МИКРОПЛАНШЕТ

Изобретение относится к микропланшету для центрифугирования множества проб. Микропланшет, содержащий множество лунок, размещенных в виде двухмерной решетки, причем микропланшет содержит рамку и несколько продольных распорок, каждая из которых содержит ряд лунок, причем распорки размещены в рамке с возможностью поворота, а каждый ряд лунок установлен в микропланшете с возможностью наклона, так что во время центрифугирования микропланшета лунки выравниваются в направлении центробежной силы. Технический результат – повышение пропускной способности при осуществлении способа определения результата реакции агглютинации. 3 н. 11 з.п. ф-лы, 11 ил.

БИОЧИП, ВКЛЮЧАЮЩИЙ ПРАЙМЕР СЕКВЕНИРОВАНИЯ И НЕСЕКВЕНИРУЮЩУЮ ЕДИНИЦУ

МИКРОЖИДКОСТНАЯ СИСТЕМА

... 1. Микрожидкостная система, содержащая, по меньшей мере, один микроканал (33), имеющий стенку (36) с внутренней стороной (35), причем микрожидкостная система дополнительно содержит ! множество исполнительных элементов (33), прикрепленных к внутренней стороне (35) стенки (36), причем каждый исполнительный элемент (30) имеет форму, ориентацию и геометрию, при этом геометрия предусматривает изменяющуюся площадь поперечного сечения вдоль продольной оси, и ! средства для приложения стимулирующего воздействия ко множеству исполнительных элементов (30) для того, чтобы вызвать изменение в их форме и/или ориентации. ! 2. Система по п.1, в которой изменяющаяся площадь поперечного сечения включает в себя одно или более отверстий вдоль продольной оси. ! 3. Система по п.2, в которой отверстия могут быть выполнены в виде квадрата, прямоугольника, круга, полукруга и/или иметь формы, схожие с ними. ! 4. Система по п.1, в которой изменяющаяся площадь поперечного сечения существенно уменьшается к внутренней ...

VERFAHREN UND VORICHTUNG ZUM ABGABEN VON TRÖPFCHEN AUF EINEM SUBSTRAT

Sample carrier comprises a sample plate having one side with receiving regions for samples to be optically investigated and illuminated using illuminating diodes connected to the sample plate from the other side of the sample plate

Sample carrier comprises a sample plate (11) having one side with receiving regions (13) for samples to be optically investigated and illuminated using illuminating diodes (15) connected to the sample plate from the other side of the sample plate. The illuminating diode are OLEDs having a common protective layer acting as the sample plate having the receiving regions on its upper surface.

Verfahren zum Herstellen einer Bilipidschicht sowie Mikrostruktur und Messanordnung

Die vorliegende Erfindung bezieht sich auf ein Verfahren zum Herstellen einer Bilipidschicht über einer einseitig offenen Mikrokavität sowie auf eine Mikrostruktur zum Untersuchen von Lipiddoppelschichten und eine diesbezügliche Messanordnung. Das Verfahren zum Herstellen einer Bilipidschicht über einer einseitig offenen Mikrokavität umfasst die folgenden Schritte: Befüllen der Mikrokavität mit einer Elektrolytlösung; Bewegen eines gelöste Lipide enthaltenden Fluids in einer ersten Richtung auf die Mikrokavität zu; Bewegen des Fluids in einer zweiten Richtung von der Mikrokavität weg; Überwachen des Ausbildens der Bilipidschicht über der Mikrokavität durch Erfassen einer Impedanz zwischen einer mit dem Fluid verbundenen Gegenelektrode und einer Messelektrode, die im Inneren der Mikrokavität angeordnet ist. Die Mikrostruktur weist ein Substrat auf, in welchem mindestens eine Mikrokavität ausgebildet ist, wobei im Inneren der Mikrokavität mindestens eine Messelektrode angeordnet ist und wobei ...

Sample chamber and DNA chip array for replication and characterization of nucleic acids, has biochip with side surfaces fitted into inner walls of sample chamber

The biochip (4) side surfaces (7) interlock and/or are interference-fitted into the inner walls (3) of the sample chamber (2). Biochip and sample chamber form a transverse pressure- or shrink connection. The connection is alternatively a snap fit. The biochip is circular or rectangular in shape. Chip edges and/or the chamber have seals. The chip is square with rounded corners. The sample chamber is a cuvette. The biochip has a plastic substrate.

Verfahren zum Herstellen eines Microarrays und Vorrichtung zum Versehen eines Trägers für ein Microarray mit Beschichtungsstoffen

Verfahren zum Herstellen eines Microarrays (1), das einen Träger (2) aufweist, auf dem mehrere unterschiedlich ausgebildete, Beschichtungsstoffe aufweisende Beschichtungsbereiche (3) nebeneinander angeordnet sind, - wobei die Oberfläche des Trägers (2) derart strukturiert wird, dass hydrophile Oberflächenbereiche (6) durch mindestens einen hydrophoben Oberflächenbereich (7) voneinander getrennt sind, - wobei für die einzelnen Oberflächenbereiche (6) jeweils ein saugfähiges Substrat (15) bereitgestellt wird, - wobei in die Oberfläche einer Trägerplatte (11) Öffnungen (12) derart eingebracht werden, dass diese, wenn die Oberfläche dem Träger zugewandt ist, spiegelbildlich den Stellen entsprechen, an denen die hydrophilen Oberflächenbereiche (6) des Trägers (2) angeordnet sind, - wobei die Substrate (15) derart in diesen Öffnungen (12) angeordnet werden, dass sie jeweils mit einem Teilbereich bis über die Oberfläche der Trägerplatte (11) aus der Öffnung (12) vorstehen, - wobei die einzelnen ...

Electrically active combinatorial-chemical (EACC) chip for biochemical analyte detection

Apparatus and methods are disclosed for electrically active combinatorial-chemical (EACC) chips for biochemical analyte detection. An apparatus includes a substrate that has an array of regions defining multiple cells, wherein each of the cells includes a reaction cavity that contains multiple functional binding groups. A method of detecting an analyte providing the reaction cavity between a source and a drain or a pair of electrodes, applying a voltage and monitoring a parameter indicative of an analyte characteristic. A process of fabricating an EACC include bonding an analyte to the multiple functional binding groups of each reaction cavity, and forming an analyte sensing structure including the substrate.

Method

Mixed-phase fluids for nucleic acid sequencing and other analytical assays

Cartridge system

Honeycomb tube

MICROFLUIDIC METERING OF FLUIDS

Device and method for the verification and quantitative analysis of analytes, particularly mycotoxins.

Honeycomb tube

MICROFLUIDIC METERING OF FLUIDS

Honeycomb tube

Device and method for the verification and quantitative analysis of analytes, particularly mycotoxins.

MICROFLUIDIC METERING OF FLUIDS

Cartridge system

MICROWELL BIOLOGICAL CHIP

DEVICE AND PROCEDURE FOR THE PROOF OF MOLECULAR RECIPROCAL EFFECTS

SAMPLE CHAMBER

PROCEDURE AND SYSTEM FOR THE TREATMENT OF ELEMENTS IN THE MICRO YARDSTICK FOR THE RE-USE

NUCLEIC ACID AMPLIFICATION ON BASIS OF BALL EMULSION

MALDI PLATE WITH REMOVE-CASH EMPLOYMENT

TWO-END SEQUENZIERUNG

SAMPLE ORDER PROCEDURE FOR APPLICATIONS OF BIO SENSORS AND SUCH SAMPLES COMPREHENSIVE DEVICES

MOVEMENT ELEMENT FOR SMALL LIQUID QUANTITIES

NUCLEIC ACID AMPLIFICATION ON BASIS OF BALL EMULSION

MICROANALYSIS MEASURING DEVICE AND MICROANALYSIS MEASURING PROCEDURE USING OF IT

SUBSTRATES WITH HIGH-LYING SURFACE RANGE FOR MICRO ARRAYS AS WELL AS PROCEDURES FOR THE PRODUCTION OF IT

APPARATUS FOR THE ENTERPRISE OF MICRO-FLUID EQUIPMENT

STRUCTURED REACTION SUBSTRATE

Methods of producing patient-specific anti-cancer therapeutics and methods of treatment therefor

A method of preparing an antibody therapeutic is provided comprising: (a) providing a dissociated cell sample from at least one solid tumor sample obtained from a patient; (b) loading the dissociated cell sample into a microfluidic device having a flow region and at least one isolation region fluidically connected to the flow region; (c) moving at least one B cell from the dissociated cell sample into at least one isolation region in the microfluidic device, thereby obtaining at least one isolated B cell; and (d) using the microfluidic device to identify at least one B cell that produces antibodies capable of binding to cancer cells. The cancer cells can be the patient's own cancer cells. Also provided are methods of treating patients, methods of labeling or detecting cancer, engineered T or NK cells comprising antibodies or fragments thereof, and engineered antibody constructs.

Compact Fluid Analysis Device And Method To Fabricate

In one aspect, a device is disclosed. In one embodiment, the device comprises: a substrate having a microfluidic component formed therein, the microfluidic component 5 configured to propagate a fluid sample via capillary force through the microfluidic component; a lid coupled to the substrate, the lid configured to at least partially cover the substrate and to enclose at least a portion of the microfluidic component, the lid including at least one waveguide configured to enable irradiating the fluid sample present in the enclosed portion of the microfluidic component with an excitation, the 10 substrate further including one or more filters configured to filter the excitation from an emission generated by the fluid sample in response to the excitation. [Figure 26] r-i 0r 0 /0 ...

Microfluid system for reactions and transfers

Apparatuses and methods for manipulating droplets on a printed circuit board

Assay apparatus and method using microfluidic arrays

Methods and apparata for precisely dispensing microvolumes of fluids

METHODS AND APPARATA FOR PRECISELY DISPENSING MICROVOLUMES OF FLUIDS

Biochip defining a channeled capillary array and associated methods

Identification and quantification of a plurality of biological (micro)organisms or their components

Electrowetting-driven micropumping

A micro-bubble plate for patterning biological and non-biological materials

Systems and methods for patterning biological and non-biological material at specific sites on a plate, as well as growing three dimensional structures. Preferred embodiments comprise a plate with regions that will trap gas, usually in the form of bubbles, when the plate is submerged in liquid. Other embodiments of the present invention include a method for placing materials on the plate at predetermined locations through the use of trapped gas to prevent materials from collecting at unwanted regions. The plate has great utility for plating cells and tissues at specific sites, such as on an array. The disclosed method can also be used to coat the surface of a plate at specific locations for patterned coating applications and to build up materials to produce three dimensional structures, including micromechanical structures where the structures may be formed from living or nonliving material, organic or inorganic, and the like.

Apparatus for high throughput chemical reactions

Micropatterned plate with micro-pallets for addressable biochemical analysis

A plate manufactured to enable samples of cells, micro-organisms, proteins, DNA, biomolecules and other biological media to be positioned at specific locations or sites on the plate for the purpose of performing addressable analyses on the samples. Preferably, some or all of the sites are built from a removable material or as pallets so that a subset of the samples of interest can be readily isolated from the plate for further processing or analysis. The plate can contain structures or chemical treatments that enhance or promote the attachment and/or function of the samples, and that promote or assist in their analyses.

Microfluidic device having a reduced number of input and output connections

DEVICES, METHODS AND SYSTEMS FOR LOW VOLUME MICROARRAY PROCESSING

METHODS FOR RAPID MULTIPLEXED AMPLIFICATION OF TARGET NUCLEIC ACIDS

Abstract A fast, multiplexed PCR system is described that can rapidly generate amplified nucleic acid products, for example, a dull SDTR profile, from a target nucleic acid. Such systems include, for example, microfluidic biochips and a custom built thermal cycler, which are also described. The resulting STR profiles can satisfy forensic guidelines for signal strength, inter-loci peak height balance, heterozygous peak height ratio, incomplete non-template nucleotide addition, and stutter. 2143555v1 ...

Microfluidics sorter for cell detection and isolation

A microfluidic device is disclosed. The device comprises at least one inlet for receiving circulating tumor cells and other cells in a sample; at least one curvilinear and/or spiral channel through which the sample is caused to undergo partial or complete Dean cycles to isolate the circulating tumor cells from the other cells; and at least one outlet configured to communicate with the channel for providing the isolated circulating tumor cells. The channel is configured to provide a predetermined Force ratio based on a desired threshold cell size of the circulating tumor cells. A corresponding method of manufacturing of the device, and a related diagnostic system are also disclosed.

Method for producing microcarriers

The present invention relates to a method for producing microcarriers comprising the following steps: (a) providing a wafer (6) having a sandwich structure comprising a bottom layer (7), a top layer (8) and a insulating layer(9) located between said bottom and top layers (7, 8), (b) etching away the top layer (8) to delineate lateral walls (12) of bodies (11) of the microcarriers, (c) depositing a first active layer (13)at least on a top surface (14) of the bodies (11), (d) applying a continuous polymer layer (16) over the first active layer(13), (e) etching away the bottom layer (7) and the insulating layer (9), (f) removing the polymer layer (16) to release the microcarriers.

Apparatus and method for synthesizing combinatorial libraries

AUTOMAT SYSTEM FOR HANDLING MICROFLUIDIC DEVICES

APPARATUSES AND METHODS FOR MANIPULATING DROPLETS ON A PRINTED CIRCUIT BOARD

METHODS AND APPARATUS FOR LABEL-INDEPENDENT MONITORING OF BIOLOGICAL INTERACTIONS ON SENSITIZED SUBSTRATES

SUBSTRATE OF TARGET SUBSTANCE DETECTION ELEMENT TO BE USED IN APPARATUS FOR DETECTING TARGET SUBSTANCE BY UTILIZING SURFACE PLASMON RESONANCE AND DETECTION ELEMENT AND DETECTION APPARATUS USING SAME

A substrate of a target substance detection element to be used for a detection apparatus for detecting a target substance, utilizing surface plasmon resonance, comprises a base and a metal structure arranged on the surface of the base in a localized manner or a metal film having an aperture and arranged on the surface of the base, the metal structure or the aperture, whichever appropriate, having at least either of a loop section and a crossing section.

APPARATUS FOR HIGH THROUGHPUT CHEMICAL REACTIONS

Apparatus, systems, chips, and methods of performing a large number of simultaneous chemical reactions are provided herein. The chips of the invention comprise addressable units that can be addressed according to the temperature of the reaction to be run. The subject apparatus, systems, and chips are particularly suited for performing polymerase chain reactions on thousands of nucleic acid sequences, up to and including sequences of an entire genome of an organism of interest.

DROPLET MANIPULATION SYSTEMS

The present invention relates to systems and methods for controlling droplet movements on a droplet microactuator and a droplet microactuator device, system and method for processing and/or analyzing samples. According to one aspect, a system is provided and includes a controller, a droplet microactuator electronically coupled to the controller, and a display device displaying a user interface electronically coupled to the controller, wherein the system is programmed and configured to permit a user to effect a droplet manipulation by interacting with the user interface. According to another aspect, a sample analyzer is provided and includes an analyzer unit comprising electronic or optical receiving means, a cartridge comprising self-contained droplet handling capabilities, and a means for coupling the cartridge to the analyzer unit which aligns electronic and/or optical outputs from the cartridge with electronic or optical receiving means on the analyzer unit.

DROPLET MANIPULATION SYSTEMS

The present invention relates to systems and methods for controlling drop let movements on a droplet microactuator and a droplet microactuator device, system and method for processing and/or analyzing samples. According to one aspect, a system is provided and includes a controller, a droplet microactu ator electronically coupled to the controller, and a display device displayi ng a user interface electronically coupled to the controller, wherein the sy stem is programmed and configured to permit a user to effect a droplet manip ulation by interacting with the user interface. According to another aspect, a sample analyzer is provided and includes an analyzer unit comprising elec tronic or optical receiving means, a cartridge comprising self-contained dro plet handling capabilities, and a means for coupling the cartridge to the an alyzer unit which aligns electronic and/or optical outputs from the cartridg e with electronic or optical receiving means on the analyzer unit.

MICROFLUIDIC DEVICE AND METHOD OF USING SAME

A microfluidic device comprising a plurality of reaction chambers in fluid communication with a flow channel formed in an elastomeric substrate, a vapor barrier for preventing evaporation from the plurality of reaction chambers, and a continuous phase fluid for isolation of each of the plurality of reaction chambers.

METHOD, APPARATUS AND ARTICLE FOR MICROFLUIDIC CONTROL VIA ELECTROWETTING, FOR CHEMICAL, BIOCHEMICAL AND BIOLOGICAL ASSAYS AND THE LIKE

An active matrix microfluidic platform employs thin film transistor active ("TFT") matrix liquid crystal display technology to manipulate small samples of fluid for chemical, biochemical, or biological assays without moving parts, for example, using a two-dimensional matrix array of drive electrodes. The active matrix microfluidic platform may employ existing active matrix addressing schemes and/or commercial "off-the-shelf" animation software to program assay protocols. A feedback subsystem may determine an actual location of a fluid in the microfluidic structure, and provides location information to for display, for example, on an active matrix display, and/or to control movement of one or more fluid bodies in the microfluidic structure.

COMPOSITE, ORDERED MATERIAL HAVING SHARP SURFACE FEATURES

MICRODEVICES HAVING A PREFERENTIAL AXIS OF MAGNETIZATION AND USES THEREOF

The invention relates generally to the field of moiety or molecule isolation, detection and manipulation and library synthesis. In particular, the invention provides a microdevice, which microdevice comprises: a) magnetizable substance; and b) a photorecognizable coding pattern, wherein said microdevice has a preferential axis of magnetization. Systems and methods for isolating detecting and manipulating moieties and synthesizing libraries using the microdevices are also provided.

METHOD FOR MAKING A MOLECULARLY SMOOTH SURFACE

A method is provided for making a molecularly smooth surface, preferably on an electrode of an assay chip. This is desirable because it allows molecules, preferably oligonucloetides, to attach to the electrode surface with greater reliability and packing density than was previously available. Such attachment of molecules to an electrode surface is of particular interest in the field of electrochemical genetic analysis.

SAMPLE HOLDER AND LOCK-IN THERMOGRAPHY SYSTEM

A sample holder (1) for magnetic nanoparticle samples comprises a plurality of sample wells (la) for holding a magnetic nanoparticle sample, which are distributed on a top surface (lb) of the sample holder (1). The sample wells (la) are distributed such that a first distance (dl) between neighboring samples wells (la) and/or a second distance (d2) between each peripheral sample well (la) and a respective edge of the top surface (lb) of the sample holder (1) and/or a third distance (d3) between a deepest point of the sample wells (la) and a bottom of the sample holder (1) is between 1 and 100 times greater than a thermal diffusion length of the sample holder material. The sample holder (1) is used in a lock-in thermography system (2).

