МНОГОСЛОЙНЫЙ АНАЛИЗ С ГОРИЗОНТАЛЬНЫМ ПОТОКОМ С ПРЕССОМ ДЛЯ ОБРАЗЦОВ

Группа изобретений относится к области медицины и может быть использована для диагностики по месту лечения. Устройство с горизонтальным потоком для обнаружения анализируемого вещества в образце включает пресс для образцов, содержащий вкладыш; пробоотборник; хроматографическую тест-полоску с горизонтальным потоком, включающую зону нанесения образца и тестовую зону; конъюгат, включающий первый связывающий партнер для анализируемого вещества и метку, второй связывающий партнер для анализируемого вещества и первый контрольный связывающий партнер, размещенный на вкладыше пресса для образцов. При этом тест-полоска дополнительно содержит контрольную зону, содержащую второй контрольный связывающий партнер, а первый контрольный связывающий партнер является связывающим партнером для второго контрольного связывающего партнера. Пресс для образцов, пробоотборник и тест-полоска образуют вертикальную стопку для нанесения образца на указанную тест-полоску путем сдавливания, причем в вертикальной стопке ...

ИММОБИЛИЗАЦИЯ МОДИФИЦИРОВАННОГО ОЛИГОНУКЛЕОТИДА НА ПОЛИМЕРНОМ СУБСТРАТЕ ПОСРЕДСТВОМ ФИЗИЧЕСКОЙ АДСОРБЦИИ

Группа изобретений относится к области биотехнологии. Предложен способ иммобилизации меченого олигонуклеотида, способ иммобилизации интересующей молекулы (варианты), микрочип, диагностический набор для определения нуклеиновой кислоты, а также применение присоединенной к олигонуклеотиду метки для иммобилизации меченого олигонуклеотида на немодифицированном полимерном субстрате. Способ иммобилизации меченого олигонуклеотида включает получение включающей жидкость и меченый олигонуклеотид смеси, нанесение смеси на немодифицированный циклический олефиновый полимер, причем олигонуклеотид иммобилизуют на полимере посредством физической адсорбции с помощью метки олигонуклеотида, где метка ковалентно связана с олигонуклеотидом. Способ иммобилизации интересующей молекулы включает стадии указанного выше способа, где в одном варианте меченый олигонуклеотид включает интересующую молекулу, а в другом варианте способ дополнительно включает гибридизацию олигонуклеотида с интересующей молекулой. Микрочип ...

МЕЧЕННОЕ ЛЮЦИФЕРАЗОЙ АНТИТЕЛО И СПОСОБ ЕГО ПОЛУЧЕНИЯ, СПОСОБ ОСУЩЕСТВЛЕНИЯ АНАЛИЗА НА СПЕЦИФИЧЕСКОЕ СВЯЗЫВАНИЕ И НАБОР ДЛЯ ПРИМЕНЕНИЯ В АНАЛИЗЕ НА СПЕЦИФИЧЕСКОЕ СВЯЗЫВАНИЕ

Изобретение относится к биотехнологии, касается способа конъюгирования люциферазы с химической частицей, в частности антителом, предусматривающий (а) смешивание люциферазы с одним или несколькими компонентами, такими как D-люциферин, ионы магния и аденозинтрифосфат, и (b) осуществление реакции ковалентного связывания между люциферазой и связывающим реагентом с использованием ковалентно связующего агента, где D - люциферин, ионы магния и/или аденозинтрифосфат присутствуют в количестве, достаточном для защиты активности люциферазы от ингибирования ковалентно связующим агентом. Стадию (а) осуществляют смешиванием люциферазы с ее субстратами, при этом предпочтительно, если магний и аденозинтрифосфат присутствуют в виде комплекса аденозинтрифосфата с магнием (Mg2+ - АТФ) необязательно вместе с D-люциферином. Во втором аспекте настоящее изобретение касается меченного люциферазой антитела, представляющего собой антитело, конъюгированное с активной люциферазой светлячка способом настоящего изобретения ...

ЦИФРОВОЙ АНАЛИЗ МОЛЕКУЛЯРНЫХ АНАЛИЗИРУЕМЫХ ВЕЩЕСТВ С ПОМОЩЬЮ ЭЛЕКТРИЧЕСКИХ СПОСОБОВ

МИКРОФЛЮИДНЫЙ КАРТРИДЖ ДЛЯ ДЕТЕКЦИИ БИОМОЛЕКУЛ

Группа изобретений относится к молекулярно-биологическому диагностированию. Микрофлюидный картридж (100) для детекции биомолекул содержит камеру (140) детекции, микрочип (142) на основе комплементарной структуры металл-оксид-полупроводник (CMOS), имеющий сенсорную область (144), расположенную в камере (140) детекции, и контактную область (146), герметично отделенную от камеры (140) детекции. Камера (140) детекции выполнена с возможностью подачи раствора пробы через впускной канал (124) и вывода анализируемого раствора пробы через выпускной канал (126). Сенсорная область (144) микрочипа (142) содержит систему функционализованных тестовых участков (130) для электрохимической детекции биомолекул в растворе пробы. Каждый тестовый участок (130) сенсорной области (140) снабжен собственным сигма-дельта модулятором (132) для аналого-цифрового преобразования электрических сигналов, генерируемых на тестовых участках (130) при электрохимической детекции. Обеспечивается упрощение и сокращение времени ...

СПОСОБ ИДЕНТИФИКАЦИИ, НАБОРЫ ДЛЯ АНАЛИЗА, ВОЛНОВОД, БИОСЕНСОР

Изобретение относится к способу обнаружения, идентификации и/или количественной оценки тканей растений или животных, микроорганизмов, или неклеточных РНК или ДНК, а также к детекторному устройству, адаптированному для осуществления этого способа. В частности, в основе этого способа лежит флуоресценция, связанная с явлением полного внутреннего отражения (ПВО-Ф) и используемая для оценки гибридизации РНК или ДНК анализируемого образца с РНК или ДНК, ассоциированных с запредельным волноводом детекторного устройства.

СИСТЕМА (ВАРИАНТЫ) И СПОСОБ ДЕТЕКТИРОВАНИЯ НАЛИЧИЯ АНАЛИТА В ЖИДКОМ ОБРАЗЦЕ

... 1. Способ детектирования наличия аналита в жидком образце, включающий:(a) контактирование раствора с магнитными частицами для получения жидкого образца, содержащего от 1×10до 1×10магнитных частиц на миллилитр жидкого образца, в котором магнитные частицы имеют средний диаметр в интервале от 150 нм до 950 нм, значение релаксивности Tна одну частицу, составляющее от 1×10до 1×10ммольс, и имеют связывающие остатки на своей поверхности, причем данные связывающие остатки действуют, изменяя агрегацию магнитных частиц в присутствии аналита;(b) помещение жидкого образца в устройство, содержащее (i) подложку, имеющую углубление для удерживания жидкого образца, содержащего магнитные частицы и аналит, РЧ катушку, расположенную вокруг данного углубления, причем данная РЧ катушка настроена на детектирование сигнала, испускаемого при подвергании жидкого образца воздействию подмагничивающего поля, создаваемого с использованием одного или более магнитов, и последовательности РЧ импульсов, и, необязательно ...

LUZIFERASE-MARKIERUNGSMETHODE

Verfahren und Vorrichtung zum Nachweis von Analyten

Es wird ein Verfahren und eine Vorrichtung zum Nachweis von Analyten in einer Meßlösung mittels Markerpartikel, deren elektrische Eigenschaften sich von den elektrischen Eigenschaften der Meßlösung unterscheiden, vorgeschlagen. Über eine Elektrodenanordnung wird ein elektrisches Feld in der Meßlösung erzeugt und die durch die Markerpartikel hervorgerufenen elektrischen Feldänderungen werden über elektrische Größen bestimmt. Vor der Elektrode, über die ein inhomogenes elektrisches Feld in der Meßlösung erzeugt wird, ist eine Blende mit einer Öffnung für den Durchtritt der elektrischen Feldlinien angeordnet und die Markerpartikel werden an oder in der Nähe der Blendenoberfläche gebunden. In einer anderen Ausführungsform wird das elektrische Feld an der Oberfläche einer potentiometrischen Elektrode durch Potentialbildungsvorgänge an der Grenzfläche zwischen Meßlösung und Elektrode gebildet und die Feldänderungen werden auf potentiometrischem Wege gemessen.

Nachweis von Nukleinsäuren durch Aufhebung der Fluoreszenz

Nachweis von Nukleinsäuren durch Aufhebung der Fluoreszenz

Bauteil zur Interaktionsanalyse mit Kooperationseffekte ausbildenden Probenmolekülspezies

Die Erfindung betrifft ein Bauteil mit einem Träger und mit auf dem Träger in definierter Anordnung angeordneten Probenmolekülfeldern, wobei jedes Probenmolekülfeld Probenmoleküle zumindest einer Probenmolekülspezies trägt, und wobei eine Zuordnung zwischen den geometrischen Positionen der Probenmolekülfelder innerhalb des Bauteils und den Probenmolekülspezies der Probenmolekülfelder getroffen ist. Sie ist dadurch gekennzeichnet, daß jedes Probenmolekülfeld Probenmoleküle einer jeweils selektierten, unterschiedlichen Probenmolekülspeziesgruppe trägt, wobei Gruppenelemente jeder Probenmolekülspeziesgruppe gemeinsam unter Ausbildung von kooperativen Effekten an ein defindiertes Targetmolekül binden.

VERFAHREN ZUR QUANTITATIVEN BESTIMMUNG EINER NUKLEINSÄURE IN EINER LÖSUNG DURCH MESSUNG DER ELEKTRISCHEN LEITFÄHIGKEIT UND VORRICHTUNG DAFÜR

SYSTEM UND VERFAHREN ZUR BESTIMMUNG DER IMPEDANZ UND HERSTELLUNGSVERFAHREN

Verfahren und Vorrichtung zur Identifikation einer Biopolymersequenz auf Festkörperoberflächen

Die Erfindung betrifft ein Verfahren zur Identifikation eines auf ein einer ersten Oberfläche eines Festkörpersubstrats aufgebrachten ersten Biopolymers, wobei das erste Biopolymer mit einem dazu affinen zweiten Biopolymer in Kontakt gebracht wird.

Nachweisverfahren zur Bestimmung der Länge von Biopolymeren

Chemical sensing device

Effecient polynucleotide sequencing using an isfet array

Ionic signal enhancement

GENE PROBE BIOSENSOR METHOD

Aptamer based analyte detection method

Sensing apparatus and method

A sensing apparatus comprising an ion sensitive field effect transistor arranged to generate an electrical output signal in response to localised fluctuations of ionic charge at or adjacent the surface of the transistor, and means for detecting the electrical output signal from the ion sensitive field effect transistor, the localised fluctuations of ionic charge indicating events occurring during a chemical reaction.

Preservative efficacy testing

Chemical sensing device

Fluidic cartridge for nucleic acid amplification and detection

Detecting nucleic acids in impure samples with an acoustic wave sensor

Method

Estimation of nucleic acid

System and method for gene detection

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

Laboratory in a disk.

An apparatus is described that includes an optical disk, adapted to be read by an optical reader, comprising a first sector having substantially self-contained assay means for localizing an analyte suspected of being in a sample to at least one, predetermined location in the first sector and a second sector containing control means for conducting the assay and analyte location information, with respect to one or more analytes suspected of being in a sample, accessible to the reader, wherein the presence or absence of the analyte at said location is determinable by the reader using the control means and the location information. Depending on the nature of the assay, the disk will include fluid storage means, fluid transfer means, such as one or more capillary ducts, valves, batteries, dialyzers, columns, filters, sources of electric fields, wires or other electrical conductive means such as metallic surface deposits and the like.

Laboratory in a disk

PHOTO GRAFTING ELECTRICAL POLYMERS, YOUR PRODUCTION AND THEIR USE AS CARRIERS FOR RECOGNITION PROBES SPECIFIC IN BIO SENSOR SYSTEMS

LIGHT-ADJUSTED, ELECTRICALKINETIC COMPOSITION OF PARTICLES AT SURFACES

PROOF OF IMMOBILIZED NUCLEUS-SOUR

ON OLIGONUKLEOTID MODIFYING PARTICLES BASING BIO BAR CODE

UNIVERSAL DAY ASSAY

PROCEDURE FOR IMPROVED LUMINESCENCE TESTS USING MICRO PARTICLES

CARBON ELECTRODE SURFACE FOR THE CONNECTION OF DNA AND PROTEIN MOLECULES TO IT

DEVICE AND PROCEDURE FOR THE PROOF OF DNA IN BIOLOGICAL SAMPLES

FIBRE OPTICS PROCEDURE FOR THE DETECTION OF SPECIFIC CONNECTION REACTIONS ACCORDING TO THE SCATTERED LIGHT METHOD

NANO-SENSORS AND APPROPRIATE TECHNOLOGIES

ELECTRICALCATALYTIC NUCLEIC ACID HYBRIDIZING PROOF

PROCEDURE FOR THE PROOF OF POLYNUCLEOTIDSEQUENZEN

DEVICE AND PROCEDURE FOR THE CONNECTION AND/OR ISOLATING A GOAL MOLECULE OR AN OBJECT FROM A SAMPLE

PROCEDURE FOR THE IDENTIFICATION AND QUANTIFICATION OF ORGANIC AND BIOCHEMICAL SUBSTANCES

MEASURING INSTRUMENT AND PROCEDURE FOR THE DETECTION OF A DNA SEQUENCE

PROCEDURE FOR THE REGULATION OF - I (IN VITRO) AMPLIFIZIERTEN NUCLEIC ACIDS

PROCEDURE WITH GENE PROBES A BIO SENSOR

MARKED DNA.

MONOLAYER AND ELECTRODE TO THE STATEMENT OF MARKED MOLECULES AND PROCEDURE FOR THEIR USE

SENSOR AND METHOD FOR THE MEASUREMENT OF THE SOLIDITY OF MAGNETIC NANO-PARTICLES ON A MICRO ARRAY

PROCEDURE AND DEVICE FOR THE PROOF AND FOR THE QUANTIFICATION OF BIO MOLECULES

ELECTRO-CHEMICAL RECOGNITION OF NUKLEINSÄUREHYBRIDATION

SOY BEANS PEROXIDASE ELECTRO-CHEMICAL SENSOR

SYSTEM AND PROCEDURE FOR THE DETERMINATION OF IMPEDANCE AND MANUFACTURING PROCESS

Integrated multiplex target analysis

INTEGRATED MULTIPLEX TARGET ANALYSIS A biochip cartridge comprising: a) a bottom substrate comprising a printed circuit board (PCB) comprising: i) an electrowetting grid of electrodes forming a droplet pathway; ii) an array of detection electrodes accessible to said droplet pathway, each comprising a self-assembled monolayer and a capture probe; iii) a plurality of interconnections from said electrowetting grid and said detection electrodes; and b) a top plate comprising a conductive surface parallel to said bottom substrate and mated thereto to form a reaction chamber. Furthermore, a method of detecting target nucleic acids, an apparatus for processing fluid, and a fluid container are also disclosed. The method of detecting target nucleic acids include adding binding buffer and capture beads to the sample, eluting the target nucleic acids from the beads and amplifying them to form amplicans, adding signalling probes to the amplicons to form hybridization complexes, and binding the hybridization ...

Chemical compositions and methods of using same

OF THE INVENTION The present disclosure relates to chemical compositions, kits, and apparatuses and methods for using these compositions, kits and apparatuses in various assays.

Generic sbe-fret protocol

Carbon electrode surface for attachment of DNA and protein molecules

Assays

A device comprising a rigid substrate, a flexible cover element at least partially covering the substrate, a first structure formed in the substrate, adapted for accommodating liquids and adapted for releasing contents of one or more cells, spores, or viruses, the contents including the target molecules, a second structure formed in the substrate, adapted for accommodating liquids and comprising at least one binding member adapted for capturing the target molecules and for determining a value indicative for the presence and/or amount of the target molecules, a microfluidic network interconnecting at least the first structure and the second structure, and an actuator member adapted for effecting a fluid flow between the first structure and the second structure by pressing the flexible cover element against the substrate to selectively close a portion of the microfluidic network.

Nanopore-facilitated single molecule detection of nucleic acids

The present invention provides a new and improved oligonucleotide detection method based on the nanopore technology with a probe containing a complementary sequence to the target oligonucleotide and a terminal extension at the probe's 3' terminus, 5' terminus, or both termini. The improved nanopore sensor with the probe enables sensitive, selective, and direct detection, differentiation and quantification of target oligonucleotides such as miRNAs. The inventive detection method may also be employed as a non-invasive and cost-effective diagnostic method for cancer detection based on miRNA levels in the patient's blood sample.

Electrochemical method to measure DNA attachment to an electrode surface in the presence of molecular oxygen

DNA CONFORMATIONAL SWITCHES AS SENSITIVE ELECTRONIC SENSORS OF ANALYTES

Detection of binding reactions using labels detected by mediated catalytic electrochemistry

Apparatus and methods for detecting DNA in biological samples

Systems and methods for detection and quantification of analytes

Devices, systems, and methods for detecting molecules of interest within a collected sample are described herein. In certain embodiments, self-contained sample analysis systems are disclosed, which include a reusable reader component, a disposable cartridge component, and a disposable sample collection component. In some embodiments, the reader component communicates with a remote computing device for the digital transmission of test protocols and test results. In various disclosed embodiments, the systems, components, and methods are configured to identify the presence, absence, and/or quantity of particular nucleic acids, proteins, or other analytes of interest, for example, in order to test for the presence of one or more pathogens or contaminants in a sample.

