УСТРОЙСТВО ДЛЯ СМЕШИВАНИЯ ВЕЩЕСТВ И СПОСОБ СМЕШИВАНИЯ ВЕЩЕСТВ

Изобретение относится к смешиванию веществ и может использоваться в биотехнологии и химии. Устройство для смешивания вещества включает в себя: два или более проточных каналов (11, 12, 13), в которых формируются отверстия (111, 121, 131), из которых выпускается наружу жидкость, колебательные устройства (112, 122, 132), которые формируют капли жидкости, выпускаемые из каждого отверстия (111, 121, 131) за счет колебаний, по меньшей мере, части проточных каналов, где находятся отверстия (111, 121, 131), на заданной частоте колебаний, и выпускают капли жидкости; а также средства, для того чтобы вызвать столкновение друг с другом капель (A, B, C) жидкости, выпускаемых из отверстий (111, 121, 131) проточных каналов (11, 12, 13). Технический результат состоит в обеспечении равномерности смешивания определенного количества микроэлементов, а также смешивания мельчайших частиц. 3 н. и 15 з.п. ф-лы, 15 ил.

ДИСПЕРГИРОВАНИЕ И НАКОПЛЕНИЕ МАГНИТНЫХ ЧАСТИЦ В МИКРОФЛЮИДНОЙ СИСТЕМЕ

Изобретение относится к микрофлюидной системе, содержащей источник магнитного поля и две камеры, соединенные каналом. Камеры и канал наполняют разными текучими средами, так что на соответствующих границах раздела текучих сред создается ненулевое поверхностное натяжение. Источник магнитного поля выполнен с возможностью обеспечения по меньшей мере двух отдельных областей градиента магнитного поля и обеспечивать притяжение имеющихся в одной из камер магнитных частиц в эти разные области, причем силы магнитного притяжения, создаваемые по меньшей мере одной из областей градиента, достаточно велики для обеспечения выталкивания или вытягивания магнитных частиц через упомянутые границы раздела текучих сред. Источник магнитного поля может быть выполнен в виде постоянного магнита шестигранной формы. Изобретение обеспечивает создание средств, дающих возможность универсального манипулирования магнитными частицами в системе. 3 н. и 10 з.п. ф-лы, 7 ил., 1 пр.

СПОСОБ И УСТРОЙСТВО ДЛЯ РАЗДЕЛЕНИЯ НЕСМЕШИВАЕМЫХ ЖИДКОСТЕЙ С ЦЕЛЬЮ ЭФФЕКТИВНОГО ОТДЕЛЕНИЯ ПО МЕНЬШЕЙ МЕРЕ ОДНОЙ ИЗ ЖИДКОСТЕЙ

Analysesystem und Analyseverfahren

Screening-Testsystem mit hohem Durchfluss durch mikrofluidische Vorrichtungen

GERICHTETE EVOLUTION VON BIOMOLEKÜLEN UNTER DER VERWENDUNG VON MIKROSTRUKTUREN

Methods for detecting target nucleic acids in sample lysate droplets

Detectors for microfluidic systems

A method for detecting and measuring samples in the form of liquid droplets or slugs in a carrier liquid comprises providing a microfluidic device with conduits and at least one detector, moving a carrier liquid containing the liquid droplets or slugs through the microfluidic device until a first droplet or slug comes into contact with the at least one detector, measuring at least one property of the liquid droplet or slug with the detector, removing the sample, flushing the detector with a flushing liquid and then repeating the detection sequence. A device for carrying out the method comprises a first conduit, 12 a detector 10 and a second conduit 14 in liquid communication with the first conduit.

Microfluidic device and methods for construction and application

Microfluidic device and a method of loading fluid therein

A microfluidic active matrix electro wetting on dielectric device (AM-EWOD) and a method of filling such a device, wherein the device comprises a chamber 109 having one or more inlet ports 111 and is configured that when the chamber contains a metered volume of a filler fluid 107 it is partially filled and the further addition of a volume of assay fluid 108 into the chamber via one or more of the inlet ports results in the displacement a volume of a venting fluid to vent from the chamber. The venting fluid may be air and the device may comprise a venting channel 115. The assay fluid within the chamber may be controlled by the actuation of electrodes. Alternatively, the chamber is completely filled with filler fluid and when assay fluid is added a sufficient amount of filler fluid is extracted.

Droplet-Based assay system

Droplet-based assay system

Bioreactor

The invention concerns a droplet-fluidic bioreactor system and method of use. The method includes introducing a first droplet 6 encapsulated by the carrier medium into the path through the first inlet and a second droplet 7 introduced through a second inlet. The method also includes inducing the first droplet 6 and the second droplet 7 to fuse into a single, third droplet 11. The method also includes inducing the third droplet to split into fourth 12 and fifth 13 droplets and extracting the fourth droplet 12 from the path. The method also includes extracting the fifth droplet 13 through the outlet 4 and re-introducing the fifth droplet 15 into the path 5 through the inlet 3. Preferably the droplets include suspensions of microorganisms and/or cells and suspensions of substances suitable for sustaining the microorganisms and/or cells. Also claimed is a method of preparing a droplet-fluidic bioreactor and a method of fabricating a feature segment for a droplet-fluidic device.

2-dimensional separation

Method for splitting droplets in microfluidic junction and system for splitting droplets in microfluidic juction

Microfluidic device and a method of loading fluid therein

Microfluidic arrangements

Microfluidic probe head for providing a sequence of separate liquid volumes separated by spacers

Microfluidic arrangements

Assemblies and methods

Improvements in or relating to a method of maintaing a microdroplet

Microfluidic particle sorter

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

MICRO-FLUID DEVICE WITH AT LEAST TWO CHANNELS A CONNECTING CONNECTION CHANNEL AND PROCEDURE FOR LEADING AND EXAMINING FLUIDS

MICRO FLUID NET TO FORMING THE DROPLET QUEUE AND PROCEDURE

MICRO FLUIDIC CIRCULATION DEVICE FOR THE REGULATION OF PARAMETERS OF A PHYSICAL AND/OR CHEMICAL TRANSFORMATION AND USE OF IT

USE OF A MICRO-FLUID DEVICE FOR IDENTIFICATION, QUANTIFICATION AND AUTHENTIFIZIERUNG LATENT MARKER

PROCEDURE FOR THE TRANSPORT OF FLUID SAMPLES BY A MICRO-FLUID CHANNEL

ELECTRICALKINETIC PIPETTE, AS WELL AS MEANS FOR COMPENSATING ELEKTROPHORETI DIVORCE EFFECTS

PROCEDURE FOR MIXTURE-FREE TRANSFERRING OF HETEROGENEOUS LIQUIDS IN MICRO-CHANNELS

THERMAL MICRO VALVES

PROCEDURE FOR THE PROMOTION OF A LIQUID IN A CAPILLARY AND FLUID MICRO-SYSTEM

MICRO FLUID DEVICES FOR THE STEERED HANDLING OF KLEINSTVOLUMEN

Method for detecting and/or characterising tumour cells and associated apparatus

The present invention is in the field of biological diagnosis in oncology. The invention concerns an apparatus for detecting and/or characterising tumour cells by detection of one or more tumour-cell secretome elements, in particular one or more peptides or proteins and especially one or more tumour markers. The invention also relates to droplets for detecting and/or characterising tumour cells and the method of preparing same.

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 ...

Microfluidic device & methods for construction & application

Fluidic droplet coalescence

MICROSYSTEM, MICROOPENING FILM, AND SYSTEM AND METHOD FOR ANALIZING INTERACTION BETWEEN BIOMOLECULES

Electrowetting-driven micropumping

METHOD AND APPARATUS FOR CONTROLLING MINUTE AMOUNT OF FLUID

Method for carrying out a biochemical protocol in continuous flow in a microreactor

Fluidic devices and systems for sample preparation or autonomous analysis

The present invention relates to fluidic devices for preparing, processing, storing, preserving, and/or analyzing samples. In particular, the devices and related systems and methods allow for preparing and/or analyzing samples (e.g., biospecimen samples) by using one or more of capture regions and/or automated analysis.

Biomolecule isolation

Methods, devices and systems for handling sample liquids, encapsulating liquids and magnetic particles are disclosed.

Compositions, methods and systems for polymerase chain reaction assays

The present disclosure provides methods, devices, systems and compositions for detecting nucleic acids in polymerase chain reaction assays, such as droplet digital polymerase chain reaction (ddPCR) assays. The present disclosure provides methods, devices, systems and compositions for detecting nucleic acids in ddPCR assays using intercalating dyes. A dual surfactant system with at least one fluorosurfactant and at least one non-ionic non-fluorosurfactant may be employed for droplet generation and nucleic acid detection.

Devices and methods for sample analysis

Integrated devices that include a sample preparation component integrated with a de-tection component are disclosed. The sample prepar-ation component may be a digital microfluidics mod-ule or a surface acoustic wave module which mod-ules are used for combing a sample droplet with a re-agent droplet and for performing additional sample preparation step leading to a droplet that contains beads/particles/labels that indicate presence or ab-sence of an analyte of interest in the sample. The beads/particles/labels may be detected by moving the droplet to the detection component of the device, which detection component includes an array of wells.

Array cytometry

Laboratory in a disk

Microfluidic device

Microfluidic device

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 ...

FORMATION AND CONTROL OF FLUIDIC SPECIES

This invention generally relates to systems and methods for the formation and/or control of fluidic species, and articles produced by such systems and methods. In some cases, the invention involves unique fluid channels, systems, controls and/or restrictions, and combinations thereof. In certain embodiments, the invention allows fluidic streams (which can be continuous or discontinuous, i.e., droplets) to be formed and/or combined, at a variety of scales, including microfluidic scales. In one set of embodiments, a fluidic stream may be produced from a channel, where a cross-sectional dimension of the fluidic stream is smaller than that of the channel, for example, through the use of structural elements, other fluids, and/or applied external fields, etc. In some cases, a Taylor cone may be produced. In another set of embodiments, a fluidic stream may be manipulated in some fashion, for example, to create tubes (which may be hollow or solid), droplets, nested tubes or droplets, arrays of ...

DROPLET-BASED ASSAY SYSTEM

Systems, including apparatus and methods, for performing assays. These systems may involve separating sample components by partitioning them into droplets or other partitions, amplifying or otherwise reacting the components within the droplets, detecting the amplified components, or characteristics thereof, and/or analyzing the resulting data, among others.

IN VITRO EVOLUTION IN MICROFLUIDIC SYSTEMS

MICROFLUIDIC MATRIX LOCALIZATION APPARATUS AND METHODS

Multiphasic microfluidic apparatus for performing product fluid manipulation and separation in a single continuous unit are provided. Related methods, kits, and compositions are also provided.

MIXED MODE MICROFLUIDIC METHOD

A method of extracting a charged species from a sample and concentrating it, in an interconnected channel network with a first (1208), second (1210) and third (1212) channel segment which intersect in a first fluid junction, the second channel terminating in a first fluid reservoir (1204), and the third channel segment (1212) intersecting at a second fluid junction (1215) a fourth channel segment (1214) which terminates in a second fluid reservoir (1206) containing a high ionic strenght buffer. The sample contains charged species in a low ionic strenght buffer and is flowed through the channel network by applying a first pressure differential across the first (1208) and second (1210) segments, and a smaller second pressure differential across the third (1212) and fourth (1214) segments. A voltage is applied across the first (1204) and second (1206) reservoirs, which is sufficient to cause a substantial part of the charged species in the sample in the first fluid junction to flow into the ...

SYSTEM AND METHOD OF PRECONCENTRATING ANALYTES IN A MICROFLUIDIC DEVICE

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

ULTRA-HIGH THROUGHPUT DETECTION OF FLUORESCENT DROPLETS USING TIME DOMAIN ENCODED OPTOFLUIDICS

A high-throughput optofluidic device for detecting fluorescent droplets is disclosed. The device uses time-domain encoded optofluidics to detect a high rate of droplets passing through parallel microfluidic channels. A light source modulated with a minimally correlating maximum length sequences is used to illuminate the droplets as they pass through the microfluidic device. By correlating the resulting signal with the expected pattern, each pattern formed by passing droplets can be resolved to identify individual droplets.

DEVICES AND METHODS FOR IDENTIFYING GENOMIC DNA OF ORGANISMS

MICROFLUID DEVICE WITH SAMPLE INJECTOR AND METHOD OF USE

A method and device for injecting a liquid sample into an electrolyte channel in a microfluidics device is disclosed. The device has a channel network that includes an electrolyte channel having upstream and downstream channel portions and first, second, and third side channels that intersect the electrolyte channel between the two channel portions at first, second, and third ports, respectively. In the method, a sample is moved electrokinetically into the electrolyte channel, to form a defined sample volume therein. By simultaneously controlling the voltage applied to the three side channels, and at least one of the upstream and downstream channel end portions, the sample volume element can be shaped to have a desired leading- and trailing-edge shape and/or distribution of sample components within the volume elements.