SYSTEM AND METHOD FOR ISOLATING AND ANALYZING CELLS

A system and method for isolating and analyzing single cells, wherein the system includes: an array of wells defined at a substrate, each well including an open surface and a well cavity configured to capture cells in one of a single-cell format and single-cluster format, and a fluid delivery module including a fluid reservoir superior to the array of wells through which fluid flow is controlled along a fluid path in a direction parallel to the broad face of the substrate; and wherein the method includes: distributing a population of cells and a population of non-cell particles across the array of wells through the fluid reservoir to increase capture efficiency of individual cell-particle pairs within the array of wells, and processing the captured cell-particle pairs at the set of wells.

LATERAL LOADING OF MICROCAPILLARY ARRAYS

Lateral loading methods of use in high-throughput methods for screening large populations of variant proteins are provided. The methods utilize a flow cell encompassing large-scale arrays of microcapillaries, where each microcapillary comprises a solution containing a variant protein, an immobilized target molecule, and a reporter element. Immobilized target molecules may include any molecule of interest, including proteins, nucleic acids, carbohydrates, and other biomolecules.

PROTECTIVE SURFACE COATINGS FOR FLOW CELLS

An example of a method includes modifying an exposed surface of a substrate to incorporate a first chemical group; reacting the first chemical group with a first reactive group of a functionalized polymer molecule to form a functionalized polymer coating layer covalently bound to the exposed surface of the substrate; grafting a primer to the functionalized polymer coating layer by reacting the primer with a second reactive group of the functionalized polymer coating layer; and forming a water-soluble protective coating on the primer and the functionalized polymer coating layer. Examples of flow cells incorporating examples of the water-soluble protective coating are also disclosed herein.

APPARATUS INCLUDING ION TRANSPORT DETECTING STRUCTURES AND METHODS OF USE

The present invention recognizes that the determination of ion transport function or properties using direct detection methods, such as whole cell recording or single channel recording, are preferable to methods that utilize indirect detection methods, such as FRET based detection system. The present invention provides biochips and other fluidic components and methods of use that allow for the direct analysis of ion transport function or properties using microfabricated structures that can allow for automated detection of ion transport function or properties. These biochips and fluidic components and methods of use thereof are particularly appropriate for automating the detection of ion transport function or properties, particularly for screening purposes.

MICROFLUIDIC MICROARRAY ASSEMBLIES AND METHODS OF MANUFACTURING AND USING SAME

The invention encompasses microfluidic microarray assemblies (MMA) and subassemblies and methods for their manufacture and use. In one embodiment, first and second channel plates are provided and are sealingly connected to a test chip in consecutive steps. Each plate includes microfluidic channels configured in a predetermined reagent distribution pattern. The test chip comprises a plurality of discrete test positions, each test position being located at the intersection between a first predetermined reagent pattern and a second predetermined reagent pattern, wherein at least one of said patterns is non-linear. The first channel plate allows the distribution of a first reagent on said test chip, wherein said first reagent is immobilized at said test positions. The second channel plate allows the distribution of a second reagent on said test chip, wherein said second reagent comprises a plurality of different test samples.

WATER DISPERSIBLE ASSAYS

The present disclosure relates to water dispersible or soluble diagnostic assay methods, devices, kits, and methods of manufacture.

DEP FORCE CONTROL AND ELECTROWETTING CONTROL IN DIFFERENT SECTIONS OF THE SAME MICROFLUIDIC APPARATUS

A microfluidic apparatus can comprise a dielectrophoresis (DEP) configured section for holding a first liquid medium and selectively inducing net DEP forces in the first liquid medium. The microfluidic apparatus can also comprise an electrowetting (EW) configured section for holding a second liquid medium on an electrowetting surface and selectively changing an effective wetting property of the electrowetting surface. The DEP configured section can be utilized to select and move a micro-object in the first liquid medium. The EW configured section can be utilized to pull a droplet of the first liquid medium into the second liquid medium.

HONEYCOMB TUBE

A honeycomb tube with a planar frame defining a fluidic path between a first planar surface and a second planar surface. A fluidic interface is located at one end of the planar frame. The fluidic interface has a fluidic inlet and fluidic outlet. The fluidic path further includes a well chamber having an well-substrate with a plurality of wells. The well chamber is arranged in the planar frame between the first or second surface and the well-substrate.

SAMPLE PROCESSING DEVICE WITH DETACHABLE SLIDE

A biological and chemical sample processing device that b. comprises a high pressure-resistant, shallow and wide area microfluidic chamber having at least one wall formed by a detachable slide containing samples such as immobilized entities, biological samples or molecules, c. comprises an arrangement of microfluidic access holes for injecting to and collecting fluid form said chamber, d. is interfaced with inlet ports and microfluidic channels which are formed external to the chamber, e. is configured so that the slide may be brought into contact with the device to form the said chamber, f. is adapted to deliver and to transport fluidic substances and reagents inside said chamber in a fast manner, preferably within less than 15 seconds, and in a regular or uniform way owing to said arrangement of microfluidic access holes.

PLASTIC MICROFLUIDIC SEPARATION AND DETECTION PLATFORMS

Plastic electrophoresis separation chips are provided comprising a plural ity of microfluidic channels and a detection window, where the detection win dow comprises a thin plastic; and the detection window comprises a detection region of each microfluidic channel. Such chips can be bonded to a support provided an aperture is provided in the support to allow detection of sample s in the electrophoresis chip at the thin plastic detection window. Further, methods for electrophoretically separating and detecting a plurality of sam ples on the plastic electrophoresis separation chip are described.

ELECTRICAL AND REUSABLE DEVICE FOR READING MICROARRAYS

The invention relates to a device for electrically reading microarrays, that can be cleaned and used more than once. The device (1, 1', 1 ") for reading microarrays (6) comprises the following elements: a base (2, 2', 2") comprising support means (3, 3', 3") for positioning the test surface (7) of the microarray (6) parallel to a reading surface (4) of the base (2, 2', 2"); a matrix of transducers (5, 5', 5") arranged on the reading surface (4) of the base (2, 2', 2"), translating a variation of an electrical or chemical value into a variation of an electrical value; and reading means (10) which are connected to the transducers (5, 5', 5") and interpret the electrical signals from the transducers (5, 5', 5").

APPARATUS FOR SUPPORTING AN ARRAY OF LAYERS OF AMPHIPHILIC MOLECULES AND METHOD OF FORMING AN ARRAY OF LAYERS OF AMPHIPHILIC MOLECULES

An apparatus for supporting an array of layers of amphiphilic molecules, the apparatus comprising: a body (11), formed in a surface of the body, an array of sensor wells (10) capable of supporting a layer of amphiphilic molecules (30) across the sensor wells, the sensor wells each containing an electrode (12) for connection to an electrical circuit, and formed in the surface of the body between the sensor wells, flow control wells capable of smoothing the flow of a fluid across the surface.

METHODS FOR RAPID MULTIPLEXED AMPLIFICATION OF TARGET NUCLEIC ACIDS

... ²²A fast, multiplexed PCR system is described that can rapidly generate ²amplified nucleic acid ²products, for example, a full STR profile, from a target nucleic acid. Such ²systems include, for ²example, microfluidic biochips and a custom built thermal cycler, which are ²also described. The ²resulting STR profiles can satisfy forensic guidelines for signal strength, ²inter-loci peak height ²balance, heterozygous peak height ratio, incomplete non-template nucleotide ²addition, and ²stutter.² ...

FLOW CELLS FOR HIGH DENSITY ARRAY CHIPS

Biochemical flow cells having sealed inlets and outlets are provided for performing high-volume assays on macromolecules. A flow cell with detachable inlet and outlet connectors comprises an inlet manifold, a coverslip, and a substrate disposed below the coverslip to form a reaction chamber, where the substrate is disposed to partially cover the inlet manifold such that a slit is formed along an entire edge of the substrate where fluids can flow from the inlet manifold through the slit, around substantially the entire edge of the substrate, and into the reaction chamber at equalized pressure and without bubbles. In another embodiment, the flow cell comprises an outlet manifold, two or more flow regions each connected to its own loading port via its own flow distribution funnel, each loading port connected to the outlet manifold, and plugs in a wall of the outlet manifold opposite each loading port.

SURFACE TREATMENTS FOR DNA PROCESSING DEVICES

The present invention discloses methodologies for the treatment of the surface(s) of DNA processing devices so as to greatly reduce DNA adsorption to the surface(s) exposed to the DNA-containing media. These aforementioned surface treatments include: (i) the deposition of thin-films of silicon-rich, silicon nitride and of hydroxyl-containing, low-temperature silicon oxide and (ii) the washing of surface with a basic, oxidative wash solution. The present invention also discloses the fabrication of DNA processing devices utilizing surface(s) treated by the methods described above. Such DNA processing devices include, for example, miniaturized electrophoresis and other DNA separation devices, miniaturized PCR reactors, and the like. The present invention further discloses methodologies for testing the degree of DNA adherence to a given surface. Additionally, the methodologies and devices of the present invention are also applicable to the processing of nucleic acids, in general.

Apparatus and platform for multiplex analysis.

La présente invention concerne un appareil pour effectuer des dosages analytiques multiplex sur des plateformes de microréseaux. Cet appareil comporte, assemblées sur un socle a) une unité chauffante connectée à une unité de contrôleur électrique externe; b) une tablette structurée pour le placement de plateformes de microréseaux, c) une ou plusieurs plateformes de microréseaux, comprenant chacune un premier substrat doté de canaux et un deuxième substrat fermant les canaux du premier substrat pour former des chambres de réaction, dans lesquelles sont imprimées une ou plusieurs molécules de ligand, et d) une plaque formant couvercle offrant des connexions traversantes d’entrée et de sortie vers les plateformes de microréseaux et un système d’activation de fluide, respectivement. L’invention concerne également une plateforme de microréseaux, son procédé de fabrication et son utilisation dans le cadre de l’appareil de l’invention.

System and device for the processing of biological samples and for the manipulation of liquids with biological samples.

Ein Aufarbeitungssystem (1) für biologische Proben, umfassend einen Behälter (2) zur Aufarbeitung grosser Volumina, einen flachen Polymerfilm (14) mit einer Unterseite (15) und einer hydrophoben Oberseite (16), die durch Vorsprünge (5) in einem Abstand d zur Unterseite (4) des Behälters (2) gehalten wird, wobei der Abstand d wenigstens einen Spalt (17) definiert, wenn der Behälter (2) auf dem Film (14) angeordnet ist, und eine Flüssigkeitströpfchen-Manipulationsvorrichtung (20), umfassend wenigstens ein Elektroden-Array (21) zur Auslösung von Bewegungen von Flüssigkeitströpfchen, ein Substrat (22), welches das wenigstens eine Elektroden-Array (21) trägt, und eine Steuereinheit (23), ist dadurch gekennzeichnet, dass der Behälter (2) und der Film (14) reversibel an der Flüssigkeitströpfchen-Manipulationsvorrichtung (20) angebracht sind, wobei das System (1) auf diese Weise die Verschiebung wenigstens eines Flüssigkeitströpfchens (19) aus dem wenigstens einen Schacht (6) durch den Kanal (12 ...

Apparatus and platform for multiplex analysis.

Sont décrites la conception et la performance dun appareil analytique et de dispositifs de plateforme de microréseaux conçus de façon correspondante, pour une analyse multiplex plus facile danalytes dans des liquides. Lappareil, en combinaison avec les dispositifs de plateforme de microréseaux, est conçu pour effectuer des dosages bioanalytiques et pour détecter la présence danalytes moléculaires organiques, éventuellement en format de microréseaux. Plusieurs dispositifs de plateforme de microréseaux, comprenant une ou plusieurs chambres de réaction de type canal, peuvent être analysés simultanément. Dans des aspects préférés, les dispositifs de plateforme de microréseaux sont des plateformes de microréseaux microstructurées stratifiées, offrant des chambres de réaction à base de canaux intégrées, ayant des molécules de capture imprimées et immobilisées dans des structures à canaux ouverts avant stratification. Lesdites plateformes de microréseaux microstructurées sont conçues pour une ...

УСТРОЙСТВО И СПОСОБ ДЛЯ ОПРЕДЕЛЕНИЯ И КОЛИЧЕСТВЕННОГО АНАЛИЗА АНАЛИТОВ, В ЧАСТНОСТИ, МИКОТОКСИНОВ

Настоящее изобретение касается устройства и способа для определения и количественного анализа аналитов и их применения для определения и количественного анализа микотоксинов.

Method of simultaneously depositing a series of patterns on a substrate by a macro stamp

The invention relates to a method for simultaneously depositing a group of patterns on a substrate via a stamp and a stamp 1 for depositing materials in the form of imprints on a surface of a substrate. The stamp 1 includes a template 12 and pins 14 joined at one end 142 to a first face 121 of the template. The pins are arranged on the first face of the template 12 so that the faces 141 of all the pins 14 joined to the template 12 can be placed in contact virtually simultaneously on the surface of the substrate. The disclosed embodiments also relate to a method for fabricating the stamp 1 and to a method for the virtually simultaneous deposition of a large number of imprints of identical or different materials on the surface of the substrate using the stamp, for an analysis.

Multipurpose sample preparation system and its the use of integrated analysis system

A cell-based platform for high throughput screening

The present invention relates to an apparatus for testing multiple sample compounds for their biological effect comprising a porous block having substantially planar top and bottom surfaces. The top surface comprises a plurality of cell adhesive regions and cell dis-adhesive regions and the bottom surface provides multiple sites to load the sample compounds. These sites are located opposite from the cell adhesive regions on the top surface of the porous block. In certain embodiments, the invention further comprises at least one dissolvable layer which provides multiple sites to load the sample compounds.

DEVICE FOR SEPARATING AND/OR ANALYSING SEVERAL MOLECULAR TARGETS DISSOLVED IN A COMPLEX MIXTURE

METHOD FOR INCREASING the HYDROPHOBICITE Of an EXTERNAL COATING Of UNDISPOSITIF Of ANALYSIS, SUCH AS a BIOCHIP, SUCH a DEVICE AND PROCESSES FOR SAFABRICATION

La présente invention concerne un procédé pour augmenter l'hydrophobicité d'un revêtement externe ajouré (3) d'un dispositif d'analyse (1) chimique et/ou biologique, tel qu'une biopuce, un tel dispositif comportant un substrat (2) et ce revêtement qui recouvre le substrat en entourant une pluralité de cuvettes (4) destinées à fixer des réactifs chimiques et/ou biologiques en vue de constituer des sites d'analyse. L'invention concerne également des procédés de fabrication de ce dispositif d'analyse. Le procédé selon l'invention pour augmenter l'hydrophobicité de ce revêtement externe (3) comprend un traitement dudit revêtement au moyen d'un plasma organique choisi dans le groupe constitué par les plasmas fluorocarbonés et les plasmas à groupes siloxanes, pour le dépôt d'un film hydrophobe (7) sur ledit revêtement, de sorte à optimiser le volume dudit réactif localisé autour dudit film dans chaque cuvette.

DEVICE OF PUMPING BY ELECTROMOUILLAGE AND APPLICATION TO MEASUREMENTS Of ELECTRIC ACTIVITY

L'invention concerne un procédé de pompage, à travers un orifice (30, 31) d'un premier substrat (1), d'un premier volume de liquide (2), en contact avec une première surface hydrophobe dudit substrat, dans lequel une variation de pression entre le premier volume de liquide et un deuxième volume de liquide (2'), situé en contact avec ledit orifice et une deuxième surface hydrophobe dudit substrat, est obtenue par électromouillage.

PROCESS OF SIMULTANEOUS DEPOSIT Of a WHOLE OF REASONS ON a SUBSTRATE BY a MACRO STAMP

L'invention concerne un timbre (1) pour le dépôt de matériels sous forme d'impressions sur une surface d'un substrat. Le timbre (1) comporte une semelle (12) et des plots (14) solidaires à une extrémité (142) à une première face (121) de la semelle. Les plots sont agencés sur la première face (121) de la semelle (12) de telle sorte que les faces (141) de tous les plots (14) solidaires de la semelle (12) puissent être mis en contact quasi simultanément sur la surface du substrat. L'invention est également relative à un procédé de réalisation dudit timbre et à un procédé de dépôt quasi simultané d'un grand nombre d'impressions de matériels identiques ou non sur la surface du substrat au moyen du timbre (1), en vue d'une analyse.

Method for manufacturing sample storage device and sample storage device

ELECTROSTATICALLY CONTROLLABLE MICROVALVES

... 개선된 마이크로밸브가 개시된다. 이 마이크로밸브는 작동 어퍼쳐 층에서 대응하는 작동 어퍼쳐를 포함한다. 제어 유체는 상기 작동 어퍼쳐를 통해서 흐른다. 상기 제어 유체의 흐름은 작동 어퍼쳐 층 근처의 전하 분포를 통해서 전형적으로 인가되는 전계에 의해 제어된다. 일 실시예에서, 상기 전계는 상기 작동 어퍼쳐의 개방 및 폐쇄를 조정함으로써, 상기 제어 유체의 흐름을 제어한다. 제 2 실시예에서, 제어 유체는 전계가 ER 유체의 점도를 제어하는 전기유변성 유체이고, 이에 따라, 상기 작동 어퍼쳐를 통한 유체 흐름을 제어한다. 두 실시예들에서, 제어 유체의 흐름은 제어될 유체가 흐르는 도관의 벽을 따라서 형성되는 가요성 멤브레인의 스트레칭을 제어한다. 가요성 멤브레인의 스트레칭이 제어될 주 유체의 흐름을 제어한다.

APPARATUS AND METHOD FOR MACHINING MICROCHAMBER FOR CELL CULTURE

LAB-ON-A-CHIP BASED MOLECULAR DIAGNOSTIC CHIP

A lab-on-a-chip based molecular diagnostic chip is disclosed. A molecular diagnostic chip according to one embodiment of the present invention comprises: an intermediate substrate on which a plurality of channels are aligned; a lower substrate bonded to a lower portion of the intermediate substrate; and an upper substrate bonded to an upper portion of the intermediate substrate. The upper substrate is provided with an inlet and an outlet so as to correspond to both ends of the channel, and the outlet is provided with an air filter. The molecular diagnostic chip according to embodiments of the present invention can remove bubbles contained in a sample in a simple manner by providing the air filter at the sample outlet. COPYRIGHT KIPO 2018 ...