SYSTEMS AND METHODS FOR DETECTION AND QUANTIFICATION OF ANALYTES

Devices, systems, and methods for detecting molecules of interest within a collected sample are described herein. In certain embodiments, self-contained sample analysis systems are disclosed, which include a reusable reader component, a disposable cartridge component, and a disposable 5 sample collection component. In some embodiments, the reader component communicates with a remote computing device for the digital transmission of test protocols and test results. In various disclosed embodiments, the systems, components, and methods are configured to identify the presence, absence, and/or quantity of particular nucleic acids, proteins, or other analytes of interest, for example, in order to test for the presence of one or more pathogens or o contaminants in a sample. XR Ml 00 -_0 ...

Methods and composition for determining pH

Described herein are nucleic acid molecules and complexes useful as i-switch pH reporters that have increased sensitivities as a pH reporter and have alternate pH reporting capacity ranges. Aspects of the disclosure relate to a method for determining pH comprising providing a nucleic acid complex comprising: a first single-stranded nucleic acid molecule comprising the sequence C ...

Substrates and optical systems and methods of use thereof

Luminescence imaging scanner

Systems, devices, and methods for accurately imaging chemiluminescence and other luminescence are disclosed. A compact, flat-bed scanner having a light-tight enclosure, one or more detector bars of linear charge-coupled device (CCD) or complementary metal oxide semiconductor (CMOS) imaging chips, and high working numerical aperture (NA) optics scans closely over a sample in one direction and then the opposite direction. Averages or other combinations of intensity readings for each pixel location (x, y) between the two or more passes are averaged together in order to compensate for luminescence that varies over time. On-chip pixel binning and multiple clock frequencies can be used to maximize the signal to noise ratio in a CCD-based scanner.

Assays for single molecule detection and use thereof

ASSAYS FOR SINGLE MOLECULE DETECTION AND USE THEREOF Abstract The invention relates to methods of detecting a genetic variation in a genetic sample from a subject using labeled probes and counting the number of labels in the probes.

Methods and systems for detection of analytes

METHODS AND SYSTEMS FOR DETECTION OF ANALYTES Embodiments provide analyte detection systems and methods for detecting the presence of one or more analytes in one or more samples. In a detection method, a sample and a sensor compound is introduced into a channel. A first potential difference is applied across the length of the channel in a first direction, and a first electrical property value is detected. Subsequently, a second potential difference is applied across the length of the channel in a second opposite direction, and a second electrical property value is detected. Presence or absence of an analyte in the channel is determined based on a comparison between the first and second electrical property values. -141- ...

Nucleic acid biosensor diagnostics

Array cytometry

Laboratory in a disk

Binding acceleration techniques for the detection of analytes

Transistor-based apparatus and method for molecular detection and field enhancement

Device and method for electrically accelerated immobilisation of molecules

Nanoparticles having oligonucleotides attached thereto and uses therefor

Biosensor for and method of electrogenerated chemiluminescent detection of nucleic acid adsorbed to a solid surface

Laminated assembly for active bioelectronic devices

DETECTION OF IMMOBILIZED NUCLEIC ACID

The present invention provides methods for determining the presence of immobilized nucleic acid employing unsymmetrical cyanine dyes that are derivatives of thiazole orange, a staining solution and select fluorogenic compounds that are characterized as being essentially non-genotoxic. The methods comprise immobilizing nucleic acid, single or double stranded DNA, RNA or a combination thereof, on a solid or semi solid support, contacting the immobilized nucleic acid with an unsymmetrical cyanine dye compound and then illuminating the immobilized nucleic acid with an appropriate wavelength whereby the presence of the nucleic acid is determined. The cyanine dye compounds are typically present in an aqueous staining solution comprising the dye compound and a tris acetate or tris borate buffer wherein the solution facilitates the contact of the dye compound and the immobilized nucleic acid. Typically the solid or semi-solid support is selected from the group consisting of a polymeric gel, a membrane ...

VIRAL NUCLEOPROTEIN DETECTION USING AN ION CHANNEL SWITCH BIOSENSOR

The present invention provides a method of detecting viruses, such as respiratory-related viruses, in a sample with a sensitivity of at least 80%, and/or specificity of at least 90%, and/or with an accuracy of at least 90%. The method comprises contacting the sample with a biosensor. The present invention also provides a biosensor comprising a membrane and a solid conducting surface, with the membrane being attached to the solid conducting surface in a manner such that a reservoir exists therebetween. The membrane comprises first and second layers each comprising closely packed amphiphilic molecules; a plurality of first and second ionophores located in the first and second layers, respectively; and a plurality of antibodies or fragments thereof directed against nucleoproteins of respiratory-related viruses, more specifically, nucleoproteins of an influenza virus, and covalently attached to the second ionophores. The present invention further provides a device comprising an array of such ...

ARRAY CYTOMETRY

A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled elektrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present ...

DETERMINATION OF NUCLEIC ACID USING ELECTROCATALYTIC INTERCALATORS

ELECTROCATALYTIC NUCLEIC ACID HYBRIDIZATION DETECTION

The detection of specific nucleic acid sequences using electrochemical readout would permit the rapid and inexpensive detection and identification of bacterial pathogens and the analysis of human genes. A new assay developed for this purpose is described that harnesses an electrocatalytic process to monitor nucleic acid hybridization. Furthermore, the new assay when used on nanoscale electrodes, provides ultrasensitive detection of nucleic acids.

NANOPARTICLES HAVING OLIGONUCLEOTIDES ATTACHED THERETO AND USES THEREFOR

The invention provides methods of detecting a nucleic acid. The methods comprise contacting the nucleic acid with one or more types of particles having oligonucleotides attached thereto. In one embodiment of the method, the oligonucleotides are attached to nanoparticles and have sequences complementary to portions of the sequence of the nucleic acid. A detectable change (preferably a color change) is brought about as a result of the hybridization of the oligonucleotides on the nanoparticles to the nucleic acid. The invention also provides compositions and kits comprising particles. The invention further provides methods of synthesizing unique nanoparticle-oligonucleotide conjugates, the conjugates produced by the methods, and methods of using the conjugates. In addition, the invention provides nanomaterials and nanostructures comprising nanoparticles and methods of nanofabrication utilizing nanoparticles. Finally, the invention provides a method of separating a selected nucleic acid from ...

METHOD AND DEVICE FOR DETECTING AND QUANTIFYING BIOMOLECULES

The invention relates to a method for detecting and quantifying a first biomolecule in a solution (5, 8), comprising the following steps: a) binding of the first biomolecule (5, 8) to a second biomolecule (3, 7) which at least along segments thereof exhibits a specific affinity to a first biomolecule and b) determination of the electrical conductivity of a complex formed from the first (3, 7) and the second biomolecule (5, 8), whereby the second biomolecule (3, 7) forms a bridge between a first 2a and a second electrode 2b.

BIOSENSORS FOR DETECTING MACROMOLECULES AND OTHER ANALYTES

Described are compositions and methods that are useful in the identification and quantification of any polypeptide or macromolecular complex using a set of co-aptamer constructs. Aptamer constructs are constructed that bind to unique epitopes of a polypeptide of macromolecular construct. Those aptamer constructs contain an epitope binding site, a co-aptamer binding site, and a detectable label. In the presence of the cognate polypeptide, analyte- polypeptide complex, or other macromolecular complex, the co-aptamers associate with one another to produce a detectable signal. The co-aptamer constructs may be joined by a linker to produce a bivalent aptamer construct.

AMPLIFICATION OF NUCLEIC ACIDS WITH ELECTRONIC DETECTION

The invention relates to compositions and methods useful in the detection of nucleic acids using a variety of amplification techniques, including both signal amplification and target amplification. Detection proceeds through the use of an electron transfer moiety (ETM) that is associated with the nucleic acid, either directly or indirectly, to allow electronic detection of the ETM using an electrode.

METHOD FOR DETECTION OF A PCR PRODUCT

A method for detecting a nucleic acid molecule in a biological sample includes amplifying a nucleic acid molecule to generate an amplicon having a single 5 '-tail and coupling the 5 '-tail to one of a plurality of capture probes on a surface of a sensor. The amplicon is converted to a single strand molecule and a target-specific catalyst cluster is bound to the single strand molecule. The catalyst cluster is subjected to metallization in order to detect the target nucleic acid.

METHODS AND SYSTEMS FOR ANALYTE DETECTION AND ANALYSIS

Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate configured to rotate. The open substrate can comprise an array of immobilized analytes. A solution comprising a plurality of probes may be directed, via centrifugal force, across the array during rotation of the substrate, to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via continuous rotational area scanning of the substrate.

THERMOCOUPLES COMPRISING A POLYMER COATING FOR DETECTING ANALYTES AND RELATED METHODS

A device (200) for detecting an analyte (132) includes a thermocouple (210) coated with an assay polymer (214). The assay polymer is formulated to bind to the analyte, and a heat transfer property of the assay polymer varies responsive to an amount of the analyte bound thereto. A method of forming a sensor includes coating a thermocouple with an assay polymer. A method for detecting an analyte includes passing a liquid containing an analyte adjacent a thermocouple coated with an assay polymer, binding an analyte to the assay polymer, detecting a temperature of the thermocouple, and calculating a concentration of the analyte in the liquid based at least in part on the heat transfer property of the assay polymer.

NUCLEIC ACID AMPLIFICATION BIOSENSOR FOR USE IN ROLLING CIRCLE AMPLIFICATION (RCA)

The present application describes a biosensor for detecting target nucleic acid. The biosensor's mode of operation is based on binding of the target nucleic acid to another nucleic acid sequence and a circular template which triggers rolling circle amplification and detection of the amplified product as the indicator of the presence of the target nucleic acid. The biosensor is immobilized on a solid support, such as paper.

METHOD AND SYSTEM FOR MONITORING THE GUT HEALTH OF AN INDIVIDUAL

A system and method for predicting gut health of an individual using non-invasive technique has been provided. The system is making use of two types of pathways i.e. one which are beneficial to gut health and the second which are harmful to gut health. These two types of pathways are annotated in the genomes of gut bacteria. Best combinations of subsets of these pathways capable of distinguishing between gut commensals and pathogens are assigned as pathway biomarkers. The identified pathway biomarkers are then used to develop scheme for prediction of gut health status.

DOUBLE-STRANDED NUCLEIC ACID PROBES AND THEIR USE

The invention relates to electronically-isolable double-strand nucleic acid probes and use thereof for rapid and easy detection of interactions between double-stranded nucleic acids and factors which interact with them either by mediated or direct means. The invention further relates to the production of said double-strand nucleic acids.

DETECTION OF NEGATIVELY CHARGED POLYMERS USING WATER-SOLUBLE, CATIONIC, POLYTHIOPHENE DERIVATIVES

Novel methods allowing for the simple optical and electrochemical detection of double-stranded oligonucleotides are disclosed. The methods are rapid, selective and versatile. Advantageously, they do not require any chemical reaction on the probes or on the analytes since they are based on different electrostatic interactions between cationic poly (3-alkoxy-4-methylthiophene) derivatives and single-stranded or double-stranded (hibridized) oligonucleotides.

BIOSENSOR

A biosensor comprising a swellable biologically sensitive element comprising a nucleic acid probe and a physicoelectrical transducer associated with the swellable biologically sensitive element. The physicoelectrical transducer converts the swelling of the swellable biologically sensitive element into a detectable electrical property. In preferred embodiments the biosensor comprises an oligonucleotide cross-linked polymer composite mounted on a suitable substrate comprising electrodes adapted to measure electrical impedance. Associated methods and devices comprising said biosensor are also provided.

Optics collection and detection system and method

Optics collection and detection systems are provided for measuring optical signals from an array of optical sources over time. Methods of using the optics collection and detection systems are also described.

Target substance detection method using aptamer

The present invention relates to a method and kit of detecting a target material using an aptamer, and more particularly to a method and kit for detecting a target material, in which a sample and a second aptamer are added to a first aptamer immobilized on a solid phase so as to form a bond sandwiched between the first aptamer, the target material and the second aptamer, to an FET sensor-based method and kit for detecting a target material, and to an AAO sensor-based method and kit for detecting a target material. The inventive method for a target material using an aptamer can detect even low-molecular-weight materials which were difficult to detect in the prior art, thereby enabling detection of disease-related metabolites, environmental pollutants and food toxins in solutions. In addition, the detection method of the present invention is a direct and simple method and is highly cost-effective, because it uses the aptamer which can be consistently reproduced and can be produced at low costs. Thus, the present invention is very useful.

Method and system for nucleic acid detection using electroconductive or electrochemically active labels

A method for electrochemically or electrically detecting nucleic acids, utilizes electrochemically active or electrically conductive reporter materials. An electric voltage is applied and electric signals are measured to the electrodes that are suitable for detecting or quantifying the nucleic acid(s) in a sample. This technique is suitable for point-of-use applications, e.g. detecting bioanalytes in remote locations. A microchip, device, kit used adapted to be used for this method is also disclosed.

Methods and Apparatus for Detecting Molecular Interactions Using FET Arrays

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

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.

Biosensor device and manufacturing method thereof

Disclosed is a biosensor device, comprising: a capillary tube with probe molecules immobilized on the inner wall surface thereof, and a liquid sample containing target molecules, said biosensor device being characterized in that a contact angle between the inner wall surface of the capillary tube and the liquid sample changes because of the specific interaction between the probe molecules and the target molecules, which leads, in turn, to a change in the height of the liquid sample in the capillary tube.

Systems and Methods for Detection and Quantitation of Analytes Using an Oscillating Stimulus

Described systems and methods allow the detection of and determination of a concentration of a target analyte such as a biological cell, a virus, a polypeptide, a toxin, a pesticide, a drug, a drug residue, or a DNA strand, in a fluid sample. A variable stimulus, such as an oscillating magnetic field or a light beam of oscillating intensity, is applied to the sample, inducing variations in a position or shape of a constituent of the sample, or variations in a fluorescence of the sample. Such variations produce measurable variations in electric and/or optical properties of a sensor, variations which allow the determination of the concentration of the target analyte.

Potentiometric dna microarray, process for producing the same and method of analyzing nucleic acid

A DNA microarray system whereby measurement can be performed at a low running cost, a low price and yet a high accuracy. A nucleic acid probe ( 3 ) is immobilized on the surface of a gate insulator of an electric field effect transistor and then hybridized with a target gene on the surface of the gate insulator. A change in the surface electric charge density thus arising is detected by using the electric effect.

Materials and methods for detection of hpv nucleic acids

Provided are nucleic acids capable of hybridizing to HPV 16 and/or HPV 18 nucleic acids, in particular, mRNA encoding E2 and E6-7 gene products. Such nucleic acids are useful in methods of isolating RNA from a biological sample, methods and means for determining the presence of particular RNA splice-form variants in a biological sample, methods and means for determining the relative ratio of RNA ratios in a biological sample, methods and means for predicting the progression of precancerous cervical lesions, and methods and means for detecting disruption of genes or gene expression.

Detection of nucleic acid amplification

Methods for detecting a target polynucleotide sequences are provided that utilize a probe having a target-complementary segment and a detectable tag. By cleaving the detectable tab and associating the tag with a tag complement coupled to an electrode, an electrochemical signal can be detected that is related to the presence of the tag:tag complement complex.

Methods And Systems For Long Distance Tagging, Tracking, And Locating Using Wavelength Upconversion

Methods and systems for plasmonically enhanced bionanoantennas for tagging, tracking, and locating targets of interest at long distances in both day and nighttime conditions. The nanoantennas are used to tag a target of interest and emit a wavelength to impart a unique biometric signature. The nanoantennas are detectable by selectively harvesting and plasmonically enhancing incident light in the visible region, then upconverting that energy through an activated phosphor. 1. A nucleic acid tag comprising:an agglomerated plurality of nanoparticle nucleotide-support platforms each attached to a plurality of nucleic acid molecules, each of said nucleic acid molecules comprising identifying information, wherein a spacer is located between said nanoparticle nucleotide-support platform and said identifying information;an upconverting fluorescent material; andan encapsulant surrounding said agglomerated plurality of nanoparticle nucleotide-support platforms and said plurality of nucleic acid molecules;wherein when the nucleic acid tag is exposed to electromagnetic radiation of a first wavelength, the upconverting fluorescent material emits electromagnetic radiation of a second wavelength, said second wavelength being shorter than said first wavelength.2. The nucleic acid tag of claim 1 , further comprising:a plasmonic enhancer.3. The nucleic acid tag of claim 1 , wherein the encapsulant is adapted to prevent degradation of the plurality of nucleic acid molecules.4. The nucleic acid tag of claim 1 , wherein each of the plurality of nucleic acid molecules is composed of nucleotides selected from the group consisting of ribonucleotides claim 1 , deoxyribonucleotides claim 1 , and nucleotide analogues.5. The nucleic acid tag of claim 1 , wherein each of the plurality of nucleic acid molecules is an oligonucleotide.6. The nucleic acid tag of claim 1 , wherein each of the plurality of nucleic acid molecules is genomic deoxyribonucleic acid ranging from two nucleotides to the ...

Methods Of Nucleic Acid Analysis

In one aspect, methods of nucleic acid analysis are described herein. In some embodiments, a method of nucleic acid analysis comprises providing a mixture of differing single-strand nucleic acid segments, including unamplified single-strand nucleic acid segments, combining the mixture of differing single-strand nucleic acid segments with a single-strand nucleic acid probe, contacting the mixture with a membrane comprising at least one nanopore, applying an electric field across the nanopore, and measuring change in current through the nanopore during one or more nucleic acid translocation events.