BIOCHEMICAL ANALYSIS OF PARTITIONED CELLS

The invention relates to compositions and methods for the analysis of bio molecules associated with cells, where the presence or absence of a particul ar biomolecule (e.g., an expressed protein or a nucleic acid gene expression product) associated with the cells is examined. The invention provides meth ods for single cell biochemical analysis, as well as instrumentation for the single-cell biochemical analysis. Most advantageously, the invention afford s methods and instrumentation for high-throughput biochemical analysis of la rge numbers of single cells.

ASSAY CARTRIDGES AND METHODS OF USING THE SAME

Assay cartridges are described that have a detection chamber, preferably having integrated electrodes, and other fluidic components which may include sample chambers, waste chambers, conduits, vents, bubble traps, reagent chambers, dry reagent pill zones and the like. In certain embodiments, these cartridges are adapted to receive and analyze a sample collected on an applicator stick. Also described are kits including such cartridges and a cartridge reader configured to analyze an assay conducted using an assay cartridge.

METHOD AND APPARATUS FOR CHARACTERIZING CLATHRATE HYDRATE FORMATION CONDITIONS EMPLOYING A MICROFLUIDIC DEVICE

A test method and test apparatus is provided that employs a microfluidic device to characterize properties of a fluid. The microfluidic device has a first inlet port, an outlet port, and a microchannel as part of a fluid path between the first inlet port and the outlet port. While generating a flow of the fluid through the microchannel of the microfluidic device, fluid pressure at the first inlet port of the microfluidic device is measured and recorded in conjunction with varying the controlled temperature of the microchannel of the microfluidic device to characterize the properties of the fluid that flows through the microchannel of the microfluidic device. The properties of the fluid can relate to the clathrate hydrate formation condition of the fluid at the pressure of the flow through the microchannel of the microfluidic device.

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

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

MICROFLUIDIC DEVICE FOR HIGH-VOLUME PRODUCTION AND PROCESSING OF MONODISPERSE EMULSIONS

A high volume microfluidic system for producing emulsions includes a fluid distribution network to produce uniformly sized emulsions and encapsulates.

PRINTED DIGITAL MICROFLUIDIC DEVICES METHODS OF USE AND MANUFACTURE THEREOF

Embodiments of the present disclosure digital microfluidic arrays that may be fabricated by a printing method, whereby digital microfluidic electrodes arrays are printed, via a printing method such as inkjet printing, onto a suitable substrate. In some embodiments, a substrate and/or ink is prepared or modified to support the printing of electrode arrays, such as via changes to the surface energy. In some embodiments, porous and/or fibrous substrates are prepared by the addition of a barrier layer, or, for example, by the addition or infiltration of a suitable material to render the surface capable of supporting printed electrodes. Various example embodiments involving hybrid devices formed by the printing of digital microfluidic arrays onto a substrate having a hydrophilic layer are disclosed.

DROPLET ACTUATOR DEVICES AND METHODS EMPLOYING MAGNETIC BEADS

A method of providing a droplet in contact with a magnetically responsive bead and having a reduced quantity of a substance. The method generally includes the steps of (a) providing a droplet actuator (200) comprising: (i) a substrate (210) comprising electrodes (214) arranged for conducting droplet operations on a surface; (ii) a starting droplet (218/222) comprising: (1) one or more magnetically responsive beads (220); (2) a starting quantity of the substance; and (3) a starting volume; (b) magnetically immobilizing the one or more magnetically responsive beads at a location which is at a distance from a target droplet splitting zone, (224); (c) conducting one or more droplet operations comprising droplet dividing operations selected to divide the combined droplet to yield a set of droplets comprising: (i) a droplet (218) comprising substantially all of the one or more magnetically responsive beads and having a decreased quantity of the substance relative to the starting concentration ...

SYSTEM FOR FORMING EMULSIONS

System, including methods, apparatus, and kits, for forming emulsions. The system may include an instrument and a microfluidic chip received by the instrument. The instrument may apply pressure to prospective emulsion phases held by the chip, to drive formation and collection of emulsions in the chip. In some embodiments, the instrument may stop applying pressure to the chip when a change in pressure meeting a predefined condition is detected by the instrument. The change may indicate that an endpoint of droplet generation has been reached.

REAGENT STORAGE ON A DROPLET ACTUATOR

A method of providing a droplet comprising one or more reagents, the method comprising, depositing a first aqueous droplet comprising the one or more reagents on a surface; drying the droplet to yield a dried composition on the surface comprising the one or more reagents; covering the dried composition with oil; and causing a second aqueous droplet in the oil to contact the dried composition and thereby resuspend one or more reagents.

METHODS AND APPARATUS FOR FLOW-CONTROLLED WETTING

Methods of determining a first position at which a dispersed phase droplet wets a surface of a channel are provided herein. The methods include immersing the dispersed phase droplet in a continuous phase fluid, wherein the continuous phase fluid is immiscible with the dispersed phase droplet, subsequently flowing the dispersed phase droplet in the continuous phase through the channel at a dispersed phase droplet velocity, wherein the dispersed phase droplet is separated from the surface by a film of the continuous phase fluid having a film thickness, and reducing the film thickness to rupture the film at the first position, wherein the droplet wets the surface at the first position.

HIGH-THROUGHPUT SCREENING ASSAY SYSTEMS IN MICROSCALE FLUIDIC DEVICES

The present invention provides microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems. The device includes a series of channels (110, 112), and optional reagent channel (114), fabricated into the surface of the substrate. At least one of these channels will typically have very small cross-sectional dimensions, e.g. in the range of from about 0.1 hem to about 500 .mu.m. The device also includes reservoirs (104, 106 and 108), disposed and fluidly connected at the ends of the channels (110 and 114). As shown, sample channel (112) is used to introduce the plurality of different test compounds into the device. As such, this channel will generally be fluidly connected to a source of large numbers of separate test compounds that will be individually introduced ...

MICROFLUIDIC DEVICES INCORPORATING IMPROVED CHANNEL GEOMETRIES

A microfluidic device comprising: a main analysis channel (100); a sample loading channel (102), sample loading channel (102) forming at intersection (108) with main analysis channel (100), sample introduction channels (104, 106) in fluid communication with sample loading channel (102) on opposite sides of intersection (108); first and second sample source (110 and 112) in fluid communication with sample introduction channels (104, 106); load/waste channels (114, 116) in fluid communication with sample loading channel (102) on opposite sides of intersection (108); and load/waste reservoirs (118, 120) in fluid communication with load/waste channels (114, 116).

Dividing drops at microfluidic junction comprising supply channel, first and second discharge channels, comprises supplying drops to microfluidic junction, and controlling ratio of flow rates by pumping or aspirating continuous liquid

Dividing drops at a microfluidic junction comprising a supply channel, a first discharge channel having an additional channel, and a second discharge channel, comprises (a) supplying the drops to the microfluidic junction through the supply channel (2) by flowing continuous liquid through the channel, the first discharge channel (5) and the second discharge channel (6), and (b) controlling the ratio of the flow rates in the discharge channels by pumping or aspirating the continuous liquid through the additional channel (9). Dividing drops at a microfluidic junction comprising a supply channel, a first discharge channel having an additional channel, and a second discharge channel, comprises (a) supplying the drops to the microfluidic junction through the supply channel (2) by flowing continuous liquid through the channel, the first discharge channel (5) and the second discharge channel (6), and (b) controlling the ratio of the flow rates in the discharge channels by pumping or aspirating ...

Procedure for the division of drops at a micro-fluid crossing.

Gegenstand der Erfindung ist ein Verfahren zur Teilung von Tropfen an einer mikrofluidischen Kreuzung, umfassend einen ersten Zufuhrkanal, einen zweiten Zufuhrkanal und einen Abfuhrkanal, gekennzeichnet dadurch, dass es die folgenden Etappen umfasst: a) Zuführung des Tropfens (1) an die mikrofluidische Kreuzung (3) durch den ersten Zufuhrkanal (2) mithilfe einer Strömung einer kontinuierlichen Flüssigkeit durch den ersten Zufuhrkanal (2) und den Abfuhrkanal, b) Einstellung der Strömung in dem ersten Zufuhrkanal (2) zu dem Zeitpunkt, wenn sich der Tropfen (1) im Lumen des zweiten Zufuhrkanals befindet, c) Öffnung der Strömung der kontinuierlichen Flüssigkeit in dem zweiten Zufuhrkanal bis zum Zeitpunkt, wenn der Tropfen (1) in zwei Teile zerteilt ist.

Dividing drops at microfluidic junction comprising first and second supply channels and discharge channel, comprises supplying drops to microfluidic junction, adjusting flow in first supply channel, and opening flow in second supply channel

Dividing drops at a microfluidic junction comprising a first supply channel, a second supply channel and a discharge channel, comprises (a) supplying the drops (1) to the microfluidic junction (3) through the first supply channel (2) by flowing continuous liquid through the channel and the discharge channel, (b) adjusting the flow in the first supply channel to a time point, at which the drops are present in a lumen of the second supply channel, and (c) opening the flow of the continuous liquid in the second supply channel up to a time point, at which the drops are divided into two portions.

Procedure for the division of drops at a micro-fluid crossing.

Gegenstand der Erfindung ist ein Verfahren zur Teilung eines Tropfens an einer mikrofluidischen Kreuzung, umfassend einen Zufuhrkanal, einen ersten Abfuhrkanal, ausgerüstet mit einem zusätzlichen Kanal, und einen zweiten Abfuhrkanal, gekennzeichnet dadurch, dass es die folgenden Etappen umfasst: a. Zuführung des Tropfens (1) an die mikrofluidische Kreuzung (3) durch den Zufuhrkanal (2) mithilfe einer Strömung einer kontinuierlichen Phase durch den Zufuhrkanal sowie den ersten Abfuhrkanal (5) und den zweiten Abfuhrkanal (6), b. Steuerung des Verhältnisses der Flussraten in den Abfuhrkanälen (5, 6) durch Fördern oder Absaugen der kontinuierlichen Phase durch den zusätzlichen Kanal (9), mindestens bis zum Zeitpunkt, wenn der sich im ersten Abfuhrkanal (5) befindende Teil des Tropfens (1) von dem sich im zweiten Abfuhrkanal (6) befindenden Teil des Tropfens abreisst.

МИКРОЖИДКОСТНОЕ УСТРОЙСТВО ДЛЯ ИДЕНТИФИКАЦИИ, КОЛИЧЕСТВЕННОГО ОПРЕДЕЛЕНИЯ И АУТЕНТИФИКАЦИИ ЛАТЕНТНЫХ МАРКЕРОВ

Предложены устройства и способы для идентификации, аутентификации и количественного определения одного или нескольких скрытых маркеров, содержащихся в материале. Устройство содержит микрожидкостную ячейку, систему переноса жидкости и систему детектора и представляет собой интегральный узел, обеспечивающий автоматизированный способ идентификации in line одного или нескольких материалов, содержащих по меньшей мере один латентный маркер, который может преобразовываться в активную форму. Микрожидкостная ячейка предназначена для приема материала, содержащего латентный маркер, и имеет по меньшей мере один вход для приема одной или нескольких жидкостей и один или несколько выходов, через которые жидкость выходит. Система переноса жидкости в рабочем состоянии соединена с микрожидкостной ячейкой и доставляет жидкости в микрожидкостную ячейку. Система детектора, которая может содержать источник и сенсор, располагается после выходов для детектирования активной формы маркера. С помощью устройства ряд ...

METHODS AND APPARATUS FOR MANUFACTURING A MICROFLUIDIC ARRANGEMENT, AND A MICROFLUIDIC ARRANGEMENT

Droplet PCR amplification detection device based on microfluidic chip

Chemical analysis device

System and method for splitting liquid droplet

Biosensor for detecting target component in sample

RECLOSABLE FASTENER OF DETERMINING PARAMETERS OF A PHYSICAL AND/OR CHEMICAL, AND USE THEREOF

SORTING EQUIPMENT FOR PARTICLES IN A FLUID SAMPLE

METHOD FOR DETECTING ELEMENTS DISPERSED FLOWS THROUGH A CAPILLARY TUBE, AND APPARATUS THEREFOR

METHOD AND APPARATUS FOR USE IN A FLUID FLOW

Biological micro-reactor suitable for high throughput screening, forms alternating mobile liquid reactors and liquid separators in parallel capillaries

L'invention concerne un dispositif microfluidique d'injection de trains de chambres mobiles de réaction (102, 103) avec séparateurs (101) non miscibles dans des micro-canaux (21 à 26), comprenant : - des moyens d'injection (10) pour injecter en alternance et en parallèle dans les micro-canaux du liquide pour former les chambres mobiles de réaction et du liquide pour former les séparateurs, - des moyens de contrôle de la progression de l'un des deux liquides, disposés pour intervenir sur une zone (31) de chaque micro-canal délimitant un volume a injecter de ce liquide, les moyens de contrôle étant aptes à provoquer l'arrêt ou le ralentissement de la progression de ce liquide sur la zone de chaque micro-canal en exerçant une action basée sur une propriété physico-chimique de ce liquide, cette action n'ayant pas d'effet direct sur l'autre liquide.