Electromagnetic multiplex assay biosensor

A method is provided for determining the presence of multiple different target analytes in a liquid sample using electrophoretic separation and magnetic labels within a self-contained reaction cartridge and an external magnetic sensor for detection. Magnetic labels are bound to target analytes through specific binding elements. By electrophoretic separation, the multiple different targets can be sorted according to their specific sizes and inherent molecular charges for better detection resolution and specificity. After the separation process, the target analytes are then recognized and trapped by the detection binding elements within the reaction cartridge. A magnetic field generator provides a changeable magnetic field that causes the bounded magnetic labels and target analytes to produce a resonance disruption detectable by a magnetic sensor. The sensor can provide a digital binary value to indicate whether or not a label particle is bound and that determines the presence of target analytes.

Polymer microfluidic biochip fabrication

Provided are microfluidic devices and methods for fabricating and bonding such devices. Also provided are kits for analyzing analyte-containing samples and for lysing cells.

Carrier with flexible microassay device and methods of use

The disclosure provides a carrier for flexible microassay devices ( 510 ). The carrier is detachably attached to the microassay device ( 510 ) and provides means for protecting and handling the flexible microassay device ( 510 ). A method of preparing a microassay device for use is also disclosed.

Apparatus for detecting target molecules and related methods

An apparatus for analysis of a sample and in particular of a biological sample. The apparatus contains a microfluidic chip with dies, adapted to be selectively activated or deactivated by presence of target molecules in the biological sample. The apparatus further contains a light source to emit light for illumination of the microfluidic chip and an optical filter to allow passage of the light from the dies once activated or deactivated by the presence of the target molecules. A method for pressurizing a microfluidic chip is also disclosed, where a chamber is provided, the chamber is connected with the microfluidic chip and pressure is applied to the chamber.

Thermal cycling apparatus and method

A system for holding at least one of sample and reagent for analysis. The system includes a pair of parallel covers, at least one of which is light transmissive, of which pair a light transmissive cover forms a top, and of which pair the other forms a bottom. A frame is disposed between the covers to define, in relation to the covers, an interior volume. The frame and the covers are associated with one another to form a case, the case being substantially tight to liquids. A microfluidic array is disposed in the interior volume. The array includes a sheet of material having a pair of opposed surfaces, a thickness, and a plurality of through-holes running through the thickness between the surfaces, the through-holes containing at least one of sample and reagent.

Novel Electrostatically Addressable Microvalves

A method of controlling a main fluid in a conduit using a microvalve is described. The microvalve includes a corresponding actuation aperture in an actuation aperture layer. A control fluid flows through the actuation aperture in response to an electric field applied via a charge distribution near an actuation aperture layer. In one embodiment, the electric field may adjust the opening and closing of the actuation aperture thereby controlling the flow of the control fluid. In a second embodiment, the control fluid is an electrorheological fluid where the electric field controls the viscosity of the ER fluid, thereby controlling fluid flow through the actuation aperture. In both embodiments the flow of the control fluid controls stretching of a flexible membrane into and out of the conduit, thereby controlling the flow of the main fluid by opening or closing the conduit.

Microfluidic device and method of manufacturing the microfluidic device

A microfluidic device having a substrate with an array of curvilinear cavities. The substrate of the microfluidic device is preferably fabricated of a polymer such as polydimethylsiloxane. The microfluidic device is manufactured using a gas expansion molding technique.

Analytical Cartridge with Fluid Flow Control

Analytical cartridges, systems and methods of processing a sample for analysis using capillary flows. Vertical gradient sample filtration provides filtrate to an incubation chamber for a time controlled by a flow modulator at the outlet of the incubation chamber. The flow modulator can include a serpentine capillary flow path without side walls. Incubated filtrate can flow from the incubation chamber to a detection channel after a predetermined time. The detection chamber can include one or more analytical regions in a porous substrate for detection of two or more analytes on the same cartridge from the same sample.

Mechanically Integrated and Closely Coupled Print Head and Mist Source

A deposition apparatus comprising one or more atomizers structurally integrated with a deposition head. The entire head may be replaceable, and prefilled with material. The deposition head may comprise multiple nozzles. Also an apparatus for three dimensional materials deposition comprising a tiltable deposition head attached to a non-tiltable atomizer. Also methods and apparatuses for depositing different materials either simultaneously or sequentially.

Plastic Microfluidic Separation and Detection Platforms

Plastic electrophoresis separation chips are provided comprising a plurality of microfluidic channels and a detection window, where the detection window comprises a thin plastic; and the detection window comprises a detection region of each microfluidic channel. Such chips can be bonded to a support provided an aperture is provided in the support to allow detection of samples in the electrophoresis chip at the thin plastic detection window. Further, methods for electrophoretically separating and detecting a plurality of samples on the plastic electrophoresis separation chip are described.

Multilayer high density microwells

A multilayer well device includes a first substrate comprising an array of wells having a first pattern disposed therein and a second substrate comprising an array of wells having a second pattern, complementary to the first pattern disposed therein, wherein the second substrate is secured adjacent to a face of the first substrate. A common channel is interposed between the array of wells of the respective first and second substrates and is coupled to an inlet and an outlet.

Device and Method for Detection and Quantification of Immunological Proteins, Pathogenic and Microbial Agents and Cells

The present invention provides a method and device for detecting and quantifying the concentration of magnetic-responsive micro-beads dispersed in a liquid sample. Also provided is a method and microfluidic immunoassay pScreen™ device for detecting and quantifying the concentration of an analyte in a sample medium by using antigen-specific antibody-coated magnetic-responsive micro-beads. The methods and devices of the present invention have broad applications for point-of-care diagnostics by allowing quantification of a large variety of analytes, such as proteins, protein fragments, antigens, antibodies, antibody fragments, peptides, RNA, RNA fragments, functionalized magnetic micro-beads specific to CD 4+ , CD 8+ cells, malaria-infected red blood cells, cancer cells, cancer biomarkers such as prostate specific antigen and other cancer biomarkers, viruses, bacteria, and other pathogenic agents, with the sensitivity, specificity and accuracy of bench-top laboratory-based assays.

Device and method for detection and identification of immunological proteins, pathogenic and microbial agents and cells

The present invention provides a method and device for detecting and quantifying the concentration of magnetic-responsive micro-beads dispersed in a liquid sample. Also provided is a method and microfluidic immunoassay pScreen™ device for detecting and quantifying the concentration of an analyte in a sample medium by using antigen-specific antibody-coated magnetic-responsive micro-beads. The methods and devices of the present invention have broad applications for point-of-care diagnostics by allowing quantification of a large variety of analytes, such as proteins, protein fragments, antigens, antibodies, antibody fragments, peptides, RNA, RNA fragments, functionalized magnetic micro-beads specific to CD 4+ , CD 8+ cells, malaria-infected red blood cells, cancer cells, cancer biomarkers such as prostate specific antigen and other cancer biomarkers, viruses, bacteria, and other pathogenic agents, with the sensitivity, specificity and accuracy of bench-top laboratory-based assays.

Bio chip

There is provided a bio-chip. The bio-chip includes: a first substrate including a plurality of micro-wells formed in one surface thereof to a predetermined depth, the bottom face of each micro-well being hydrophilic and a lateral side thereof being hydrophobic; and a second substrate combined with the first substrate and including amounts of biomaterials inserted into the micro-wells, the amounts of biomaterials being provided at predetermined intervals.

Architectural layout for dilution with reduced wastage in digital microfluidic based lab-on-a-chip

Systems and methods are provided for producing fluids with desired concentration factors. According to one embodiment, an arrangement of digital microfluidic (DMF) based electrode platforms are provided. The arrangement may be configured to carry out a sequence of mix steps that may demand storage of resultant fluid mixtures produced in intermediate mix steps. Such sequences of mix steps may be desirable as a result of the decreased demand for initial fluid samples, and reduced wastage.

Integrated Nucleic Acid Analysis

The present disclosure provides fully integrated microfluidic systems to perform nucleic acid analysis. These processes include sample collection, nucleic acid extraction and purification, amplification, sequencing, and separation and detection. The present disclosure also provides optical detection systems and methods for separation and detection of biological molecules. In particular, the various aspects of the invention enable the simultaneous separation and detection of a plurality of biological molecules, typically fluorescent dye-labeled nucleic acids, within one or a plurality of microfluidic chambers or channels. The nucleic acids can be labeled with at least 6 dyes, each having a unique peak emission wavelength. The present systems and methods are particularly useful for DNA fragment sizing applications such as human identification by genetic fingerprinting and DNA sequencing applications such as clinical diagnostics.

Direct Clone Analysis and Selection Technology

The present invention describes a spatial addressing technique that uses a very high-density micro-pore array for high-throughput screening of biological interactions. The therapeutic, diagnostic and drug-discovery implications of being able to identify, select and characterize specific protein-protein, protein-DNA and/or protein-carbohydrate interactions from heterogeneous populations of millions (to billions) of cells is discussed. Importantly, this technique possesses the screening and selection capacity of current display-based screening systems (i.e., millions-billions) but with greater efficiency and shorter time.

Microfluid control device and method of manufacturing the same

Provided are a plastic microfluid control device having a multi-step microchannel and a method of manufacturing the same. The device includes a lower substrate, and a fluid channel substrate contacting the lower substrate and having a multi-step microchannel having at least two depths in a side coupling to the lower substrate. Thus, the device can precisely control the fluid flow by controlling capillary force in a depth direction of the channel by controlling the fluid using the multi-step microchannel having various channel depths. A multi-step micropattern is formed by repeating photolithography and transferred, thereby easily forming the multi-step microchannel having an even surface and a precisely controlled height.

Flow cells for high density array chips

Biochemical flow cells having sealed inlets and outlets are provided for performing high-volume assays on macromolecules. In one example embodiment, a flow cell with detachable inlet and outlet connectors comprises an inlet manifold, a coverslip, and a substrate disposed below the coverslip to form a reaction chamber, where the substrate is disposed to partially cover the inlet manifold such that a slit is formed along an entire edge of the substrate where fluids can flow from the inlet manifold through the slit, around substantially the entire edge of the substrate, and into the reaction chamber at equalized pressure and without bubbles. In another embodiment, a flow cell comprises an outlet manifold, two or more flow regions each connected to its own loading port via its own flow distribution funnel, each loading port connected to the outlet manifold, and plugs in a wall of the outlet manifold opposite each loading port, such that when a plug is absent from the wall of the outlet manifold, a loading tip may be inserted in its place, passing through the outlet manifold and connecting directly to a loading port.

Peristaltic micropump and related systems and methods

A peristaltic micropump comprising one or more conduits configured to transfer one or more pumped fluids, wherein each conduit comprises: an inlet ( 106 ), an outlet ( 107 ), a central portion ( 102 ) between the inlet and the outlet, and an actuator ( 103, 105 ) configured to engage the central portions of the one or more conduits.

Bead sealing method, method for detecting target molecule, array, kit, and target molecule detection device

This invention provides a technique enabling to detect target molecules of low concentration with high sensitivity. This invention includes (i) a step of introducing a hydrophilic solvent ( 42 ) containing beads ( 40 ),( 41 ′) into a space ( 30 ) between (a) a lower layer section ( 10 ) including a plurality of receptacles ( 13 ) each of which is capable of storing only one of the beads ( 41 ),( 41 ′) and which are separated from each other by a side wall ( 12 ) having a hydrophobic upper surface and (b) an upper layer section ( 20 ) facing a surface of the lower layer section ( 10 ) on which surface the plurality of receptacles ( 13 ) are provided; and (ii) a step of introducing a hydrophobic solvent ( 43 ) into the space ( 30 ), the step (ii) being carried out after the step (i).

Substrate for surface enhanced raman spectroscopy analysis and manufacturing method of the same, biosensor using the same, and microfluidic device using the same

A substrate for surface enhanced Raman spectroscopy analysis (SERS) comprises a ferroelectric single crystal having polarization-inverted patterns of spontaneous polarizations including polarization-inverted portions and non-inverted polarization portions, and metallic dots positioned at only either one polarized surfaces of the polarization-inverted portions and the non-inverted polarization portions. The provided SERS substrate produces a high enhancement effect. A microfluidic device incorporating the SERS substrate is also provided.

Valved, Microwell Cell-Culture Device And Method

A valved microfluidics device, microfluidics cell-culture device and system incorporating the devices are disclosed. The valved microfluidics device includes a substrate, a microchannel through which liquid can be moved from one station to another within the device, and a pneumatic microvalve adapted to be switched between open and closed states to control the flow of fluid through a microchannel. The microvalve is formed of three flexible membranes, one of which is responsive to pneumatic pressure applied to the valve and the other two of which deform to produce a more sealable channel cross-section. The cell culture device provides valving to allow controlled loading of cells into the individual well of the device, and exchange of cell-culture components in the wells.

Methods, compositions and systems for sample deposition

Methods, compositions, systems, apparatus, and kits are provided for depositing samples onto surfaces. The samples can include one or more particles, and the surface can include one or more reaction chambers. In some embodiments, the depositing can include the use of companion particles in combination with sample particles.

Screening assays and methods

Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody.

TIP OVERLAY FOR CONTINUOUS FLOW SPOTTING APPARATUS

The present disclosure provides apparatuses, systems, and methods involving a spotter apparatus for depositing a substance from a carrier fluid onto a deposition surface in an ordered array, the spotter apparatus comprising a loading surface including a first well and a second well; and a different outlet surface, including a first opening and a second opening, where a first microconduit fluidly couples the first well with the first opening and a second microconduit fluidly couples the second well with the second opening. An overlay is sealed to the outlet surface and penetrated by a deposition channel that is situated to communicate carrier fluid among the first opening, the second opening, and the deposition surface when the overlay is pressed against the deposition surface. 1. A method of depositing at least one substance from a carrier fluid on a deposition surface , the method comprising: i) a loading surface including the first well and a second well;', 'ii) an outlet surface, different than the loading surface, including a first opening and a second opening;', 'iii) a first microconduit fluidly coupling the first well with the first opening;', 'iv) a second microconduit fluidly coupling the second well with the second opening; and', 'v) an overlay positioned on the outlet surface and penetrated by a deposition channel, wherein the deposition channel is situated to communicate carrier fluid among the first opening, the second opening, and a deposition surface when the overlay is pressed against the deposition surface, and, 'a) loading a carrier fluid having at least one substance into a first well of a spotter apparatus, wherein the spotter apparatus comprisesb) flowing the carrier fluid in series from the first well, through the first microconduit to the deposition channel, through the second microconduit and into the second well, wherein the deposition channel directs at least one substance from the carrier fluid onto the deposition surface.2. The method of ...

Droplet digital pcr chip

The present invention discloses a droplet digital PCR chip. The droplet digital PCR chip includes at least one chip unit, each chip unit includes a chip body formed by bonding a top piece and a bottom piece, the chip body is internally provided with an inlet chamber, a droplet storage chamber, and an injection hole. The injection hole connects with the inlet chamber, a plurality of droplet generating channels are disposed between the inlet chamber and the droplet storage chamber, a height of the droplet generating channel is smaller than a height of the droplet storage chamber, an injection fluid is injected into the inlet chamber through the injection hole, and the injection fluid is emulsified and enters the droplet storage chamber at a junction of the droplet generating channels and the droplet storage chamber.

BIOLOGICAL DETECTION SYSTEM

A biological detection system for detecting a liquid sample containing a plurality of target biological particles includes a capturing device including a cell structure, an inlet, an outlet, a monolithic chip, and a layer of binding agent. The monolithic chip includes a substrate and a plurality of discrete nano-sized structures which are displaced from each other and each of which extends uprightly from the substrate to terminate at a top end. The layer of binding agent is formed on the top end of each of the discrete nano-sized structures for capturing the target biological particles. 1. A biological detection system adapted for detecting a liquid sample containing a plurality of target biological particles , comprising: [ [ a lower major surface, and', 'a lower adjoining surface opposite to said lower major surface in a transverse direction and having a lower recess which extends downwardly to terminate at an inner floor surface and which includes an upper sub-recess configured to permit passage of the liquid sample and a lower sub-recess, and, 'a lower cell body having'}, a top major surface, and', 'an upper adjoining surface which is opposite to said top major surface in the transverse direction and which has an upper recess extending toward said top major surface to terminate at a ceiling surface and configured to permit passage of the liquid sample;, 'an upper cell body having'}], 'a cell structure including'}, 'an inlet disposed upstream of said lower recess for introducing the liquid sample into said upper sub-recess of said lower recess;', 'an outlet disposed downstream of said lower recess and opposite to said inlet in a longitudinal direction;', 'a monolithic chip configured to be matingly fitted in said lower sub-recess and including a substrate and a plurality of discrete nano-sized structures which are displaced from each other in the longitudinal direction and each of which extends uprightly from said substrate to terminate at a top end; and', 'a ...

SAMPLE PROCESSING DEVICE WITH DETACHABLE SLIDE

A biological and chemical sample processing device that b. comprises a high pressure-resistant, shallow and wide area microfluidic chamber having at least one wall formed by a detachable slide containing samples such as immobilized entities, biological samples or molecules, c. comprises an arrangement of microfluidic access holes for injecting to and collecting fluid form said chamber, d. is interfaced with inlet ports and microfluidic channels which are formed external to the chamber, e. is configured so that the slide may be brought into contact with the device to form the said chamber, f. is adapted to deliver and to transport fluidic substances and reagents inside said chamber in a fast manner, preferably within less than 15 seconds, and in a regular or uniform way owing to said arrangement of microfluidic access holes. 1. A biological and chemical sample processing device thata. comprises a high pressure-resistant, shallow and wide area microfluidic chamber having at least one wall formed by a detachable slide containing samples such as immobilized entities, biological samples or molecules,b. comprises an arrangement of microfluidic access holes for injecting to and collecting fluid form said chamber,c. is interfaced with inlet ports and microfluidic channels which are formed external to the chamber,d. is configured so that the slide may be brought into contact with the device to form the said chamber,e. is adapted to deliver and to transport fluidic substances and reagents inside said chamber in a fast manner, preferably within less than 15 seconds, and in a regular or uniform way owing to said arrangement of microfluidic access holes.2. A device according to comprising pressure-driven flow generating means for creating a fluid flow inside the chamber claim 1 , i.e. which induces a pressure difference between inlets and outlets.3. A device according to comprising electrokinetic flow generating means for creating a fluid flow inside the chamber claim 1 , by ...