Scanning multifunctional particles

The present invention provides, among other things, methods and systems for characterizing multifunctional objects using a flow-through device, such as, a flow cytometer. In some embodiments, an inventive method according to the present invention includes one more steps of (a) interrogating a plurality of objects (e.g., particles), wherein each individual object (e.g., particle) comprises one or more interrogation regions detectable as a sequence of events; (b) recording multiple events, wherein each individual event corresponds to each individual interrogation region detectable above a pre-determined triggering threshold; (c) grouping the recorded multiple events, and (d) characterizing the plurality of objects based on the grouped events.

Nmr systems and methods for the rapid detection of analytes

This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of disease.

NMR SYSTEMS AND METHODS FOR THE RAPID DETECTION OF ANALYTES

This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of disease. 1166-. (canceled)167. A method for detecting the presence of an analyte in a liquid sample , the method comprising:{'sup': 6', '13', '8', '12', '−1', '−1, 'sub': '2', '(a) contacting a solution with magnetic particles to produce a liquid sample comprising from 1×10to 1×10magnetic particles per milliliter of the liquid sample, wherein the magnetic particles have a mean diameter of from 150 nm to 950 nm, a Trelaxivity per particle of from 1×10to 1×10mMs, and have binding moieties on their surface, the binding moieties operative to alter an aggregation of the magnetic particles in the presence of the analyte;'}(b) placing the liquid sample in a device, the device comprising a support defining a well holding the liquid sample comprising the magnetic particles, the multivalent binding agent, and the analyte, and having an RF coil disposed about the well, the RF coil configured to detect a signal produced by exposing the liquid sample to a bias magnetic field created using one or more magnets and an RF pulse sequence;(c) exposing the sample to a bias magnetic field and an RF pulse sequence;(d) following step (c), measuring the signal; and(e) on the basis of the result of step (d), detecting the presence or concentration of an analyte.168. The method of claim 167 , wherein the magnetic particles are substantially monodisperse.169. The method of claim 167 , wherein step (d) comprises measuring the Trelaxation response of the liquid sample claim 167 , and wherein increasing agglomeration in the liquid sample produces an increase in the observed Trelaxation rate of the sample.170. The method of claim 167 , wherein the analyte is a target nucleic acid from a leukocyte.171. The method of claim 167 , wherein the analyte is a target nucleic acid extracted from a pathogen.172. A method for detecting the presence of a pathogen in a whole blood sample ...

Sensor

A sequencer that measures a nucleic acid sequence in a nucleic acid strand includes: a base material having a surface made of silicon, and a fibrous protrusion that is made of silicon dioxide and is directly joined to the surface of the base material made of silicon, wherein a plurality of the nucleic acid strands are fixed onto the fibrous protrusion.

Nucleotide-Based Probes and Methods for the Detection and Quantification of Macromolecules and Other Analytes

Provided are unimolecular oligonucleotide probes for detecting a target in a sample. The probes use target binding-induced structural changes to detect the presence of the target in the sample. Also provided are methods of using the probes to detect a target in a sample. 1. A system for detecting one or more targets in a sample , the system comprising: a first target binding moiety and a second target binding moiety;', 'a first hybridization sequence and a second hybridization sequence, wherein the first hybridization sequence and the second hybridization sequence are configured to form a duplex in the absence of the target binding to both the first target binding moiety and the second target binding moiety, such that the first target binding moiety is positioned adjacent the second target binding moiety; and', 'a first signaling moiety and a second signaling moiety configured such that the position of the first signaling moiety is changed relative to the second signaling moiety upon binding of the one or more targets to both the first target binding moiety and the second target binding moiety, and, 'a unimolecular oligonucleotide probe configured to produce a detectable change in signal when contacted by the one or more targets, the probe comprisingwherein in the presence of binding of the one or more targets to both the first target binding moiety and the second target binding moiety, formation of the duplex is inhibited such that the probe is configured to position the first signaling moiety relative to the second signaling moiety such that the probe produces a detectable change in signal.2. The system of claim 1 , wherein the probe claim 1 , comprises a stem-loop structure in the absence of the one or more targets binding to the first target binding moiety and the second target binding moiety.3. The system of claim 1 , wherein the first target binding moiety and the second target binding moiety are bound directly to the probe.4. The system of claim 1 , wherein ...

Optical analyte detection systems and methods of use

Various embodiments are drawn to systems and methods for detecting an analyte of interest in a sample including an optical sensor, a capture probe attached to a surface of the optical sensor wherein the capture probe is capable of binding to the analyte to form a duplex or complex, and an antibody capable of binding to the analyte, duplex, or complex. In several embodiments, systems and methods further include a particle attached to the antibody or capable of binding to the antibody. In several embodiments, systems and methods for analyte detection feature one or more of the following: high detection sensitivity and specificity, scalability and multiplex capacity, ability to analyze large analytes, and ability to detect or measure multiple individual binding events in real-time.

HIGH RESOLUTION DNA DETECTION METHODS AND DEVICES

The present invention provides methods and devices for detecting a target nucleic acid molecule. A set of oligonucleotide probes integrated into an electric circuit, where the oligonucleotide probes are positioned such that they cannot come into contact with one another, are contacted with a sample. If the sample contains a target nucleic acid molecule, one which has sequences complimentary to both probes, the target nucleic acid molecule can bridge the gap between the probes. The resulting bridge can then carry electrical current between the two probes, indicating the presence of the target nucleic acid molecule. 1. A device for detecting the presence of a target nucleic acid molecule , comprising:two electronic leads, where an end of a first lead is located near an end of second lead but where the leads are not in contact,one or more sets of two oligonucleotide probes attached to the electronic leads, where the oligonucleotide probes are positioned such that the probes can not come into contact with one another and such that a target nucleic acid molecule, which has two sequences, a first sequence complimentary to a first probe attached to the first lead and a second sequence complimentary to a second probe attached to the second lead, can bind to both probes concurrently completing an electrical circuit, when the target nucleic acid molecule is present,a fluidic channel for introducing a reagent to coat the target nucleic acid molecule with a metal conductor,an electric potential for generating a current flow through the electrical circuit,a computer for detecting an electrical current and correlating the presence or absence of an electrical current to the presence or absence of the target nucleic acid molecule;wherein a bridged probe having an electrical current flowing through the two electrical leads and a target nucleic acid molecule denotes the presence of the target nucleic acid molecule; and an unbridged probe lacks an electrical current denoting the ...

Metallic nanoparticle synthesis with carbohydrate capping agent

The disclosure relates to metal nanoparticle compositions and their methods of formation and use, in particular gold nanoparticles (AuNP) and gold-coated magnetic nanoparticles. Compositions according to the disclosure include aqueous suspensions of metal nanoparticles that are stabilized with one or more carbohydrate capping agents and/or that are functionalized with one or more binding pair members for capture/detection of a target analyte. The nanoparticle suspensions are stable for extended periods and can be functionalized as desired at a later point in time, typically prior to use in an assay for the detection of a target biological analyte. The stable nanoparticle suspension can be formed by the aqueous reduction of oxidized metal precursors at non-acidic pH values in the presence of a carbohydrate-based capping agent such as dextrin or other oligosaccharides.

DETECTION OF NUCLEIC ACIDS USING A CANTILEVER SENSOR

Detection of miniscule amounts of nucleic acid is accomplished via binding of target nucleic acid to probe material, composed of nucleic acid, which is bound to a sensor configured to sense mass. The sensor is prepared by immobilizing a probe material to a surface of the sensor, wherein the probe material is known to bind to the target nucleic acid. The prepared sensor is exposed to the target nucleic acid. The target nucleic acid binds to the probe material. The mass accumulated on the sensor reflects the amount of target nucleic acid bound to the probe material. 1. A method comprising: a piezoelectric layer comprising a proximate end and a distal end;', 'a base portion coupled to the proximate end of the piezoelectric layer;', at least a portion of the piezoelectric layer is coupled to at least a portion of the non-piezoelectric layer such that the piezoelectric layer and the non-piezoelectric layer are not coextensive; and', 'the base portion is not attached to the non-piezoelectric layer; and', 'electrodes operatively associated with the piezoelectric layer;, 'a non-piezoelectric layer, wherein], 'exposing a sensor to a medium, the sensor comprisingmeasuring a first resonance frequency of the sensor;increasing an electrical parameter of excitation of the sensor;measuring a second resonance frequency of the sensor;comparing the first resonance frequency and the second resonance frequency; anddetermining, based on the comparing, a difference between the first resonance frequency and the second resonance frequency, wherein a value of the difference is indicative of whether nucleic acid has accumulated on a surface of the sensor.2. The method of claim 1 , further comprising determining claim 1 , based on the determined difference claim 1 , an amount of nucleic acid accumulated on a surface of the sensor.3. The method of claim 1 , further comprising:determining that a value of the difference is insufficient to determine if nucleic acid has accumulated on a surface of ...

Methods and Systems for Detecting Nucleic Acids

Methods and kits for detecting a target nucleic acid in a sample are described. In some embodiments, the sample to be analyzed includes a primer which hybridizes to at least a portion of the target nucleic acid, a probe having a first region which hybridizes to at least a portion of the target nucleic acid and a second region having a detectable label, a polymerase which extends the hybridized primer and an enzyme comprising nuclease activity that can cleave the hybridized hybridization probe to thereby release a labeled probe fragment. In some embodiments, the sample can then be contacted with a solid support comprising surface bound capture probes which can hybridize to the labeled probe fragment(s). These capture probes more readily bind to the probe fragment(s) than to the intact hybridization probe. The label can then be detected on the support surface. In this manner, improved discrimination between the probe fragments and the intact hybridization probes can be achieved.

Systems, devices, and methods for identifying a disease state in a biological host using internal controls

Contemplated methods and devices comprise detecting the presence of a pathogen in a biological host. In certain implementations, a sample is provided from a biological host. A biosensor is provided, the biosensor having a first probe configured to detect a control marker in the sample, the control marker being an endogenous element of the biological host. The biosensor has a second probe configured to detect the presence of a target marker in the sample, the target marker being from a pathogen in the biological host. The sample is applied to the biosensor, and the presence or absence of the control marker in the sample is identified using the first probe. The presence or absence of the target marker in the sample is identified using the second probe.

NANO-SENSOR ARRAY

In one embodiment, a method is provided for the manufacture of a nano-sensor array. A base having a sensing region is provided along with a plurality of nano-sensors. Each of the plurality of nano-sensors is formed by: forming a first nanoneedle along a surface of the base, forming a dielectric on the first nanoneedle, and forming a second nanoneedle on the dielectric layer. The first nanoneedle of each sensor has a first end adjacent to the sensing region of the base. The second nanoneedle is separated from the first nanoneedle by the dielectric and has a first end adjacent the first end of the first nanoneedle. The base is provided with a fluidic channel. The plurality of nano-sensors and the fluidic channel are configured and arranged with the first ends proximate the fluidic channel to facilitate sensing of targeted matter in the fluidic channel. 1. A method for the detection of target chemical and biological particles comprising:providing a sensing device comprising a base and a plurality of nano-sensors in a fluidic channel, each of said plurality of nano-sensors comprising a first nanoneedle and a second nanoneedle, wherein the first and second nanoneedles are separated by a solid state dielectric and have ends that are adjacent to one another;passing target particles through said fluidic channel with the aid of fluidic pressure; andsensing the presence of said target particles proximate to the plurality of nano-sensors by detecting a change in electric signals through the nanoneedles.2. The method of claim 1 , wherein the plurality of nano-sensors further comprise a probe proximate to an exposed portion of the solid state dielectric between the first and second nanoneedles at a first end of the second nanoneedle claim 1 , the probe configured and arranged to bind to said target particles.3. The method of claim 2 , wherein the probe is provided on one of the first and second nanoneedles.4. The method of claim 2 , wherein the sensing device further comprises a ...

Detection of Immobilized Nucleic Acid

The present invention provides methods for determining the presence of immobilized nucleic acid employing unsymmetrical cyanine dyes that are derivatives of thiazole orange, a staining solution and select fluorogenic compounds that are characterized as being essentially non-genotoxic. The methods comprise immobilizing nucleic acid, single or double stranded DNA, RNA or a combination thereof, on a solid or semi solid support, contacting the immobilized nucleic acid with an unsymmetrical cyanine dye compound and then illuminating the immobilized nucleic acid with an appropriate wavelength whereby the presence of the nucleic acid is determined. The cyanine dye compounds are typically present in an aqueous staining solution comprising the dye compound and a tris acetate or tris borate buffer wherein the solution facilitates the contact of the dye compound and the immobilized nucleic acid. 1. A compound for the detection of nucleic acid immobilized on a solid or semi solid support , wherein the compound is an unsymmetrical cyanine dye compound that is characterized as being essentially non-genotoxic in eukaryotic cells.2. The compound according to claim 1 , wherein the compound is in an aqueous solution.3. The compound according to claim 1 , wherein the compound is immobilized on or in a solid or semi-solid matrix.4. The compound according to claim 3 , wherein the solid or semi-solid matrix comprises agarose.53. The compound according to claim 3 , wherein the solid or semi-solid matrix is a polymeric membrane.8. The kit according to claim 7 , wherein the compound is in an aqueous solution.9. The kit according to claim 8 , wherein the aqueous solution comprises tris borate or tris acetate.10. The kit according to claim 7 , wherein the compound is dissolved in an alcohol or DMSO.11. The kit according to claim 7 , wherein the compound is immobilized on or in a solid or semi-solid matrix.12. The kit according to claim 11 , wherein the matrix comprises agarose.13. The lit ...

The Use of Microfluidic Systems in the Electrochemical Detection of Target Analytes

The invention relates generally to methods and apparatus for conducting analyses, particularly microfluidic devices for the detection of target analytes.

MULTIPHASE NUCLEIC ACID AMPLIFICATION

Improved methods for use in nucleic acid amplification, including multiplex amplification, where the amplification is carried out in two or more distinct phases are disclosed. The first phase amplification reaction preferably lacks one or more components required for exponential amplification. The lacking component is subsequently provided in a second, third or further phase(s) of amplification, resulting in a rapid exponential amplification reaction. The multiphase protocol results in faster and more sensitive detection and lower variability at low analyte concentrations. Compositions for carrying out the claimed methods are also disclosed. 114-. (canceled)15. A method of quantifying a target nucleic acid sequence in a sample , comprising the steps of:(a) contacting the sample with a first amplification oligonucleotide, specific for a first portion of the target nucleic acid sequence, under conditions allowing hybridization of the first amplification oligonucleotide to the first portion of the target nucleic acid sequence, thereby generating a pre-amplification hybrid that comprises the first amplification oligonucleotide and the target nucleic acid sequence;(b) isolating the pre-amplification hybrid by target capture onto a solid support followed by washing to remove any of the first amplification oligonucleotide that did not hybridize to the first portion of the target nucleic acid sequence in step (a); wherein the first phase amplification reaction mixture comprises a second amplification oligonucleotide, the second amplification oligonucleotide being complementary to a portion of an extension product of the first amplification oligonucleotide and wherein the second amplification oligonucleotide is not enzymatically extended in the first phase of isothermal transcription-associated amplification reaction, and', 'wherein the first amplification product is not a template for nucleic acid synthesis during the first phase, substantially isothermal, transcription- ...

Nanopore-Facilitated Single Molecule Detection of Nucleic Acids

The present invention provides a new and improved oligonucleotide detection method based on the nanopore technology with a probe containing a complementary sequence to the target oligonucleotide and a terminal extension at the probe's 3′ terminus, 5′ terminus, or both termini. The improved nanopore sensor with the probe enables sensitive, selective, and direct detection, differentiation and quantification of target oligonucleotides such as miRNAs. The inventive detection method may also be employed as a non-invasive and cost-effective diagnostic method for cancer detection based on miRNA levels in the patient's blood sample. 160-. (canceled)61. A method of detecting one or more target oligonucleotides in a sample with a nanopore system , the method comprising:combining the sample with a probe molecule that comprises a domain and a tag attached to the domain, wherein a sequence of the domain is complementary or partially complementary to a sequence of at least one of the target oligonucleotides, such that the probe molecule and the target oligonucleotide form a probe molecule-target oligonucleotide complex wherein the domain is hybridized to the target oligonucleotide;applying a voltage across a nanopore of the nanopore system to drive a portion of the probe molecule-target oligonucleotide complex at least partially inside the nanopore; andanalyzing an electrical current of the nanopore system over time, wherein a presence of the target oligonucleotide is indicated by a signature electrical current pattern corresponding to:(a) trapping the double-stranded molecule in a trans opening of the nanopore; or(b) detaching the target oligonucleotide from the probe molecule and translocating at least one of the probe molecule or the target oligonucleotide completely through the nanopore,the signature electrical current pattern comprising an electrical current having an amplitude and a duration respectively different from an amplitude and a duration of each of an electrical ...