METHOD AND SYSTEM FOR CHARACTERIZING A FLUID

L'invention concerne un procédé pour caractériser un fluide, mis en œuvre dans un système de traitement (UC) et à l'aide d'une architecture de mesure. L'architecture de mesure comporte un dispositif microfluidique du type à génération de gouttes d'une phase dispersée dans une phase continue, qui comporte un canal de phase dispersée destiné à recevoir un échantillon du fluide à caractériser formant la phase dispersée et un canal de phase continue destiné à recevoir un fluide formant la phase continue et débouchant dans le canal de phase dispersée en un point de jonction. Le procédé consiste à déterminer la viscosité dynamique (ηd) de la phase dispersée à partir de la variation de pression de la phase dispersée entre la pression à l'entrée du canal de phase dispersée et la pression (Pmffd) au point de jonction déterminée à partir d'un modèle et du débit de phase dispersée.

PROCESS OF FOLLOW-UP OF REACTION AND REACTIONAL SYSTEM FOR SA IMPLEMENTED

L'invention propose un procédé de suivi de réaction et un système réactionnel économiques, peu encombrants, faciles à mettre en œuvre, et permettant de contrôler totalement le milieu de réactionnel tout au long de l'expérimentation. A cette fin, l'invention a pour objet un système réactionnel, notamment de cultures de micro-organismes, comprenant : • au moins un réservoir (M1) de milieu réactionnel (1, 1') relié de manière fluidique à un tube d'injection (10) ; • au moins un réservoir (F1) d'un fluide porteur (11) non miscible avec le milieu réactionnel (1, 1'), relié de manière fluidique à un tube de réaction (20), • le tube d'injection (10) étant monté débouchant dans le tube de réaction (20) de sorte que des gouttes individuelles (30) de milieu réactionnel puissent être injectées dans le tube de réaction (20), au sein du fluide porteur (11) non miscible, de manière à former un train de réacteurs, • au moins un détecteur de suivi de réaction, • un moyen de référencement des réacteurs, ...

PROCESS Of EVAPORATION CONTROLEE Of a LIQUID DROP IN a DEVICE MICROFLUIDIQUE.

L'invention porte sur un procédé d'évaporation contrôlée d'une goutte (2) liquide dans un dispositif microfluidique (1) de type fermé ou confiné, permettant l'augmentation de la concentration en analytes éventuellement présents dans la goutte (2) Selon l'invention, on amène une goutte (2) et/ou une bulle (4) au contact l'une de l'autre, ledit contact permettant l'évaporation de la goutte (2) dans la bulle (4).

METHOD FOR TREATING DROPS IN A MICROFLUID CIRCUIT

Droplet dispensing system

Digital microfluidic devices including dual substrates with thin-film transistors and capacitive sensing

An active matrix electrowetting on dielectric (AM-EWoD) device including dual substrates with thin-film transistors (TFT) and capacitive sensing. As depicted herein the bottom substrate includes a first plurality of electrodes to propel various droplets through a microfluidic region, while the top substrate includes a second plurality of electrodes that are configured to interrogate the droplets with capacitive sensing. In some embodiments, the top substrate has zones of high-resolution sensing and zones of low-resolution sensing.

MICROFLUIDIC DEVICES

The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.

A LIQUID BRIDGE AND SYSTEM

A bridge (30) comprises a first inlet port (31) at the end of a capillary, a narrower second inlet port (32) which is an end of a capillary, an outlet port (33) which is an end of a capillary, and a chamber (34) for silicone oil. The oil is density-matched with the reactor droplets such that a neutrally buoyant environment is created within the chamber (34). The oil within the chamber is continuously replenished by the oil separating the reactor droplets. This causes the droplets to assume a stable capillary- suspended spherical form upon entering the chamber (34). The spherical shape grows until large enough to span the gap between the ports, forming an axisymmetric liquid bridge. The introduction of a second droplet from the second inlet port (32) causes the formation of an unstable funicular bridge that quickly ruptures from the, finer, second inlet port (32), and the droplets combine at the liquid bridge (30). In another embodiment, a droplet (55) segments into smaller droplets which ...

A MICROFLUIDIC DROPLET QUEUING NETWORK

A multi-port liquid bridge (1) adds aqueous phase droplets (10) in an enveloping oil phase carrier liquid (11) to a draft channel (4, 6). A chamber (3) links four ports, and it is permanently full of oil (11) when in use. Oil phase is fed in a draft flow from an inlet port (4) and exits through a draft exit port (6) and a compensating flow port (7). The oil carrier and the sample droplets (3) ("aqueous phase") flow through the inlet port (5) with an equivalent fluid flow subtracted through the compensating port (7). The ports of the bridge (1) are formed by the ends of capillaries held in position in plastics housings. The phases are density matched to create an environment where gravitational forces are negligible. This results in droplets (10) adopting spherical forms when suspended from capillary tube tips. Furthermore, the equality of mass flow is equal to the equality of volume flow. The phase of the inlet flow (from the droplet inlet port (5) and the draft inlet port (4) is used to ...

MICROFLUIDIC DEVICE FOR PERFORMING OPERATIONS ON MICRODROPLETS

The invention provides a microfluidic device and method for performing operations on droplets. The device comprises a microfluidic channel with a side-channel and a barrier. A liquid droplet is introduced in the device and its movement is influenced by the position and dimension of the barrier and the side-channel. The use is comprises metering, merging or trapping small quantities of liquid. The invention extends to microfluidic systems comprising one or more of the microfluidic devices.

METHOD AND APPARATUS FOR THE DISCRETIZATION AND MANIPULATION OF SAMPLE VOLUMES

Embodiments of the present invention relate to methods and apparatuses for the discretization and manipulation of sample volumes that is simple, robust, and versatile. It is a fluidic device that partitions a sample by exploiting the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the formed droplet and/or discretized volume. These compartmentalized volumes allow for isolation of samples and partitioning into a localized array that can subsequently be manipulated and analyzed. The isolation of the discretized volumes along with the device's inherent portability render our invention versatile for use in many areas, including but not limited to PCR, digital PCR, biological assays for diagnostics and prognostics, cancer diagnosis and prognosis, high throughput screening, single molecule and single cell reactions or assays, the study crystallization and other statistical processes, protein crystallization, drug screening, environmental testing ...

METHOD FOR TREATING A POPULATION OF OBJECTS SUSPENDED IN FLUID DROPLETS COMPRISING A TARGET AND RESIDUAL PARTICLE, AND DEVICE FOR CARRYING OUT SAID METHOD

The present application discloses a method for treating a population of in particular biological objects that are different from each other and suspended in fluid droplets comprising a target and residual particle population, using at least one substrate and one digital microfluidic circuit or controller allowing digital microfluidic droplet displacement, wherein fluid droplets of suitable composition are generated from target and residual particles, and each fluid droplet is analyzed in a first analysis position for the presence of at least one target or residual particle, wherein fluid droplets without target particles are subsequently remove from the substrate by means of a residual particle sump and fluid droplets having at least one target particle or a prescribed minimum number of target particles are fed to a next treatment stage by means of the substrate.

APPARATUS AND METHODS FOR SAMPLE ANALYSIS

The present invention is directed to apparatus and methods for rapid, automated, microscale sample analysis using pressure differentials. The invention includes an apparatus having intersecting channels for introduction of a sample and separation of that sample into its components. The sample introduction and separation channels preferably are etched in a microfabricated device, such as a microchip, to form a junction. Pressure gradients are applied to the channels to form a sample plug in the separation channel. The separation channel may have disposed within it a medium for separation of the components suspected to be contained in the sample. For example, with the proper medium, a voltage gradient may be applied along the separation channel to separate the components of the sample electrophoretically. The apparatus also may include means for detecting the components of the sample subsequent to separation.

System and method for automated generation and handling of liquid mixtures

The invention relates to a system ( 1 ) for supplying a microfluidic subsystem with liquids, comprising a first valve ( 14, 29, 46 ) and a first fluidic duct ( 10, 25, 28 ), for connecting said first valve ( 14, 29, 46 ) with said microfluidic subsystem and supplying a first liquid, and a second fluidic duct ( 11 ), for connecting with said microfluidic subsystem and supplying a second liquid characterized in that said first valve ( 14, 29, 46 ) is suitable for closing with time resolution not worse than 100 msec, and parameters of said first fluidic duct ( 10, 15, 28 ) are chosen such that the value of X 1 [Pa −1 ], defined as: X 1 [Pa −1 ]=(0.5×10 −9+1/ E 1 )(α R1 L 1 2 /A 1 ) is lower than 10 4 Pa −1 , where E 1 is the Young modulus of the material, of which said first fluidic duct ( 10, 25, 28 ) is made, L 1 is the length of the said first fluidic duct ( 10, 25, 28 ), A 1 is the surface area of the lumen of the said first fluidic duct ( 10, 25, 28 ) and α R1 is a constant characterizing the geometry of the said first fluidic duct ( 10, 25, 28 ) in an equation for the hydraulic resistance R 1 of the said first fluidic duct: R 1 =α R1 ( L 1 μ/A 1 2 ) with μ denoting the dynamic viscosity coefficient of the fluid filling the said first fluidic duct ( 10, 25, 28 ) in the measurement of R 1 . The invention relates also to a method for producing microdroplets on demand in such a system.

Thermal Microvalves

The movement and mixing of microdroplets through microchannels is described employing silicon-based microscale devices, comprising microdroplet transport channels, reaction regions, electrophoresis modules, and radiation detectors. The discrete droplets are differentially heated and propelled through etched channels. Electronic components are fabricated on the same substrate material, allowing sensors and controlling circuitry to be incorporated in the same device.

Variable Volume Mixing and Automatic Fluid Management for Programmable Microfluids

A microfluidic arrangement including a fluid channel configured to receive a first fluid from a first inlet and a second fluid from a second inlet, and a mixer connected to the fluid channel, the mixer including a mixer channel configured to receive a volume of the first fluid and a volume of the second fluid from the fluid channel, the mixer channel defining a mixer capacity, wherein the mixer is (i) configured to mix the volume of the first fluid and the volume of the second fluid in order to provide a mixture of the first fluid and the second fluid when the combined volume of the first fluid and the second fluid is less than the mixer capacity, and (ii) further configured to mix the volume of the first fluid and the volume of the second fluid in order to provide a mixture of the first fluid and the second fluid when the combined volume of the first fluid and the second fluid is equal to the mixer capacity.

Control of operation conditions within fluidic systems

The invention provides methods of controlling environmental conditions within a fluidic system, where such environmental conditions can affect the operation of the system in its desired function, and fluidic channels, devices, and systems that are used in practicing these methods. Such methods are generally directed to environmental control fluids, the movement of such fluids through these systems, and the interaction of these fluids with other components of the system, e.g., other fluids or solid components of the system.

Device and method for particle complex handling

An embodiment of the invention relates to a device for detecting an analyte in a sample. The device comprises a fluidic network and an integrated circuitry component. The fluidic network comprises a sample zone, a cleaning zone and a detection zone. The fluidic network contains a magnetic particle and/or a signal particle. A sample containing an analyte is introduced, and the analyte interacts with the magnetic particle and/or the signal particle through affinity agents. A microcoil array or a mechanically movable permanent magnet is functionally coupled to the fluidic network, which are activatable to generate a magnetic field within a portion of the fluidic network, and move the magnetic particle from the sample zone to the detection zone. A detection element is present which detects optical or electrical signals from the signal particle, thus indicating the presence of the analyte.

System and Methods for Making and Processing Emulsions

An automated on-touch template bead preparation system is provided and includes a membrane-based emulsion generation subsystems, an emulsion PCR (ePCR) thermocycling plate and subsystem, and a continuous centrifugation emulsion breaking and templated bead collection subsystem. The emulsion generation subsystem provides uniformity in the preparation of an inverse emulsion and may be used to create large or small volume inverse emulsions rapidly and reproducibly. An emulsion-generating device is provided that can supply a continuous stream of an inverse emulsion to a thermocycling subsystem, in automated fashion. The ePCR subsystem can continuously thermocycle an inverse emulsion passed therethrough and includes static temperature zones and a consumable thermocycling plate. The continuous centrifugation subsystem can continuously break a thermally cycled inverse emulsion and collect template beads formed in the aqueous microreactor droplets of the inverse emulsion.

Isolation and cultivation of stem/progenitor cells from the amniotic membrane of umbilical cord and uses of cells differentiated therefrom

The present invention relates to the generation of a mucin-producing cell using stem/progenitor cells obtained from the amniotic membrane of umbilical cord and therapeutic uses of such mucin-producing cells.

Moving microdroplets in a microfluidic device

The present invention relates to a system and method for moving samples, such as fluid, within a microfluidic system using a plurality of gas actuators for applying pressure at different locations within the microfluidic. The system includes a substrate which forms a fluid network through which fluid flows, and a plurality of gas actuators integral with the substrate. One such gas actuator is coupled to the network at a first location for providing gas pressure to move a microfluidic sample within the network. Another gas actuator is coupled to the network at a second location for providing gas pressure to further move at least a portion of the microfluidic sample within the network. A valve is coupled to the microfluidic network so that, when the valve is closed, it substantially isolates the second gas actuator from the first gas actuator.