HANDHELD SENSOR FOR RAPID, SENSITIVE DETECTION AND QUANTIFICATION OF SARS-CoV-2 FROM SALIVA

Various examples are provided for disposable medical sensors that can be used for detection of SARS-CoV-2 antigen, cardiac troponin I, or other biosensing applications. In one example, a medical sensing system includes single-use disposable test strip comprising a functionalized sensing area configured to detect SARS-CoV-2 antigen and a portable sensing and readout device including pulse generation circuitry that can generate synchronized gate and drain pulses for detection and quantification of SARS-CoV-2 antigen in biological samples. In another example, a method includes providing a saliva sample to a functionalized sensing area configured to detect SARS-CoV-2 antigen, generating synchronized gate and drain pulses for a transistor, the gate pulse provided via electrodes of the functionalized sensing area, and sensing an output of the transistor that is a function of a concentration of SARS-CoV-2 antigen in the sample. 1. A medical sensing system , comprising:a single-use disposable test strip comprising a functionalized sensing area disposed between first and second electrodes, the functionalized sensing area configured to detect SARS-CoV-2 antigen; and pulse generation circuitry configured to generate synchronized gate and drain pulses, the first electrode of the disposable test strip electrically coupled to a gate pulse output of the pulse generation circuitry; and', 'a transistor having a drain electrically controlled by a drain pulse output of the pulse generation circuitry, and a gate electrically coupled to the second electrode of the disposable test strip., 'a portable sensing and readout device comprising2. The medical sensing system of claim 1 , wherein the functionalized sensing area is functionalized with anti-SARS-CoV-2 antibody.3. The medical sensing system of claim 2 , wherein the anti-SARS-CoV-2 antibody is bound to a gold (Au) sensing area surface.4. The medical sensing system of claim 3 , wherein the Au sensing area surface is treated with thio- ...

Cartridges for sample partitioning

Cartridges for sample partitioning and methods of making and using the cartridges are provided. The cartridges include a pouch to receive a mated stem-well film and a sealing film covered by a release liner. The stem film and the sealing film can be respectively separated from the well film and sealing film simultaneously by pulling a pull tab.

PORTABLE SAMPLE LOADING DEVICE

A portable sample loading device () include a base () and a fixing device () connected to the base (). The base () can support a chip () and a sample loading connector (). The fixing device () can detachably retain the chip () and the sample loading connector () on the base (). The base () includes a front surface () and a back surface () opposite to the front surface (). The front surface () includes a supporting surface for supporting the chip (). A region of the supporting surface () corresponds to a sample inlet of the chip () is recessed toward the back surface () to form a receiving space () for receiving the sample loading connector (). The receiving space () further defines a sample injection hole () corresponding to the sample inlet of the chip (). 1. A portable sample loading device , comprising:a base; anda fixing device connected to the base;wherein the base is configured to support a chip and a sample loading connector, the fixing device is configured to detachably retain the chip and the sample loading connector on the base, the base comprises a front surface and a back surface opposite to the front surface, the front surface comprises a supporting surface configured for supporting the chip, a region of the supporting surface corresponds to a sample inlet of the chip is recessed toward the back surface to form a receiving space configured for receiving the sample loading connector, and the receiving space further defines a sample injection hole corresponding to the sample inlet of the chip.2. The portable sample loading device of claim 1 , further comprising a locking device claim 1 , wherein the locking device is operable to engage the fixing device with the base or disengaged the fixing device from the base.3. The portable sample loading device of claim 2 , wherein one end of the fixing device is pivotally connected and rotate around the base claim 2 , when the end of the fixing device rotates around the base claim 2 , another end of the fixing ...

IMPROVED DROPLET SEQUENCING APPARATUS AND METHOD

An apparatus for sequencing a polynucleotide analyte is provided and comprises; •a first zone in which a stream of single nucleotides is generated by progressive digestion of a molecule of the analyte attached to a particle located therein and exposed to a flowing aqueous medium; •a second zone in which a corresponding stream of aqueous droplets is generated from the aqueous medium and the nucleotide stream and wherein at least some of the droplets contain a single nucleotide and •a third zone in which each droplet is stored and/or interrogated to reveal a property characteristic of the single nucleotide it may contain; characterised in that the first zone comprises a microfluidic channel through which the aqueous medium flows and the location comprises a hollow seating in a wall thereof to which suction can be applied and into which the particle can be close-fitted. 2. The apparatus as claimed in claim 1 , characterised in that the hollow seating is located immediately upstream of the second zone.3. The apparatus as claimed in claim 1 , characterised in that the particle comprises a bead having a surface to which the analyte molecule can be physically or chemically bound.4. The apparatus as claimed in claim 1 , characterised in that the digestion method is selected from exonucleolysis claim 1 , phosphorolysis or pyrophosphorolysis.5. The apparatus as claimed in claim 1 , characterised in that the third zone includes a laser and a photodetector to detect Raman-scattered light.6. The apparatus as claimed in claim 1 , characterised by being capable of processing an aqueous medium which in at least one of the second or third zones contains at least one single-nucleotide probe selective for one of the nucleobase types from which the analyte is constituted; said probe(s) being capable of fluorescing substantially only after it has captured a single nucleotide and undergone subsequent exonucleolysis.7. The apparatus as claimed in claim 6 , characterised by further ...

Two-Dimensional Cell Array Device and Apparatus for Gene Quantification and Sequence Analysis

In order to conduct gene expression analysis of a number of genes in a number of cells, it has been necessary to separate cells, extract genes therefrom, amplify nucleic acids, and perform sequence analysis. However, separation of cells imposes damages on the cells, and it requires the use of an expensive system. Gene expression analysis in each cell can be carried out with high accuracy by arranging a pair of structures comprising a cell trapping section and a nucleic acid trapping section in a vertical direction to extract individual genes in relevant cells, synthesizing cDNA in the nucleic acid trapping section, amplifying nucleic acids, and analyzing the sequences using a next-generation sequencer.

Tools and methods for isolation and analysis of individual components from a biological sample

The present invention describes a device(s) and assay(s) for the isolation and analysis of individual components from a sample. The invention provides a means of both isolating a multitude of individual components into an organized array and the subsequent analysis of such components by various detection and analysis methodologies. The invention provides a significant advancement in both the number of individual components that can be individually analyzed as well as enabling the quality and number of analytical methodologies that can be applied to them.

Sensor arrays and methods for making same

A system includes a sensor including a sensor pad and includes a well wall structure defining a well operatively connected to the sensor pad. The sensor pad is associated with a lower surface of the well. The well wall structure defines an upper surface and a wall surface extending between the upper surface and the lower surface. The upper surface is defined by an upper buffer material having an intrinsic buffer capacity of at least 2×10 17 groups/m 2 . The wall surface is defined by a wall material having an intrinsic buffer capacity of not greater than 1.7×10 17 groups/m 2 .

HIGH EFFICIENCY, SMALL VOLUME NUCLEIC ACID SYNTHESIS

The disclosure generally relates to compositions and methods for the production of nucleic acid molecules. In some aspects, the invention allows for the microscale generation of nucleic acid molecules, optionally followed by assembly of these nucleic acid molecules into larger molecules. In some aspects, the invention allows for efficient production of nucleic acid molecules (e.g., large nucleic acid molecules such as genomes). 1. A method for removing a bead from a fluid-filled well of a microchip for synthesizing nucleic acid molecules , wherein a nucleic acid molecule is attached to the bead , the method comprising:providing a voltage between a first electrode that is arranged at a bottom of the fluid-filled well and a second electrode, wherein the voltage is sufficient to cause fluid in the fluid-filled well to undergo electrolysis producing one or more bubbles in the fluid to rise to a top of the fluid-filled well along with the bead or to lift the bead to the top of the fluid-filled well.2. The method of claim 1 , further comprising collecting the bead that has risen to the top of the fluid-filled well with a bead-collection device.3. The method of claim 2 , further comprising transferring the bead that was collected to a well of a first multiwell collection plate.4. The method of claim 1 , wherein the fluid comprises an aqueous or a non-aqueous buffer solution.5. The method of claim 1 , wherein the fluid comprises water claim 1 , methanol claim 1 , acetonitrile claim 1 , and Net4pTsO.6. The method of claim 1 , wherein the first electrode is composed of platinum and the voltage is about 0.1 to about 100 volts.7. The method of claim 1 , wherein each well of the microchip is individually addressable by a controller.8. The method of claim 1 , wherein the bead is composed of: a synthetic polymer claim 1 , a modified naturally occurring polymer claim 1 , glass claim 1 , controlled pore glass claim 1 , magnetic controlled pore glass claim 1 , magnetic beads claim 1 ...

SYSTEMS AND METHODS FOR THERMAL ACTUATION OF MICROFLUIDIC DEVICES

A microfluidic processing device includes a substrate defining a microfluidic network. The substrate is in thermal communication with a plurality of N independently controllable components and a plurality of input output contacts for connecting the substrate to an external controller. Each component has at least two terminals. Each terminal is in electrical communication with at least one contact. The number of contacts required to independently control the N components is substantially less than the total number of terminals. Upon actuation, the components typically heat a portion of the microfluidic network and/or sense a temperature thereof. 130-. (canceled)31. A system , comprising:a first substrate defining a microfluidic network comprising a reaction chamber configured to receive a polynucleotide-containing sample;a second substrate defining a plurality of resistive heaters and temperature sensors, wherein in use, the first substrate and the second substrate mate to bring the microfluidic network and the plurality of resistive heaters and temperature sensors into thermal communication;andwherein each resistive heater is individually actuatable by supplying electric current to an appropriate pair of contacts, wherein the number of contacts is reduced by structuring the contacts to serve more than one resistive heater while allowing control of each resistive heater independently of other resistive heaters.32. The system of claim 31 , further comprising a controller.33. The system of claim 31 , further comprising a processor.34. The system of claim 31 , further comprising a heat source driver configured to supply a specified amount of current.35. The system of claim 31 , further comprising a heat source driver configured to supply a particular voltage.36. The system of claim 31 , wherein a resistive heater and a temperature sensor of the plurality of resistive heaters and temperature sensors are combined.37. The system of claim 31 , wherein the first substrate ...

SCREENING ASSAYS AND METHODS

Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody. 1. A printed microarray of unknown cell-derived products , each position of said array comprising a deposit corresponding to a composition of a single cell , said deposit being less than 100 micrometers in diameter.2. The microarray of claim 1 , wherein said deposit is a secreted cell-derived product selected from the group consisting of an antibody claim 1 , cytokine claim 1 , chemokine claim 1 , and inflammatory mediator.3. The microarray of claim 1 , wherein said microarray comprises a capture ligand for a class of secreted products.4. The microarray of claim 3 , wherein said capture ligand binds to a single immunoglobulin isotype. This application claims priority to U.S. Ser. No. 60/717,976 filed Sep. 16, 2005, which is incorporated herein by reference in its entirety.This invention was funded in part by the U.S. Government under grant numbers NAKFI Nano08 awarded by the National Academy of Sciences and/or grant 5R01AI034893-1 awarded by the National Institutes of Health. The Government has certain rights in the invention.The invention relates to screening assays and methods to identify secreted products.Assays exist to identify compounds or molecules of interest that may be involved in a disease process or other condition or in treating a disease process or condition. Existing assays have some drawbacks. One significant drawback is the time required to screen for many compounds or molecules. Another drawback is that it may not be possible to recover the compound or molecule post-screening. There remains a need for better screening assays and methods.The invention provides a printed microarray of unknown cell-derived products. Each ...

MICROFLUIDIC CONTROL CHIP, MICROFLUIDIC APPARATUS, AND MANUFACTURING METHOD THEREOF

The disclosure relates to a microfluidic control chip. The microfluidic control chip may include an upper cover, a lower cover, and a chip functional layer between the upper cover and the lower cover. The chip functional layer may include a first region. The chip functional layer in the first region may include at least one chamber unit, an inlet flow channel to the chamber unit, and an outlet flow channel from the chamber unit. The chamber unit may include a main flow channel, a plurality of secondary flow channels, and a plurality of microcavity structures. The chamber unit may be configured to allow a liquid to flow from the main flow channel to the plurality of secondary flow channels, and then to the plurality of microcavity structures. 1. A microfluidic control chip , comprising: an upper cover , a lower cover , and a chip functional layer between the upper cover and the lower cover , the chip functional layer comprising a first region ,the chip functional layer in the first region comprising at least one chamber unit, an inlet flow channel to the chamber unit, and an outlet flow channel from the chamber unit,the chamber unit comprising a main flow channel, a plurality of secondary flow channels, and a plurality of microcavity structures,wherein the plurality of secondary flow channels are on both sides of the main flow channel and respectively connected to the main flow channel, and each of the plurality of microcavity structures is connected with one end of one of the secondary flow channels opposite from the main flow channel, andthe chamber unit is configured to allow a liquid to flow from the main flow channel to the plurality of secondary flow channels, and then to the plurality of microcavity structures.2. The microfluidic control chip of claim 1 , wherein the chip functional layer further comprises a second region claim 1 , the chip functional layer in the second region comprises a cavity and a plurality of capture structures in the cavity claim 1 , ...

BIOCHIP STRUCTURE AND METHOD FOR MAKING SAME

A method for making a biochip structure, includes: providing a substrate and forming a plurality of biochips on a surface of the substrate; forming a carrier on a side of the substrate having the biochips, defining a plurality of through holes in the substrate from a side of the substrate away from the carrier; and filling conductive material in each of the through holes to connect one of the biochips. The carrier defines a plurality of openings. Each opening cooperates with substrate to form a micro-channel, and one of the biochips is exposed in the micro-channel. 1. A method for making a biochip structure , comprising:providing a substrate having a plurality of biochips on a surface of the substrate;forming a carrier on a side of the substrate having the plurality of biochips, the carrier defining a plurality of openings, each of the plurality of openings cooperating with substrate to form a micro-channel, one of the plurality of biochips being exposed from the micro-channel;defining a plurality of through holes in the substrate from a side of the substrate away from the carrier; andfilling conductive material in each of the plurality of through holes to connect one of the plurality of biochips.2. The method of claim 1 , further comprising forming a plurality of connection pads on the substrate claim 1 , wherein each of the plurality of connection pads is electrically coupled to the conductive material in one of the plurality of through holes.3. The method of claim 1 , further comprising reducing a thickness of the substrate from a side of the substrate away from the carrier before defining the plurality of through holes in the substrate.4. The method of claim 3 , wherein the thickness of the substrate is reduced to be less than 100 micrometers.5. The method of claim 1 , further comprising cutting the substrate to form a plurality of biochip structures claim 1 , wherein each of the plurality of biochip structures comprises one of the plurality of biochip claim 1 , ...

MICROFLUIDIC METHOD FOR ANALYZING METALS

The present invention relates to a microfluidic method for analyzing a fluid containing a metal trace element, in particular arsenic, comprising the following steps of introducing a fluid sample into at least one micro-channel of a microfluidic circuit; mixing, within the micro-channel of the microfluidic circuit, the introduced fluid sample with nitric acid and L-cysteine, and measuring the quantity of metal trace element present in the sample, using an electrochemical detection method. 1. A microfluidic method for analyzing a fluid containing at least one metal trace element comprising the following steps:a) introduction of a fluid sample into at least one microchannel of a microfluidic circuit;b) mixing, within the microchannel of the microfluidic circuit, the fluid sample introduced in step a) with the reagents, andc) measuring the quantity of the metal trace element present in the sample obtained in b), using an electrochemical detection method,the said step c) comprising mixing the sample obtained in b) with at least one solution comprising a metal trace element of known concentration, and then assaying the metal trace element by electrochemical detection method.2. The microfluidic method according to claim 1 , wherein the metal trace element is arsenic claim 1 , and in that the method comprises the following steps:a) introducing a fluid sample into at least one microchannel of a microfluidic circuit;b) mixing, within the microchannel of the microfluidic circuit, the fluid sample introduced in the step a), with nitric acid and L-cysteine, andc) measuring the quantity of arsenic present in the sample obtained in b), using an electrochemical detection method, preferably with, at least 2 electrodes, preferably at least 3 electrodes, one of which is gold.3. The microfluidic method according to claim 1 , wherein the measurement in the step c) is carried out using the following three electrodes:a gold electrode as a working electrode,a platinum electrode, as a ...

CAPSULE CONTAINMENT OF DRIED REAGENTS

Disclosed herein are methods and devices for preparing a dried reagent for long term storage and rehydrating and mixing the dried reagent. 1. A microfluidic device comprising:an oval-shaped raised surface on the microfluidic device, wherein said oval-shaped raised surface comprises an inlet, an outlet, and an edge; anda reagent storage component having a capsule capable of holding a liquid or a solid sample, said capsule comprising an inner surface extending from the bottom of said capsule to an oval-shaped opening at the top of the capsule, wherein said inner surface is substantially smooth and comprises a concave shape extending from the bottom of the capsule,wherein engagement between said oval-shaped opening and said edge forms a fluid tight seal to compartmentalize said capsule with respect to the inlet and the outlet of the oval shaped raised surface.2. The device of the reagent storage component further comprising:a planar layer affixed around the oval-shaped opening of said capsule and oriented in the same plane as the oval-shaped opening of said capsule, wherein said planar layer comprises a top surface and a bottom surface, said top surface aligned with the inner surface of said capsule at said oval-shaped opening to provide a continuous surface.3. The device of claim 1 , wherein said capsule comprises a mixing element.4. The device of claim 3 , wherein said mixing element comprises a magnetic bead.5. The device of claim 1 , wherein said capsule comprises a dried reagent. This application is a divisional of U.S. patent application Ser. No. 16/468,588 filed Jun. 11, 2019, now U.S. Patent Application Publication No. 2021/0008559, which is a national phase application under 35 USC 371 of International Patent Application No. PCT/US2017/065444, filed Dec. 8, 2017, now International Publication No. WO 2018/111728, which claims the benefit of U.S. Provisional Patent Application No. 62/433,134, filed Dec. 12, 2016, and U.S. Provisional Patent Application No. 62/ ...

APPARATUS AND PLATFORM FOR DETECTION OF ALLERGEN

Provided is an allergen detecting apparatus that can combine with an allergen microarray chip, and the apparatus comprises a microfluidic chip and a clamping unit. The allergen microarray chip can be any commercial chip and a reaction region of the microfluidic chip is configured to fit tightly with a microarray region of the allergen microarray chip allowing a sample or a reagent to contact with a protein allergen disposed on the microarray region. The present invention also provides a platform comprising a control system configured to automatically perform the mixing/binding reactions of the antibody/antigen in the apparatus of the present invention to achieve a faster, more cost-effective, and accurate detection of allergens. 1. An allergen detecting apparatus for incorporating an allergen microarray chip having a microarray region , comprising:a microfluidic chip having an air control layer and a fluid channel layer, wherein the air control layer comprises at least an air control inlet, and the fluid channel layer comprises at least a liquid injection port and a reaction region; anda clamping unit having a housing space for accommodating the microfluidic chip, and at least a clamping member for fixing the microfluidic chip to allow the reaction region to align and tightly fit with the microarray region.2. The allergen detecting apparatus according to claim 1 , wherein an area of the reaction region is not less than that of the microarray region.3. The allergen detecting apparatus according to claim 1 , wherein the clamping unit comprises a cover and at least one clamping member claim 1 , and the housing space is formed by the cover.4. The allergen detecting apparatus according to claim 1 , wherein the microfluidic chip further comprises a leakage-proof wall disposed in the fluid channel layer to prevent leakage when the microfluidic chip is incorporated with the allergen micro array chip.5. The allergen detecting apparatus according to claim 1 , wherein the ...