METHODS AND KITS FOR SIMULTANEOUSLY DETECTING GENE OR PROTEIN EXPRESSION IN A PLURALITY OF SAMPLE TYPES USING SELF-ASSEMBLING FLUORESCENT BARCODE NANOREPORTERS

The present invention relates to, among other things, probes, compositions, methods, and kits for simultaneously detecting nucleic acids or proteins in a plurality of samples. 1. A single-stranded nucleic acid probe comprising at least three regions:at least a first region capable of binding to a target nucleic acid in a sample;at least a second region capable of binding to at least a first plurality of labeled single-stranded oligonucleotides, wherein the first plurality of labeled single-stranded oligonucleotides identifies the target nucleic acid in the sample; andat least a third region capable of binding to at least a second plurality of labeled single-stranded oligonucleotides, wherein the second plurality of labeled single-stranded oligonucleotides identifies the sample.2. The single-stranded nucleic acid probe of claim 1 , wherein the target nucleic acid is a synthetic oligonucleotide.3. The single-stranded nucleic acid probe of or claim 1 , wherein the target nucleic acid is obtained from a biological sample.4. The single-stranded nucleic acid probe of any one of to claim 1 , wherein the second region comprises at least two positions for binding to at least two first pluralities of labeled single-stranded oligonucleotides.5. The single-stranded nucleic acid probe of claim 4 , wherein the second region comprises at least three positions for binding to at least three first pluralities of labeled single-stranded oligonucleotides.6. The single-stranded nucleic acid probe of claim 5 , wherein the second region comprises at least four positions for binding to at least four first pluralities of labeled single-stranded oligonucleotides.7. The single-stranded nucleic acid probe of claim 6 , wherein the second region comprises at least five positions for binding to at least five first pluralities of labeled single-stranded oligonucleotides.8. The single-stranded nucleic acid probe of claim 7 , wherein the second region comprises at least six positions for binding to ...

Encoded Nanopore Sensor for Multiplex Nucleic Acids Detection

The present invention provides a new and improved multiplexed oligonucleotide detection method based on the nanopore technology with one or more probes containing a sequence with complementarity to the target oligonucleotide, a terminal extension at the probe's 3′ terminus, 5′ terminus, or both termini and a label attached to the terminus. The improved probes and probe sets enable sensitive, selective, and direct multiplex detection, differentiation and quantification of distinct target oligonucleotides such as miRNAs. The inventive detection method may also be employed as a non-invasive and cost-effective diagnostic method based on miRNA levels in the patient's tissue sample.

TRANSLOCATION CONTROL FOR SENSING BY A NANOPORE

Translocation control for sensing by a nanopore, as well as methods and products related to the same, are provided. Such methods optimize duplex stability to provide high fill rate (of the hybridization sites) but do not prevent rapid dissociation required for high read rates, as well as controlling the translocation of a target molecule for sensing by a nanopore by use of a selective pulsed voltage. Products related to the same include a reporter construct comprising two or more phosphoramidites. 120-. (canceled)21. A method for controlling the translocation of a target molecule for sensing by a nanopore , comprising passing the target molecule through the nanopore subjected to a base line voltage and a pulsed voltage , wherein the target molecule comprises two or more features which provide translocation control by steric hindrance , and wherein the periodicity of the pulsed voltage ranges from between greater than 100 Hz (10 milliseconds) to 4 ,000 Hz (250 microseconds).22. The method of claim 21 , wherein the pulsed voltage is sufficient to allow translocation of the feature engaged with the nanopore by steric hindrance claim 21 , while leaving the next feature of the target molecule free to engage with the nanopore.23. The method of claim 22 , wherein the feature of the target molecule engaged with the nanopore by steric hindrance translocates upon each pulse of the pulsed voltage.24. The method of claim 22 , wherein the feature of the target molecule engaged with the nanopore by steric hindrance translocates upon multiple pulses of the pulsed voltage.25. The method of claim 21 , wherein the target molecule is sensed by the nanopore during the time period between pulses of the pulsed voltage.26. The method of claim 21 , wherein the periodicity of the pulsed voltage is 500 Hz (2 milliseconds).27. The method of claim 21 , wherein the pulsed voltage has a duration of less than 100 microseconds.28. The method of claim 21 , wherein the pulsed voltage has a duration ...

METHODS AND SYSTEMS FOR AMPLIFICATION IN COMPLEX SAMPLES

The invention features methods, systems, and cartridges for amplification of target nucleic acids in complex samples, for example, whole blood. The invention also features diagnostic and therapeutic methods based on amplification of target nucleic acids characteristic of pathogens present in complex samples containing cells and/or cell debris, for example, whole blood. 1. A method for amplifying a target nucleic acid in a biological sample obtained from a subject , wherein the biological sample comprises subject-derived cells or cell debris , the method comprising:(a) lysing the cells in the biological sample to form a lysate;(b) adding to the lysate a buffer solution comprising a buffering agent to form a reaction mixture, wherein the buffer solution has a moderately alkaline pH at ambient temperature;(c) following step (b), heating the reaction mixture to form a denatured reaction mixture;(d) adding a thermostable nucleic acid polymerase to the denatured reaction mixture; and(e) amplifying the target nucleic acid to form an amplified solution comprising an amplicon.2. The method of claim 1 , wherein the final concentration of the thermostable nucleic acid polymerase in step (d) is at least about 0.02 units per microliter of the denatured reaction mixture.3. The method of or claim 1 , wherein step (d) comprises adding to the denatured reaction mixture at least about 2.4×10micrograms of a thermostable nucleic acid polymerase per microliter of denatured reaction mixture.4. The method of any one of - claim 1 , wherein the biological sample is about 0.2 mL to about 5 mL.5. The method of claim 6 , wherein the biological sample is about 0.9 mL.6. The method of any one of - claim 6 , wherein the biological sample is selected from the group consisting of blood claim 6 , bloody fluids claim 6 , tissue samples claim 6 , and sputum.7. The method of claim 6 , wherein the blood is whole blood claim 6 , a crude blood lysate claim 6 , serum claim 6 , or plasma.8. The method of ...

METHOD AND ELECTRONIC DEVICE FOR DETERMINING THE CONCENTRATION OF AN ANALYTE

A method is provided for determining, the presence and concentration of an analyte by contacting said sample with a solution comprising: magnetic beads, a capture probe capable of binding said analyte, a reporter probe and cellulose, whereby, if the analyte is present, an MB-analyte-reporter-cellulase sandwich is formed; and then contacting said solution comprising said sandwich with an electrode covered with an electrically insulating layer comprising or consisting of cellulose and/or a cellulose derivative, wherein the MB-analyte-reporter-cellulase sandwich leads to degradation of the insulating layer thereby causing a measurable change in electrical properties at the electrode surface, wherein said change in electrical properties is a function of the amount of analyte in said sample. Devices and biosensor applying the method are also provided. 115.-. (canceled)17. The method according to claim 16 , wherein the cellulase is added to the solution after addition of the magnetic beads claim 16 , the capture probe and the reporter probe claim 16 , whereby claim 16 , if the analyte is present claim 16 , an MB-analyte-reporter complex is formed before addition of cellulase.18. The method according to claim 16 , wherein said reporter probe is added to the solution after addition of the magnetic beads and the capture probe claim 16 , whereby claim 16 , if the analyte is present claim 16 , an MB-analyte complex is formed before addition of reporter probe.19. The method according to claim 16 , further comprising a step of isolating said MB-analyte-reporter-cellulase sandwich from the sample using a magnet.20. The method according to claim 17 , further comprising a step of isolating said MB-analyte-reporter complex from the sample using a magnet.21. The method according to claim 18 , further comprising a step of isolating said MB-analyte complex from the sample using a magnet.22. The method according to claim 16 , wherein said analyte is an oligonucleotide claim 16 , a ...

Detecting Chemical And Biological Agents Using Textile-Based Sensors

Methods and systems for detecting chemical and biological agents using oligonucleotide aptamers. A sensor includes a detection aptamer that has a binding domain for the chemical or biological agent, and is bound to fibers of a textile such as a patch or article of clothing. The detection aptamer can be stabilized and enhanced through a stabilization agent such as trehalose or through binding to a nanoparticle which is then bound to the fiber. Binding of the chemical and biological agent of interest to the detection aptamer can be reported to the user or wearer of the textile in a variety of ways, including visually and electrically. 1. A textile-based sensor for detecting the presence of a biological or chemical target , the sensor comprising:a plurality of textile fibers; anda plurality of aptamer molecules, each comprising a target binding domain, immobilized to the plurality of textile fibers;a stabilizing agent to stabilize the plurality of aptamer molecules, wherein the stabilizing agent is selected from the group consisting of trehalose, a natural polymer, a synthetic polymer, and combinations thereof;wherein, in the presence of the target, the target binds to the target binding domain of one or more of the plurality of aptamer molecules and a reporter signal is generated by the sensor.2. The textile-based sensor of claim 1 , wherein the stabilizing agent is a hydrogel.3. The textile-based sensor of claim 1 , further comprising a nanoparticle immobilized to a terminal end of said aptamer molecules claim 1 , wherein said nanoparticle is released when the target binds to the target binding domain of one or more of the plurality of aptamer molecules.4. The textile-based sensor of claim 3 , wherein release of the nanoparticle generates the reporter signal.5. The textile-based sensor of claim 1 , further comprising a plurality of metal nanoparticles immobilized to said plurality of textile fibers claim 1 , wherein said plurality of aptamer molecules are immobilized ...

Detecting nucleic acid

This document provides methods and materials for detecting target nucleic acid. For example, methods and materials for detecting the presence or absence of target nucleic acid, methods and materials for detecting the amount of target nucleic acid present within a sample, kits for detecting the presence or absence of target nucleic acid, kits for detecting the amount of target nucleic acid present within a sample, and methods for making such kits are provided.

Heterodimeric core-shell nanoparticle in which raman-active molecules are located at a binding portion of a nanoparticle heterodimer, use thereof, and method for preparing same

The present invention relates to a nanoparticle heterodimer in which Raman-active molecules are located at a binding portion of the nanoparticle heterodimer, and more particularly, to a core-shell nanoparticle heterodimer comprising: a gold or silver core having a surface to which oligonucleotides are bonded; and a gold or silver shell covering the core. In addition, the present invention relates to the core-shell nanoparticle dimer, to a method for preparing same, and to the use thereof.

ANALYSIS DEVICE, ANALYSIS KIT, AND ANALYSIS SYSTEM

A device including a well array including wells in which a target substance is detected based on a biochemical reaction thereof. Each of the wells has an aspect ratio of 1 or more as calculated by Formula (1) such that the biochemical reaction of the target substance is detected, 1. A device , comprising:a well array including a plurality of wells in which a target substance is detected based on a biochemical reaction thereof, {'br': None, 'Aspect ratio=Depth of each well/Diameter of largest circle among circles included in a region enclosed by a rim of each well\u2003\u2003Formula (1).'}, 'wherein each of the wells has an aspect ratio of 1 or more as calculated by Formula (1) such that the biochemical reaction of the target substance is detected,'}2. The device according to claim 1 , wherein each of the wells has a volume of 100 fL to 5 claim 1 ,000 fL.3. A kit claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the device of ;'}a detection reagent for causing the biochemical reaction of the target substance; anda sealing liquid for sealing the wells.4. A kit claim 1 , comprising:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'the device of ;'}a detection reagent for causing the biochemical reaction of the target substance; anda sealing liquid for sealing the wells.5. The kit according to claim 3 , wherein the sealing liquid comprises an oil.6. The kit according to claim 4 , wherein the sealing liquid comprises an oil.7. A system claim 4 , comprising:{'claim-ref': {'@idref': 'CLM-00003', 'claim 3'}, 'the kit of ;'}a detector configured to detect the biochemical reaction; andan analysis unit configured to analyze a value measured by the detector.8. The system according to claim 7 , wherein the biochemical reaction is an isothermal reaction.9. The system according to claim 7 , wherein each of the wells has a depth that is larger than a depth of field of the detector and 100 times or less the depth of field.10. The system according to claim 7 , ...

Method and system for substance detection with a magnetic sensor

Methods, systems and programing for substance detection with a magnetic sensor are presented. In one example, a magnetic sensor having one or more layers is formed on a base for sensing a magnetic field created by magnetic particles present in proximity to the magnetic sensor. A first end of each of a first set of strands is immobilized with respect to the magnetic sensor. A magnetic particle is attached to a second end of each of the first set of strands so that when a material containing a substance is in contact with the base, the substance causes at least some of the first set of strands to break resulting in that the magnetic particle attached to the second end of each of the at least some of the first set of strands is no longer in proximity to the magnetic sensor.

Detection Of Chemical And Biological Agents Using Oligonucleotide Aptamers

Methods and systems for detecting chemical and biological agents using oligonucleotide aptamers. A sensor includes a detection complex between an aptamer that has a binding domain for the chemical or biological agent, and a first oligonucleotide with a sequence complementary to a region of the aptamer. In the absence of the agent, the aptamer and the first oligonucleotide form an intermediate combination. In the presence of the agent, the intermediate combination dissociates. The sensor further includes a second oligonucleotide with a sequence that interacts with a region of the first oligonucleotide to form a duplex structure only when the first oligonucleotide is dissociated from the aptamer. When the duplex structure is formed, it can interact with a reporter molecule which in turn initiates a signal reporting detection of the chemical or biological agent. 1. A sensor for detecting a target , comprising:a detection complex comprising: (i) an aptamer having a binding domain for said target, and (ii) a first oligonucleotide having a sequence complementary to a region of said aptamer, wherein in the absence of said target the aptamer and said complementary region of said first oligonucleotide form an intermediate combination, and wherein in the presence of said target the intermediate combination dissociates;a second oligonucleotide having a sequence that interacts with a region of said first oligonucleotide to form a duplex structure only when said first oligonucleotide is dissociated from said intermediate combination; anda reporter molecule having a region that interacts with said duplex structure to form a reporter complex, wherein said reporter complex initiates a reporter signal.2. The sensor of claim 1 , wherein said target is a chemical or biological agent.3. The sensor of claim 1 , wherein said second oligonucleotide further comprises a metal nanoparticle claim 1 , a redox reporter claim 1 , an electrically-conducting or -insulating group claim 1 , a ...

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- ...

NUCLEIC ACID NANOSTRUCTURE BARCODE PROBES

Provided herein are, inter alia, barcode probes comprised of transiently or stably fluorescently labeled nucleic acid nanostructures that are fully addressable and able to be read using standard fluorescent microscope and methods of use thereof including methods of use as detectable labels for probes. 1. A method of detecting a target comprising:contacting a sample with a nucleic acid barcode probe comprising a nucleic acid nanostructure comprising a target binding moiety and at least two fluorescently labeled regions, wherein the nucleic acid nanostructure is a nucleic acid-nanorod structure, and each of the fluorescently-labeled regions has a center that is located at least 200 nm from the centers of the other fluorescently-labeled regions, anddetermining whether the nucleic acid barcode probe binds to one or more components in the sample,wherein binding of the nucleic acid barcode probe to one or more components of the sample indicates presence of a target in the sample.2. The method of claim 1 , further comprising identifying the target based on the color and/or orientation of the fluorescently labeled regions of the nucleic acid barcode probe bound to one or more components of the sample.3. The method of claim 1 , wherein the at least two fluorescently labeled regions of the nucleic acid barcode probe comprise soluble claim 1 , transiently binding fluorophore-bearing oligonucleotides.4. The method of claim 1 , wherein the at least two fluorescently labeled regions of the nucleic acid barcode probe comprise stably bound fluorophore-bearing oligonucleotides.5. A method of detecting a target comprisingcontacting the target with a nucleic acid barcode probe that comprises a nucleic acid nanostructure comprising a target binding moiety and at least two fluorescently labeled regions, wherein the nucleic acid nanostructure is a nanorod structure, and each of the fluorescently-labeled regions has a center that is located at least 200 nm from the centers of the other ...

Optical analyte detection systems and methods of use

Various embodiments are drawn to systems and methods for detecting an analyte of interest in a sample including an optical sensor, a capture probe attached to a surface of the optical sensor wherein the capture probe is capable of binding to the analyte to form a duplex or complex, and an antibody capable of binding to the analyte, duplex, or complex. In several embodiments, systems and methods further include a particle attached to the antibody or capable of binding to the antibody. In several embodiments, systems and methods for analyte detection feature one or more of the following: high detection sensitivity and specificity, scalability and multiplex capacity, ability to analyze large analytes, and ability to detect or measure multiple individual binding events in real-time.

Biosensor device and method for manufacturing thereof and method for detecting biological molecules

A biosensor device includes a substrate plate, a metal conductive layer, a plurality of working electrodes and an insulating layer. The metal conductive layer is disposed over the substrate plate and has an upper surface. The working electrodes are disposed over the upper surface of the metal conductive layer, wherein each of the working electrodes has a top surface and each of the top surfaces is higher than the upper surface of the metal conductive layer. The insulating layer covers the metal conductive layer and surrounds the working electrodes, wherein an upper surface of the insulating layer is located between the top surfaces and the upper surface of the metal conductive layer such that the working electrodes protrude beyond the upper surface of the insulating layer. A method for manufacturing the biosensor device and a method for detecting biological molecules by using the biosensor device are also provided herein.

BINDING PROBE CIRCUITS FOR MOLECULAR SENSORS

In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and a binding probe molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the binding probe. In various examples, the binding probe is an antibody, the Fab domain of an antibody, a protein, a nucleic acid oligomer hybridization probe, or an aptamer. The circuit may further comprise molecular arms used to wire the binding probe to the electrodes. In various embodiments, the circuit functions as a sensor wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as targets interact with the binding probe. In various embodiments, the circuit provides a means to measure the presence, absence, or concentration of an analyte in a solution. 1. A circuit comprising:a first electrode;a second electrode spaced apart from the first electrode;a binding probe electrically connected to both the first and second electrodes to form a conductive pathway between the first and second electrodes; andat least one arm molecule having first and second ends, the first end bonded to the binding probe and the second end bonded to the first electrode,wherein the at least one arm molecule acts as an electrical wire between the binding probe and the first electrode.2. The circuit of claim 1 , wherein the first electrode is a positive electrode and the second electrode is a negative electrode claim 1 , or wherein the first electrode is a negative electrode and the second electrode is a positive electrode.3. The circuit of claim 1 , wherein the at least one arm molecule is selected from the group consisting of a double stranded oligonucleotide claim 1 , a peptide nucleic acid duplex claim 1 , a peptide nucleic acid-DNA hybrid duplex claim 1 , a protein alpha-helix claim 1 , a graphene-like ...