Device for Forming Drops in a Microfluidic Circuit

The invention relates to a device ( 1 ) for forming droplets in a microfluidic circuit, the device comprising a chamber ( 3 ) containing a first fluid and defined by two opposite walls ( 10, 11 ) that diverge relative to each other in at least one given direction, and a microchannel ( 8 ) containing a second fluid and leading into a zone of said chamber ( 3 ) that is upstream relative to the given direction, the outlet of the microchannel ( 8 ) into the chamber ( 3 ) constituting an enlargement in the flow section for the second fluid, and the enlargement giving rise to droplets ( 14 ) of the second fluid forming within the first fluid.

HIGH THROUGHPUT AND VOLUMETRIC ERROR RESILIENT DILUTION WITH DIGITAL MICROFLUIDIC BASED LAB-ON-A-CHIP

Systems and methods are provided for producing fluids with desired concentration factors from the given supply of any two concentration factors, one greater than the target CF and one less than the target CF, of the same fluid. According to one embodiment, a method is provided that stores intermediate waste droplets from a sequence of mix and split steps and repeats certain steps of the sequence using the stored intermediate waste droplets. Such a method may produce additional target CF droplets faster than repeating the entire sequence. In another embodiment, a method of volumetric error resilient target CF droplet generation has been described, and includes reusing the stored intermediate waste droplets and involves a collection of capacitive sensing circuits associated with some electrode platforms. 1. A method for producing a number (M) of diluted fluid droplets having a target concentration factor (CF) on a digital microfluidic (DMF) biochip , the biochip comprising a plurality of DMF-based electrode platforms arranged to carry out a sequence of mixing and splitting steps , the method comprising:determining a target CF for a end resultant fluid mixture;expressing the target CF as an N-bit binary fraction; mixing together two input sample fluid droplets having different CFs to produce a first resultant mixture having a given resultant CF;', 'splitting the first resultant mixture into a first resultant droplet and a second resultant droplet;', wherein when the N-bit binary fraction is a first binary value indicating that the resultant mixture produced in the given mixing step has a resultant CF larger than the target CF, mixing the first resultant droplet with a droplet of a first one of two input sample fluids in the next mixing step of the sequence of mixing steps;', 'wherein when the N-bit binary fraction is a second binary value indicating that the resultant mixture produced in the given mixing step has a resultant CF smaller than the target CF, mixing the ...

Microfluidic device, microfluidic dosing system and method for microfluidic flow measurement and dosing

A microfluidic device for detecting a flow parameter, includes a channel configured within a base body, the channel including a first inlet for feeding a first fluid and a second inlet for feeding a second fluid so as to form a fluid stream having the first and second fluids within the channel, and further including an output for providing the fluid stream on the output side, a first feeder including a micropump associated with the first inlet for selectively feeding the first fluid to the channel, a second feeder associated with the second inlet for feeding the second fluid to the channel; and a detector for detecting, on the basis of a different physical property of the first fluid and the second fluid within the channel, a measurement value dependent on a current flow parameter of the first or second fluid.

Microfluidic devices

The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.

Microfluidic Device for the Manipulation of Particles

A microfluidic device for isolating particles of at least one given type of a sample; the device is designed to be connected to an apparatus through a plurality of electrical connectors and comprises a system of microfluidic channels and a flash memory, which contains information on the structure (arrangement and geometry of the various components) of the system of microfluidic channels, a map of non-functioning parts of the device, the maximum number of uses and the maximum time of use of the device; the memory has portions allocated for storing the number of times and the time of use of the device.

Paired Laser and Electrokinetic Separation, Manipulation, and Analysis Device

The combined value of integrating optical forces and electrokinetics allows for the pooled separation vectors of each to be applied, providing for separation based on combinations of features such as size, shape, refractive index, charge, charge distribution, charge mobility, permittivity, and deformability. The interplay of these separation vectors allow for the selective manipulation of analytes with a finer degree of variation. Embodiments include methods of method of separating particles in a microfluidic channel using a device comprising a microfluidic channel, a source of laser light focused by an optic into the microfluidic channel, and a source of electrical field operationally connected to the microfluidic channel via electrodes so that the laser light and the electrical field to act jointly on the particles in the microfluidic channel. Other devices and methods are disclosed. 1. A device comprising:a microfluidic channel comprising an inlet and a plurality of exits, anda source of laser light focused by an optic to cross the microfluidic channel at a critical angle matched to velocity of flow in the microfluidic channel so as to produce an optical force on the particles while maximizing residence time in the laser light of selected particles, thus separating the particles into the plurality of exits,wherein the laser light is operable to apply forces to particles flowing through the microfluidic channel, thereby separating the particles into the plurality of exits.2. The device of claim 1 , further comprising electrodes configured to produce electroosmotic flow in the microfluidic channel.3. A device comprising:a microfluidic channel configured to supply a linear or non-linear dielectrophoretic (DEP) field to an interior of the channel via a (1) DEP electrode system or (2) insulator DEP system having shaped wall geometry or obstruction geometry, anda source of laser light focused by an optic into the microfluidic channel,wherein the laser light and DEP ...

Microdroplet/bubble-producing device

The invention provides a microdroplet- or bubble-producing device that does not require separate through-holes for different liquid droplet/air bubble-producing flow channels. The droplet-producing flow channels are configured in a three-dimensional manner unlike in a conventional device where they are configured in a two-dimensional plane, and therefore the flow channels can be provided in a more high-density configuration than the prior art. In the microdroplet/bubble-producing device comprising slit(s) and the row of the plurality of microflow channels, the slit(s) is/are a continuous phase supply slit, a dispersion phase supply slit and a discharge slit, the plurality of microflow channels are configured so that the ends of the slit(s) and the two supply ports on both sides or the supply port and discharge port on either side are mutually connected, and at the sites of connection between the microflow channels and the slit(s), the dispersion phase undergoes shear with the continuous phase flow as the driving force, producing droplets or air bubbles of the dispersion phase, which are recovered from the discharge port.

APPARATUS AND METHODS FOR MAKING VESICLES

A microfluidic device includes a substrate and a microfluidic channel embedded in the substrate. The microfluidic channel includes a plurality of fluid inlets, at least one waste outlet, at least one vesicle outlet, a flow junction joining the at least one vesicle outlet and the at least one waste outlet in fluid communication, the flow junction having a fluid flow path that is orthogonal to the plane of the substrate, and at least one membrane between the at least one vesicle outlet and the at least one waste outlet configured to intercept a portion of the fluid flow path. 1. A microfluidic device for generating vesicles comprising:a substrate; and a plurality of fluid inlets;', 'at least one waste outlet;', 'at least one vesicle outlet;, 'a microfluidic channel embedded in the substrate, the microfluidic channel includingto a flow junction joining the at least one vesicle outlet and the at least one waste outlet in fluid communication, the flow junction having a fluid flow path that is orthogonal to the plane of the substrate; andat least one membrane between the at least one vesicle outlet and the at least one waste outlet configured to intercept a portion of the fluid flow path.2. The microfluidic device of claim 1 , wherein the substrate is comprised of a polymer.3. The microfluidic device of claim 2 , wherein the substrate is comprised of polydimethylsiloxane.4. The microfluidic device of claim 1 , wherein the plurality of fluid inlets comprises a fluid inlet for a liquid and a fluid inlet for an emulsion.5. The microfluidic device of claim 4 , wherein the emulsion comprises a plurality of water-in-oil emulsion droplets.6. The microfluidic device of further comprising at least one emulsion droplet generator in fluid communication with the emulsion inlet.7. The microfluidic device of claim 1 , wherein the at least one membrane is a nanoporous membrane.8. The microfluidic device of claim 7 , wherein the nanoporous membrane is selected from the group consisting ...

METHODS AND DEVICES FOR SAMPLE ANALYSIS

Methods for detecting target analytes utilizing an array of wells are advantageous for detection of low concentrations of target analytes. Use of an array of wells requires sealing of the wells. The methods provided herein utilize digital microfluidics to seal wells of an array with a fluid that is immiscible with the aqueous liquid present in the wells to prevent evaporation and contamination of the aqueous fluid during analysis of signals from the wells. The disclosed method include generating a biphasic droplet composed of the immiscible fluid and an aqueous fluid. The immiscible fluid present in the biphasic droplet is moved over the array of wells to seal the wells by electrically actuating the aqueous fluid present in the biphasic droplet which in turn pulls the immiscible fluid. 121.-. (canceled)22. An automated or semi-automated method for sealing an array of wells having an aqueous fluid disposed therein by disposing a layer of immiscible fluid over the array of wells , using a processor to run a program to instruct a device to perform the steps comprising:actuating movement of a droplet of aqueous fluid towards a droplet of immiscible fluid by using digital microfluidics (DMF) electrodes such that the two droplets contact each other thereby forming a biphasic droplet comprising an aqueous phase formed by the droplet of aqueous fluid and a non-aqueous phase formed by the droplet of immiscible fluid;actuating movement of the aqueous phase of the biphasic droplet by using DMF electrodes thereby pulling the non-aqueous phase present in the biphasic droplet towards an array of wells;contacting the array of wells with the aqueous phase of the biphasic droplet by actuating movement of the aqueous phase of the biphasic droplet over the array of wells by using DMF electrodes; andcontacting the array of wells with the non-aqueous phase of the biphasic droplet by actuating movement of the aqueous phase of the biphasic droplet to a position adjacent the array of wells ...

Droplet digital pcr chip

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

ELECTRO-KINETIC DEVICE FOR SPECIES EXCHANGE

A scanning micro-fluid device for an exchange of species with a surface and with an intermediate immersion liquid is disclosed. The device comprises a first and a second micro-channel comprising a fluid. The first micro-channel comprises a first aperture and the second micro-channel comprises a second aperture. They have a distance to each other in an apex area in proximity of the surface of a substrate. The surface, the apex area is immersed with the intermediate immersion liquid. The device also comprises a first electrode reaching into the fluid on the first micro-channel and a second electrode reaching into the fluid on the second micro-channel, and an apex electrode. Different voltage levels are applicable to the first, the second and the apex electrode such that species are interacting at surface of the substrate. 1. A scanning micro-fluid device for an exchange of species with a surface and an intermediate immersion liquid , said device comprising:a first micro-channel comprising a fluid;a second micro-channel comprising said fluid;wherein said first micro-channel comprises at its first end a first aperture and wherein said second micro-channel comprises at its first end a second aperture, said first and said second aperture having a distance to each other in an apex area in a proximity of said surface of a substrate;wherein said surface, said apex area comprising said first aperture of said first micro-channel and said second aperture of said second micro-channel is immersed with said intermediate immersion liquid;a first electrode reaching into said fluid in said first micro-channel;a second electrode reaching into said fluid in said second micro-channel; andan apex electrode reaching into said apex area;wherein different voltage levels are applicable to said first, said second and said apex electrode;wherein the apex electrode reaches into the apex area such that species are exchangeable between said fluid of said first and said second micro-channel and ...

ASSAYS AND OTHER REACTIONS INVOLVING DROPLETS

The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention. 120-. (canceled)21. A composition , comprising:a collection of hardened droplets comprising a library of distinguishable nucleic acid species, wherein a hardened droplet of said collection of hardened droplets comprises a nucleic acid species distinguishable from other nucleic acid species in other hardened droplets of said collection of hardened droplets, and wherein said collection of hardened droplets is contained within a plurality of aqueous droplets in a water-in-oil emulsion.22. The composition of claim 21 , wherein said collection of hardened droplets is a collection of gel particles23. The composition of claim 22 , wherein said collection of gel particles comprises a polyacrylamide polymer.24. The composition of claim 23 , wherein said polyacrylamide polymer comprises a ...

SYSTEM AND METHOD FOR SYNTHESIS OF DNA PARTICLES AND USE THEREOF

Disclosed is a system and method for production of DNA particles and use thereof. The DNA particles can be produced by amplification of nucleic acid molecule(s). Alternatively, DNA particles can be prepared by condensing multiple DNA molecules. The DNA condensation into a particle is mainly triggered by pyrophosphate and positively charged cations (e.g. magnesium). DNA particles can be applied for numerous biological applications but not limited to directed evolution, proteomics, drug delivery and imaging. DNA particles can be used to synthesize proteins using in vitro transcription/translation reaction. 139-. (canceled)40. A method of generating a nucleic acid particle from a single nucleic acid template by means of enzymatic amplification.41. The method of claim 40 , wherein a nucleic acid particle comprise nucleic acid(s) claim 40 , pyrophosphate(s) claim 40 , metal ions and/or other ingredients.42. The method of claim 41 , wherein the metal ions are magnesium.43. The method of claim 41 , wherein the metal ions are different than magnesium.44. The method of claim 41 , wherein “other ingredients” further comprise chemical reagents such as polyamines claim 41 , inorganic cations claim 41 , positively charged molecules claim 41 , proteins claim 41 , lipids claim 41 , carbohydrates and/or agents.45. The method of claim 40 , wherein a nucleic acid is DNA claim 40 , RNA claim 40 , or a modified nucleic acid such as locked nucleic acid (LNA) claim 40 , peptide nucleic acid claim 40 , etc.46. The method of claim 40 , wherein the particle contains a single nucleic acid molecule.47. The method of claim 40 , wherein the particle comprises of a plurality of nucleic acid molecules.48. The method of claim 40 , wherein individual nucleic acid molecules within the particle have different nucleic acid sequences.49. The method of claim 40 , wherein all nucleic acid molecules within the particle have substantially the same nucleic acid sequence.50. The method of claim 40 , wherein ...