Method for detecting the presence of a target nucleic acid sequence in a sample

A method comprises loading a sample portion into a sample chamber which comprises means for minimizing diffusion of the sample portion, subjecting the sample portion to an amplification step, and determining whether the sample portion contains at least one molecule of a target nucleic acid. If the sample portion contains a single molecule of the target nucleic acid, the sample portion would attain a detectable concentration of the target nucleic acid after a single round of amplification. Also, a microfluidic device comprising a sample portion and a sample chamber comprising means for minimizing diffusion of the sample portion. Also, a microfluidic device comprising a sample chamber and an amplification targeting reagent positioned in the first sample chamber.

MOLECULAR ANALYSIS SYSTEM AND USE THEREOF

A molecular testing device comprises a heating and cooling module having a thin-film thermoelectric heating and cooling device, and a removable test module having a combined amplification and hybridization reaction chamber. The reaction chamber comprises a thermo-conductive exterior surface and a microarray on an interior surface. The thin-film thermoelectric heating and cooling device has a heat transfer surface that is adapted to make contact with the thermo-conductive exterior surface of the reaction chamber. The molecular testing device may be used to perform a PCR in the reaction chamber. 120-. (canceled)21. A molecular testing device , comprising:a heating and cooling module comprising a thermoelectric heating and cooling device; anda removable test module comprising a combined amplification and hybridization reaction chamber comprising a thermo-conductive first exterior surface, a second exterior surface and a microarray on an interior surface, wherein the microarray is an ordered array of spots presented for binding to ligands of interest, wherein said thermoelectric heating and cooling device comprises a heat transfer surface that is adapted to make contact with said thermo-conductive first exterior surface of said reaction chamber, and wherein said thermoelectric heating and cooling device heats and cools said reaction chamber through said thermo-conductive first exterior surface of said reaction chamber depending on the direction of an electrical current, and wherein said second exterior surface of said reaction chamber is not in contact with said heat transfer surface of said thermoelectric heating and cooling device and is insulated with a thermal insulation material; anda programmable control module configured to control the direction of an electrical current flowing through said thermoelectric heating and cooling device to control the heating or cooling of said thermoelectric heating and cooling device.22. The molecular testing device of claim 21 , ...

SYSTEM AND METHOD FOR INTEGRATION OF BIOLOGICAL CHIPS

An apparatus () including multiple biological chips () includes a substrate (), a first adhesive layer () disposed on the substrate (), a first biological chip () and a second biological chip () disposed on the first adhesive layer () and attached to the substrate () by the adhesive layer (). The apparatus () further includes a filler () disposed between the first biological chip () and the second biological chip (). The filler () includes a second adhesive layer () extending between a side surface () of the first biological chip () and a side surface () of the second biological chip (), the second adhesive layer () attaching the first biological chip () to the second biological chip (). The filler () also includes a surface layer () disposed over the second adhesive layer (). The surface layer () has a hydrophobic surface that is co-planar with a top surface () of the first biological chip () and a top surface () of the second biological chip (). 1. An apparatus including multiple biological chips , comprising:a substrate;a first adhesive layer disposed on the substrate;a first biological chip and a second biological chip disposed on the first adhesive layer and attached to the substrate by the first adhesive layer; anda filler disposed between the first biological chip and the second biological chip; a second adhesive layer disposed between a side surface of the first biological chip and a side surface of the second biological chip, the second adhesive layer attaching the first biological chip to the second biological chip; and', 'a surface layer disposed over the second adhesive layer, wherein the surface layer has a hydrophobic surface that is co-planar with a top surface of the first biological chip and a top surface of the second biological chip., 'wherein the filler includes2. The apparatus of claim 1 , wherein the surface layer in the filler comprises a mold release material claim 1 , or a poly(p-xylylene) polymer.3. The apparatus of claim 1 , wherein the ...

Liquid sample loading

The assembly includes a docking console and a manifold. The docking console includes a cartridge support surface having a first end and a second end. The manifold has one or more wells defined therein. The docking console further includes a manifold retention bracket to releasably hold the manifold against a fluid cartridge supported on the cartridge support surface at an interface position such that the one or more wells are in fluid communication with the fluid cartridge and a biased seal bar to press the fluid cartridge against the manifold held by the manifold retention bracket. A hydrophilic porous frit disposed within at least one of the wells and is to permit liquid to flow through the outlet aperture but prevent gas from passing through the outlet aperture.

MICROFLUIDIC DEVICE WITH DEP ARRAYS

Microfluidic device having a plurality of microfluidic channels and corresponding dielectrophoresis (DEP) electrode arrays, each channel arranged to direct fluid over a DEP electrode array such that in use target particles are manipulated by the DEP electrode array. The device also has a first connection point and second connection point for connecting the device to an alternating current source, a first input of each DEP electrode array connected to the first connection point via the first conductor and second input of each DEP electrode array connected to the second connection point via the second conductor. A resistance of the first conductor between the first input of each electrode and the first connection point, and a resistance of the second conductor between the second input of each electrode and the second connection point is substantially at least an order of magnitude less than a total resistance of the connected electrode arrays. 1. A microfluidic device comprising:a plurality of microfluidic channels and a plurality of corresponding dielectrophoresis (DEP) electrode arrays, wherein each microfluidic channel is configured to direct fluid over a DEP electrode array, andat least one first connection point and at least one second connection point configured to connect the microfluidic device to an alternating current source, a first input of each DEP electrode array is connected to the first connection point via a first conductor, and', 'a second input of each DEP electrode array is connected to the second connection point via a second conductor, and', 'an electrical resistance of the first conductor between the first input of each electrode and the first connection point, and an electrical resistance of the second conductor between the second input of each electrode and the second connection point is substantially at least an order of magnitude less than a total electrical resistance of the connected electrode arrays., 'wherein2. The microfluidic device ...

Thermal Isolation of Reaction Sites on a Substrate

A thermal block assembly is provided. The assembly can comprise a substrate comprising a first surface configured with a plurality of reaction sites each reaction site configured to contain a biological sample and a sample block comprising a plurality of pedestals configured to thermally modulate the plurality of biological samples wherein each pedestal is thermally coupled to one of the reaction sites. The assembly can further comprise cooling blocks, slots and insulating rings associated with reaction sites each capable of minimizing heat flow between reaction sites. A method for thermally isolating reaction sites is also provided. The method can comprise providing a substrate including a plurality of reaction sites, each reaction site configured to contain a biological sample, providing a sample block comprising pedestals, each pedestal having a dimension substantially equal to a dimension of the reaction site and thermally coupled to the reaction site, thermally isolating the reaction sites with a thermal isolating feature, modulating the temperature of the pedestals through a sequence of temperature and hold times and cooling the reaction sites with cooling blocks. 1. A thermal block assembly comprising:a substrate comprising a substrate surface configured with a plurality of reaction sites each reaction site configured to contain a biological sample;a sample block; anda thermal isolating feature configured to restrict heat flow from one reaction site to another.2. The block assembly of claim 1 , wherein the thermal isolation feature comprises a feature selected from the group consisting of pedestals claim 1 , slots claim 1 , cooling blocks claim 1 , rings claim 1 , reaction site spacing and combinations thereof.3. The block assembly of claim 1 , wherein the thermal isolation feature comprises pedestals and are provided on the sample block.4. The block assembly of claim 1 , wherein the thermal isolation feature comprises a pedestal claim 1 , and a top of each ...

MOLECULAR ANALYSIS SYSTEM AND USE THEREOF

A molecular testing device comprises a heating and cooling module having a thin-film thermoelectric heating and cooling device, and a removable test module having a combined amplification and hybridization reaction chamber. The reaction chamber comprises a thermo-conductive exterior surface and a microarray on an interior surface. The thin-film thermoelectric heating and cooling device has a heat transfer surface that is adapted to make contact with the thermo-conductive exterior surface of the reaction chamber. The molecular testing device may be used to perform a PCR in the reaction chamber. 120-. (canceled)21. A method for performing a polymerase chain reaction (PCR) , comprising the step of:placing a test module in a PCR device; andheating and cooling the test module based on a predetermined PCR program stored in the PCR device,wherein the test module comprises a reaction chamber having a thermo-conductive first exterior surface, a second exterior surface and a microarray on an interior surface, wherein the microarray is an ordered array of spots presented for binding to ligands of interest, and a heating and cooling module comprising a thermoelectric heating and cooling device comprising a heat transfer surface;', 'a sample holder for receiving the removable test module, wherein the thermoelectric heating and cooling device heats and cools depending on the direction of an electrical current the reaction chamber by contacting the heat transfer surface with the thermo-conductive first exterior surface of the reaction chamber, and wherein the sample holder comprises a thermal insulation layer to insulate the second exterior surface of the reaction chamber;', 'a moving system that brings the heat transfer surface in contact with the thermo-conductive first exterior surface when the test module is placed in the sample holder, wherein the heat transfer surface undergoes thermal cycling during the PCR; and', 'a programmable control module configured to control the ...

HIGH RESOLUTION SYSTEMS, KITS, APPARATUS, AND METHODS USING MAGNETIC BEADS FOR HIGH THROUGHPUT MICROBIOLOGY APPLICATIONS

A method of transferring material from a first microfabricated device to a second microfabricated device. At least one magnetic bead is loaded into at least one microwell of the first microfabricated device, where a plurality of cells are cultivated. The second microfabricated device is positioned such that the at least one microwell of the first array of microwells is aligned with at least one microwell of the second array of microwells. A magnetic field is applied so as to move the at least one magnetic bead contained in the at least one microwell of the first microfabricated device into the at least one microwell of the second microfabricated device. In this manner, at least one cell from the plurality of cells in the at least one microwell of the first microfabricated device is transferred to the at least one microwell of the second microfabricated device. 1. A method of transferring material from a first microfabricated device including a first array of microwells to a second microfabricated device including a second array of microwells , the method comprising:loading at least one magnetic bead into at least one microwell of the first array of microwells;incubating the first microfabricated device to cultivate a plurality of cells in at least one microwell of the first array of microwells;positioning the second microfabricated device relative to the first microfabricated device such that the at least one microwell of the first array of microwells of the first microfabricated device is aligned with at least one microwell of the second array of microwells of the second microfabricated device; andapplying a magnetic field so as to move the at least one magnetic bead contained in the at least one microwell of the first array of microwells into the at least one microwell of the second array of microwells, whereby at least one cell from the plurality of cells in the at least one microwell of the first array of microwells is transferred to the at least one microwell ...

SYSTEM AND METHOD FOR SINGLE CELL GENETIC ANALYSIS

Provided are methods and systems for parallel analysis of a single cell's nucleic acid. 125.-. (canceled)26. A method for parallel analysis of a single cells' nucleic acid , the method comprising:(a) receiving into a cell reservoir a liquid medium containing a suspension of cells to be analyzed;(b) inducing said liquid medium to flow from said cell reservoir through a cell cage array with a plurality of cell cages, to thereby cause cells to enter each into a cell cage of said cell cage array;(c) associating said cell cage array with a microarray comprising a plurality of DNA spots, wherein each DNA spot comprises a probe and a nucleic acid identifier sequence unique for said DNA spot, such that each of the DNA spots is exposed to one of the cell cages;(d) introducing a buffer and inducing conditions for cell lysis and nucleic acid synthesis and amplification, to produce amplified nucleic acid molecules in the cells; and(e) sequencing the amplified nucleic acid molecules, and determining the nature of the amplified and sequenced nucleic acid molecules according to the nucleic acid identifier sequence.27. The method of claim 26 , further comprises removing excess cells or debris between steps (b) and (c).28. The method of claim 26 , wherein step (d) comprises mounting on said cell cage array a gel pad comprising at least one buffer selected from the lysis buffer and the buffer suitable for nucleic acid amplification.29. The method of claim 26 , wherein said conditions comprise: (i) an reverse transcriptase reaction; (ii) a second strand synthesis reaction claim 26 , and (iii) an amplification reaction to produce amplified RNA.30. The method of claim 29 , wherein said second strand synthesis is selected from claim 29 , DNA polymerase reaction claim 29 , PCR-based amplification and rolling circle amplification; and comprises the use of a DNA polymerase 1 and RNase H.31. The method of claim 26 , wherein said probe comprises a promoter.32. The method of claim 26 , wherein ...

Waveguide-based detection system with scanning light source

The invention provides methods and devices for generating optical pulses in one or more waveguides using a spatially scanning light source. A detection system, methods of use thereof and kits for detecting a biologically active analyte molecule are also provided. The system includes a scanning light source, a substrate comprising a plurality of waveguides and a plurality of optical sensing sites in optical communication with one or more waveguide of the substrate, a detector that is coupled to and in optical communication with the substrate, and means for spatially translating a light beam emitted from said scanning light source such that the light beam is coupled to and in optical communication with the waveguides of the substrate at some point along its scanning path. The use of a scanning light source allows the coupling of light into the waveguides of the substrate in a simple and cost-effective manner.

IMMOBILIZATION OF CELLS OR VIRUS PARTICLES ON PROTEIN STRUCTURES USING A MICROFLUIDIC CHAMBER

The present invention relates to methods for the immobilization of cells or virus particles of interest expressing one or more predetermined surface marker(s) on defined spots on a solid support, comprising the steps of providing a biological fluid sample suspected of containing cells or virus particles of interest; labeling the cells or virus particles of interest with antibodies, antibody fragments or antibody mimetics directed against the one or more predetermined surface marker(s) and carrying a first binding agent; and contacting the labeled cells or virus particles of interest with a solid support (biochip), said solid support comprising an array of defined isolated spots of a solid support-bound second binding agent, wherein the first and second binding agents can bind to each other. The present invention further relates to devices for the isolation of cells or virus particles of interest expressing one or more predetermined surface marker(s). 1. A method for the immobilization of cells or virus particles of interest expressing one or more predetermined surface marker(s) on defined spots on a solid support , comprising the steps:(a) providing a biological fluid sample suspected of containing cells or virus particles of interest;(b) labeling the cells or virus particles of interest with antibodies, antibody fragments or antibody mimetics directed against the one or more predetermined surface marker(s) and carrying a first binding agent; and(c) contacting the labeled cells or virus particles of interest with a solid support, said solid support comprising an array of defined isolated spots of a solid support-bound second binding agent, wherein the first and second binding agents can bind to each other.2. The method according to claim 1 , further comprising claim 1 , after step (c) claim 1 , the step of identifying solid support-bound cells or virus particles of interest microscopically.3. The method according to claim 1 , further comprising claim 1 , after step ...

Portable digital diagnostic device

A computerized device provides microscopy and electrochemistry tests, performed in dual channels. The device can be brought to the field, for on-site testing with instant results. The dual channels include an imaging channel and a signal channel.

PHOTONIC SUPERLATTICE-BASED DEVICES AND COMPOSITIONS FOR USE IN LUMINESCENT IMAGING, AND METHODS OF USING THE SAME

Under one aspect, a device is provided for use in luminescent imaging. The device can include a photonic superlattice including a first material, the first material having a first refractive index. The first material can include first and second major surfaces and first and second pluralities of features defined through at least one of the first and second major surfaces, the features of the first plurality differing in at least one characteristic from the features of the second plurality. The photonic superlattice can support propagation of a first wavelength and a second wavelength approximately at a first angle out of the photonic superlattice, the first and second wavelengths being separated from one another by a first non-propagating wavelength that does not selectively propagate at the first angle out of the photonic superlattice. 1. A device comprising:a photonic superlattice comprising a surface having wells of different sizes, the photonic superlattice supporting propagation of a first wavelength and a second wavelength, the photonic superlattice inhibiting propagation of a third wavelength between the first and second wavelengths; andan optical component facing the surface, the optical component receiving first luminescence at the first wavelength at an angle, the optical component receiving second luminescence at the second wavelength at approximately the angle.2. The device of claim 1 , wherein the angle is approximately normal to the surface.3. The device of claim 1 , wherein the photonic superlattice comprises a first material that comprises the wells claim 1 , the device further comprising a second material in contact with the first material.4. The device of claim 3 , wherein the second material has a higher refractive index than the first material.5. The device of claim 3 , further comprising a third material in contact with at least the second material claim 3 , the third material comprising first and second luminophores claim 3 , the first ...

ON-CHIP ORGANIC SYNTHESIS ENABLED BY ENGINE-AND-CARGO IN AN ELECTROWETTING-ON-DIELECTRIC DIGITAL MICROFLUIDIC DEVICE

A method of moving a solvent without electrowetting properties on an electro-wetting-on-dielectric (EWOD) microfluidic device comprises disposing a first droplet of a first fluid having electrowetting properties on a surface of the EWOD microfluidic device; disposing a second droplet of a second fluid without electrowetting properties on the surface; applying a voltage to the surface to move the first droplet towards the second droplet; contacting the first droplet with the second droplet to form a encapsulated droplet, where the second droplet encapsulates the first droplet. 1. A method of moving a solvent without electrowetting properties on an electro-wetting-on-dielectric (EWOD) microfluidic device , the method comprising:disposing a first droplet of a first fluid having electrowetting properties on a surface of the EWOD microfluidic device;disposing a second droplet of a second fluid without electrowetting properties on the surface;applying a voltage to the surface to move the first droplet towards the second droplet;contacting the first droplet with the second droplet to form a encapsulated droplet, where the second droplet encapsulates the first droplet.2. The method of claim 1 , further comprising transporting the encapsulated droplet across the surface by applying a voltage to the surface.3. The method of claim 1 , wherein the first fluid comprises an ionic liquid.4. The method of claim 3 , wherein the ionic liquid comprises an organic cation that is imidazolium-based claim 3 , pyridinium-based claim 3 , pyrrolidinium-based claim 3 , phosphonium-based claim 3 , ammonium based claim 3 , sulfonium-based claim 3 , or any combination thereof.5. The method of claim 4 , wherein the ionic liquid comprises an anion that is an alkylsulfate claim 4 , tosylate claim 4 , methansulfonate claim 4 , trifluoromethanesulfonate (triflate) claim 4 , bis(trifluoromethylsulfonyl)imide claim 4 , tetrafluoroborate claim 4 , hexafluorophosphate claim 4 , a halide claim 4 , or an ...