BINDING PROBE CIRCUITS FOR MOLECULAR SENSORS

In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and a binding probe molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the binding probe. In various examples, the binding probe is an antibody, the Fab domain of an antibody, a protein, a nucleic acid oligomer hybridization probe, or an aptamer. The circuit may further comprise molecular arms used to wire the binding probe to the electrodes. In various embodiments, the circuit functions as a sensor wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as targets interact with the binding probe. In various embodiments, the circuit provides a means to measure the presence, absence, or concentration of an analyte in a solution. 1a first electrode;a second electrode spaced apart from the first electrode;a binding probe electrically connected to both the first and second electrodes to form a conductive pathway between the first and second electrodes; andat least one arm molecule having first and second ends, the first end bonded to the binding probe and the second end bonded to the first electrode,wherein the at least one arm molecule acts as an electrical wire between the binding probe and the first electrode.. A circuit comprising: This application is a continuation of U.S. patent application Ser. No. 16/015,049 filed on Jun. 21, 2018, entitled “Binding Probe Circuits for Molecular Sensors,” which is a continuation of PCT Application No. PCT/US18/29393, filed on Apr. 25, 2018 entitled “Binding Probe Circuits for Molecular Sensors.” PCT Application No. PCT/US18/29393 claims priority to and the benefit of U.S. Provisional Patent Application Ser. No. 62/503,812 filed May 9, 2017 and entitled “Binding Probe Circuits for Molecular Sensors,” the disclosures ...

Methods and Devices for Performing Real Time Digital PCR

Disclosed are devices that can perform multiple independent digital PCRs with real-time monitoring capability. The device comprises multiple PCR mini-reactors thermally coupled with its own temperature control element, a detection unit, and a motor for moving the PCR mini-reactors or the detection unit. The real-time digital PCR device can simultaneously perform multiple digital PCRs, generate amplification curves of thousands and millions of individual PCR processes, evaluate binary readouts based on the kinetic properties of individual amplification curves, and identify different target sequences based on the amplification curves. Methods of using the real-time digital PCR device to detect target nucleic acids and count circulating tumor cells are also disclosed. 1. A method for detecting a plurality of target sequences in a sample using a real-time dPCR device of the invention , comprising:a) partitioning a mixture of the sample and PCR reagents into many small individual reaction volumes of a PCR microchip of the real-time dPCR device such that more than 50% of the reaction volumes contain no more than one target sequence, wherein the mixture comprises primer pairs for amplification of the plurality of target sequences and sequence-specific reporter probes for detection of the plurality of target sequences;b) performing multiplexed real-time quantitative PCR to amplify the plurality of target sequences in each reaction volume;c) recording an amplification curve for each reaction volume during the PCR amplification; andd) determining the presence of individual target sequence in each reaction volume based on the amplification curve of the reaction volume.2. The method of claim 1 , wherein all the sequence-specific reporter probes are linked to the same fluorophore.3. The method of claim 1 , wherein different sequence-specific reporter probes are linked to different fluorophores.4. The method of claim 2 , wherein concentrations of the primers and the sequence- ...

DETECTION OF RNA WITH SUBSTITUTED UNSYMMETRICAL CYANINE DYES

Substituted unsymmetrical cyanine dyes are provided herein, including kits, assays systems and methods for their use in the detection of RNA compounds (e.g., miRNA). 1. A method of detecting the presence of single-stranded RNA (ssRNA) in a sample , comprising:(a) combining a sample suspected of containing ssRNA, wherein the ssRNA comprises 25 or fewer nucleotides, with a substituted, unsymmetrical cyanine dye compound;(b) incubating the sample for a time sufficient for the dye compound to combine with the ssRNA in the sample, if present, to form a dye-ssRNA complex that emits a detectable fluorescent signal; and(c) detecting for the emission of the fluorescent signal, wherein the detectable fluorescent signal is indicative of the presence of a dye-ssRNA complex.215-. (canceled)1723-. (canceled)24. The method of claim 16 , wherein the water-soluble group comprises a polymer.2526-. (canceled)27. The method of claim 16 , wherein if p is 0 claim 16 , and wherein Rand R claim 16 , which can be the same or different claim 16 , are independently H; or a substituted or unsubstituted alkyl group claim 16 , wherein the substitution on the alkyl group claim 16 , if present claim 16 , is a carboxyl or (alkyl)ammonium group.2829-. (canceled)30. The method of claim 16 , wherein if p is not 0 claim 16 , Rand R claim 16 , which can be the same or different claim 16 , are independently a substituted or unsubstituted alkyl group claim 16 , wherein the substitution on the alkyl group claim 16 , if present claim 16 , is a carboxyl or (alkyl)ammonium group.31. The method of claim 16 , wherein the dye compound is selected from the group consisting of Compound 4 claim 16 , Compound 5 claim 16 , Compound 6 claim 16 , Compound 7 claim 16 , Compound 8 claim 16 , Compound 9 claim 16 , Compound 10 claim 16 , Compound 11 claim 16 , Compound 12 claim 16 , Compound 13 claim 16 , Compound 14 claim 16 , Compound 15 claim 16 , Compound 16 claim 16 , Compound 17 claim 16 , Compound 18 claim 16 , ...

Method and system for substance detection with a magnetic sensor

Methods, systems and programing for substance detection with a magnetic sensor are presented. In one example, a magnetic sensor having one or more layers is formed on a base for sensing a magnetic field created by magnetic particles present in proximity to the magnetic sensor. A first end of each of a first set of strands is immobilized with respect to the magnetic sensor. A magnetic particle is attached to a second end of each of the first set of strands so that when a material containing a substance is in contact with the base, the substance causes at least some of the first set of strands to break resulting in that the magnetic particle attached to the second end of each of the at least some of the first set of strands is no longer in proximity to the magnetic sensor.

MOLECULAR ZIPPER TWEEZERS AND SPRING DEVICES

Techniques, structures, devices and systems are disclosed for implementing molecular zipper tweezers and springs. In one aspect, a molecular device includes three molecular components including at least a passive side molecular component, a binding side molecular component and a target molecular component adapted to interact together as a zipper that separate two of the molecular components held together by molecular interaction forces. 1. A method of capturing a target molecule , comprising:deploying a double-stranded molecule into a fluid environment, the double-stranded molecule including a binding strand having a sequence of nucleotides that is coupled to a passive strand having a complementary sequence of nucleotides; andattaching a target molecule in the fluid environment to the binding strand, the target molecule including an opening strand having a complement sequence of nucleotides corresponding to the binding strand, wherein the attaching uncouples the passive strand as the nucleotides of the opening strand bond to the corresponding complement nucleotides of the binding strand.2. The method of claim 1 , wherein the fluid environment is within an organism.3. The method of claim 1 , wherein the attaching the target molecule to the binding strand includes the nucleotides of the opening strand forming a bond with the corresponding complement nucleotides of the binding strand at an energy greater than a bond between the passive strand and the binding strand.4. The method of claim 1 , wherein the attaching the target molecule to the binding strand includes detaching the passive strand from the double-stranded molecule.5. The method of claim 1 , wherein the attaching the target molecule to the binding strand uses no external energy.6. The method of claim 1 , wherein the opening strand includes less nucleotides than each of the binding strand and the passive strand.7. The method of claim 6 , wherein the attaching the target molecule to the binding strand does not ...

SIGNAL ENCODING AND DECODING IN MULTIPLEXED BIOCHEMICAL ASSAYS

This disclosure provides methods, systems, compositions, and kits for the multiplexed detection of a plurality of analytes in a sample. In some examples, this disclosure provides methods, systems, compositions, and kits wherein multiple analytes may be detected in a single sample volume by acquiring a cumulative measurement or measurements of at least one quantifiable component of a signal. In some cases, additional components of a signal, or additional signals (or components thereof) are also quantified. Each signal or component of a signal may be used to construct a coding scheme which can then be used to determine the presence or absence of any analyte. 121.-. (canceled)22. A method of unambiguously detecting any unique combination of presence or absence of a plurality of analytes corresponding with a plurality of respiratory viral pathogens , the method comprising:(a) providing a sample from a subject comprising, or potentially comprising, said plurality of analytes,(b) forming a mixture of said sample and hybridization probes, wherein at least one of said hybridization probes is configured to bind to at least one of said plurality of analytes corresponding with a respiratory viral pathogen, and wherein said hybridization probes further comprises at least one fluorophore and at most four fluorophores;(c) exciting said at least one fluorophore to generate one or more signals if one or more of said plurality of analytes is present, wherein said one or more signals comprise at least one signal generated by excitement of said one or more fluorophores;(d) measuring said one or more signals to generate a cumulative intensity measurement, wherein said cumulative intensity measurement corresponds to the presence of a unique combination of presence or absence of said plurality analytes in said sample; and(e) determining whether said at least one of said plurality of analytes corresponding with said respiratory viral pathogen is present, in any unique combination of ...

Light-controlled electrokinetic assembly of particles near surfaces

A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations. In addition, the present invention provides a procedure for the creation of material surfaces with desired properties and for the fabrication of surface-mounted optical components.

DNA Methylation Detection

The present invention relates to a method for detecting methylation of a target oligonucleotide molecule. The method comprises obtaining an electrical change occurring due to the binding of an electrically charged methylation detecting molecule and the target oligonucleotide molecule; wherein the electrically charged methylation detecting molecule has affinity to a methylated cytosine nucleotide. The invention improves the detection sensitivity and accuracy of the oligonucleotide methylation detection. 1. A method for detecting methylation of a target oligonucleotide molecule , comprising obtaining an electrical change occurring due to the binding of an electrically charged methylation detecting molecule and the target oligonucleotide molecule; wherein the electrically charged methylation detecting molecule has affinity to a methylated cytosine nucleotide.2. The method according to claim 1 , wherein the electrically charged methylation detecting molecule is selected from the group consisting of an anti-methylcytosine antibody claim 1 , a methyl binding domain protein and a restriction enzyme.3. The method according to claim 1 , wherein the electrical change is a threshold voltage shift change.4. The method according to claim 1 , wherein the target oligonucleotide molecule has a target sequence with at least one methylated cytosine nucleotide claim 1 , and the method comprises:capturing a single strand of the target oligonucleotide molecule by a recognizing single-stranded oligonucleotide molecule to form a duplex according to base complementarity;providing the electrically charged methylation detecting molecule; andbinding the duplex with the electrically charged methylation detecting molecule and detecting the electrical change due to the binding.5. The method according to claim 4 , wherein the duplex formed by the single strand of the target oligonucleotide molecule and the recognizing single-stranded oligonucleotide molecule comprises a bulge and the methylated ...

Electrochemical substrate patterning and analyte detection on a two-electrode platform

A two-electrode detection system having target substrates including nucleic acids, proteins, and/or small molecules on specifically defined regions of a single surface. The spatial distribution of the target substrate on the surface allows for more accurate substrate interactions and analysis. Additionally, the detection system of the present invention allows for patterning of different target substrates, thereby affording more accurate analysis of multiple substrate targets.

ASSAY FOR DETECTING A NUCLEIC ACID ANALYTE IN A BIOLOGICAL SAMPLE

An assay for detecting an analyte in a biological sample. The assay comprises a surface probe linked to the surface of a measuring electrode and the surface probe has a nucleic acid sequence complementary to a first target nucleic acid sequence. The assay also comprises a signal probe, having a nucleic acid sequence complementary to a second target nucleic acid sequence and a binding element capable of binding a ligand. The ligand is associated with a catalytic element or precursor thereof capable of reacting with a substrate to alter electrical potential of the measuring electrode.

NANO-SENSOR ARRAY

In one embodiment, a method is provided for the manufacture of a nano-sensor array. A base having a sensing region is provided along with a plurality of nano-sensors. Each of the plurality of nano-sensors is formed by: forming a first nanoneedle along a surface of the base, forming a dielectric on the first nanoneedle, and forming a second nanoneedle on the dielectric layer. The first nanoneedle of each sensor has a first end adjacent to the sensing region of the base. The second nanoneedle is separated from the first nanoneedle by the dielectric and has a first end adjacent the first end of the first nanoneedle. The base is provided with a fluidic channel. The plurality of nano-sensors and the fluidic channel are configured and arranged with the first ends proximate the fluidic channel to facilitate sensing of targeted matter in the fluidic channel. 13.-. (canceled)4. A method for sensing , comprising:(a) providing a sensor array including a plurality of sensors, wherein a sensor of said plurality of sensors includes a first electrode and a second electrode adjacent to a base, wherein said first electrode and said second electrode are separated by a dielectric and include ends that are adjacent to one another, and wherein said first electrode and said second electrode are disposed in different planes relative to a surface of said base;(b) flowing a species through a channel in fluid communication with said ends of said first electrode and said second electrode of said sensor; and(c) using a detection circuit coupled to said sensor to detect a local change in a signal within a sensing region adjacent to said ends of said first electrode and said second electrode, wherein said local change in said signal is indicative of a presence of said species within said sensing region.5. The method of claim 4 , wherein said local change in said signal is a change in local ion concentration.6. The method of claim 4 , wherein said local change in said signal is a change in local ...

CANCER DIAGNOSTIC APPARATUS AND CANCER DIAGNOSTIC SYSTEM USING THE SAME

The present invention relates to a cancer diagnostic apparatus for checking a cancer incidence by allowing an antibody (captured antibody), which reacts with an rpS3 (ribosomal protein S3; antigen) capable of checking a phenomenon of a cancer, to react with the rpS3, and performing concentration measurement after extracting an emission signal of the reacted antigen (rpS3), and a cancer diagnostic system using the cancer diagnostic apparatus. The cancer diagnostic system includes: the cancer diagnostic apparatus for irradiating an ultraviolet ray (UV) from a bottom of a bio-chip provided with an antibody reacting with an antigen (ribosomal protein S3; rpS3), making an image from a visible ray obtained from the ultraviolet ray, which is converted by the antigen and the antibody bound to each other while passing through the bio-chip, and extracting only a specific frequency color from the visible ray to generate cancer diagnosis information; and a user terminal. 1. A cancer diagnostic apparatus comprising:a power supply unit for supplying a power;a bio-chip provided at an upper portion thereof with an antibody reacting with an antigen (ribosomal protein S3; rpS3);an ultraviolet diode for irradiating an ultraviolet ray (UV) from a bottom of the bio-chip;a sensor for making an image from a visible ray obtained from the ultraviolet ray, which is converted by the antigen and the antibody bound to each other while passing through the bio-chip;a central processing unit (CPU) for extracting only a specific frequency color for a cancer diagnosis from image information outputted from the sensor as a combine ratio coefficient to generate cancer diagnosis information from a pre-set graph of an antibody-and-antigen combine ratio based on the extracted combine ratio coefficient; anda communication unit for converting the cancer diagnosis information generated by the CPU into wireless communication format data to transmit the converted wireless communication format data.2. The ...

DIGITAL LSPR FOR ENHANCED ASSAY SENSITIVITY

Systems, methods, and devices related to detecting a presence of an analyte and/or determining a concentration of analytes are provided. An analyte may be provided on an LSPR-active surface. The LSPR-active surface may comprise sensitivity enhancing labels. The analyte may induce a local change near the LSPR-active surface. The LSPR-active surface may be imaged with an imaging device for images before, during, or after a reaction takes place. Local regions of interest within the images may be analyzed to detect the local changes. 1. A method for detecting an analyte in a sample , comprising:capturing a series of two or more images of a nanostructured sensor surface comprising one or more metallic thin films, wherein the nanostructured sensor surface is capable of sustaining a localized surface plasmon resonance;randomly selecting one or more corresponding regions of interest in the series of two or more images;measuring a change in RGB value or greyscale value within the selected regions of interest over the series of two or more images; anddetecting an analyte based on the measured changes in RGB value or greyscale value.2. The method of claim 1 , wherein a limit of detection for detecting the analyte is better than 1 ng/mL.3. The method of claim 1 , wherein a limit of detection for detecting the analyte is better than 1 pg/mL.4. (canceled)5. The method of claim 1 , further comprising determining a concentration of the analyte based on the measured changes in RGB value or greyscale value.6. (canceled)7. The method of claim 1 , wherein the measured change in RGB value or greyscale value is a change in RGB value or greyscale value of light reflected from the nanostructured sensor surface.89.-. (canceled)10. The method of claim 1 , wherein the series of two or more images are captured before and after a local analyte-induced change occurs.11. (canceled)12. The method of claim 1 , wherein the nanostructured sensor surface is contacted with a primary binding component ...

Electrochemical proximity assay

The present disclosure includes an electrochemical proximity assay (ECPA) which leverages two aptamer or antibody-oligonucleotide probes and proximity-dependent DNA hybridization to move a redox active molecule near an electrically conductive base. The ECPA of the present disclosure produces rapid, quantitative results, enabling point-of-care use in the detection of biomarkers of disease.

Microfluidic system for high-throughput, droplet-based single molecule analysis with low reagent consumption

A microfluidic device for a confocal fluorescence detection system has an input channel defined by a body of the microfluidic device, a sample concentration section defined by the body of the microfluidic device and in fluid connection with the input channel, a mixing section defined by the body of the microfluidic device and in fluid connection with the concentration section, and a detection region that is at least partially transparent to illumination light of the confocal fluorescence detection system and at least partially transparent to fluorescent light when emitted from a sample under observation as the sample flows through the detection region.