SYSTEM AND METHOD FOR DROPLET DETECTION

Systems and methods for detection of a signal from droplets of an emulsion. An exemplary system may comprise a fluid transporter having a tube with an open end for aspirating droplets, a singulator to arrange the droplets in single file and to space the single-file droplets from one another, and a detection channel in optical communication with a detector configured to detect a signal from droplets. In some embodiments, the singulator may have a channel junction at which a stream of droplets in single file is combined with a stream of spacing fluid, and a tapered spacing channel extending downstream from the channel junction toward the detection channel. In some embodiments, the fluid transporter may suck droplet-containing fluid and spacing fluid through the detection channel from respective sources. In some embodiments, droplets may be subjected to a disaggregation routine before they are passed through the detection channel. 1. A method of droplet detection , the method comprising:generating a single-file stream of droplets in carrier liquid;combining at least one stream of spacing fluid with the single-file stream of droplets in carrier liquid;directing the combined streams to a detection channel using a spacing channel that tapers toward the detection channel, wherein a distance between adjacent droplets is increased as such droplets travel along the spacing channel toward the detection channel; anddetecting a signal from droplets passing through the detection channel.2. The method of claim 1 , wherein the step of generating includes a step of passing droplets through an alignment region of a sample inlet channel claim 1 , wherein a taper of the alignment region arranges droplets in single file before reaching a channel junction claim 1 , and wherein the step of combining includes a step of combining at least one stream of spacing fluid with the single-file stream of droplets in carrier liquid at the channel junction.3. The method of claim 2 , wherein the step ...

PARTITION-BASED METHOD OF ANALYSIS

Methods of partition-based analysis. In an exemplary method, a device having a port fluidically connected to a chamber may be selected. A sample-containing fluid may be placed into the port. The sample-containing fluid may be moved from the port to the chamber. Partitions of the sample-containing fluid may be formed. A monolayer of the partitions in the chamber may be created. At least a portion of the monolayer may be imaged. 1. A method of analysis , the method comprising:selecting a device having a port fluidically connected to a chamber;placing a sample-containing fluid into the port;moving the sample-containing fluid from the port to the chamber;forming partitions of the sample-containing fluid;creating a monolayer of the partitions in the chamber; andimaging at least a portion of the monolayer.2. The method of claim 1 , wherein placing a sample-containing fluid includes placing the sample-containing fluid as a continuous phase into a well of the device.3. The method of claim 1 , wherein forming partitions includes forming aqueous droplets that are separated from one another by an immiscible carrier liquid.4. The method of claim 1 , wherein forming partitions includes forming partitions each having a dimension corresponding to a height of the chamber.5. The method of claim 1 , wherein moving the sample-containing fluid includes creating a pressure differential that drives the sample-containing fluid to the chamber.6. The method of claim 5 , wherein creating a pressure differential includes applying positive gas pressure or negative gas pressure to a port of the device.7. The method of claim 1 , further comprising thermally cycling the monolayer of the partitions to promote nucleic acid amplification in a subset of the partitions of the monolayer.8. The method of claim 1 , wherein imaging at least a portion of the monolayer includes detecting fluorescence from the monolayer.9. The method of claim 1 , wherein imaging at least a portion of the monolayer includes ...

A MICRO-DROPLET ARRAY FOR MULTIPLE SCREENING OF A SAMPLE

The invention provides an apparatus for formation of a micro-droplet array of a desired fluid. The apparatus comprises of a first plate configured for delivering and/or extracting fluids, a second plate aligned to the first plate and configured for preparing the fluid and a third plate removably aligned to the second plate and is configured for forming a micro-droplet array of the prepared fluid. The second plate has a first microfluidic circuit present on the top surface and is operatively connected to a second microfluidic circuit on the bottom surface. The microfluidic channel on the bottom surface of the second plate is provided with circular slots and is configured for trapping a single cellular entity in the wells. 1. An apparatus for formation of a micro-droplet array of a desired fluid , the apparatus comprising ,a first plate configured for delivering and/or extracting the fluid;a second plate aligned with the first plate wherein the second plate is configured for preparing the fluid; anda third plate removably aligned with the second plate wherein the third plate is configured for forming a micro-droplet array of the prepared fluid.2. The apparatus of claim 1 , wherein the first plate has at least two ports provided wherein the ports are spatially distributed over the surface area of the first plate.3. The apparatus of claim 1 , wherein the first plate has at least two input ports for delivering at least two distinct fluids.4. The apparatus of claim 1 , wherein the alignment of the second plate to the first plate is either reversible or irreversible.5. The apparatus of claim 1 , wherein the second plate has a top surface having a first microfluidic circuit and a bottom surface having a second microfluidic circuit.6. The apparatus of claim 5 , wherein the first microfluidic circuit is operatively connected to the second microfluidic circuit on the bottom surface of the second plate.7. The apparatus of claim 5 , wherein the first microfluidic circuit ...

MANIPULATION OF FLUIDS AND REACTIONS IN MICROFLUIDIC SYSTEMS

Microfluidic structures and methods for manipulating fluids and reactions are provided. Such structures and methods may involve positioning fluid samples, e.g., in the form of droplets, in a carrier fluid (e.g., an oil, which may be immiscible with the fluid sample) in predetermined regions in a microfluidic network. In some embodiments, positioning of the droplets can take place in the order in which they are introduced into the microfluidic network (e.g., sequentially) without significant physical contact between the droplets. Because of the little or no contact between the droplets, there may be little or no coalescence between the droplets. Accordingly, in some such embodiments, surfactants are not required in either the fluid sample or the carrier fluid to prevent coalescence of the droplets. Structures and methods described herein also enable droplets to be removed sequentially from the predetermined regions. 1. A method of coalescing droplets , the method comprising:providing a microfluidic network comprising a plurality of separate regions and a microfluidic channel in fluid communication with the plurality of separate regions;flowing an oil in the microfluidic channel;flowing a plurality of first aqueous droplets in the microfluidic channel;positioning at least one of the first aqueous droplets into a separate region;flowing a plurality of second aqueous droplets in the microfluidic channel; andcoalescing at least one of the plurality of second aqueous droplets with the positioned first aqueous droplet to form a coalesced aqueous droplet.2. The method of claim 1 , wherein each of the plurality of separate regions comprises a microwell.3. The method of claim 2 , wherein each microwell comprises a constricted fluidic path that exits the microwell.4. The method of claim 1 , wherein the oil does not comprise a surfactant.5. The method of claim 1 , wherein positioning at least one first aqueous droplet is independent of a flow rate of the oil in the microfluidic ...

Methods and Systems for Enhanced Microfluidic Processing

Methods and systems are provided for a microfluidic cartridge including a high performance actuator useful for analyte detection, labeling and analysis. Microfluidic processing systems are to carry out chemical or biochemical reactions, or sequences of reactions, with small volumes (typically between 1 microliter and 10 milliliters) of reactants and products. A microfluidic processing system can comprise a network of tubes interfaced with discrete components such as valves and sensors, or an integrated device made of plastic, glass, metal, or other materials, or a combination of materials, with components such as valves and sensors built into the device and connected by flow passageways formed in the material.

FLUIDIC DEVICES, SYSTEMS, AND METHODS FOR ENCAPSULATING AND PARTITIONING REAGENTS, AND APPLICATIONS OF SAME

The disclosure provides devices, systems and methods for the generation of encapsulated reagents and the partitioning of encapsulated reagents for use in subsequent analyses and/or processing, such as in the field of biological analyses and characterization. 1. A microfluidic system , comprising:a microfluidic channel network comprising at least first, second and third channels in fluid communication with a droplet generation junction;a first fluid source fluidly connected to the first channel and comprising a first fluid that comprises an aqueous fluid and a plurality of microcapsules;a second fluid source fluidly connected to the second channel and comprising a second fluid that is immiscible with the aqueous fluid; anda flow control system connected to the microfluidic channel network that (i) subjects the first fluid from the first fluid source to flow along the first channel in a manner such that microcapsules from the plurality of microcapsules flow at a flow frequency that is substantially regular in the first channel as determined by a number of microcapsules that flow past a given point in the first channel within a one second period of time, and (ii) subjects the second fluid from the second fluid source to flow along the second channel, such that the first fluid and the second fluid meet at the droplet generation junction to generate a plurality of droplets comprising microcapsules from the plurality of microcapsules, which plurality of droplets flow along the third channel.2. The microfluidic system of claim 1 , wherein the flow frequency has a coefficient of variation of less than 30%.3. The microfluidic system of claim 2 , wherein the flow frequency has a coefficient of variation of less than 20%.4. The microfluidic system of claim 3 , wherein the flow frequency has a coefficient of variation of less than 10%.5. The microfluidic system of claim 4 , wherein the flow frequency has a coefficient of variation of less than 5%.6. The microfluidic system of ...

IMPROVED DROPLET SEQUENCING APPARATUS AND METHOD

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

Sequencing of nucleic acids via barcoding in discrete entities

Microfluidic methods for barcoding nucleic acid target molecules to be analyzed, e.g., via nucleic acid sequencing techniques, are provided. Also provided are microfluidic, droplet-based methods of preparing nucleic acid barcodes for use in various barcoding applications. The methods described herein facilitate high-throughput sequencing of nucleic acid target molecules as well as single cell and single virus genomic, transcriptomic, and/or proteomic analysis/profiling. Systems and devices for practicing the subject methods are also provided.

Fluid handling device

The objective of the present invention is to provide a fluid handling device capable of easily isolating droplets. This objective is achieved by means of a fluid handling device which includes a first flow passage through the interior of which, when a fluid containing a droplet is delivered, the droplet can move, a first chamber which captures the droplet moving through the first flow passage, a second chamber into which the droplet captured by the first chamber can move, and a second flow passage providing communication between the first chamber and the second chamber, wherein the second flow passage is capable of selectively allowing the droplet to pass, or restricting passage of the droplet.

MANIPULATION OF FLUIDS AND REACTIONS IN MICROFLUIDIC SYSTEMS

Microfluidic structures and methods for manipulating fluids and reactions are provided. Such structures and methods may involve positioning fluid samples, e.g., in the form of droplets, in a carrier fluid (e.g., an oil, which may be immiscible with the fluid sample) in predetermined regions in a microfluidic network. In some embodiments, positioning of the droplets can take place in the order in which they are introduced into the microfluidic network (e.g., sequentially) without significant physical contact between the droplets. Because of the little or no contact between the droplets, there may be little or no coalescence between the droplets. Accordingly, in some such embodiments, surfactants are not required in either the fluid sample or the carrier fluid to prevent coalescence of the droplets. Structures and methods described herein also enable droplets to be removed sequentially from the predetermined regions. 110.-. (canceled)11. A method for forming and collecting a plurality of droplets , the method comprising:providing a microfluidic device comprising a substrate comprising a microfluidic channel operably coupled to a fluidic region;providing a solution of an aqueous fluid containing at least one target molecule and one or more reagents for conducting a reaction with the at least one target molecule;introducing the solution of aqueous fluid into the microchannel and flowing the solution of aqueous fluid through the microfluidic channel to form a plurality of droplets of the aqueous fluid based, at least in part, on the flow of the aqueous fluid and surface tension of the aqueous fluid relative to a carrier fluid;positioning each of the plurality of aqueous droplets in the fluidic region, wherein each of the plurality of droplets is substantially surrounded by the carrier fluid;maintaining separation of each of the plurality of aqueous droplets from one another within the carrier fluid; andconducting the reaction on one or more of the plurality of droplets ...

Microfluidic Bubble Logic Devices

Fluid-based no-moving part logic devices are constructed from complex sequences of micro- and nanofluidic channels, on-demand bubble/droplet modulators and generators for programming the devices, and micro- and nanofluidic droplet/bubble memory elements for storage and retrieval of biological or chemical elements. The input sequence of bubbles/droplets encodes information, with the output being another sequence of bubbles/droplets or on-chip chemical synthesis. For performing a set of reactions/tasks or process control, the modulators can be used to program the device by producing a precisely timed sequence of bubbles/droplets, resulting in a cascade of logic operations within the micro- or nanofluidic channel sequence, utilizing the generated droplets/bubbles as a control. The devices are based on the principle of minimum energy interfaces formed between the two fluid phases enclosed inside precise channel geometries. Various devices, including logic gates, non-volatile bistable memory, ring oscillators, bubble synchronizers, analysis chips, sample collectors, and printers have been designed.