Microfluidic Metering of Fluids

This document provides methods and devices for metering fluids. In some cases, the methods and devices include intersecting channels that include capillary-stop geometries at each intersection point that guides the fluids on a desired path, which is controlled by the opening and closing of valves. For example, a metering channel can intersect a loading channel and intersect an outflow channel and a metering portion can be defined by the geometry of the metering channel between the intersection points. 1. A device for metering fluids , comprising:(a) a metering channel having a metering inlet and a metering outlet;(b) an outflow channel intersecting the metering channel at a metering-outflow intersection point, the outflow channel having an outflow outlet; and(c) a loading channel intersecting the metering channel at a loading-metering intersection point, the loading channel having a loading inlet,the metering channel defining a volume of fluid to be metered between the metering-outflow intersection point and the loading-metering intersection point.2. The device of claim 1 , wherein one or more of said inlets comprise a valve.3. The device of claim 1 , wherein one or more of said outlets comprise a valve.4. The device of claim 1 , wherein one or more of said intersection points comprises capillary-stop geometry.5. The device of claim 1 , wherein the metering-outflow intersection point comprises capillary-stop geometry.6. The device of claim 1 , wherein the metering inlet comprises a valve claim 1 , the metering outlet comprises a valve claim 1 , the loading channel comprises a valve claim 1 , and the metering-outflow intersection point comprises capillary-stop geometry.7. The device of claim 1 , further comprising a controller configured to meter a first predetermined volume of a metered fluid through said outflow channel claim 1 , wherein the controller is configured to:(a) deliver a volume of a loading fluid through the loading channel to fill the loading channel ...

Flow cells

An example of a flow cell includes a substrate, a plurality of chambers defined on or in the substrate, and a plurality of depressions defined in the substrate and within a perimeter of each of the plurality of chambers. The depressions are separated by interstitial regions. Primers are attached within each of the plurality of depressions, and a capture site is located within each of the plurality of chambers.

MICROFLUIDIC CHANNEL BACKPLANE AND METHOD OF MANUFACTURING THE SAME, AND MICROFLUIDIC DETECTION CHIP

A microfluidic channel backplane includes a base, and a plurality of microfluidic channels, a sample-adding channel and an enrichment channel that are disposed above the base. Each microfluidic channel of the plurality of microfluidic channels includes a first end and a second end. The sample-adding channel is communicated with first ends of the plurality of microfluidic channels. The enrichment channel includes a first enrichment sub-channel and a second enrichment sub-channel. The first enrichment sub-channel is communicated with second ends of the plurality of microfluidic channels, and one end of the second enrichment sub-channel is communicated with the first enrichment sub-channel. 1. A microfluidic channel backplane , comprising:a base;a plurality of microfluidic channels disposed above the base, each microfluidic channel of the plurality of microfluidic channels including a first end and a second end;a sample-adding channel communicated with first ends of the plurality of microfluidic channels; andan enrichment channel including a first enrichment sub-channel and a second enrichment sub-channel; the first enrichment sub-channel being communicated with second ends of the plurality of microfluidic channels, and one end of the second enrichment sub-channel being communicated with the first enrichment sub-channel.2. The microfluidic channel backplane according to claim 1 , wherein the sample-adding channel includes a first sample-adding sub-channel and at least two second sample-adding sub-channels claim 1 , whereinone side of the first sample-adding sub-channel is communicated with the first ends of the plurality of microfluidic channels, and another side of the first sample-adding sub-channel is communicated with one side of each second sample-adding sub-channel of the at least two second sample-adding sub-channels;a dimension of the first sample-adding sub-channel in a first direction is greater than a dimension of each second sample-adding sub-channel of the ...

METHODS, TOOLS, AND TOOL ASSEMBLIES FOR BIOMOLECULAR ANALYSIS USING MICROARRAYS

Disclosed herein are methods, tools, pillar plates, and tool assemblies for biomolecular analysis using microarrays that reduces the likelihood of air bubbles being trapped by the microarrays. Embodiments of the tools include two clamps that have a tool mount portion and a grasping portion. The tool mount portion is configured to engage a lifting mechanism of a plate handling robot for moving a pillar plate that include microarrays. The grasping portion is configured to freely suspend the pillar plate at an inclination of a non-zero tilt angle relative to a plane normal to the tool mount portion. Embodiments of pillar plates include two protruding edges on opposite sides of the pillar plate and a plurality of pillars with one or more affixed microarrays. Embodiments of the tool assembly include the tool and the pillar plate, wherein the protruding edges are configured to engage with the gasping portions. 1. A tool for assaying microarrays that reduces the likelihood of air bubbles being trapped by the microarrays , comprising:two clamps, each of the two clamps comprising:a tool mount portion, the tool mount portion configured to engage a lifting mechanism of a plate handling robot for moving a pillar plate comprising microarrays, anda grasping portion, the grasping portion configured to freely suspend the pillar plate at an inclination of a non-zero tilt angle relative to a plane normal to the tool mount portion.2. The tool of claim 1 , wherein the grasping portion of each clamp comprises two pairs of receiving bars claim 1 , the receiving bars of the first pair being separated at a first vertical width claim 1 , the receiving bars of the second pair being separated at a second vertical width claim 1 , and the first vertical width exceeding the second vertical width by a pre-defined threshold distance whereby the pillar plate assumes the non-zero tilt angle if the pillar plate is freely suspended by the two clamps.3. The tool of claim 2 , wherein the upper receiving ...

Pens For Biological Micro-Objects

Individual biological micro-objects can be deterministically selected and moved into holding pens in a micro-fluidic device. A flow of a first liquid medium can be provided to the pens. Physical pens can be structured to impede a direct flow of the first medium into a second medium in the pens while allowing diffusive mixing of the first medium and the second medium. Virtual pens can allow a common flow of medium to multiple ones of the pens.

Monolithic magnets with magnetic field domains for diamagnetic levitation

The invention comprises a monolithic magnet or a combination of monolithic magnets with magnetic field domains for diamagnetic levitation of diamagnetic objects wherein the magnetic field pattern, the magnetic field strength and the magnetic field gradient of the magnetic field domains are chosen in such way that levitation of diamagnetic objects is achieved.

Methods for High-Content Drug Screening

Provided herein are methods and systems for screening a candidate agent to determine whether the candidate agent modulates an activity of cultured cells. Compositions for screening a candidate agent are also provided herein. 1. A method of screening a candidate agent to determine whether the candidate agent modulates an activity of cultured cells , the method comprising:positioning a hydrogel comprising at least one candidate agent in a lumen of a hollow micropillar, wherein the hollow micropillar comprises a first surface having an open end and a second surface having a closed end in contact with a first substrate, wherein the hollow micropillar is orthogonal to the first substrate;bringing the first surface of the hollow micropillar into communication with a surface of cultured cells on a second substrate to provide an interaction gap between the first surface of the hollow micropillar and the surface of the cultured cells, wherein the first surface of the hollow micropillar is in a spaced apart and in facing relationship with the surface of cultured cells;adding a solution to the interaction gap such that the at least one candidate agent is released from the hydrogel onto the surface of cultured cells; andmeasuring a signal from the cultured cells, wherein the signal indicates whether the at least one candidate agent modulates the activity of the cultured cells.2. The method of claim 1 , wherein the hydrogel comprises alginate.3. The method of or claim 1 , wherein the at least one candidate agent comprises at least two candidate agents.4. The method of or claim 1 , wherein the at least one candidate agent comprises at least one thousand candidate agents.5. The method of any one of - claim 1 , wherein the positioning comprises filling the lumen of the hollow micropillar such that a surface of the hydrogel in the lumen is coplanar with the first surface of the hollow micropillar.6. The method of any one of - claim 1 , wherein the positioning comprises filling a ...

HIGH-THROUGHPUT PARTICLE CAPTURE AND ANALYSIS

Microfluidic systems and methods are described for capturing magnetic target entities bound to one or more magnetic beads. The systems include a well array device that includes a substrate with a surface that has a plurality of wells arranged in one or more arrays on the surface. A first array of wells is arranged adjacent to a first location on the surface. A second and subsequent arrays, if present, are arranged sequentially on the surface at second and subsequent locations. When a liquid sample is added onto the substrate and caused to flow, the liquid sample will flow across the first array first and then flow across the second and subsequent arrays in sequential order. The wells in the first array each have a size that permits entry of only one target entity into the well and each well in the first array has approximately the same size. 140-. (canceled)41. A system for capturing target entities that are , or are made to be , magnetic , the system comprising:a body comprising a chamber having an inlet and an outlet; and a substrate;', 'a first array of micro-wells arranged on the substrate at or near the inlet, wherein micro-wells in the first array have a size that permits entry of only one target entity per micro-well and wherein each micro-well in the first array has approximately the same size; and', 'a second array of micro-wells arranged on the substrate at or near the outlet, such that when a liquid is flowed across the substrate from the inlet to the outlet the liquid flows first across the first array and then across the second array, wherein micro-wells in the second array each have a size that is at least ten percent larger than the size of the micro-wells in the first array, and wherein each micro-well in the second array has approximately the same size., 'a micro-well array device arranged within the chamber between the inlet and the outlet, wherein the micro-well array device comprises42. The system of claim 41 , wherein the micro-wells in both the ...

BIO CHIP STRUCTURE FOR COMPARATIVE EXPERIMENT

Provided is a bio chip structure for a comparative experiment. The bio chip structure for a comparative experiment according to the present invention may include: a first pillar substrate including at least one first pillar where a first sample is disposed; a second pillar substrate including at least one second pillar where a second sample is disposed; and a well substrate including wells to which at least one pair of the first pillars of the first pillar substrate and the second pillar of the second pillar substrate is inserted. Accordingly, a comparative experiment to culture a different kind of samples may be conducted in an identical environment, a different kind of samples, which are the subjects of a comparative experiment, may be rapidly and accurately disposed on a plurality of pillars, and an experimental group or a control group may be easily replaced. 1. A bio chip structure for a comparative experiment comprising:a first pillar substrate comprising at least one first pillar where a first sample is disposed;a second pillar substrate comprising at least one second pillar where a second sample is disposed; anda well substrate comprising wells to which at least one pair of the first pillars of the first pillar substrate and the second pillar of the second pillar substrate is inserted.2. The bio chip structure of claim 1 , wherein the first pillar substrate and the second pillar substrate are combined with each other.3. The bio chip structure of claim 2 , wherein the first pillar substrate and the second pillar substrate are combined with each other by using a magnet member.4. The bio chip structure of claim 2 , wherein the first pillar substrate comprises a plurality of first protruding members having at least one first pillar and a first support member for supporting the plurality of first protruding members so that the plurality of first protruding members is spaced apart from each other and placed in order claim 2 , and the second pillar substrate ...

Devices, processes, and systems for determination of nucleic acid sequence, expression, copy number, or methylation changes using combined nuclease, ligase, polymerase, and sequencing reactions

The present invention relates to methods, devices, instruments, processes, and systems for the highly specific, targeted molecular analysis of regions of human genomes and transcriptomes from the blood, i.e. from cell free circulating DNA, exosomes, microRNA, IncRNA, circulating tumor cells, or total blood cells. The technology enables highly sensitive identification and enumeration of mutation, expression, copy number, translocation, alternative splicing, and methylation changes using spatial multiplexing and combined nuclease, ligation, polymerase, and sequencing reactions. Such technology may be used for non-invasive early detection of cancer, non-invasive cancer prognosis, and monitoring both treatment efficacy and disease recurrence of cancer.

SAMPLE HOLDER, METHOD FOR MANUFACTURING THE SAMPLE HOLDER, AND APPARATUS FOR RECEIVING THE METALLIC SAMPLE HOLDER

The present invention relates in a first aspect to a metallic sample holder (), in particular for capturing sample volumes for digital polymerase chain detection. The sample holder () comprises an array of indentations (), wherein each indentation () is adapted to capture a maximal sample volume v, with v=2 nl, in particular with v=1 nl, in particular with v=0.8 nl. Each indentation () of the array () has an area cross-section section a, with a ≤8*10mm, in particular with a ≤5*10mm. A second aspect of the invention relates to a method for manufacturing the sample holder (). A third aspect of the invention relates to an apparatus (), in particular for polymerase chain reaction detection, adapted for receiving the metallic sample holder (). A fourth aspect of the invention relates to the use of the sample holder () by means of the apparatus (). 11. A metallic sample holder () , in particular for capturing sample volumes for digital polymerase chain detection reactions , comprising{'b': '10', 'an array of indentations (),'}{'b': '11', 'sub': max', 'max', 'max', 'max, 'wherein each indentation () is adapted to capture a maximal sample volume v, with v=2 nl, in particular with v=1 nl, in particular with v=0.8 nl,'}{'b': 11', '10, 'sup': −3', '2', '−3', '2, 'wherein each indentation () of the array () has an area cross-section a, with a≤8*10mm, in particular with a 5*10mm,'}{'b': '11', 'wherein the indentations () have a bottom area.'}21101111. The metallic sample holder () of claim 1 , comprising an array () with at least 10 claim 1 ,000 indentations () claim 1 , in particular at least 40 claim 1 ,0000 indentations ().31. The metallic sample holder () according to claim 1 , consisting of aluminum claim 1 , silver claim 1 , gold claim 1 , copper claim 1 , or alloys thereof.4111111. The metallic sample holder () according claim 1 , wherein each indentation () is of cylindrical shape claim 1 , of conical shape claim 1 , or of elliptical cone shape and/or has at least ...

POLYMER MICROFLUIDIC BIOCHIP FABRICATION

Provided are microfluidic devices and methods for fabricating and bonding such devices. Also provided are kits for analyzing analyte-containing samples and for lysing cells. 157-. (canceled)58. A microfluidic workpiece , comprising: the microfluidic channel defining a depth,', 'the microfluidic channel being adjacent to at least one secondary region, the secondary region defining a depth that is less than the depth of the microfluidic channel;', 'a wall defining a boundary between the microfluidic channel and the secondary region; and, 'a microfluidic channel in the surface of a thermoplastic substrate,'}a radiation-absorbing compound residing in the secondary region, wherein the wall separates the radiation-absorbing compound from the microfluidic channel; anda thermoplastic member that is disposed above and opposite to the thermoplastic substrate and that at least partially overlaps the microfluidic channel of the thermoplastic substrate, the thermoplastic member being bonded to the thermoplastic substrate at the location of the radiation-absorbing compound.59. (canceled)60. The microfluidic workpiece of claim 58 , wherein the wall comprises a characteristic dimension in the range of from about 0.5 micrometers to about 100 micrometers.61. The microfluidic workpiece of claim 58 , wherein the microfluidic channel comprises at least one roughened surface.62. The microfluidic workpiece of claim 58 , wherein the wall resides proximate to the microfluidic channel.63. (canceled)64. (canceled)65. The microfluidic workpiece of claim 58 , wherein the thermoplastic substrate is essentially transparent to light.66. The microfluidic workpiece of claim 58 , wherein the thermoplastic substrate is essentially transparent to at least a portion of the visible light spectrum.67. The microfluidic workpiece of claim 58 , wherein the thermoplastic substrate is essentially transparent to at least a portion of the infrared light spectrum.68. The microfluidic workpiece of claim 58 , ...

DEP FORCE CONTROL AND ELECTROWETTING CONTROL IN DIFFERENT SECTIONS OF THE SAME MICROFLUIDIC APPARATUS

A microfluidic apparatus can comprise a dielectrophoresis (DEP) configured section for holding a first liquid medium and selectively inducing net DEP forces in the first liquid medium. The microfluidic apparatus can also comprise an electrowetting (EW) configured section for holding a second liquid medium on an electrowetting surface and selectively changing an effective wetting property of the electrowetting surface. The DEP configured section can be utilized to select and move a micro-object in the first liquid medium. The EW configured section can be utilized to pull a droplet of the first liquid medium into the second liquid medium. 1. An apparatus comprising:an enclosure configured to hold a first liquid medium disposed on a first surface in a first section of said enclosure and a second liquid medium disposed on an electrowetting surface in a second section of said enclosure; anda boundary between said first section and said second section of said enclosure;wherein:said first section of said enclosure comprises a DEP configuration configured to induce selectively net dielectrophoresis (DEP) forces in said first liquid medium sufficiently to capture and move, relative to said first surface, micro-objects in said first liquid medium in said first section of said enclosure while connected to a biasing device, andsaid second section of said enclosure comprises an electrowetting (EW) configuration configured to change selectively an effective wetting characteristic of regions of said electrowetting surface sufficiently to move a liquid droplet within said second medium in said second section of said enclosure while connected to a biasing device.2. The apparatus of claim 1 , wherein said boundary comprises a physical barrier located in said enclosure between said first section of said enclosure and said second section of said enclosure.3. The apparatus of claim 2 , wherein said boundary further comprises a passage from said first section of said enclosure through ...

MOLECULAR ANALYSIS SYSTEM AND USE THEREOF

A molecular testing device comprises a heating and cooling module having a thin-film thermoelectric heating and cooling device, and a removable test module having a combined amplification and hybridization reaction chamber. The reaction chamber comprises a thermo-conductive exterior surface and a microarray on an interior surface. The thin-film thermoelectric heating and cooling device has a heat transfer surface that is adapted to make contact with the thermo-conductive exterior surface of the reaction chamber. The molecular testing device may be used to perform a PCR in the reaction chamber. 1. A molecular testing device , comprising:a heating and cooling module comprising a thin-film thermoelectric heating and cooling device; anda removable test module comprising a combined amplification and hybridization reaction chamber comprising a thermo-conductive exterior surface and a microarray on an interior surface;wherein said thermoelectric heating and cooling device comprises a heat transfer surface that is adapted to make contact with said thermo-conductive exterior surface of said reaction chamber.2. The molecular testing device of claim 1 , wherein said thin-film thermoelectric heating and cooling device is a Peltier device.3. The molecular testing device of claim 2 , wherein said Peltier device is a ceramic Peltier device.4. The molecular testing device of claim 1 , wherein said thin-film thermoelectric heating and cooling device comprises a thin-film semiconductor comprising bismuth antimony claim 1 , bismuth telluride claim 1 , lead telluride or silicon germanium.5. The molecular testing device of claim 4 , wherein said thin-film semiconductor comprises bismuth telluride.6. The molecular testing device of claim 1 , wherein the thin-film thermoelectric heating and cooling device is a thermoelectric couple made of p and n type semiconductors.7. The molecular testing device of claim 6 , wherein the p and n type semiconductors are selected from the group consisting ...