DETECTION AND QUANTIFICATION OF METHYLATION IN DNA

Provided are methods and systems for characterizing a biomolecular parameter of a polynucleotide. A polynucleotide of interest from a sample comprising a heterogeneous mixture of polynucleotides is concentrated and provided to a first fluid compartment of a solid-state nanopore. An electric potential is established across the solid-state nanopore to force the polynucleotide of interest from a first fluid compartment to a second fluid compartment via the nanopore. A passage parameter output is monitored during passage of the polynucleotide of interest through the nanopore, wherein the passage parameter output depends on the biomolecular parameter status of the polynucleotide of interest. In this manner, the methods and systems are compatible with a wide range of applications, including epigenetic modifications to DNA indicative of a disease state such as cancer, in an integrated, reliable and low cost system. 1. A method for characterizing a biomolecular parameter of a polynucleotide , the method comprising the steps of:concentrating a polynucleotide of interest from a sample comprising a heterogeneous mixture of polynucleotides;providing the concentrated polynucleotide of interest to a first fluid compartment of a solid-state nanopore, wherein the solid-state nanopore separates the first fluid compartment from a second fluid compartment, and a nanopore fluidically connects the first fluid compartment and the second fluid compartment;establishing an electric potential across the solid-state nanopore to force the polynucleotide of interest from the first fluid compartment to the second fluid compartment via the nanopore; andmonitoring a passage parameter output during passage of the polynucleotide of interest through the nanopore, wherein the passage parameter output depends on the biomolecular parameter status of the polynucleotide of interest;thereby characterizing the biomolecular parameter of the polynucleotide of interest.2. The method of claim 1 , wherein the ...

Amplification of nanoparticle based assay

An automated multiplex detector system includes: (a) a nucleic acid amplification compartment for amplifying nucleic acid of one or more targets in a sample, and (b) an analysis compartment in fluid communication with the amplification compartment, the analysis compartment housing a nanoparticle-based multiplex detector capable of using the amplified nucleic acid of the amplification compartment and producing a signal that correlates with the presence of the one or more targets in the sample.

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.

A CAPACITIVE SENSOR AND METHOD OF USE

An analyte in a liquid sample is detected using a capacitive sensor having electrodes and a sensor surface, and a signal processor. The sample is dried to reduce its liquid content, and capacitive measurements are made after the drying and preferably also before the drying. The sample may include particles, and the analyte is part of or attached to the particles, and the particles provide a major part of the capacitance change compared to absence of particles. In another example the particles are degenerative and form an integral mass upon application of heat, enhancing the extent of capacitance change. 153-. (canceled)54. A method of detecting an analyte in a liquid sample using a capacitive sensor having electrodes and a sensor surface , and a processor linked with the electrodes , the method comprising steps of:bringing the sample into contact with said sensor surface, drying the sample,measuring capacitance of the dried sample, andusing said measurement to provide data concerning the analyte.55. The method as claimed in claim 54 , comprising the further step of:measuring capacitance of the sample before drying, andderiving analyte data from both said measurements made before and after drying.56. The method as claimed in claim 54 , wherein the sample includes particles claim 54 , and the analyte is part of or attached to said particles claim 54 , and said particles provide a major part of a capacitance change; wherein the particles are beads which are attached to analyte molecules; wherein the analyte molecules are target nucleic acid (NA) molecular strands such as DNA or RNA.57. The method as claimed in claim 54 , wherein the sample includes particles claim 54 , and the analyte is part of or attached to said particles claim 54 , and said particles provide a major part of a capacitance change; wherein the sensor includes a probe fixed on the sensor surface claim 54 , said probe being selected to attach to a target NA analyte in the sample claim 54 , and the ...

DETECTION OF ANALYTES BY ENZYME-MEDIATED STRAND DISPLACEMENT REACTIONS

The subject invention pertains to composition and methods of using said composition as an in vitro biosensor of small molecules in biological and/or environmental samples using enzyme-assisted nucleic acid reactions. The methods and compositions can be used to sense and/or transduce the signal of a sensing event mediated by allosteric proteins, endonucleases and nucleic acid reactions. This invention allows the rapid development and setup of one-pot assays to provide results in minutes. The methods and compositions may be used to generate an electrochemical, fluorescent, colorimetric, and/or luminescent output and the methods can be performed in different modalities, including a solution-based or paper-based assay. 1. A composition for analyte detection , the composition comprising a restriction enzyme , a DNA template , a sensor molecule , and an invading probe , wherein the analyte binds to the sensor molecule and permits recognition of a restriction site in the DNA template by the restriction enzyme and wherein the invading probe generates a detectable signal in conjunction with a reporter molecule.2. The composition of claim 1 , wherein the sensor molecule is an allosteric transcription factor or an aptamer.3. The composition of claim 1 , wherein the analyte is a ligand that binds to the sensor molecule.4. The composition of claim 1 , wherein the restriction enzyme is a type IIS restriction enzyme that generates an overhang at the 3′ end or 5′ end of the DNA template and the overhang is at least four nucleotides in length.5. The composition of claim 1 , wherein the DNA template is a double-stranded DNA sequence that contains at least one restriction site upstream or downstream of at least one operator sequence or a single-stranded DNA sequence that contains restriction site in the loop region of a hairpin structure and a domain complementary to an aptamer molecule.6. The composition of claim 2 , wherein the DNA template sequence and the aptamer sequence are ...

Methods and Devices for Performing Real Time Digital PCR

Disclosed are devices that can perform multiple independent digital PCRs with real-time monitoring capability. The device comprises multiple PCR mini-reactors thermally coupled with its own temperature control element, a detection unit, and a motor for moving the PCR mini-reactors or the detection unit. The real-time digital PCR device can simultaneously perform multiple digital PCRs, generate amplification curves of thousands and millions of individual PCR processes, evaluate binary readouts based on the kinetic properties of individual amplification curves, and identify different target sequences based on the amplification curves. Methods of using the real-time digital PCR device to detect target nucleic acids and count circulating tumor cells are also disclosed.

NUCLEIC ACID AMPLIFICATION BIOSENSOR FOR USE IN ROLLING CIRCLE AMPLIFICATION (RCA)

The present application describes a biosensor for detecting target nucleic acid. The biosensor's mode of operation is based on binding of the target nucleic acid to another nucleic acid sequence and a circular template which triggers rolling circle amplification and detection of the amplified product as the indicator of the presence of the target nucleic acid. The biosensor is immobilized on a solid support, such as paper. 1. A nucleic acid sensor probe for detection of target nucleic acid comprising:a) a capture oligonucleotide that comprises a nucleic acid sequence that is complementary to a first nucleic acid sequence of the target oligonucleotide;b) a solid support immobilizing the capture oligonucleotide; andc) reagents for performing rolling-circle amplification (RCA) of the target oligonucleotide.2. The nucleic acid sensor probe of claim 1 , wherein the reagents for performing RCA are comprised in a stabilized composition.3. The nucleic acid sensor probe of claim 2 , wherein the reagents are encapsulated in a stabilizing matrix or are freeze dried.4pullulan.. The nucleic acid sensor probe of claim 3 , wherein the reagents for performing RCA are encapsulated with5. The nucleic acid sensor probe of claim 1 , wherein the capture oligonucleotide is biotinylated and bound with streptavidin on a membrane surface.6. The nucleic acid sensor probe of claim 1 , wherein the solid support is paper or a paper-based material.7. The nucleic acid sensor probe of claim 1 , wherein the reagents for performing RCA comprise a circular template comprising a nucleic acid sequence that is complementary to a second nucleic acid sequence of the target oligonucleotide and a nucleic acid polymerase having exonuclease activity.8. The nucleic acid sensor probe of claim 7 , wherein the nucleic acid polymerase is a DNA polymerase having 3′ to 5′ exonuclease activity or an RNA polymerase having 3′ to 5′ exonuclease activity.9. The nucleic acid sensor probe of claim 8 , wherein the nucleic ...

GENE ANALYSIS METHOD

Provided is a highly reliable gene analysis method using a flow cytometry method. The gene analysis method includes a staining step of staining cells, a sorting step of obtaining first information derived from cells in a sample solution by using a flow cytometry method, analyzing the first information according to predetermined extraction conditions, and sorting target cells into a container having arrays of a plurality of wells based on the analyzed results, an amplification step of amplifying DNA of the cells sorted into the container, an analysis step of performing gene analysis on the amplified DNA, and a condition determination step of redetermining the extraction conditions based on at least a piece of information between second information obtained in the amplification step and third information obtained in the analysis step. 1. A gene analysis method comprising:a staining step of staining cells;a sorting step of obtaining first information derived from cells in a sample solution by using a flow cytometry method, analyzing the first information according to predetermined extraction conditions, and sorting target cells into a container having arrays of a plurality of wells based on the analyzed results;an amplification step of amplifying DNA of the cells sorted into the container;an analysis step of performing gene analysis on the amplified DNA; anda condition determination step of redetermining the extraction conditions based on at least a piece of information between second information obtained in the amplification step and third information obtained in the analysis step.2. The gene analysis method according to claim 1 ,wherein the staining of cells is immunostaining by an antigen-antibody reaction.3. The gene analysis method according to claim 2 ,wherein the first information is at least a piece of information among fluorescence emission, forward-scattered light, and side-scattered light resulting from the immunostaining.4. The gene analysis method ...

Nanopipette Analysis of Polymers

The disclosure relates to devices and instruments for detecting and individually analyzing biomolecules, biomolecular complexes and biomolecules with ligands attached thereon. 142-. (canceled)43. A method of analyzing one or more macromolecules , the method comprising:i. attaching one or more macromolecules to a fixed location on a solid phase surface;ii. providing a first electrode in fluidic communication with said one or more macromolecules through an ionic aqueous buffer;iii. providing a nanopipette containing a second electrode;iv. applying a potential difference between the first and second electrodes to induce the flow of ions;v. bringing the nanopipette in sufficient proximity to a macromolecule such that the macromolecule enters into the nanopipette; andvi. measuring an ion flow,wherein the nanopipette is one of an array of nanopipettes configured for entry of a macromolecule.4443. The method according to where the array of nanopipettes comprise pulled glass capillaries or monolithic , nano-fabricated or micro-fabricated structures.4543. The method according to where the array of nanopipettes are configured to obtain measurements of a number of macromolecules in parallel.4643. The method according to where the array of nanopipettes are configured to obtain measurements of a number of macromolecules in a cell in parallel.4743. The method according to where the array of nanopipettes are configured to obtain measurements of macromolecules in a number of cells in parallel.4843. The method according to , wherein each nanopipette in the array is located precisely at a location of individual wells in a microwell array4943. The method according to , wherein the array comprises individual reference nanopipettes with no macromolecules as a control.5043. The method according to , wherein the nanopipettes comprise nanopores.5150. The method according to , wherein the nanopores are embedded within a surface and the surface containing the nanopores is translated in the z ...

Target Polynucleotide Detection and Sequencing by Incorporation of Modified Nucleotides for Nanaopore Analysis

Disclosed herein are methods and compositions for target polynucleotide identification by using modified nucleotides incorporated into the polynucleotide to facilitate detection via a nanopore device. 1. A method of determining the presence or absence of a target polynucleotide suspected of being present in a sample , comprising:providing a sample suspected of comprising a target polynucleotide;providing one or more modified nucleotides;performing a template-driven polymerization reaction on said sample to incorporate said one or more modified nucleotides into a growing strand complementary to said target polynucleotide, if present, to generate an polynucleotide reaction product comprising said one or more modified nucleotides;loading said sample into a device comprising a nanopore, wherein said nanopore separates an interior space of the device into two volumes;configuring the device to pass the polynucleotide reaction product, if present, through said nanopore, wherein the device comprises a sensor configured to detect an electrical signal generated by objects passing through the nanopore; anddetecting the presence or absence of said target polynucleotide in said sample by determining whether a polynucleotide comprising said one or more modified nucleotides passed through the nanopore using said electrical signal from the sensor.2. The method of claim 1 , wherein said one or more modified nucleotides comprises a direct label modified nucleotide or an indirect label modified nucleotide.3. The method of claim 1 , wherein said one or more modified nucleotides comprises a charged chemical moiety claim 1 , a neutral chemical moiety claim 1 , a hydrophobic moiety claim 1 , or a hydrophilic moiety.4. The method of claim 1 , wherein said one or more modified nucleotides comprises a linker capable of binding to a charged chemical moiety claim 1 , a neutral chemical moiety claim 1 , a hydrophobic moiety claim 1 , or a hydrophilic moiety.5. The method of claim 1 , wherein ...

NUCLEIC ACID ANALYSIS METHOD AND APPARATUS

Methods of detecting target nucleic acid is a sample are described. A first probe is attached to first beads, and the first beads are placed in the sample so that any target nucleic acid attaches to the first probe. A second probe also attaches to the target nucleic acid so that any of the target nucleic acid links or “tethers” the first and second probes. A capacitive sensor detects capacitance of the beads and processes capacitance data to quantify target nucleic acid presence in the sample. The second probe may be immobilised on the sensor surface. Alternatively the second beads are introduced into the sample with the second probe attached, and the extent of tethering of the first beads to the second beads is indicative of the extent of target NA present. 148-. (canceled)49. A method for detecting an analyte , the method comprising:binding at least one copy of an analyte from a sample with a bead;capturing, with the bound analyte, a corresponding quantity of a reporter;collecting the captured reporter on a sensing element of a sensor; anddetecting, with the sensing element, a quantity of reporter as a measure of an amount of the analyte in the sample.50. The method of claim 49 , wherein the analyte is a nucleic acid.51. The method of claim 49 , wherein the amount of the analyte is indicative of a presence of a microbiological entity.52. The method of claim 49 , wherein the reporter comprises a plurality of particles.53. The method of claim 50 , wherein the reporter further comprises a probe that binds to the nucleic acid by complementary base pairing.54. The method of claim 53 , wherein the probe comprises a peptide nucleic acid.55. The method of claim 49 , wherein the bead is magnetic.56. The method of claim 55 , wherein the magnetic bead is used to collect the reporter on the sensor.57. The method of claim 49 , further comprising denaturing the reporter from the bound analyte prior to detection.58. The method of claim 57 , wherein denaturing is performed on the ...

ELECTROCHEMICAL MOISTURE MEASUREMENT

Disclosed are methods of measuring moisture. Specifically, methods of measuring moisture on dry or nearly dry surfaces using an electrochemical sensor are disclosed. The method comprises applying a coating comprising an electrolyte to an electrode wherein water in the air can permeate the coating, applying a voltage to the electrode, detecting a current and, determining if the current indicates the presence of moisture. As a voltage is applied, oxygen in the water is reduced and produces a measurable signal. The method includes measuring the amount of or decrease of dissolved oxygen (in the form of water) at the surface of the electrode over time. Reduction of oxygen acts as a surrogate for water/moisture and, as such, the dryness of the surface of the electrode is calculated based on a predetermined relationship between current and dissolved oxygen (in the form of water). 1. A method to detect water on a coated substrate comprising the steps of: contacting the substrate with a voltage under conditions that allow dissolved oxygen in the form of water in the coating to reduce at the surface of the substrate to create an electrical current , measuring the electrical current output created by the reduction of the oxygen , and determining if the current output indicates the presence of water on the coating.2. The method of claim 1 , wherein the substrate comprises an electrode on a PCB.3. The method of claim 1 , wherein the coated substrate comprises an electrode on a PCB coated with capture probes.4. The method of claim 1 , wherein the coated substrate comprises an electrode on a PCB coated with capture probes and a permeation layer.5. The method of claim 1 , wherein the coating further comprises 6-Mercapto-1-hexanol claim 1 , chlorine claim 1 , nitrogen claim 1 , fluorine claim 1 , sulfur claim 1 , magnesium claim 1 , sodium claim 1 , potassium claim 1 , or calcium.6. The method of claim 1 , wherein the conditions suitable for the reduction of oxygen is between −0.01 ...

Detecting analytes with a ph meter

Provided herein are sensors, kits that include such sensors, and methods for making and using such sensors. The sensors permit detection of a broad array of target molecules, such as nucleic acids (e.g., DNA and RNA), proteins, toxins, pathogens, cells, and metals, and can be used in combination with pH meters and pH paper. Thus, this disclosure provides a new methodology that allows pH meters and pH paper to be used for the detection of analytes other than pH.

METHOD OF DNA DETECTION AND QUANTIFICATION BY SINGLE-MOLECULE HYBRIDIZATION AND MANIPULATION

The present invention relates to a fast method for the detection and the quantification of a nucleic acid, DNA or RNA. Specifically, the invention provides a method for detecting and quantifying the presence of a specific nucleic acid molecule which is based on physical and electronic treatments. The method of the invention is particularly useful for applications as diverse as detection of chromosomal abnormal distributions or gene expression analysis. 1. A method for quantifying a species of double-stranded nucleic acid molecules comprising a specific nucleic acid sequence in a sample , said method comprising:a) denaturing said double-stranded nucleic acid molecules in the sample by applying a physical force to said molecules;b) providing a single-stranded nucleic acid molecule corresponding to said sequence;c) renaturing said denatured double-stranded nucleic acid molecules of a) in the presence of said single-stranded nucleic acid molecule;d) detecting the double-stranded nucleic acid molecules where renaturation is blocked; ande) numerating the double-stranded nucleic acid molecules of d).2. A method for quantifying a species of double-stranded nucleic acid molecules comprising one or more specific sequence in a sample , said method comprising:a) denaturing said double-stranded nucleic acid molecules in the sample by applying a physical force to said molecules;b) providing one or more single-stranded nucleic acid molecule corresponding to said one or more sequences;c) renaturing said denatured double-stranded nucleic acid molecules of a) in the presence of said single-stranded nucleic acid molecule; andd) detecting the double-stranded nucleic acid molecules where renaturation is blocked by said one or more single-stranded nucleic acid molecules; ande) numerating the double-stranded nucleic acid molecules of d).3. The method of any of claim 1 , wherein the said double-stranded nucleic acid molecule is a hairpin.4. The method of claim 1 , wherein at least one base ...