ENHANCED CELL/BEAD ENCAPSULATION METHODS AND APPARATUSES

A method of encapsulating a solid sample in a droplet, the method including flowing a continuous phase through a first fluid channel at a first flow rate; flowing a dispersed phase through a second fluid channel at a second flow rate, the dispersed phase including a plurality of particles, cells or beads; trapping the plurality of particles, cells or beads in a mixing region that receives the dispersed phase and the continuous phase; and reducing the first flow rate to encapsulate the trapped particles, cells or beads in droplets of the dispersed phase generated when the dispersed phase and the continuous phase exit the mixing region through an orifice. 1. A method of encapsulating a solid sample in a droplet , the method comprising:flowing a continuous phase through a first fluid channel at a first flow rate;flowing a dispersed phase through a second fluid channel at a second flow rate, the dispersed phase comprising a plurality of particles, cells or beads;trapping the plurality of particles, cells or beads in a mixing region that receives the dispersed phase and the continuous phase; andreducing the first flow rate to encapsulate the trapped plurality of particles, cells or beads in droplets of the dispersed phase generated when the dispersed phase and the continuous phase exit the mixing region through an orifice.2. The method according to claim 1 , wherein a pump and/or a pressure regulator is used to:adjust a flow rate and/or a pressure of the continuous phase or the dispersed phase to trap the plurality of particles cells or beads of the dispersed phase in the mixing region in a first mode such that the plurality of particles, cells or beads of the dispersed phase are prevented from flowing through the orifice; andadjust a flow rate and/or a pressure of the continuous phase or the dispersed phase to allow the plurality of particles, cells or beads to flow through the orifice such that the plurality of particles, cells or beads are encapsulated in droplets of ...

MANIPULATION OF FLUIDS, FLUID COMPONENTS AND REACTIONS IN MICROFLUIDIC SYSTEMS

Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply. 120-. (canceled)21. A method for partitioning a fluid sample , the method comprising:providing a microfluidic device having a substrate comprising a plurality of microwells in fluid communication with an inlet;introducing a first fluid into the inlet of the microfluidic device, the first fluid comprising a biological sample and a plurality of beads, each bead comprising a reactive component for binding a target molecule from the biological sample to the bead; a subvolume of the first fluid,', 'a portion of the biological sample, and', 'more than one bead; and, 'introducing a second fluid immiscible with the first fluid into the microfluidic device and flowing the second fluid towards each of the plurality of microwells so as to form partitions of fluid in corresponding microwells, wherein at least some of the partitions include'}maintaining each partition of fluid in corresponding microwells for detection of contents in each partition of fluid.22. The method of claim 21 , wherein a subset of the partitions do not include any beads and a second subset of the partitions each include a single bead.23. The method of claim 21 , wherein each partition of fluid is separated from the others by the second fluid.24. The method of claim 21 , wherein the second fluid is an oil.25. The method of claim 21 , further ...

Droplet generating apparatus, system

A droplet generating apparatus includes: a micro-pipe having an outlet end and extending along a longitudinal axis; a liquid driving device; a connecting tube with its one end connected to the micro-pipe and the other end extending to the liquid driving device; a container positioned at least in-part below the micro-pipe and containing a second liquid; and a vibrating equipment connected to the micro-pipe and adapted to form a relative periodic vibration between the micro-pipe and the container in a perpendicular direction with respect to the longitudinal axis of the outlet end of the micro-pipe; wherein the vibrating equipment in coordination with the liquid driving device dispense the first liquid from the micro-pipe and form a plurality of droplets of the first liquid in the second liquid which is induced by a force of the second liquid imposed on the first liquid at the outlet end of the micro-pipe.

APPARATUS FOR INLINE TRACE ANALYSIS OF A LIQUID

The invention relates to an apparatus for the inline trace analysis of a liquid, preferably of an aqueous process solution, comprising: a housing (); a micro-channel () through which the liquid to be examined is allowed to flow and into which light of a light source () is coupled; a detector () for light emerging from the micro-channel (); and a user interface () for monitoring and/or operating the apparatus. The micro-channel (), the detector () and/or the user interface () are arranged in the housing () and/or are integrated into the housing (), and the housing () has a connection () for feeding the liquid in the micro-channel () and a connection () for power supply of the apparatus. 115-. (canceled)16. Apparatus for inline trace analysis of a fluid , said apparatus comprising:{'b': '1', 'a housing ();'}{'b': 2', '3, 'a microchannel (), through which the fluid to be analyzed is allowed to flow and into which light of a light source () is coupled;'}{'b': 4', '2, 'a detector () for light emerging from the microchannel (); and'}{'b': '5', 'a user interface () for at least one of monitoring or operating the apparatus,'} [{'b': 2', '4', '5', '1, 'at least one of the microchannel (), the detector () or the user interface () is at least one of arranged in or integrated into the housing (), and'}, {'b': 1', '6', '2', '7, 'the housing () has a port () for feeding the fluid into the microchannel () and a terminal () for supplying power to the apparatus.'}], 'wherein17. Apparatus claim 16 , as claimed in claim 16 , wherein either:{'b': 3', '1, 'the light source () is arranged in the housing (), or'}{'b': 1', '3', '2, 'the housing () has a port for feeding the light of the light source () into the microchannel ().'}18. Apparatus claim 16 , as claimed in claim 16 , wherein either:{'b': 1', '8', '2, 'the housing () has a port () for discharging the fluid from the microchannel (), or'}{'b': 2', '1, 'a collecting container for fluid emerging from the microchannel () is arranged ...

Bead incubation and washing on a droplet actuator

Methods are provided for separating magnetically responsive beads from a droplet in a droplet actuator. Droplet operations electrodes and a magnet are arranged in a droplet actuator to manipulate a bead-containing droplet and position it relative to a magnetic field region that attracts the magnetically responsive beads. The droplet operations electrodes are operated to control the droplet shape and transport it away from the magnetic field region to form a concentration of beads in the droplet. The continued transport of the droplet away from the magnetic field causes the concentration of beads to break away from the droplet to yield a small, concentrated bead-containing droplet immobilized by the magnet.

Wafer level sequencing flow cell fabrication

A method for forming sequencing flow cells can include providing a semiconductor wafer covered with a dielectric layer, and forming a patterned layer on the dielectric layer. The patterned layer has a differential surface that includes alternating first surface regions and second surface regions. The method can also include attaching a cover wafer to the semiconductor wafer to form a composite wafer structure including a plurality of flow cells. The composite wafer structure can then be singulated to form a plurality of dies. Each die forms a sequencing flow cell. The sequencing flow cell can include a flow channel between a portion of the patterned layer and a portion of the cover wafer, an inlet, and an outlet. Further, the method can include functionalizing the sequencing flow cell to create differential surfaces.

APPARATUS, SYSTEM, AND METHOD USING IMMISCIBLE-FLUID-DISCRETE-VOLUMES

Various embodiments of the teachings relate to a system or method for sample preparation or analysis in biochemical or molecular biology procedures. The sample preparation can involve small volume processed in discrete portions or segments or slugs, herein referred to as discrete volumes. A molecular biology procedure can be nucleic acid analysis. Nucleic acid analysis can be an integrated DNA amplification/DNA sequencing procedure. 1. A method comprising:contacting a stream of aqueous sample fluid flowing in a first conduit with a stream of non-aqueous spacing fluid that is immiscible with the aqueous sample fluid to form discrete volumes of the aqueous sample fluid separated from one another by the non-aqueous spacing fluid, wherein the aqueous sample fluid comprises target nucleic acid, and wherein a first plurality of the discrete volumes contains at least one molecule comprising the target nucleic acid and a second plurality of the discrete volumes contains no molecules comprising the target nucleic acid;amplifying the target nucleic acid in one or more of the first plurality of the discrete volumes to form an amplicon;in a second conduit, detecting a fluorescence signal from the amplicon in the one or more of the first plurality of the discrete volumes; andbased on the detecting, discriminating between the one or more of the first plurality of the discrete volumes and the second plurality of the discrete volumes.2. The method of claim 1 , wherein the contacting comprises continuously flowing at least one of the aqueous sample fluid and the non-aqueous spacing fluid into the first conduit.3. The method of claim 1 , further comprising separating the second plurality of the discrete volumes from the first plurality of the discrete volumes.4. The method of claim 1 , wherein less than 37% of the first plurality of the discrete volumes comprise a single molecule comprising the target nucleic acid.5. The method of claim 4 , wherein 1% or more of the first plurality ...

FLUIDIC DEVICES, SYSTEMS, AND METHODS FOR ENCAPSULATING AND PARTITIONING REAGENTS, AND APPLICATIONS OF SAME

The disclosure provides devices, systems and methods for the generation of encapsulated reagents and the partitioning of encapsulated reagents for use in subsequent analyses and/or processing, such as in the field of biological analyses and characterization. 1. A method for manufacturing a droplet generator , comprising:injection molding a polymeric structure comprising a microfluidic channel network comprising at least (i) a first channel, a second channel and a third channel in fluid communication with a droplet generation junction, and (ii) a flow regulator that is configured to provide flow of microcapsules from a suspension of a plurality of microcapsules along said first channel towards said droplet generation junction at a substantially regular flow frequency,wherein said first channel is in fluid communication with a first fluid source configured to contain a first fluid comprising said suspension of said plurality of microcapsules,wherein said second channel is in fluid communication with a second fluid source configured to contain a second fluid that is immiscible with said first fluid,wherein said droplet generation junction is configured to bring said first fluid comprising said microcapsules from said first channel in contact with said second fluid from said second channel to generate a droplet comprising a single microcapsule from said plurality of microcapsules, andwherein said third channel is configured to flow said droplet away from said droplet generation junction.2. The method of claim 1 , wherein said first channel claim 1 , said second channel and said third channel are in a first layer of said polymeric structure.3. The method of claim 2 , wherein said first fluid source and said second fluid source are in a second layer of said polymeric structure claim 2 , which second layer is different than said first layer.4. The method of claim 3 , wherein said second layer comprises a planar surface claim 3 , a first reservoir and second reservoir claim ...

FLUIDIC DEVICES, SYSTEMS, AND METHODS FOR ENCAPSULATING AND PARTITIONING REAGENTS, AND APPLICATIONS OF SAME

The disclosure provides devices, systems and methods for the generation of encapsulated reagents and the partitioning of encapsulated reagents for use in subsequent analyses and/or processing, such as in the field of biological analyses and characterization. 1. A device for generating a droplet comprising a single microcapsule , comprising:a polymeric structure comprising a microfluidic channel network comprising at least (i) a first channel, a second channel and a third channel in fluid communication with a droplet generation junction, and (ii) a flow regulator that is configured to provide flow of microcapsules from a suspension of a plurality of microcapsules along said first channel towards said droplet generation junction at a substantially regular flow frequency,wherein said first channel is in fluid communication with a first fluid source configured to contain a first fluid comprising said suspension of said plurality of microcapsules,wherein said second channel is in fluid communication with a second fluid source configured to contain a second fluid that is immiscible with said first fluid,wherein said droplet generation junction is configured to bring said first fluid comprising said microcapsules from said first channel in contact with said second fluid from said second channel to generate a droplet comprising a single microcapsule from said plurality of microcapsules, andwherein said third channel is configured to flow said droplet away from said droplet generation junction.2. The device of claim 1 , wherein said first channel claim 1 , said second channel and said third channel are in a first layer of said polymeric structure.3. The device of claim 2 , wherein said first fluid source and said second fluid source are in a second layer of said polymeric structure claim 2 , which second layer is different than said first layer.4. The device of claim 3 , wherein said second layer comprises a planar surface claim 3 , a first reservoir and second reservoir ...

BIOMOLECULE ISOLATION

Methods, devices and systems for handling sample liquids, encapsulating liquids and magnetic particles are disclosed. 119-. (canceled)20. A liquid handling system comprising:a conduit having a predetermined trapping site,a pump configured to apply positive pressure, negative pressure, or no external pressure to a location in the conduit,a magnetic field source configured to apply a magnetic field at the trapping site when activated and substantially no magnetic field when not activated, anda controller operably attached to the pump and the magnetic field source so that the controller can activate the pump and/or the magnetic field source, the controller being programmed to:activate the pump so that an encapsulating liquid is flowed in the conduit;activate the pump so that a sample liquid is flowed in the conduit in such a way that the sample liquid is (a) surrounded by the encapsulating liquid and (b) located at the trapping site within the conduit, the sample liquid containing magnetic particles;activate the magnetic field source so that the magnetic particles are immobilized at the trapping site; andactivate the pump so that an elution liquid is flowed in the conduit in such a way that (a) the elution liquid is surrounded by the encapsulating liquid, (b) the sample liquid is flowed away from the trapping site, and (c) the elution liquid is flowed to the trapping site and surrounds the magnetic particles.21. The system of wherein the conduit is a capillary tube.22. The system of wherein the encapsulating liquid claim 20 , sample liquid and elution liquid are flowed by negative pressure applied by the pump to the conduit.23. The system of wherein the encapsulating liquid claim 20 , sample liquid and elution liquid are flowed by positive pressure applied by the pump to the conduit.24. A system for handling a first sample liquid containing magnetic particles claim 20 , a second sample liquid claim 20 , and an encapsulating liquid claim 20 , both sample liquids being ...