SCREENING ASSAYS AND METHODS

Screening assays and methods of performing such assays are provided. In certain examples, the assays and methods may be designed to determine whether or not two or more species can associate with each other. In some examples, the assays and methods may be used to determine if a known antigen binds to an unknown monoclonal antibody. 1. A printed microarray of unknown cell-derived products , each position of said array comprising a deposit corresponding to a composition of a single cell , said deposit being less than 100 micrometers in diameter.2. The microarray of claim 1 , wherein said deposit is a secreted cell-derived product selected from the group consisting of an antibody claim 1 , cytokine claim 1 , chemokine claim 1 , and inflammatory mediator.3. The microarray of claim 1 , wherein said microarray comprises a capture ligand for a class of secreted products.4. The microarray of claim 3 , wherein said capture ligand hinds to a single immunoglobulin isotype. This application claims priority to U.S. Ser. No. 60/717,976 filed Sep. 16, 2005, which is incorporated herein by reference in its entirety.This invention was funded in part by the U.S. Government under grant numbers NAKFI Nano08 awarded by the National Academy of Sciences and/or grant 5R01A1034893-1 awarded by the National Institutes of Health. The Government has certain rights in the invention.The invention relates to screening assays and methods to identify secreted products.Assays exist to identify compounds or molecules of interest that may be involved in a disease process or other condition or in treating a disease process or condition. Existing assays have some drawbacks. One significant drawback is the time required to screen for many compounds or molecules. Another drawback is that it may not be possible to recover the compound or molecule post-screening. There remains a need for better screening assays and methods.The invention provides a printed microarray of unknown cell-derived products. Each ...

EQUAL-LIQUID-LEVEL RESERVOIR AND A MICROFLUIDIC BIOCHIP

A microfluidic biochip includes an equal-liquid-level reservoir disposed on a cover. The equal-liquid-level reservoir includes some tanks that have a substantially same liquid level. Each tank has an opening on a bottom surface, each opening communicating with a corresponding microfluidic channel. 1. An equal-liquid-level reservoir , adapted to a microfluidic biochip , the equal-liquid-level reservoir comprising:a plurality of tanks that have a substantially same liquid level, each said tank having an opening on a bottom surface thereof, and each said opening communicating with a corresponding microfluidic channel.2. The equal-liquid-level reservoir of claim 1 , comprising:a container; andat least one partition wall disposed in the container to partition the container into the plurality of tanks, in a manner that a liquid surface of the plurality of tanks is not blocked by the partition wall such that liquid levels of the plurality of tanks are substantially equal.3. The equal-liquid-level reservoir of claim 1 , comprising:a plurality of containers acting as the plurality of tanks respectively; anda leveling tube disposed below and near a liquid surface of the plurality of tanks such that liquid levels of the plurality of tanks are substantially equal.4. The equal-liquid-level reservoir of claim 1 , further comprising:a blocking wall disposed in one of the plurality of tanks, a top of the blocking wall blocking a liquid surface in said tank, and a bottom of the blocking wall not completely blocking liquid in said tank.5. A microfluidic biochip claim 1 , comprising:a substrate with microfluidic channels formed therein;a cover disposed above the substrate; andan equal-liquid-level reservoir disposed on the cover, the equal-liquid-level reservoir comprising a plurality of tanks that have a substantially same liquid level, each said tank having an opening on a bottom surface thereof, and each said opening communicating with a corresponding microfluidic channel.6. The ...

HIGH-SPEED POLYMERASE CHAIN REACTION ANALYSIS PLATE

The present invention relates to the structure of an analysis plate applied to a high-speed polymerase chain reaction (PCR), and to a PCR analysis plate used for implementing an analysis of a real-time PCR, a real-time nested PCR and a post-PCR lateral flow hybridization reaction. The present invention is provided with: a check valve for enabling the maintaining of positive pressure when an elastic film expands into a convex form by having a solution pushed therein by the positive pressure; a lateral flow analysis module for analyzing a post-PCR follow-up PCR or lateral flow; and a shut-off valve enabling the controlling of the movement of the solution after each reaction ends. A high-speed PCR analysis plate may be provided whereby, by pressing, by means of a temperature-controllable heating block, the elastic film, which is in a convex form by the solution, of a PCR unit, a PCR solution may undergo rapid temperature circulation with minimum heat resistance, and a PCR dried material and a nucleic acid solution may be homogenized and mixed. 1. A high-speed polymerase chain reaction (PCR) analysis plate comprising:a base substrate in which an inlet is formed;a reaction unit formed as a closed structure on the base substrate by fusing a sealing film having elasticity to the base substrate into a shape of a closed line including the inlet; anda shut-off valve provided between the reaction unit and a flow channel unit connected to the inlet of the reaction unit.2. A high-speed polymerase chain reaction (PCR) analysis plate comprising:a base substrate in which an inlet is formed;a reaction unit formed as a closed structure on the base substrate by fusing a sealing film having elasticity to the base substrate into a shape of a closed line including an inlet; anda valve unit including a check valve configured to prevent a backflow of a solution injected into the reaction unit and a flow channel unit connected to the inlet of the reaction unit.3. The high-speed PCR analysis ...

PERISTALTIC MICROPUMP AND RELATED SYSTEMS AND METHODS

A peristaltic micropump includes one or more flexible channels configured to transfer one or more pumped fluids, and an actuator configured to engage the one or more flexible channels and rotate about a central axis. The actuator includes a plurality of rolling elements and a driving element configured such that the driving element operably rotates about the central axis and each rolling element operably rolls about a respective axis that is not parallel to the central axis. The plurality of rolling elements is disposed between the one or more flexible channels and the driving element. The driving element includes a cage configured to capture the plurality of rolling elements such that the plurality of rolling elements is located at different radii from a center of the cage. 1. A peristaltic micropump , comprising:one or more flexible channels configured to transfer one or more pumped fluids; andan actuator configured to engage the one or more flexible channels, and rotate about a central axis, wherein the actuator comprises a plurality of rolling elements and a driving element configured such that the driving element operably rotates about the central axis and each rolling element operably rolls about a respective axis that is not parallel to the central axis, wherein the plurality of rolling elements is disposed between the one or more flexible channels and the driving element, and wherein the driving element comprises a cage configured to capture the plurality of rolling elements such that the plurality of rolling elements is located at different radii from a center of the cage.2. The peristaltic micropump of claim 1 , wherein the driving element and the one or more flexible channels have a coefficient of friction that is substantially matched to each other claim 1 , and the driving element and the bulk material that contains one or more flexible channels have a coefficient of elasticity that is substantially matched to each other.3. The peristaltic micropump of ...

Droplet Assembly By 3D Printing

The invention relates to an apparatus for producing a droplet assembly, which apparatus comprises a droplet generator. A process for producing a droplet assembly, using an apparatus comprising a droplet generator is also described. The invention also relates to droplet assemblies comprising a plurality of droplets. Various uses of the droplet assemblies are also described. 1. A droplet assembly which is obtainable by a process for producing a droplet assembly using an apparatus for producing the droplet assembly ,which droplet assembly comprises: a plurality of droplets, wherein each of said droplets comprises: (i) a droplet medium, and (ii) an outer layer of amphipathic molecules around the surface of the droplet medium, wherein the droplet medium is an aqueous medium or a hydrophobic medium, and wherein at least one of said droplets contacts another of said droplets to form a layer of said amphipathic molecules as an interface between the contacting droplets;which apparatus comprises: at least one droplet generator; a container which is moveable relative to the at least one droplet generator; and a control unit, which control unit is adapted to control the dispensing of droplets from the at least one droplet generator and the movement of the container relative to the at least one droplet generator;wherein said container of the apparatus contains a bulk medium, wherein:when the droplet medium is an aqueous medium the bulk medium is a hydrophobic medium, and when the droplet medium is a hydrophobic medium the bulk medium is an aqueous medium; (a) a plurality of dispensing steps, wherein each dispensing step comprises dispensing a droplet of the droplet medium from a said droplet generator into the bulk medium, in the presence of amphipathic molecules, and thereby forming in the bulk medium a droplet which comprises (i) said droplet medium and (ii) an outer layer of amphipathic molecules around the surface of the droplet medium; and', '(b) moving the container ...

FULLY AUTOMATED BIOCHIP WORKSTATION AND DETECTION METHOD USING SAME

The present application relates to the field of biochip detection apparatus, and in particular to a fully automated biochip workstation and a detection method using same. Biochip detection apparatus comprises a cavity for carrying a test tube vial, the test tube vial being used for accommodating a sample to be detected and a biochip, the cavity having a temperature control function; a liquid storage device for storing liquid; a pumping device for pumping the liquid in the liquid storage device to the test tube vial, the pumping device being in fluid communication with a separation needle for injecting a mixed liquid into the test tube vial; an imaging device for monitoring the chip state in the test tube vial; and a data processing device configured to acquire hybridization results on the basis of information about a biochip state acquired by the imaging device. The biochip workstation provided in the present application implements the integration of biochip reactions and the output of detection results, improves the processing efficiency of samples, saves manpower, and has more stable and reliable results. 1. A biochip detection apparatus , comprising a cavity configured to carry a test tube vial , wherein the test tube vial is configured to accommodate a sample to be detected and a biochip , and the cavity has a temperature control function;a liquid storage device, configured to store a liquid;a pumping device, configured to pump the liquid in the liquid storage device to the test tube vial, wherein the pumping device is in fluid communication with a liquid separating needle for injecting a mixed liquid into the test tube vial;an imaging device, configured to monitor a chip state in the test tube vial; anda data processing device, configured to acquire a hybridization result based on information of a state of the biochip acquired by the imaging device.2. The biochip detection apparatus according to claim 1 , wherein a plurality of test tube vials are provided ...

Apparatuses and Methods for Manipulating Droplets

Apparatuses and methods for manipulating droplets are disclosed. In one embodiment, an apparatus for manipulating droplets is provided, the apparatus including a substrate, multiple arrays of electrodes disposed on the substrate, wherein corresponding electrodes in each array are connected to a common electrical signal, and a dielectric layer disposed on the substrate first side surface and patterned to cover the electrodes. 1. (canceled)2. An apparatus for manipulating droplets , the apparatus comprising:(a) a first printed circuit board substrate comprising a first side surface and a second side surface;(b) an array of drive electrodes disposed on the first printed circuit board substrate first side surface;(c) a dielectric layer disposed on the first printed circuit board substrate first side covering the drive electrodes;(d) a second substrate comprising a first side surface and a second side surface, the second substrate being substantially parallel to and spaced apart from the first printed circuit board substrate by a distance to define a space between the second substrate second side surface and the first printed circuit board substrate first side surface, wherein the distance is sufficient to contain a droplet disposed in the space; and(e) one or more reference elements disposed on the second substrate second side surface.3. The apparatus according to wherein the first printed circuit board substrate comprises a plurality of substrate apertures defined therein and extending from the first side surface of the first printed circuit board substrate to the second side surface of the first printed circuit board substrate and each electrode comprises an electrode aperture claim 2 , wherein each electrode aperture is aligned with one of the plurality of substrate apertures to define a plurality of via holes through the apparatus.4. The apparatus according to wherein the via holes are filled with a dielectric substance.5. The apparatus according to wherein the via ...

Drop recovery system and associated method

The present invention relates to a recovery system for drops comprising: a conduit for the circulation of a working fluid comprising a plurality of pockets that are isolated by separators, a recovery substrate comprising multiple compartments, a displacement device that is able to successively position the outlet of the conduit opposite at least two different compartments, a preparation device that is able to inject, into the conduit, an additional volume of separator fluid and an additional volume of carrier fluid, such that the volume of at least one separator is greater than or equal to a critical separation volume, and that the volume of at least one bubble formed by a pocket and a part of the separator is greater than or equal to a critical detachment volume. 1. A drop recovery system comprising:a conduit for the circulation of a working fluid, the circulation conduit comprising an outlet,a device for circulating a working fluid in the circulation conduit, the working fluid comprising a plurality of pockets, each pocket comprising a carrier fluid and a pocket containing a drop of internal fluid, the internal fluid being immiscible with the carrier fluid, each pocket being isolated from the following pocket by a separator, each separator being made up of a separator fluid that is immiscible with the carrier fluid,a recovery substrate of the pockets of the working fluid, the recovery substrate comprising several compartments, a compartment being placed opposite the outlet of the circulation conduit,a relative displacement device of the substrate with respect to the circulation conduit, the displacement device being able to successively place the outlet of the conduit opposite at least two different compartments of the substrate, andwherein the recovery system further comprises:a preparation device for the distribution of the pockets, able to inject, into the circulation conduit, an additional volume of carrier fluid, and able to inject, into the circulation ...

PORTABLE NUCLEIC ACID ANALYSIS SYSTEM AND HIGH-PERFORMANCE MICROFLUIDIC ELECTROACTIVE POLYMER ACTUATORS

Devices, systems and methods for the parallel detection of a set of distinct nucleic acid sequences use multiple sequence amplification and simultaneous hybridization readout. An automated nucleic acid analysis system comprises in microfluidic connection sample lysis, purification, PCR and detection modules configured to detect in parallel distinct nucleic acid sequences via multiple sequence amplification and simultaneous microarray hybridization readout. High performance microfluidic electroactive polymer (μEAP) actuators comprising a dead-end fluid chamber in which the floor of the chamber is an electrode covered with an EAP layer of dielectric elastomer are configured for particle sorting. 111-. (canceled)12. A microfluidic chip apparatus comprising:a board assembly with fluidic chambers and channels; a reagent module configured and arranged to contain and deliver reagents to the other two or more portable-modules,', 'a lysis module configured and arranged to breakdown a sample input to the board assembly,', 'a purification module configured and arranged purify targets in the sample from other material in the sample,', 'a polymerase chain reaction (PCR) module configured and arranged to amplify and label the targets, and', 'a detection module configured and arranged to bind the labeled targets to a surface for detection of the labeled targets;, 'at least three portable-modules in controlled fluidic communication with one another and each configured and arranged for nucleic acid analysis, the at least three portable-modules selected from the group consisting ofan input port configured and arranged to receive the sample and introduce the sample to the fluidic chambers and channels;a plurality of additional ports and valves configured and arranged to control a flow of fluid within the fluidic chambers and channels, the fluid including the sample and the reagents; andat least one vent configured and arranged to remove bubbles from at least one of fluidic chambers ...

Flexible optical biosensor for point of use multi-pathogen detection

A fully integrated miniaturized optical biosensor and methods of making the same are disclosed. The biosensor may include a fluid transport system and an optical system.

Multidimensional hydrodynamic focusing chamber

Systems, including apparatus and methods, for the microfluidic manipulation, dispensing, and/or sorting of particles, such as cells and/or beads. The systems may include a shaped focusing chamber and/or a branched diverting mechanism.

SYSTEMS AND METHODS FOR CYCLIC FLUORESCENCE IMAGING

Methods and systems for improved labeling and/or de-labeling a molecule or cell in the context of scientific experimentation, industrial applications, and clinical investigation, including the means to repeat the process of labeling and de-labeling in an efficient manner. 1. A method of labeling and de-labeling a cell , the method comprising:providing a cell associated with a substrate;contacting the cell with a detectable agent;labeling a plurality of sites of the cell with the detectable agent;applying a voltage across the cell; andde-labeling the cell, wherein de-labeling comprises removal of or quenching of the detectable agent on the cell.2. A method of labeling and de-labeling a cell , the method comprising:providing a cell associated with a substrate;contacting the cell with a detectable agent;labeling a plurality of sites of the cell with the detectable agent;applying a voltage to a solution in contact with the cell; andde-labeling the cell.3. The method of or , wherein applying voltage to a solution in contact with the cell generates one or more reactive chemical species.4. The method of or , wherein de-labeling the cell comprises contacting the detectable agent with the one or more reactive chemical species.5. The method of or , further comprising detecting the detectable agent after labeling the plurality of sites.6. The method of any one of - , wherein the detecting comprises optically detecting the detectable agent.7. The method of any one of - , wherein the labeling and de-labeling is performed in less than 20 minutes , less than 15 minutes , less than 10 minutes , less than 9 minutes , less than 8 minutes , less than 7 minutes , less than 6 minutes , less than 5 minutes , less than 4 minutes , or less than 3 minutes.8. The method of any one of - , wherein the method is repeated for at least 2 times , at least 3 times , at least 4 times , at least 5 times , at least 10 times , or at least 50 times.9. The method of any one of - , wherein the method is ...

INTEGRATED SENSORS

Examples of integrated sensors are disclosed herein. An example of an integrated sensor includes a substrate and a sensing member formed on a surface of the substrate. The sensing member includes collapsible signal amplifying structures and an area surrounding the collapsible signal amplifying structures that enables self-positioning of droplets exposed thereto toward the collapsible signal amplifying structures. 1. An integrated sensor , comprising:a substrate; and collapsible signal amplifying structures; and', 'an area surrounding the collapsible signal amplifying structures that enables self-positioning of droplets exposed thereto toward the collapsible signal amplifying structures., 'a sensing member formed on a surface of the substrate, the sensing member including2. The integrated sensor as defined in wherein the area surrounding the collapsible signal amplifying structures is more hydrophobic than the collapsible signal amplifying structures.3. The integrated sensor as defined in wherein the area surrounding the collapsible signal amplifying structures includes a gradient of polymer pillars formed on the substrate claim 2 , the gradient of polymer pillars being more dense at a periphery of the sensing member.4. The integrated sensor as defined in wherein:the collapsible signal amplifying structures include metal-capped polymer-pillars, metal-coated polymer nanoflakes, metal-coated mushroom-shaped structures, or metal-ringed polymer pillars; andthe polymer pillars in the gradient are free of signal amplifying material.5. The integrated sensor as defined in wherein the area surrounding the collapsible signal amplifying structures includes hydrophobic molecules deposited thereon.6. The integrated sensor as defined in wherein the area surrounding the collapsible signal amplifying structures includes grooves defined in the surface of the substrate claim 1 , the grooves having a shape that directs the droplets toward the collapsible signal amplifying structures.7. ...

Opto-Fluidic Array for Radical Protein Foot-Printing

Systems and methods of in vivo and in vitro radical protein foot-printing using an opto-fluidic array are presented. These teachings may be used to, for example, study three-dimensional protein structure or bio-kinetics. Radical dosimetry including an optional intrinsic standard is used. Real-time feedback based on an internal standard provides comparability between different experiments and in vivo and in vitro analysis results in data that is representative of actual biological conditions. 1. An opto-fluidic chip for radical protein footprinting comprising:a substrate;a first port, a second port, and a third port each defined into the substrate;a mixing zone comprising a first cavity defined within the substrate and in fluid communication with both the second and third ports;a photolysis zone comprising a second cavity defined within the substrate and in fluid communication with the mixing zone, the photolysis zone further comprising a first optically transparent window sealed to the substrate and bounding one side of the second cavity, the second cavity comprising a channel configured in a serpentine pattern; the photolysis zone is transparent on both sides.a dosimetry zone comprising a third cavity defined within the substrate and in fluid communication with the photolysis zone and in further fluid communication with the first port, the dosimetry zone further comprising a second optically transparent window sealed to the substrate and bounding one side of the third cavity.2. The opto-fluidic chip of wherein the substrate comprises a plastic.3. The opto-fluidic chip of wherein the substrate comprises quartz.4. The opto-fluidic chip of wherein the substrate comprises a middle layer of silicon claim 3 , a top layer of quartz claim 3 , and a bottom layer of quartz claim 3 , the middle layer being disposed between the top and bottom layers.5. The opto-fluidic chip of wherein the substrate comprises a middle layer of silicon claim 3 , a top layer of fused silica claim ...