Methods and apparatus for detecting molecular interactions using fet arrays

Methods and apparatuses relating to large scale FET arrays for analyte detection and measurement are provided. ChemFET (e.g., ISFET) arrays may be fabricated using conventional CMOS processing techniques based on improved FET pixel and array designs that increase measurement sensitivity and accuracy, and at the same time facilitate significantly small pixel sizes and dense arrays. Improved array control techniques provide for rapid data acquisition from large and dense arrays. Such arrays may be employed to detect a presence and/or concentration changes of various analyte types in a wide variety of chemical and/or biological processes.

METHODS OF USING FET LABELED OLIGONUCLEOTIDES THAT INCLUDE A 3′-5′ EXONUCLEASE RESISTANT QUENCHER DOMAIN AND COMPOSITIONS FOR PRACTICING THE SAME

Methods and compositions are provided for detecting a primer extension product in a reaction mixture. In the subject methods, a primer extension reaction is conducted in the presence of a polymerase having 3′→5′ exonuclease activity and at least one FET labeled oligonucleotide probe that includes a 3′→5′ exonuclease resistant quencher domain. Also provided are systems and kits for practicing the subject methods. The subject invention finds use in a variety of different applications, and are particularly suited for use in high fidelity PCR based reactions, including•SNP detection applications, allelic variation detection applications, and the like. 128-. (canceled)29. A FET labeled probe comprising nucleic acid intercalator bonded to a FET labeled oligonucleotide.30. The FET labeled probe according to claim 29 , wherein said intercalator covalently bonded to said FET labeled oligonucleotide.31. The FET labeled probe according to claim 29 , wherein said nucleic acid intercalator is located at the 3 end of said FET labeled oligonucleotide.32. The FET labeled probe according to claim 29 , wherein said nucleic acid intercalator is located at the 5′ end of said FET labeled oligonucleotide.33. The FET labeled probe according to claim 29 , wherein said nucleic acid intercalator provides increased stability to the hybrid formed from said FET labeled oligonucleotide.34. The FET labeled probe according to claim 29 , wherein said nucleic acid intercalator provides exonuclease activity resistance to said FET labeled oligonucleotide.35. The FET labeled probe according to claim 29 , wherein said nucleic acid intercalator comprises a polycyclic compound.36. The FET labeled probe according to claim 35 , wherein said polycyclic compound comprises an aromatic ring.37. The FET labeled probe according to claim 35 , wherein said polycyclic compound comprises at least three rings and not more than six rings.38. The FET labeled probe according to claim 35 , wherein said polycyclic compound ...

NOVEL COMPOSITIONS AND PROCESSES FOR ANALYTE DETECTION, QUANTIFICATION AND AMPLIFICATION

This invention provides novel compositions and processes for analyte detection, quantification and amplification. Nucleic acid arrays and libraries of analytes are usefully incorporated into such compositions and processes. Universal detection elements, signaling entities and the like are employed to detect and if necessary or desirable, to quantify analytes. Amplification of target analytes are also provided by the compositions and processes of this invention. 1. A process for detecting or quantifying more than one nucleic acid of interest in a library comprising the steps of: (i) an array of fixed or immobilized nucleic acids complementary to said nucleic acids of interest;', '(ii) a library of nucleic acid analytes which may contain the nucleic acids of interest sought to be detected or quantified, wherein each of said nucleic acids of interest comprise at least one non-inherent universal detection target (UDT), wherein said non-inherent UDT is attached to said nucleic acid analytes; and', '(iii) universal detection elements (UDE) which generate a signal directly or indirectly;, 'a) providingb) hybridizing said library (ii) with said array of nucleic acids (i) to form hybrids if said nucleic acids of interest are present;c) contacting said UDEs with said UDTs to form a complex bound to said array;d) detecting or quantifying said more than one nucleic acid of interest by detecting or measuring the amount of signal generated from UDEs bound to said array.2. The process of claim 1 , wherein said nucleic acid array is selected from the group consisting of DNA claim 1 , RNA and analogs thereof.3. The process of claim 2 , wherein said analogs comprise PNA.4. The process of or claim 2 , wherein said nucleic acids or analogs are modified on any one of the sugar claim 2 , phosphate or base moieties.5. The process of claim 1 , wherein said solid support is porous or non-porous.6. The process of claim 5 , wherein said porous solid support is selected from the group ...

Methods and systems for integrated on-chip single-molecule detection

The present disclosure provides methods and systems for performing single-molecule detection using fabricated integrated on-chip devices. In an aspect, the present disclosure provides a method for on-chip detection of an array of biological, chemical, or physical entities, comprising: (a) providing an array of light sensing devices; (b) immobilizing the array of biological, chemical, or physical entities on a substrate of the array of light sensing devices; (c) exposing the array of biological, chemical, or physical entities to electromagnetic radiation sufficient to excite the array of biological, chemical, or physical entities, thereby producing an emission signal of the array of biological, chemical, or physical entities; (d) using the array of light sensing devices, acquiring pixel information of the emission signal of the array of biological, chemical, or physical entities without scanning the array of light sensing devices across the array of biological, chemical, or physical entities; and (d) detecting the array of biological, chemical, or physical entities based at least in part on the acquired pixel information.

BIO-FIELD EFFECT TRANSISTOR DEVICE

A bioFET device includes a semiconductor substrate having a first surface and an opposite, parallel second surface and a plurality of bioFET sensors on the semiconductor substrate. Each of the bioFET sensors includes a gate formed on the first surface of the semiconductor substrate and a channel region formed within the semiconductor substrate beneath the gate and between source/drain (S/D) regions in the semiconductor substrate. The channel region includes a portion of the second surface of the semiconductor substrate. An isolation layer is disposed on the second surface of the semiconductor substrate. The isolation layer has an opening positioned over the channel region of more than one bioFET sensor of the plurality of bioFET sensors. An interface layer is disposed on the channel region of the more than one bioFET sensor in the opening. 1. A bio-field effect transistor (bioFET) device comprising:a semiconductor substrate having a first surface and an opposite, parallel second surface; a gate formed on the first surface of the semiconductor substrate; and', 'a channel region formed within the semiconductor substrate beneath the gate and between source/drain (S/D) regions in the semiconductor substrate, wherein the channel region includes a portion of the second surface of the semiconductor substrate;, 'a plurality of bioFET sensors disposed on the semiconductor substrate, each bioFET sensor comprisingan isolation layer disposed on the second surface of the semiconductor substrate, the isolation layer having an opening positioned over the channel region of more than one bioFET sensor of the plurality of bioFET sensors; andan interface layer disposed on the channel region of the more than one bioFET sensor in the opening.2. The bioFET device of claim 1 , further comprising a plurality of access FETs claim 1 , each of the access FETs including an access gate formed on the first surface of the semiconductor substrate and a channel region formed within the ...

MULTIPLEX BEAD ARRAY ASSAY

The present disclosure relates to a system, method, and kit for particle detection and analysis. Devices disclosed herein may include at least an optical source, a fluidic chip containing a multiplex bead array, and a detection module, wherein the sample flows within the fluidic chip past a detection window, where the cells or particles are imaged by an image acquisition and analysis module that may include an optical detector. The image acquisition and analysis module counts the labeled particles and software allows for analysis of bead population. 1. A system for detecting analytes in a sample comprising:a. one or more housing units;b. a bead array, wherein the bead array comprises at least one detection bead labelled with a detectable signal and a capture probe attached to the detection bead surface and wherein the bead array is capable of detecting at least two unique analytes in a sample;c. an analyte detection molecule;d. a fluidic chip, the fluidic chip incorporating at least one microfluidic channel that one or more detection beads flows through within the fluidic chip;e. a detection window incorporated in one of the one or more housings, the detection window being operable to facilitate the capture of one or more images of one or more detection beads flowing within the detection window; andf. a detection module, the detection module comprising an optical imaging system and software for image analysis, that allows communication to and from a central database.2. The system of claim 1 , wherein the bead array comprises fluorescent detection beads claim 1 , wherein each detection bead is coupled with a capture probe.3. The system of claim 2 , wherein the bead array comprises detection beads having at least one of varying fluorescent wavelengths and intensities.4. The system of claim 1 , wherein the detection beads comprise a magnetic microbead core.5. The system of claim 1 , wherein the detection beads comprise quantum dots.6. The system of claim 2 , wherein ...

Systems and Methods for Bead-Free Detection of Nucleotides

Methods and systems of quantifying a target material in solution include detection of a size change of a hybridized nucleic acid complex, without the use of nanobeads. In particular, the examples include providing a plurality of nucleic acid fragments and a species-specific oligonucleotide tags, measuring the size of the nucleic acid fragments and/or oligonucleotides to predetermine a standard distribution of the solution(s), introducing the oligonucleotides in a solution containing nucleic acid target materials and/or non-target materials, and hybridizing the oligonucleotides with the species-specific target material if present in the solution. The size of the nucleic acid complexes in solution are then measured after hybridization, and the presence or non-presence of the species-specific target material is detected and/or quantified by comparing the measured size of the nucleic acid complexes after hybridization to the standard distribution. 1. A method of quantifying a target material in solution comprising:providing a plurality of nucleic acid fragments in solution;exposing the solution containing nucleic acids to a oligonucleotide tags such that the nucleic acid fragments may hybridize with oligonucleotide tag;measuring the size of particles in the solution, including the size of at least one of the nucleic acid fragments or hybridized nucleic acid complexes, after a sufficient time for hybridization; andat least one of detecting or quantifying nucleic acid material by comparing the measured size of the solution particle sized distribution after hybridization to a standard distribution of non-hybridized nucleic acid fragments to determine whether at least a subset of the nucleic acid fragments have hybridized with the species-specific target material.2. A method as defined in claim 1 , wherein the oligonucleotide tag is a sequence of nucleotides.3. A method as defined in claim 1 , wherein measuring the particle size dsitribution in solution after a sufficient ...

NUCLEIC ACID STRUCTURE COMPLEX INCLUDING NUCLEIC ACIDS, RAMAN-ACTIVE MOLECULES, AND METAL PARTICLES, METHOD OF PREPARING THE SAME, AND METHOD OF DETECTING TARGET MATERIAL BY USING THE NUCLEIC ACID STRUCTURE COMPLEX

Provided are nucleic acid structures suitable for reproducible Raman spectroscopy, methods of preparing the same, and methods of detecting a target material using the nucleic acid structures, whereby various target materials may be analyzed by using reproducible Raman spectroscopy. 1. A nucleic acid structure complex comprising a nucleic acid comprising a hybridization region that is double stranded; at least one Raman-active molecule attached to the nucleic acid and at least one metal particle attached to the nucleic acid.2. The nucleic acid structure complex of claim 1 , wherein the nucleic acid is configured as a polyhedron.3. The nucleic acid structure complex of claim 2 , wherein the polyhedron has three or more sides claim 2 , and at least a portion of the sides of the polyhedron are provided by double stranded regions of the nucleic acid.4. The nucleic acid structure complex of claim 3 , wherein the polyhedron has two or more vertices claim 3 , and metal particles are adhered to the vertices.5. The nucleic acid structure complex of claim 4 , wherein the polyhedron is a tetrahedron claim 4 , an octahedron claim 4 , a dodecahedron claim 4 , a trigonal bipyramid claim 4 , or a bipyramid.6. The nucleic acid structure complex of claim 1 , wherein the nucleic acid structure complex further comprises a linker compound claim 1 , and the metal particle is attached to the nucleic acid by the linker compound.7. The nucleic acid structure complex of claim 1 , wherein the metal particle is Au (gold) claim 1 , Ag (silver) claim 1 , Cu (copper) claim 1 , Na (sodium) claim 1 , Al (aluminum) claim 1 , Cr (chromium) claim 1 , Pt (platinum) claim 1 , Ru (ruthenium) claim 1 , Pd (palladium) claim 1 , Fe (iron) claim 1 , Co (cobalt) claim 1 , Ni (nickel) claim 1 , or a combination thereof.8. The nucleic acid structure complex of claim 1 , wherein the metal particle is chemically reduced or is subjected to laser ablation.9. The nucleic acid structure complex of claim 1 , wherein ...

Random Array DNA Analysis by Hybridization

The invention relates to methods and devices for analyzing single molecules, i.e., nucleic acids. Such single molecules may be derived from natural samples, such as cells, tissues, soil, air and water without separating or enriching individual components. In certain aspects of the invention, the methods and devices are useful in performing nucleic acid sequence analysis by probe hybridization. 1. A system for analyzing a target nucleic acid , comprising:(a) a reaction platform;(b) an array on a surface of the platform, wherein the array comprises a solid substrate comprising a plurality of areas, each area configured for immobilization of a polynucleotide comprising a fragment of the target nucleic acid;(c) a light source configured to excite fluorescent molecules at or near the surface;(d) a megapixel camera positioned above the reaction platform; and(e) a lens configured to focus areas of the platform such that each area of the array is focused on an individual pixel of the camera.2. The system of claim 1 , wherein each area is 1 μm.3. The system of claim 1 , wherein the array comprises one million or more of the areas.4. The system of claim 1 , wherein the light source is a laser claim 1 , and the system further comprises galvanometers to control light from the laser.5. The system of claim 1 , comprising fragments of the target nucleic acid immobilized on the surface at an average density of approximately one polynucleotide per pixel.6. The system of claim 5 , comprising fluorescently labeled probes hybridized to the fragments of the target nucleic acid.7. The system of claim 1 , wherein the camera is a CCD camera.8. The system of claim 1 , wherein the polynucleotide comprises a fragment of the target nucleic acid and an adapter sequence at each end of the fragment.9. The system of claim 8 , wherein each area comprises an attached oligonucleotide claim 8 , wherein the oligonucleotide is complementary to the adapter sequence.10. A method for analyzing a target ...

SIGNAL ENCODING AND DECODING IN MULTIPLEXED BIOCHEMICAL ASSAYS

This disclosure provides methods, systems, compositions, and kits for the multiplexed detection of a plurality of analytes in a sample. In some examples, this disclosure provides methods, systems, compositions, and kits wherein multiple analytes may be detected in a single sample volume by acquiring a cumulative measurement or measurements of at least one quantifiable component of a signal. In some cases, additional components of a signal, or additional signals (or components thereof) are also quantified. Each signal or component of a signal may be used to construct a coding scheme which can then be used to determine the presence or absence of any analyte. 1. A method of unambiguously detecting any unique combination of presence or absence of at least five polynucleotide analytes in a plurality of droplets , the method comprising:(a) providing a sample comprising, or potentially comprising, at least one of said at least five polynucleotide analytes;(b) forming a mixture of said sample and at least five hybridization probes, each comprising one or more fluorophores selected from at most four fluorophores;(c) partitioning said mixture into said plurality of droplets;(d) exciting said fluorophores to generate one or more signals if one or more of said at least five polynucleotide analytes is present in said plurality of droplets, wherein said one or more signals comprise at least one signal generated by excitement of said one or more fluorophores; and(e) measuring said one or more signals to generate a cumulative measurement, wherein said cumulative measurement corresponds to the presence of a unique combination of presence or absence of said at least five polynucleotide analytes in said sample, thereby detecting the presence or absence of said at least five polynucleotide analytes, in any unique combination of presence or absence;wherein the method does not require any step of immobilization of said at least five polynucleotide analytes or mass spectrometry.2. The ...

MULTIPLEXED IDENTIFICATION OF NUCLEIC ACID SEQUENCES

A method for the rapid identification of a target nucleic acid sequence is provided, as well as corresponding devices, products and kits. Such methods are useful for the rapid detection, identification and/or quantification of target nucleic acid sequences associated with, for example, a pathogen. 1. A method for identifying a target nucleic acid sequence in a sample , the method comprising:contacting the target nucleic acid sequence with a capture probe under conditions that provide for selective hybridization of the capture probe to a first portion of the target nucleic acid sequence, wherein the capture probe comprises a reporter tether and a probe complementary to the first portion of the target nucleic acid sequence;ligating a terminal probe to the capture probe under conditions that provide for transient hydridization of the terminal probe to a second portion of the target nucleic acid sequence adjacent to the first portion of the target nucleic acid sequence to form a target identifier, wherein the terminal probe comprises a reporter tether and a probe complementary to the second portion of the target nucleic acid sequence; anddetecting the target identifier and thereby identifying the target nucleic acid sequence in the sample.2. The method of wherein the probe of the capture probe comprises from 10 to 100 nucleobases.3. The method of wherein the capture probe is tethered to a solid support by a linker claim 1 , or comprises a linker for tethering to a solid support.4. The method of wherein the reporter tether of the capture probe comprises a reporter code that claim 1 , upon detection claim 1 , parses the genetic information of the first portion of the target nucleic acid sequence to which the probe of the capture probe is complementary.5. The method of wherein the probe of the terminal probe comprises from 3 to 8 nucleobases.6. The method of wherein the terminal probe is tethered to a solid support by a linker claim 1 , or comprises a linker for tethering ...