SYSTEMS, METHODS, AND KITS FOR AMPLIFYING OR CLONING WITHIN DROPLETS

The present invention generally relates to droplet-based microfluidic devices, including systems, methods, and kits for amplifying or cloning within droplets. In some embodiments, the present invention is generally directed to systems, methods, or kits for amplifying a plurality of nucleic acids, e.g., without substantially selectively amplifying some nucleic acids over others. The nucleic acids may be contained within the droplets. In addition, in some embodiments, a plurality of microfluidic droplet containing a species of interest, such as a nucleic acid, may be mixed with microfluidic droplets free of the species, then pipetted or otherwise transferred such that, on average, a predetermined number of droplets containing species of interest is transferred. 1. A method , comprising:fragmenting a nucleic acid to produce nucleic acid fragments;containing at least some of the nucleic acid fragments in a plurality of microfluidic droplets; andamplifying at least some of the nucleic acid fragments contained within the microfluidic droplets.2. The method of claim 1 , comprising using PCR to amplifying at least some of the nucleic acid fragments contained within the microfluidic droplets.3. The method of any one of or claim 1 , wherein amplifying at least some of the nucleic acid fragments comprises adding a polymerase to at least some of the microfluidic droplets.4. The method of claim 3 , wherein the polymerase is DNA polymerase.5. The method of claim 3 , wherein the polymerase is RNA polymerase.6. The method of any one of - claim 3 , wherein amplifying at least some of the nucleic acid fragments comprises adding Taq polymerase to at least some of the microfluidic droplets.7. The method of any one of - claim 3 , wherein at least some of the microfluidic droplets comprise Taq polymerase.8. The method of any one of - claim 3 , comprising exposing at least some of the microfluidic droplets to a temperature of at least about 50° C.9. The method of any one of - claim 3 , ...

Long-Throw Microfluidic Actuator

A microfluidic device includes a three-dimensional slat structure having a plurality of interstices configured to generate a high power, high flow rate of fluids by electroosmotic flow. The microfluidic device includes a housing for holding and moving fluids through the slat structure, and a plurality of electrodes that generate an electric field within the plurality of interstices. 156.-. (canceled)57. A microfluidic cartridge comprising:a plurality of fluid passageways;at least one junction connecting said plurality of fluid passageways; and {'sup': '−8', 'a fluid power generation capacity of at least 10watts and capable of sustaining said power for at least 30 seconds; and'}, 'at least two fluid transport means, including at least one high-performance fluidic actuator, the at least one high-performance fluidic actuator being a discrete component within the cartridge, and the at least one high-performance fluidic actuator havinga response time for fluid power generation of less than 10 seconds.58. The cartridge of claim 57 , wherein said cartridge has a displaced volume less than or equal to five hundred cubic centimeters or less than or equal to fifty cubic centimeters.59. The cartridge of claim 57 , wherein said at least one high-performance fluidic actuator is capable of transducing electrical power into fluidic power.60. The cartridge of claim 57 , wherein said actuator is capable of pressurizing at least 10 microliters of liquid claim 57 , such that said liquid flows through a fluidic resistance associated with a back pressure of at least 1 kPa at a flow rate of at least 0.1 mL per minute.61. The cartridge of claim 57 , wherein said high-performance actuator is coupled to a pulse generator or other controlled time-varying voltage source and at least one electrode.62. The cartridge of claim 57 , wherein said at least one high-performance fluidic actuator is capable of producing fluidic power through an electrokinetic effect.63. The cartridge of claim 62 , ...

MICROFLUIDIC SYSTEM

The present invention provides microfluidic technology enabling rapid and economical manipulation of reactions on the femtoliter to microliter scale. 1. (canceled)2. A method for forming and collecting a plurality of droplets , the method comprising:providing a microfluidic device comprising at least a first channel and a second channel intersecting with each other at a junction and a microchannel extending from the junction and having at least one outlet downstream of the junction;providing a detachable holding component comprising a microchannel having an inlet and an outlet, wherein the inlet is detachably coupled to the outlet of the microchannel of the microfluidic device;forming a plurality of droplets in an immiscible carrier fluid within the microfluidic device; andtransferring the plurality of droplets from the microfluidic device to the holding component by flowing the plurality of droplets through the microchannel of the microfluidic device and into the microchannel of the holding component via a suction force applied by a pump operably coupled to the holding component, wherein each droplet is separated from an immediately adjacent droplet within the microchannel of the holding component.3. The method of claim 2 , wherein the pump is operably coupled to the microfluidic device by way of the holding component.4. The method of claim 3 , wherein the pump is coupled to the outlet of the microchannel of the holding component such that claim 3 , upon application of a suction force thereto claim 3 , the suction force is further applied to the microchannel of the microfluidic device.5. The method of claim 2 , wherein the holding component is configured to maintain separation of at least two immediately adjacent droplets of the plurality of droplets upon detachment of the inlet from the microfluidic device.6. The method of claim 2 , wherein the holding component is configured to induce merging of a least two immediately adjacent droplets of the plurality of ...

MICROFLUIDIC ANALYSIS SYSTEM

A biological sample analysis system including a sample preparation system forming droplets of segmented sample separated by a carrier fluid immiscible with the sample. The droplets include reaction mixtures for amplification of at least one target nucleic acid. A thermal cycling device having a sample block having a plurality of controlled thermal zones, and a containment structure in thermal communication with the plurality of controlled thermal zones. The containment structure receives and contains the droplets of segmented sample separated by the immiscible carrier fluid from the sample preparation system. A controller for controlling a temperature in each thermal zone of the sample block. A detection system detects electromagnetic radiation emitted from each of the droplets individually from the queue of droplets as they flow past the detection system. A positioning system to facilitate moving a queue of the droplets in the thermal cycling device relative to the detection system. 1. A microfluidic analysis system comprising a thermal cycling device, the device having a plurality of fixed thermal zones and a fixed conduit passing through the thermal zones, a controller for maintaining each thermal zone including its section of conduit at a constant temperature, means for flowing a series of droplets through the conduit so that each droplet is thermally cycled, and a detection system for detecting electromagnetic radiation from droplets at a plurality of said thermal cycles. This application is a continuation of U.S. application Ser. No. 15/429,765, filed Feb. 10, 2017, which is a divisional of U.S. application Ser. No. 14/486,987, filed Sep. 15, 2014 (now abandoned), which is a continuation of U.S. application Ser. No. 12/093,132, filed May 20, 2008 (now abandoned), which is a 371 of International Application No. PCT/IE2007/000015, filed Feb. 7, 2007 (now expired), and claims the benefit of U.S. Provisional Application No. 60/765,670, filed Feb. 7, 2006 (now ...

SAMPLE PREPARATION DEVICES AND SYSTEMS

Devices and system for preparing samples are described. Such devices can comprise fluidic chambers, reservoirs, and movable structures for controlling the movement of samples. The device can also comprise functional elements for performing specific operations. 19.-. (canceled)10. A device for performing fluidic operations , comprising:an adapter comprising at least one pair of ports;a plurality of reservoirs fluidly connectable with the at least one pair of ports, the plurality of reservoirs configured to flow fluid from at least a first reservoir to at least a second reservoir; anda first structure associated with the adapter and displaceable with respect to the adapter, the first structure comprising a first channel arrangement configured to fluidly connect the at least first reservoir with the at least second reservoir, the first channel arrangement being alignable with a desired pair of ports through displacement of the first structure.11. The device according to claim 10 , wherein the first channel arrangement comprises a functional element claim 10 , whereby the functional element is located in a flow path of a fluid when the fluid flows through the first channel arrangement.12. The device according to claim 10 , wherein the displaceable first structure is rotatable in a radial direction of the device.13. The device according to claim 11 , wherein movement of the functional element through displacement of the first structure is synchronous with movement of the first channel arrangement comprising the functional element.14. The device according to claim 10 , wherein the first channel arrangement is one or more channels.15. The device according to claim 10 , wherein each reservoir of the plurality of reservoirs comprises a fluidic pressuring mechanism adapted facilitate movement of the fluid from the first reservoir to the second reservoir claim 10 , and vice versa.16. The device according to claim 15 , wherein the pressuring mechanism is selected from the group ...

SYSTEMS AND METHODS FOR EPIGENETIC SEQUENCING

The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation. 1111-. (canceled)112. A method comprising:providing a solution comprising a plurality of nucleic acid sequences originating from a plurality of cells, at least some of the nucleic acid sequences being attached to an adapter, the adapter comprising an identification sequence, wherein sequences originating from the same cell contain identical identification sequences, and sequences originating from different cells contain different identification sequences; and sequencing at least some of the sequences.113. The method of claim 112 , wherein the adapter comprises a restriction site.114. The method of claim 112 , comprising cleaving the adapter at the restriction site.115. The method of claim 112 , wherein the solution is contained within a droplet.116. The method of claim 112 , wherein the plurality of nucleic acid sequences comprise DNA.117. The method of claim 112 , wherein the plurality of nucleic acid sequences comprise RNA.118. The method of claim 112 , wherein the primer site comprises a universal primer ...

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.

SYSTEMS AND METHODS FOR SERIAL FLOW EMULSION PROCESSES

Disclosed herein are systems and methods for serial flow emulsion processes. Systems and methods as described herein result in reduced cross-contamination. 1. A system comprising a detector for detecting one or more characteristics of single partitions in a plurality of partitions , wherein the partitions comprise a first fluid and are dispersed in a second fluid , and flow through an interrogation region of a conduit comprising(i) a conduit configured to flow the partitions within the conduit in single file, comprising an interrogation region wherein the one or more characteristics of the partitions is detected, wherein the interrogation region has a cross-sectional area in a plane substantially normal to the direction of flow of the partitions that is less than 80% of the average spherical cross-sectional area of the partitions; and(ii) a detection element for detecting electromagnetic radiation emitted by at least one component of the partitions in the interrogation region, if present.2. The system of wherein the interrogation region has a cross-sectional area of 10-100 claim 1 ,000 um.3. The system of further comprising(iii) an optical restriction configured and positioned between the interrogation region and the detection element so that the amount of the electromagnetic radiation incident on the detection element is reduced to less than 50% of the electromagnetic radiation that would be incident on the detection element in the absence of the optical restriction.4. The system of further comprising an excitation source for supplying electromagnetic radiation to the interrogation region claim 1 , wherein the system is configured for lock-in amplification.5. The system of wherein the interrogation region comprises a wall wherein the transmittance of electromagnetic radiation in the range of wavelengths emitted by at least one component of the partition is the same or substantially the same around the circumference of the interrogation region.6. The system of ...

MICROFLUIDIC DEVICES WITH TUNABLE WETTABILITY AND SOLVENT RESISTANCE AND METHODS FOR MANUFACTURING THE SAME

Microfluidic devices having a construct formed from perfluoropolyether and poly(ethylene glycol) diacrylate. The construct includes an inlet for receiving a continuous phase fluid, an inlet for receiving a dispersed phase fluid, and a plurality of channels extending through the construct. The plurality of channels are in fluid communication with both the inlet of the continuous phase fluid and the inlet of the dispersed phase fluid. The construct further includes a plurality of microdroplet generators configured to produce microdroplets, each of the microdroplet generators in fluid communication with the plurality of channels. Additionally, the construct includes an outlet formed in the construct and in fluid connection with the plurality of microdroplet generators. 1. A microfluidic device comprising:a construct formed from a perfluoropolyether (PFPE) and a poly(ethylene glycol) acrylate compound, the construct comprisingan inlet formed in the construct for receiving a continuous phase fluid,an inlet formed in the construct for receiving a dispersed phase fluid,a plurality of channels extending through the construct, the plurality of channels in fluid communication with both the inlet of the continuous phase fluid and the inlet of the dispersed phase fluid,a plurality of microdroplet generators configured to produce microdroplets, each of the microdroplet generators in fluid communication with the plurality of channels, andan outlet formed in the construct and in fluid connection with the plurality of microdroplet generators.2. The microfluidic device of claim 1 , wherein the poly(ethylene glycol) acrylate compound is poly(ethylene glycol) diacrylate (PEGDA) and the construct has a ratio of PFPE to PEGDA of 99.999:0.0001 to 90:10.3. The microfluidic device of claim 1 , wherein the poly(ethylene glycol) acrylate compound is poly(ethylene glycol) diacrylate (PEGDA) and the construct has a ratio of PFPE to PEGDA of 99.999:0.0001 to 98:2.4. The microfluidic device of ...