NANOSCALE BIOCHEMICAL SAMPLE PREPARATION AND ANALYSIS

Provided herein are methods and systems for biochemical analysis, including compositions and methods for processing and analysis of small cell populations and biological samples (e.g., a robotically controlled chip-based nanodroplet platform). In particular aspects, the methods described herein can reduce total processing volumes from conventional volumes to nanoliter volumes within a single reactor vessel (e.g., within a single droplet reactor) while minimizing losses, such as due to sample evaporation. 1. A platform for biological sample preparation , comprising:{'sup': '2', '#text': 'a substrate comprising at least one reactor vessel having one or more hydrophilic surfaces configured for containment of a biological sample, wherein the hydrophilic surfaces have a non-zero total surface area less than 25 mm;'}a spacer containing an aperture, wherein the aperture is dimensioned to surround the at least one reactor vessel when the spacer is positioned on the substrate; anda cover positioned on the spacer.2. The platform of claim 1 , further comprising a membrane interposed between the spacer and the cover claim 1 , the membrane configured to form a gas-tight seal between the spacer and the cover to minimize evaporation.3. The platform of claim 1 , wherein the platform is formed from a material that is substantially optically transparent.4. The platform of claim 1 , wherein the platform is formed from glass.5. The platform of claim 1 , further comprising at least one hydrophobic surface surrounding the at least one reactor vessel.6. The platform of claim 1 , further comprising at least two reactor vessels claim 1 , wherein the at least two reactor vessels are separated by a hydrophobic surface.7. The platform of claim 1 , wherein the hydrophilic surface is formed on an upper surface of a pillar and defines the lateral boundary of the least one reactor vessel.8. The platform of claim 1 , wherein the at least one reactor vessel is a well having a depth extending below a ...

Droplet operations device

The invention provides droplet actuators with droplet operations surfaces for manipulating droplets, e.g., by conducting droplet operations. The droplet operations surfaces are typically exposed to a droplet operations gap. One or more regions of a droplet operation surface may include patterned topographic features. The invention also provides a droplet actuator in which one or both gap-facing droplet operations surfaces is formed using a removable film. The removable film may, in various embodiments, also include other components ordinarily associated with the droplet actuator substrate, such as the dielectric layer and the electrodes. Further, the invention provides droplet actuator devices and methods for coupling and/or sealing substrates of a droplet actuator, such as techniques for self-aligning assembly of droplet actuator substrates. The invention provides droplet actuators and methods of disassembling the droplet actuator in order to provide access for cleaning and/or recycling of droplet actuator surfaces.

ELECTROCHEMICAL DETECTION OF BACTERIAL AND/OR FUNGAL INFECTIONS

The present disclosure relates to methods and devices for amplifying a plurality of targets in a single PCR run while distinguishing between clinically relevant amplification and amplification from other sources such as from background contamination. The methods and devices further enable discrimination between gram-positive, gram-negative and fungal infections as wells as identify antimicrobial resistance genes. When applying the methods and devices of the invention, the species or genus of an infection(s), and genus of a fungal co-infection(s) or category of bacterial (gram-positive or negative) co-infection(s) are identified. Species identification of co-infections can also be achieved. Further, when applying the methods and devices of the invention, organisms which are likely to be contaminating organisms from a blood draw are identified. 1. An in vitro method for identifying a first microorganism and second microorganism that infects a subject comprising:(a) loading a portion of a sample comprising (i) reagents for amplifying pan-targets for gram-negative bacteria, species or genus targets for gram-positive bacteria, and species targets for fungi or (ii) reagents for amplifying species or genus targets for gram-positive bacteria, species or genus targets for gram-negative bacteria and species targets for fungi;(b) amplifying nucleic acid in the portion of the sample using the reagents in step (a) in the first cartridge to produce at least a first amplicon corresponding to the first microorganism and a second amplicon corresponding to the second microorganism;(c) detecting the first amplicon and the second amplicon produced in step (b) thereby generating a first signal indicative of the first microorganism and a second signal indicative of the second microorganism; and(d) the method identifies the first microorganism by its genus or species using the first signal and the method identifies the second microorganism as either gram-positive, gram-negative or fungal ...

Biochip and method of making the same

A biochip includes a substrate and a patterned polymer layer molded over the substrate and formed with at least one recess that is adapted to receive biological analytes to be detected using a reader. The patterned polymer layer is bonded to the substrate through molding techniques and has structural characteristics indicative of the patterned polymer layer being formed by molding techniques. A method for making the biochip is also disclosed.

Reaction container and biochemical analysis method

A reaction container including a transparent base having a first surface having at least one region where recessed portions are formed and recessed from the first surface, and a cover member positioned such that the cover member forms a gap from the first surface inside the region and is welded to the transparent base outside the region. The cover member absorbs infrared light and transmits light having a wavelength within a range of visible light.

Manipulation of Cell Nuclei in a Micro-Fluidic Device

Aspects of the present disclosure are directed to the manipulation of a cell nucleus in a micro-fluidic device as well as compositions, systems, and kits for performing such methods. In some aspects, the disclosure provides methods for placing one or more selected cell nuclei into an isolation region of a sequestration pen in a micro-fluidic device. The isolated nucleus/nuclei may then be retrieved from the isolation region of the sequestration pen and used in any desired downstream assay or process. 158.-. (canceled)59. A method of selecting a cell nucleus , said method comprising: a flow region containing a first liquid medium;', 'a first sequestration pen comprising an isolation region and a connection region, wherein the connection region has a proximal opening to the flow region and a distal opening to the isolation region and wherein the isolation region opens to the connection region; and', 'a substrate comprising a covalently linked coating material;', 'wherein the isolation region of the first sequestration pen is an unswept region of the flow region and the substrate is configured to selectively generate forces capable of moving cell nuclei; and, 'identifying a cell nucleus associated with at least one characteristic, wherein the cell nucleus is identified within a microfluidic device comprisingrepositioning the cell nucleus within the microfluidic device using dielectrophoretic force responsive to identifying that the cell nucleus is associated with the at least one characteristic.60. The method of claim 59 , wherein the microfluidic device comprises a plurality of inner surfaces claim 59 , wherein the plurality of inner surfaces has been treated with a blocking solution to prevent or reduce nuclei adherence.61. The method of claim 60 , wherein the blocking solution comprises a polymer comprising alkylene ether moieties.62. The method of claim 61 , wherein the polymer comprises polyethylene glycol.63. The method of claim 60 , wherein the blocking solution ...

METHODS AND DEVICES FOR AMPLIFICATION OF NUCLEIC ACID

The present invention relates to methods and devices for amplifying nucleic acid, and, in particular, amplifying so as to generate products on a surface without the use of emulsions. In a preferred embodiment, a plurality of groups of amplified product are generated on the surface, each group positioned in different (typically predetermined) locations on said surface so as to create an array. 16-. (canceled)7. A method of amplifying and sequencing nucleic acid , comprising: i) a population of different nucleic acid template molecules,', 'ii) a plurality of first and second single stranded oligonucleotides immobilized on a glass surface,', 'iii) amplification reagents,', 'iv) sequencing reagents, and', 'v) a plurality of first and second sequencing primers;, 'a) providing'}b) hybridizing at least a portion of said population of nucleic acid template molecules to said plurality of first oligonucleotides immobilized on said glass surface;c) amplifying said nucleic acid template molecules so as to create a plurality of forward strands;d) sequencing said forward oligonucleotide strands with said first sequencing primers;e) amplifying said nucleic acid template molecules so as to create a plurality of reverse single stranded strands; andf) sequencing said reverse oligonucleotide strands with said second sequencing primers.8. The method of claim 7 , wherein said amplification reagents comprise polymerase and dNTPs.9. The method of claim 7 , wherein said sequencing reagents comprise reagents for sequencing by synthesis.10. The method of claim 7 , wherein said plurality of first and second single stranded oligonucleotides are immobilized to said glass surface through a linker.11. The method of claim 10 , wherein said linker elevates said oligonucleotides away from said glass surface.12. The method of claim 7 , wherein when the first sequencing primers are used in step d) claim 7 , said second sequencing primers are not active.1331-. (canceled) The present invention relates ...

METHOD FOR DIAGNOSING AND MONITORING INFLAMMATORY DISEASE PROGRESSION

Methods for diagnosing or monitoring endometriosis in a mammal are provided. The methods include the steps of determining the expression levels of BDNF, glycodelin and optionally ZAG, in a biological sample from the mammal, and determining that the mammal has endometriosis when the biomarker expression levels in the sample are elevated. 1. A method of diagnosing endometriosis in a mammal comprising the steps of: determining the expression levels of BDNF , glycodelin , and optionally ZAG , in a biological sample from the mammal and comparing the level of each to a pre-determined level associated with endometriosis; and diagnosing the mammal with endometriosis when the levels of BDNF , glycodelin and optionally ZAG are each elevated to the predetermined level associated with endometriosis.2. The method of claim 1 , wherein the level of BDNF associated with endometriosis is 800 pg/ml or greater claim 1 , the level of glycodelin associated with endometriosis is 39 ng/ml or greater claim 1 , and the level of ZAG associated with endometriosis is 92 pg/ml or greater.3. The method of claim 1 , wherein the BDNF is total plasma BDNF.4. The method of claim 1 , wherein the BDNF is mBDNF.5. The method of claim 1 , including the additional step of treating endometriosis in the mammal with pain medication claim 1 , hormone therapy or surgery.6. The method of claim 5 , wherein hormone therapy is selected from hormonal contraceptives claim 5 , gonadotropin-releasing hormone (Gn-RH) agonists or antagonists optionally in combination with estrogen or progestin claim 5 , progestin therapy claim 5 , contraceptive implant claim 5 , contraceptive injection and steroid treatment to suppress the growth of the endometrium.7. A method of monitoring a mammal following treatment of endometriosis comprising:determining the level of a biomarker selected from BDNF or glycodelin in a biological sample from the mammal and comparing the biomarker level to a control pre-treatment biomarker level to ...

Well plate and suction device provided with well plate

A well plate is formed with a well for holding a subject to be sucked by a suction nozzle on an inner bottom part and storing liquid and, a clearance forming member for forming a clearance to allow the liquid to flow in a state where a tip part of the suction nozzle is inserted into and held in contact with the well is provided in the well. According to the present invention, the clearance enabling the liquid to flow is formed even in the state where the tip part of the suction nozzle is inserted into and held in contact with the well in sucking the subject held in the well by the suction nozzle. The suction nozzle can suck the liquid around through the clearance and the subject held in the well is efficiently sucked through the suction port along the flow of the sucked liquid.

SYSTEMS AND METHODS FOR HIGH THROUGHPUT ANALYSIS OF CONFORMATION IN BIOLOGICAL ENTITIES

Methods, devices, and systems are disclosed for performing high throughput analysis of conformational change in biological molecules or other biological entities using surface-selective nonlinear optical detection techniques. 1. A method for determining interactions between target molecules and test compounds , comprising:a) contacting at least one target molecule with at least one test compound, wherein the at least one target molecule is labeled with a nonlinear-active label and is tethered to at least one discrete region on an upper surface of a planar substrate;b) illuminating the at least one target molecule with one or more excitation light beams using total internal reflection of the one or more excitation light beams from the upper surface of the planar substrate, wherein the planar substrate comprises an array of prisms integrated with a lower surface, wherein the one or more excitation light beams are directed by an entrance prism to a single discrete region that is adjacent to but not directly above the entrance prism, wherein the one or more reflected excitation light beams and a nonlinear optical signal generated by the at least one labeled target molecule tethered to the single discrete region are collected by an exit prism that is also adjacent to but not directly underneath the single discrete region, and wherein the entrance prism and the exit prism for the single discrete region are different, non-unique elements of the array of prisms; andc) determining if a conformational change was induced in the at least one target molecule through contact with the at least one test compound by detecting a change in a property of the nonlinear optical signal;wherein determinations of conformational change are performed at an average rate of at least 10 test entities tested per hour.2. The method of claim 1 , wherein the determinations of conformational change are performed at an average rate of at least 100 test compounds tested per hour.3. The method of claim ...

SAMPLE PROCESSING DROPLET ACTUATOR, SYSTEM AND METHOD

Sample processing droplet actuators, systems and methods are provided. According to one embodiment, a stamping device including a droplet microactuator is provided and includes: (a) a first plate including a path or network of control electrodes for transporting droplets on a surface thereof; (b) a second plate mounted in a substantially parallel orientation with respect to the first plate providing an interior volume between the plates, the second plate including one or more stamping ports for transporting some portion or all of a droplet from the interior volume to an exterior location; (c) a port for introducing fluid into the interior volume between the plates; and (d) a path or network of reference electrodes corresponding to the path or network of control electrodes. Associated systems and methods including the stamping device are also provided. 123-. (canceled)24. A cartridge comprising: (i) one or more input ports for introduction of one or more reagents and/or samples;', '(ii) a regular array of processing wells;', '(iii) a network of droplet transport pathways comprising pathways that provide direct or indirect droplet transport from each of the input ports to each of the one or more processing wells; and', '(iv) one or more storage wells interconnected with the network of droplet transport pathways., '(a) a substrate comprising(b) a top plate mounted parallel to the substrate thereby creating a sealable interior volume between the substrate and the top plate; and(c) one or more ports for inputting a substance into one or more of the wells;and25. The cartridge of wherein the regular array of processing wells of the substrate comprises microliter-volume or nanoliter-volume wells.26. The cartridge of wherein the substrate comprises 384 processing wells in a 16 by 24 format having a well-to-well pitch of 4.5 mm.27. The cartridge of wherein the substrate comprises 1 claim 24 ,536 processing wells in a 32 by 48 format having a well-to-well pitch of 2.25 mm.28. ...

Droplet Dispensing Device and Methods

The invention provides nonlimiting examples of structures for and methods of dispensing droplets in a droplet actuator. The droplet actuator structures and methods of the invention exhibit numerous advantages over droplet actuators of the prior art. In various embodiments, the structures and methods of the invention provide, among other things, improved efficiency, throughput, scalability, and/or droplet uniformity, as compared with existing droplet actuators. Further, in some embodiments, the droplet actuators provide configurations for improved methods of loading and/or unloading fluid and/or droplets. In yet other embodiments, the droplet actuators provide fluid loading configurations for loading numerous fluid reservoirs in a substantially simultaneous and/or substantially sequential manner. 1173-. (canceled)174. A method of manipulating a droplet on a droplet actuator , the method comprising: (i) a reservoir electrode assembly comprising an array of multiple, independently controllable electrodes;', '(ii) a structure proximate the reservoir electrode assembly comprising an opening;', '(iii) a transfer electrode positioned in fluid communication with both the reservoir electrode assembly and the opening; and', '(iv) a flow path through the opening, transfer electrode and the reservoir electrode assembly; and, '(a) providing a droplet actuator comprising(b) flowing fluid through the flow path.175. The method of further comprising forming a droplet on the reservoir electrode assembly.176. The method of wherein the reservoir electrode assembly is generally larger than the transport electrode.177. The method of wherein the droplet comprises beads.178. The method of wherein the droplet comprises biological cells.179. The method of further comprising dispensing a droplet through the opening.180. The method of further comprising configuring the reservoir electrode assembly to perform at least one of disposing of and forming the droplet.181. The method of wherein the ...

MASSIVELY PARALLEL ON-CHIP COALESCENCE OF MICROEMULSIONS

Embodiments disclosed herein are directed to microfluidic devices that allow for scalable on-chip screening of combinatorial libraries and methods of use thereof. Droplets comprising individual molecular species to be screened are loaded onto the microfluidic device. The droplets are labeled by methods known in the art, including but not limited to barcoding, such that the molecular species in each droplet can be uniquely identified. The device randomly sorts the droplets into individual microwells of an array of microwells designed to hold a certain number of individual droplets in order to derive combinations of the various molecular species. The paired droplets are then merged in parallel to form merged droplets in each microwell, thereby avoiding issues associated with single stream merging. Each microwell is then scanned, e.g., using microscopy, such as high content imaging microscopy, to detect the optical labels, thereby identifying the combination of molecular species in each microwell. 1. A microfluidic device comprising:at least one droplet input for receiving one or more sets of droplets, each set of droplets comprising one or more agents; andan array of microwells for receiving one or more droplets from the one or more sets of droplets.2. The microfluidic device of claim 1 , further comprising;at least one flow channel from which droplets from each droplet set are randomly distributed into the array of microwells such that droplets from each droplet set are randomly co-located in individual microwells of the array;a loading mechanism, wherein the loading mechanism comprises a bottom clamp on which the array of microwells is placed, one or more removable spacers that when inserted define a flow channel beneath the array of microwells, a top clamp, and one or more connectors for securing the top clamp to the bottom clamp such that the array of microwells is secured against the spacer when inserted or the bottom clamp when the spacers are removed; orboth ...

INTEGRATED MICROFLUIDIC EJECTOR CHIPS

Integrated microfluidic ejector chips and methods of use are provided. An example of an integrated microfluidic ejector chip includes a first set of microfluidic ejectors fed with a reference solution, and a second set of microfluidic ejectors fed with a sample solution. The first set of microfluidic ejectors and the second set of microfluidic ejectors are disposed on the integrated microfluidic ejector chip to print a pattern of proximately located spots on a sensor. 1. A system , comprising an integrated microfluidic ejector chip , comprising:a first set of microfluidic ejectors fed with a reference solution; anda second set of microfluidic ejectors fed with a sample solution, wherein the first set of microfluidic ejectors and the second set of microfluidic ejectors are disposed on the integrated microfluidic ejector chip to print a pattern of proximately located spots on a sensor.2. The system of claim 1 , wherein the first set of microfluidic ejectors is interspersed with the second set of microfluidic ejectors.3. The system of claim 1 , wherein the integrated microfluidic ejector chip comprises a third set of microfluidic ejectors fed with a third solution.4. The system of claim 3 , wherein the third set of microfluidic ejectors is interspersed with the first set of microfluidic ejectors and the second set of microfluidic ejectors.5. The system of claim 1 , comprising:a reference reservoir to contain the reference solution;a sample reservoir to contain the sample solution;a mixing chamber fluidically coupled to the first set of microfluidic ejectors;a first fluid control device coupling the reference reservoir to the mixing chamber; anda second fluid control device coupling the sample reservoir to the mixing chamber.6. The system of claim 5 , wherein the first fluid control device claim 5 , the second fluid control device claim 5 , or both claim 5 , comprises a microfluidic pump.7. The system of claim 5 , comprising a fluidic coupling between the sample ...