Nanotube-Based Biosensor for Pathogen Detection

A simple and highly sensitive single walled carbon nanotube (SWNT) sensor is provided for detection of a variety of analytes, including small molecules, macromolecules, and pathogens. The high sensitivity, specificity, stability, and rapid operation of the sensor render it useful for detection and quantification of low level contaminants such as pharmaceuticals and pathogens in environmental samples, including wastewater and natural bodies of water. 2. The sensor of claim 1 , wherein the bridge comprises a plurality of aligned SWNT that are assembled on the substrate by a directed assembly method and not grown in situ.3. The sensor of claim 2 , wherein the assembled and aligned SWNT comprises SWNT that do not extend the full length from one of the pair of electrodes to the other.4. The sensor of claim 1 , wherein the recognition agent is an antibody claim 1 , a nucleic acid aptomer claim 1 , or a nucleic acid probe that hybridizes to a nucleic acid aptomer.5. The sensor of claim 1 , wherein the recognition agent is covalently attached to a coupling agent that is non-covalently attached to the SWNT via π-π stacking interactions.6. The sensor of claim 1 , wherein the coupling agent is 1-pyrenebutanoic acid succinimidyl ester.7. The sensor of claim 1 , wherein the conductometric circuit is built into the sensor.8. The sensor of claim 1 , wherein the conductometric circuit is external to the sensor.9. The sensor of or claim 1 , which is configured to connect to an external sensor reading device.10. The sensor of claim 7 , further comprising a wireless transmitter.11. The sensor of claim 7 , further comprising a processor.12. The sensor of claim 7 , further comprising a display.13. The sensor of claim 7 , configured as a microfluidic or nanofluidic device.14. The sensor of claim 13 , further comprising a sample processing module.15. The sensor of or claim 13 , further comprising one or more additional components selected from the group consisting of pumps claim 13 , ...

METHOD FOR THE DETECTION OF BIOLOGICAL MOLECULES USING A TWO PARTICLE COMPLEX

Methods, compositions and kits for detecting analytes of interest in a sample using electrogenerated chemiluminescence are provided. Compositions comprising at least one solid support that entraps or contains an electrogenerated chemiluminescent moiety also provided. 1. A method of detecting an analyte of interest in a sample , comprising {'br': None, 'sub': k', 'u', 'x, '(A)(B), (C), (D)'}, '(a) forming a composition comprisingwherein A is an electrogenerated chemiluminescent (ECL) moiety which can be induced to repeatedly emit electromagnetic radiation by direct exposure to an electrochemical energy source; and the ECL moiety is soluble in organic solvent and insoluble in aqueous solvent;B is a synthetic organic polymer bead comprising a plurality of the ECL moieties entrapped within its interior; and B is either linked to the analyte of interest or linked to a first specific binding partner of the analyte of interest;C is the sample which may contain the analyte of interest; andD is a magnetizable bead which is either linked to the analyte of interest or linked to a second specific binding partner of the analyte of interest;wherein k, u, and x are each an integer equal to or greater than 1;(b) separating a complex comprising A, B, D and the analyte of interest from other components of the composition;(c) inducing the ECL moiety in the complex to repeatedly emit electromagnetic radiation by directly exposing the moiety to electrochemical energy; and(d) detecting the emitted electromagnetic radiation and thereby detecting the presence of the analyte of interest,provided that B and D are not both linked to the analyte of interest.2. The method of claim 1 , wherein B is linked to the first specific binding partner;and D is linked to the second specific binding partner.3. The method of claim 1 , wherein the analyte of interest is a protein.4. The method of claim 3 , wherein the first specific binding partner is an antibody claim 3 , a part of an antibody claim 3 , or ...

SYSTEMS, METHODS AND DEVICES FOR ELECTROCHEMICAL DETECTION USING HELPER OLIGONUCLEOTIDES

Disclosed herein are systems, devices, and methods for the electrochemical detection of a target using a helper oligonucleotide (each a helper oligo, or collectively, helper oligos). 1. A method for detecting a target , the method comprising:contacting a sample with a helper oligonucleotide capable of forming a first complex with a target in the sample;contacting the sample with a probe affixed to a biosensor, wherein the probe is capable of forming a second complex with the first complex; andmeasuring a first electrochemical signal at the biosensor, wherein the first electrochemical signal is indicative of the presence of the second complex.2. The method of claim 1 , further comprising determining that the target is present in the sample by comparing the first electrochemical signal to a second electrochemical signal measured absent the presence of the second complex.3. The method of claim 1 , wherein the first electrochemical signal is generated by charge accumulation at the surface of the biosensor in response to the formation of the second complex.4. The method of claim 1 , further comprising contacting the sample with an enzyme claim 1 , wherein the helper oligonucleotide is capable of being enzymatically extended when the second complex is formed.5. The method of claim 4 , further comprising contacting the sample with a circular template claim 4 , wherein a portion of the helper oligonucleotide is capable of binding to the circular template.6. The method of claim 5 , wherein the helper oligonucleotide is capable of being enzymatically extended by rolling circle amplification when the portion of the helper oligonucleotide is bound to the circular template.7. The method of claim 1 , wherein the helper oligonucleotide is tagged with a charged moiety.8. The method of claim 1 , wherein the helper oligonucleotide is partially hybridized to a branched oligonucleotide structure.9. The method of claim 1 , wherein the helper oligonucleotide is between 30 and 200 bases ...

CHEMICAL SENSING DEVICE

An apparatus with a transducer having a first output signal and arranged to receive an electrical input. The transducer switches the first output signal between an ON and OFF state. The apparatus has a chemical sensing surface coupled to the transducer arranged to receive a chemical input. A signal generator oscillates one or more of said inputs to vary the switching point of the transducer. The oscillating input may be the chemical input and/or the electrical input. The output signal may be a pulse whose period ON or OFF is determined by the oscillating input modulated by the chemical input. 1. A method of measuring ion concentration in a buffered fluid , the method comprising:(i) monitoring an electrical output signal from an ISFET exposed to the fluid;(ii) releasing or adsorbing a chemical from a titration electrode to the fluid to change said ion concentration until the output signal reaches a predetermined threshold; and(iii) when that predetermined threshold is reached, determining the quantity of chemical released or adsorbed.2. A method according to claim 1 , further comprising (iv) determining the initial ion concentration from knowledge of the buffer capacity and amount of chemical released or adsorbed.3. A method according to claim 1 , further comprising repeating parts (ii) and (iii) at two different times or with different fluids and then:(iv) determining the difference in initial ion concentration from knowledge of the difference in amount of chemical released or adsorbed in each part (ii), wherein the buffer capacity before each part (ii) is substantially the same.4. A method according to claim 3 , further comprising (v) undoing the effects of part (ii) by adsorbing to or releasing from the titration electrode a substantially equal quantity of said chemical from or to the fluid.5. A method according to claim 1 , wherein the threshold is selected from the group consisting of: a predetermined change in the output signal; a predetermined rate of change ...

Molecular dna strand-displacement controllers for directing material expansion

The present invention is of compositions and methods including modular material controllers that combine amplification with logic, translation of input signals, and response tuning to directly and precisely program dramatic material size changes.

Systems and methods for facilitating fluid flow during enhanced detection and quantification of analytes

Devices, systems, and methods for detecting molecules of interest within a collected sample are described herein. In certain embodiments, self-contained sample analysis systems are disclosed, which include a reusable reader component, a disposable cartridge component, and a disposable sample collection component. The reader component may communicate with a remote computing device for the digital transmission of test protocols and test results. In various disclosed embodiments, the systems, components, and methods are configured to identify the presence, absence, and/or quantity of particular nucleic acids, proteins, or other analytes of interest, for example, in order to test for the presence of one or more pathogens or contaminants in a sample.

Cartridges, collectors, kits, and methods for enhanced detection and quantification of analytes in collected fluid samples

Devices, systems, and methods for detecting molecules of interest within a collected sample are described herein. In certain embodiments, self-contained sample analysis systems are disclosed, which include a reusable reader component, a disposable cartridge component, and a disposable sample collection component. The reader component may communicate with a remote computing device for the digital transmission of test protocols and test results. In various disclosed embodiments, the systems, components, and methods are configured to identify the presence, absence, and/or quantity of particular nucleic acids, proteins, or other analytes of interest, for example, in order to test for the presence of one or more pathogens or contaminants in a sample.

METHODS FOR BIOLOGICAL SAMPLE PROCESSING AND ANALYSIS

Provided are methods for biological sample processing and analysis. A method can comprise providing a substrate configured to rotate. The substrate can comprise an array having immobilized thereto a biological analyte. A solution comprising a plurality of probes may be directed, via centrifugal force, across the substrate during rotation of the substrate, to couple at least one of the plurality of probes with the biological analyte. A detector can be configured to detect a signal from the at least one probe coupled to the biological analyte, thereby analyzing the biological analyte. 1. A method for processing an biological analyte , comprising:(a) directing a solution comprising a plurality of probes from a dispensing unit to a fluid medium and from said fluid medium to a first location and a second location of a substrate, wherein said first location and said second location are disposed at different radial distances from a central axis of said substrate;(b) coupling at least one probe of said plurality of probes to said biological analyte; and(c) detecting one or more signals or signal changes from said biological analyte having said at least one probe coupled thereto.2. The method of claim 1 , wherein said fluid medium comprises air.3. The method of claim 1 , wherein said dispensing unit comprises a dispensing nozzle configured to dispense said solution to both said first location and said second location of said substrate.4. The method of claim 3 , wherein said directing in (a) comprises subjecting said substrate to movement relative to said dispensing nozzle.5. The method of claim 4 , wherein said movement comprises rotational motion of said substrate.6. The method of claim 4 , wherein said movement comprises non-rotational motion of said substrate.7. The method of claim 1 , wherein said dispensing unit comprises a first dispensing nozzle configured to dispense said solution to said first location and a second dispensing nozzle configured to dispense said ...

DETECTION OF NUCLEIC ACIDS

Provided herein is technology relating to detecting and identifying nucleic acids and particularly, but not exclusively, to compositions, methods, kits, and systems for detecting, identifying, and quantifying target nucleic acids with high confidence at single-molecule resolution. 1. A complex for detecting a target nucleic acid , the complex comprising:a) a target nucleic acid comprising a first region and a second region;b) a capture probe comprising a target binding region hybridized to the first region of the nucleic acid to form a thermodynamically stable duplex; and{'sub': off', 'on, 'sup': −1', '−1, 'c) a detectably labeled query probe that hybridizes repeatedly to the second region of the target nucleic acid with a kinetic rate constant kthat is greater than 0.1 minand/or a kinetic rate constant kthat is greater than 0.1 min.'}2. The complex according to wherein:{'sub': off', 'on, 'sup': −1', '−1, 'a) the kinetic rate constant kis greater than 1 minand/or the kinetic rate constant kis greater than 1 min;'}b) the detectably labeled query probe hybridizes to the target nucleic acid with a standard free energy that is greater than −12 kcal/mol at approximately 37° C.; and/orc) the detectably labeled query probe hybridizes to the target nucleic acid with a melting temperature of less than 35° C. to less than 40° C.3. The complex according to wherein the capture probe comprises a nucleic acid or a locked nucleic acid.4. The complex according to wherein the detectably labeled query probe is a nucleic acid or a fluorescent query probe.5. The complex according to wherein:a) the first region of the target nucleic acid consists of from 5 to 500 nucleotides;b) the target binding region of the capture probe consists of from 5 to 500 nucleotides;c) the second region of the target nucleic acid consists of 5 to 15 nucleotides; and/ord) the detectably labeled query probe consists of 5 to 15 nucleotides.6. The complex according to wherein the capture probe is bound to a ...

BINDING PROBE CIRCUITS FOR MOLECULAR SENSORS

In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and a binding probe molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the binding probe. In various examples, the binding probe is an antibody, the Fab domain of an antibody, a protein, a nucleic acid oligomer hybridization probe, or an aptamer. The circuit may further comprise molecular arms used to wire the binding probe to the electrodes. In various embodiments, the circuit functions as a sensor wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as targets interact with the binding probe. In various embodiments, the circuit provides a means to measure the presence, absence, or concentration of an analyte in a solution. 1. A circuit comprising:a first electrode;a second electrode spaced apart from the first electrode by a gap; anda binding probe electrically connected to the first electrode by a first peptide arm molecule and electrically connected to the second electrode by a second peptide arm molecule;wherein the binding probe comprises a DNA or RNA oligonucleotide hybridization probe.2. The circuit of claim 1 , wherein the first peptide arm molecule is attached to the first electrode and the second peptide arm molecule is attached to the second electrode by material binding peptide-metal interactions.3. The circuit of claim 1 , wherein the binding probe comprises a single stranded DNA oligonucleotide or a single stranded RNA oligonucleotide.4. The circuit of claim 1 , wherein at least one of the first peptide arm molecule or the second peptide arm molecule comprises tension claim 1 , twist or torsion dependent conductivity.5. The circuit of claim 1 , wherein the circuit is configured to sense information on the presence of or a concentration ...

Apparatuses and methods for determining analyte charge

The present disclosure provides a sensor including a pore and an applied electric field that is capable of detecting analytes such as nucleic acids. In accordance with various embodiments, the sensor comprises a fluidic chamber having electrically opposing portions with a membrane between, the membrane providing a pore suitable for the passage of an electrolyte between the electrically opposing portions of the fluidic chamber, and having at least one charged analyte tethered in proximity to the pore, a first circuit configured to apply an electric field capable of passing the electrolyte through the pore and pulling the at least one charged analyte into the pore, and a second circuit configured to measure a signal indicative of the charge of the at least one charged analyte. Also provided are methods for using the sensor, for example, to sequence a nucleic acid molecule.

Electrochemical detection systems and methods using modified coated multi-labeled magnetic beads with polymer brushes

An immunosensor is provided that includes polymer coated particles, wherein the polymer coated particles are labelled with an enzyme and used for at least one of protein biomarker detection and DNA biomarker detection.

METHOD OF DETECTING TARGET MATERIAL, SENSOR CHIP, AND DETECTING DEVICE

A method of detecting a target material () includes: a step of preparing a complex (), the complex including an aptamer () to which a target material () in a specimen specifically binds, a first nucleic acid fragment () that has a base sequence complementary to the aptamer (), and a fixing member () to which a part of the aptamer () and a part of the first nucleic acid fragment () are fixed, in which the aptamer () has a double strand-forming site () capable of forming a double strand with the first nucleic acid fragment (); a step of separating the first nucleic acid fragment ) from the double strand-forming site () of the aptamer () by binding the target material () to the aptamer (); and a step of detecting the cleavage of the double strand. 1. A method of detecting a target material , the method comprising:a step of preparing a complex, the complex includingan aptamer to which a target material in a specimen specifically binds,a first nucleic acid fragment that has a base sequence complementary to the aptamer, anda fixing member to which a part of the aptamer and a part of the first nucleic acid fragment are fixed,in which the aptamer has a double strand-forming site capable of forming a double strand with the first nucleic acid fragment;a step of separating the first nucleic acid fragment from the double strand-forming site of the aptamer by binding the target material to the aptamer; anda step of detecting the cleavage of the double strand where the first nucleic acid fragment is separated from the aptamer.2. The method of detecting a target material according to claim 1 ,wherein the double strand-forming site of the aptamer has only a base sequence complementary to the base sequence of the first nucleic acid fragment.3. The method of detecting a target material according to claim 1 ,wherein the complex includes a linking portion through which a part of the aptamer and a part of the first nucleic acid fragment are linked to each other, andthe linking portion ...

METHODS, DEVICES, AND SYSTEMS FOR ANALYTE DETECTION AND ANALYSIS

Provided are systems and methods for analyte detection and analysis. A system can comprise an open substrate. The open substrate may be configured to rotate or otherwise move. The open substrate can comprise an array of individually addressable locations, with analytes immobilized thereto. The substrate may be spatially indexed to identify nucleic acid molecules from one or more sources, and/or sequences thereof, with the respective one or more sources. A solution comprising a plurality of probes may be directed across the array to couple at least one of the plurality of probes with at least one of the analytes to form a bound probe. A detector can be configured to detect a signal from the bound probe via scanning of the substrate while minimizing temperature fluctuations of the substrate or optical aberrations caused by bubbles.

Magnetic beads-based electrochemical biosensor

The present invention is generally directed to methods for detecting and/or quantifying miRNA, RNA or DNA molecules of interest in at least one isolated biological sample. Basically the general procedure followed by the methods of the present invention involve four main steps: (i) homogeneous hybridization of the synthetic DNA or RNA probe and the target miRNA, RNA or DNA molecule of interest; (ii) capture of the resultant DNA/RNA, DNA/DNA or RNA/RNA duplex by the antibody-modified magnetic particles, preferably MBs, in solution; (iii) enzymatic labeling of the biotinylated DNA/RNA, DNA/DNA or RNA/RNA duplex captured onto the antibody-modified magnetic particles, preferably MBs and (iv) electrochemical detection of the modified-magnetic particles on an electrochemical sensor, preferably on screen-printed carbon electrodes (SPCEs).

Exchange-induced remnant magnetization for label-free detection of dna, micro-rna, and dna/rna-binding biomarkers

A method of using an exchange-induced remnant magnetization (EXIRM) technique for label free detection of short strands of nucleotides and cancer biomarkers, such as DNA and microRNA strands, DNA/RNA-binding biomarkers, and cancer-specific antigens, with high sensitivity, high specificity, and broad dynamic range. The method may provide a label-free approach aimed to facilitate high reliability, and to require a minimum amount of biochemical reagents.