surface of the sample, the micronization device, and the sample holding unit that is the closest is greater than or equal to 0.01 mm and less than or equal to 10 mm.2. The ionization device according to claim 1 , wherein the closest distance between the spatial area in which the sample microparticles are present and the distal end of the light guide path is greater than or equal to 0.1 mm and less than or equal to 10 mm.3. The ionization device ...

ESI-MS VIA AN ELECTROKINETICALLY PUMPED INTERFACE

An electrokinetically pumped sheath flow nanospray interface for capillary electrophoresis coupled to negative mode electrospray mass spectrometer is described. At this interface, application of an electric field generates electro-osmotic flow at the interior of a glass emitter having an orifice. Electroosmotic flow pumps liquid around the distal tip of the separation capillary, ensheathing analyte into the electrospray electrolyte. In negative ion mode, negative potential applied to an untreated emitter drives sheath flow away from the emitter orifice, decreasing the stability and efficiency of the spray. In contrast, when the interior of the electrospray emitter is grafted with aminoalkylsilanes, the amines have a positive charge, which reverses electroosmosis and generates stable sheath flow to the emitter orifice under negative potential. Limits of detection were about 150 to 900 attomoles injected. Negative mode operation was demonstrated by analyzing a metabolite extract from stage 1 embryos. 1. An electrospray ionization interface for a mass spectrometer comprising:a glass emitter for electroosmotic flow (EOF) of a sheath-liquid in negative mode, wherein the glass emitter's surface comprises a coating of one or more organic chemicals covalently bonded to the surface wherein the organic chemicals comprise one or more functional moieties; andan inlet for a sheath liquid;wherein when an electrospray voltage is applied to a sheath liquid introduced to the glass emitter, positive charges formed on the functional moieties stabilize the direction of the EOF in negative mode.2. The interface of wherein the glass emitter is a hollow cylinder comprising an orifice at a distal end and the inner diameter of the orifice is smaller than the inner diameter of the cylinder body claim 1 , wherein the EOF of the sheath liquid traverses in a direction toward the orifice and an ionized electrospray is formed as the sheath liquid exits the orifice.3. The interface of wherein a ...

METHODS FOR DETECTING CHROMOGRANIN A BY MASS SPECTROMETRY

Provided are methods for detecting chromogranin A by mass spectrometry. In another aspect, provided herein are methods for quantitating chromogranin A by mass spectrometry. In another aspect, provided herein are methods for prognosis of or measuring the size of neuroendocrine tumors by mass spectrometry. 1. A method for determining the amount of chromogranin A (CgA) in a sample , said method comprising:(a) purifying CgA in the sample;(b) ionizing CgA to produce one or more ion(s) of CgA detectable by mass spectrometry;(c) determining the amount of the ion(s) from step (b) by mass spectrometry, wherein the amount of ions is related to the amount of CgA in the sample.2. The method of claim 1 , wherein said purifying comprises extraction by solid phase extraction (SPE).3. The method of claim 2 , wherein the SPE is an anion exchange solid phase extraction.4. The method of claim 2 , wherein the SPE is a mixed-mode anion exchange solid phase extraction.5. The method of claim 2 , wherein extracted samples are enzymatically digested.6. The method of claim 5 , wherein the digestion comprises trypsin digestion.7. The method of claim 1 , wherein said purifying comprises liquid chromatography.8. The method of claim 7 , wherein said liquid chromatography comprises high performance liquid chromatography (HPLC).9. The method of claim 7 , wherein said liquid chromatography comprises high turbulence liquid chromatography (HTLC).10. The method of claim 1 , wherein said ionization comprises electrospray ionization (ESI).11. The method of claim 1 , further comprising adding an internal standard.12. The method of claim 11 , wherein said internal standard is isotopically labeled.13. The method of claim 1 , wherein the sample is serum.14. The method of claim 1 , wherein the sample is cerebrospinal fluid (CSF).15. The method of claim 1 , wherein the method comprises measuring the amount of precursor ion having a mass-to-charge ratio of 729.6±0.5.16. The method of claim 1 , wherein the ...

C PEPTIDE DETECTION BY MASS SPECTROMETRY

Methods are described for measuring the amount of C peptide in a sample. More specifically, mass spectrometric methods are described for detecting and quantifying C peptide in a sample utilizing on-line extraction methods coupled with tandem mass spectrometric or high resolution/high accuracy mass spectrometric techniques. 1. A method for determining the amount of C peptide in a sample by tandem mass spectrometry , the method comprising:(a) purifying a sample containing C peptide by high performance liquid chromatography (HPLC);(b) ionizing C peptide under conditions suitable to generate one or more C peptide ions detectable by mass spectrometry;(c) determining the amount of one or more C peptide ions by tandem mass spectrometry, wherein the determined ions comprise a fragment ion with mass to charge ratio of 646.1±0.5;wherein the amount of ions determined in step (c) is related to the amount of a C peptide in said sample.2. The method of claim 1 , wherein said HPLC is 1-D HPLC.3. The method of claim 1 , wherein said ionization source is an electrospray (ESI) ionization source.4. The method of claim 1 , wherein further comprising subjecting to solid phase extraction (SPE).5. The method of claim 4 , wherein said SPE and HPLC are conducted with on-line processing.6. The method of claim 1 , wherein said sample is from a human.7. The method of claim 1 , wherein said sample is a body fluid sample.8. The method of claim 1 , wherein said sample is plasma or serum.9. The method of claim 1 , wherein said mass spectrometry is high resolution/high accuracy mass spectrometry.10. The method of claim 9 , wherein said high resolution/high accuracy mass spectrometry is conducted at a FWHM of 10 claim 9 ,000 and a mass accuracy of 50 ppm.11. The method of claim 9 , wherein said high resolution/high accuracy mass spectrometer is a high resolution/high accuracy time-of-flight (TOF) mass spectrometer. This application is a continuation of U.S. application Ser. No. 16/259,606, filed Jan ...