Liquid bridge and system

A bridge (30) comprises a first inlet port (31) at the end of a capillary, a narrower second inlet port (32) which is an end of a capillary, an outlet port (33) which is an end of a capillary, and a chamber (34) for silicone oil. The oil is density-matched with the reactor droplets such that a neutrally buoyant environment is created within the chamber (34). The oil within the chamber is continuously replenished by the oil separating the reactor droplets. This causes the droplets to assume a stable capillary-suspended spherical form upon entering the chamber (34). The spherical shape grows until large enough to span the gap between the ports, forming an axisym metric liquid bridge. The introduction of a second droplet from the second inlet port (32) causes the formation of an unstable funicular bridge that quickly ruptures from the, finer, second inlet port (32), and the droplets combine at the liquid bridge (30). In another embodiment, a droplet (55) segments into smaller droplets which bridge the gap between the inlet and outlet ports.

Microfluidic platform and method for controlling the same

A microfluidic platform including a microfluidic layer and a contact layer. The microfluidic layer is embedded with a microfluidic structure including a micro-channel and a fluidic sample contained in the micro-channel. The contact layer is able to be attached to the microfluidic layer, and includes a first heater for heating a first area of the microfluidic structure to a first temperature and a second heater for heating a second area of the microfluidic structure to a second temperature. The microfluidic layer and the contact layer rotate together during operation. A method for controlling a sample in the micro-channel of the microfluidic structure.

Droplet actuator and method

The invention provides droplet actuators and droplet actuator cassettes including reagent storage capabilities, as well as methods of making and using the droplet actuators and cassettes. The invention also provides continuous flow channel elements and techniques for using electrodes to manipulate droplets in flowing streams. The invention also discloses methods of separating compounds on a droplet actuator. Various other aspects of the invention are also disclosed.

System and Method for Charging Fluids

Devices, systems, and methods for charging fluids are disclosed. The charging of fluids improves the mixing of fluids in microfluidic systems. The charging is performed by producing an ion field ( 50 ) between an ionizing electrode ( 20 ) and an opposed ground electrode ( 30 ). A fluid-containing vessel ( 40 ) is positioned between the opposed electrodes and the ion field charges the fluid ( 41 ) in the vessel.

Detection and mixing in a conduit in integrated bioanalysis systems

Apparatuses and methods in which detection is integrated with various liquid processing and environmental control functions to create integrated bioanalysis systems are disclosed. Though the various integrated bioanalysis systems are useful for any number of analysis formats, they are adaptable to high-throughput processing of samples.

NUCLEIC ACID AMPLIFICATION REACTION APPARATUS AND NUCLEIC ACID AMPLIFYING METHOD

A nucleic acid amplification reaction apparatus includes (A) a rotating body mounted with a nucleic acid amplification reaction container including reaction liquid in which nucleic acid is eluted and oil phase-separated from the reaction liquid, (B) a control section for rotating the rotating body and moving the reaction liquid back and forth between a first region and a second region, and (C) a fluorescence measuring device for performing fluorescence measurement of the reaction liquid in a position along a rotation track of the nucleic acid amplification reaction container at the time when the rotating body rotates. 1. A nucleic acid amplification reaction apparatus comprising:(A) a rotating body mountable with a nucleic acid amplification reaction container including reaction liquid in which nucleic acid is eluted and oil phase-separated from the reaction liquid;(B) a control section for rotating the rotating body and moving the reaction liquid back and forth between a first region and a second region of the nucleic acid amplification reaction container; and(C) a fluorescence measuring device for performing fluorescence measurement of the reaction liquid in a position along a rotation track of the nucleic acid amplification reaction container at the time when the rotating body rotates.2. The nucleic acid amplification reaction apparatus according to claim 1 , wherein the fluorescence measuring device rotates integrally with the rotating body.3. The nucleic acid amplification reaction apparatus according to claim 1 , wherein the fluorescence measuring device moves according to the rotation of the rotating body along the rotation track of the nucleic acid amplification reaction container.4. The nucleic acid amplification reaction apparatus according to claim 1 , wherein a detecting section of the fluorescence measuring device moves claim 1 , according to the rotation of the rotating body claim 1 , the position along the rotation track of the nucleic acid ...

FLUIDIC CHIP

A fluidic chip comprising: a sealing layer having an upper surface and a lower surface; and a formed part comprising a generally planar body having a lower surface sealed with the upper surface of the sealing layer, the generally planar body having a number of through holes and a number of wells in fluid communication with the number of through holes, wherein together with the upper surface of the sealing layer, the number of through holes and the number of wells respectively define a number of fluid inlets and a number of fluid chambers in fluid connection with each other in the fluidic chip. 1. A fluidic chip comprising:a sealing layer having an upper surface and a lower surface; anda formed part comprising a generally planar body having a lower surface sealed with the upper surface of the sealing layer, the generally planar body having a number of through holes and a number of wells in fluid communication with the number of through holes,wherein together with the upper surface of the sealing layer, the number of through holes and the number of wells respectively define a number of fluid inlets and a number of fluid chambers in fluid connection with each other in the fluidic chip;wherein each of the number of wells comprises a well bottom connected to and spaced apart from an upper surface of the planar body by a well wall encircling the well bottom.2. The fluidic chip of claim 1 , wherein the lower surface of the sealing layer is electrically non-conductive and provided with a dc heater having a discrete heating area made of a heat conductive material disposed on the lower surface of the sealing layer and a conductive trace configured to be supplied with a dc voltage and to heat the discrete heating area to a uniform temperature when supplied with the dc voltage claim 1 , the conductive trace disposed in an undulating configuration on the lower surface of the sealing layer at least partially around the discrete heating area claim 1 , the discrete heating area ...

Microperturbation Assembly System and Method

Microperturbation fluidic assembly systems and methods are provided for the fabrication of emissive panels. The method provides an emissive substrate with a top surface patterned to form an array of wells. A liquid suspension is formed over the emissive substrate top surface, comprising a first liquid and emissive elements. Using an array of micropores, a perturbation medium, which optionally includes emissive elements, is injected into the liquid suspension. The perturbation medium may be the first liquid, a second liquid, or a gas. A laminar flow is created in the liquid suspension along the top surface of the emissive substrate in response to the perturbation medium, and emissive elements are captured in the wells. The ejection of the perturbation medium can also be used to control the thickness of the liquid suspension overlying the top surface of the emissive substrate.

METHODS AND COMPOSITIONS FOR DETECTION OF AMPLIFICATION PRODUCTS

Some embodiments of the systems, devices, kits and methods provided herein relate to amplifying and detecting a target nucleic acid. Some such embodiments include a droplet comprising an aqueous reaction mixture and an oil, and a detection unit. Some embodiments include a passageway or conduit configured to transport the droplet. In some embodiments, the detection unit includes an electric field-generating unit and an electro-sensing element. 1. A system for detection of an amplification product of a template nucleic acid , comprising: a sample reservoir comprising an aqueous reaction mixture comprising a template nucleic acid or a cell comprising the template nucleic acid, a buffer and nucleic acid amplification reagents,', 'an oil phase reservoir comprising an oil and, optionally, a surfactant such as a nonionic surfactant, and', 'a mixing chamber in fluid communication with the sample reservoir and the oil phase reservoir, wherein said mixing chamber is configured to mix the oil and the aqueous reaction mixture so as to form droplets comprising the aqueous reaction mixture and the oil;, 'a droplet generating unit comprisinga temperature control unit comprising a heating unit, configured to heat the droplets to a desired temperature for a desired period of time; and a passageway or conduit configured to transport the droplets, wherein said passageway or conduit is in fluid communication with the mixing chamber,', 'an electric field-generating unit configured to apply an electric field to said droplets when said droplets are in the passageway or conduit, and', 'an electro-sensing element configured to measure a modulation of an electric signal, such as impedance or capacitance, in each of the droplets when the droplets are subjected to the electric field, as compared to a control, the modulation of the electric signal indicating the presence of an amplification product of the template nucleic acid., 'a detection unit comprising248-. (canceled) This application ...

MICROFLUIDIC DEVICE WITH DROPLET PRE-CHARGE ON INPUT

An EWOD device includes opposing substrates defining a gap and each including an insulating surface facing the gap. Array elements include electrode elements to which actuation voltages are applied. A pre-charging structure defines a channel in fluid communication with the gap wherein the channel receives an input of a fluid reservoir for generation of the liquid droplet, and the pre-charging structure includes an electrical element electrically exposed to the channel. The electrical element pre-charges the fluid reservoir within the channel, and a portion of the gap containing the liquid droplet spaced apart from the channel is electrically isolated from the electrical element such that the liquid droplet is at a floating electrical potential when located within said portion of the gap. The electrical element may be an electrode portion that is exposed to the channel, or an externally connected pre-charging element inserted into the channel. 1. An electrowetting on dielectric (EWOD) device comprising:a first substrate and an opposing second substrate defining a gap between the first and second substrates, each substrate including an insulating surface facing the gap;an array of elements comprising a plurality of individual elements that are actuatable for manipulation of a liquid droplet within the gap, each individual element including a plurality of electrode elements to which actuation voltages are applied; anda pre-charging structure that includes a channel in fluid communication with the gap and that is configured to receive a fluid reservoir for generation of the liquid droplet, and the pre-charging structure includes an electrical element electrically exposed to the channel;wherein the electrical element pre-charges the fluid reservoir within the channel, and a portion of the gap containing the liquid droplet spaced apart from the channel is electrically isolated from the electrical element such that the liquid droplet is at a floating electrical potential ...

DEVICE AND METHOD FOR PRESSURE-DRIVEN PLUG TRANSPORT AND REACTION

The present invention provides microfabricated substrates and methods of conducting reactions within these substrates. The reactions occur in plugs transported in the flow of a carrier-fluid. 115.-. (canceled)16. A fluidic system comprising:a microfluidic device comprising substrate having a plurality of traps in fluidic communication with an inlet and arranged along one side of the substrate, wherein each trap comprises an opening along the side of the substrate and is separated from another trap by a region along the side of the substrate, each trap is configured to accommodate a partition of aqueous fluid comprising a bead particle within; anda detector configured to detect, monitor, or analyze each partition of aqueous fluid and associated bead particle retained within a corresponding trap of the substrate, the detector configured to detect emissions from one or more detectable markers associated with one or more bead particles for quantitative analysis.17. The system of claim 16 , wherein each partition of aqueous fluid is at least partially surrounded by a fluid immiscible with the aqueous fluid.18. The system of claim 17 , wherein the immiscible fluid is an oil.19. The system of claim 17 , wherein each partition of aqueous fluid is separated from one another by way of each corresponding trap of the substrate and the immiscible fluid partially surrounding each partition of aqueous fluid.20. The system of claim 16 , wherein the detector is configured to measure at least one property associated with one or more bead particles based on detection of emissions from the one or more detectable markers.21. The system of claim 20 , wherein the detector is configured to detect a signal emitted from a detectable marker associated with a bead particle.22. The system of claim 21 , wherein the at least one property is an optical property.23. The system of claim 22 , wherein the detector is at least one of an optical detector and a fluorescence detector.24. The system of ...

METHOD AND DEVICE FOR SEPARATING IMMISCIBLE LIQUIDS TO EFFECTIVELY ISOLATE AT LEAST ONE OF THE LIQUIDS

A phase-separation device and method of use is provided for separating immiscible liquids. The phase-separation device has a porous membrane with a filter surface having a non-planar contour that forms a receiving cavity to receive a liquid mixture. The filter surface is configured to impede flow of a polar liquid into the porous membrane and permit flow of a non-polar liquid into the porous membrane. 1. A phase-separation device comprising a porous membrane having a filter surface , the filter surface having a non-planar contour that forms a receiving cavity , wherein the filter surface is configured to impede flow of a polar liquid into the porous membrane and permit flow of a non-polar liquid into the porous membrane.2. The device of claim 1 , wherein the polar liquid is denser than the non-polar liquid.3. The device of claim 1 , wherein the filter surface is hydrophobic.4. The device of claim 1 , wherein the polar liquid and non-polar liquid are part of a liquid mixture deposited in the receiving cavity claim 1 , the liquid mixture contacting the filter surface at different depths of the receiving cavity.5. The device of claim 1 , wherein at least a portion of the filter surface has a radius of curvature.6. The device of claim 1 , wherein a majority of the filter surface has a slope that changes a depth of the receiving cavity at a linear rate.7. The device of claim 1 , wherein the receiving cavity has a bottom representing a maximum depth of the receiving cavity claim 1 , the filter surface having a slope that increases from the bottom to an access opening of the receiving cavity.8. The device of claim 1 , wherein the receiving cavity has an access opening that is defined by a cavity edge claim 1 , the receiving cavity having a maximum depth that is less than a maximum diameter of the access opening.9. The device of claim 1 , wherein the receiving cavity has an access opening that is defined by a cavity edge claim 1 , the receiving cavity having a maximum depth ...

SYSTEMS AND METHODS FOR SERIAL FLOW EMULSION PROCESSES

Disclosed herein are systems and methods for serial flow emulsion processes. Systems and methods as described herein result in reduced cross-contamination. 1. A system for producing a serial flow emulsion comprising(i) an intake system to sequentially transport a plurality of separate samples or portions of samples from a series of sample containers;(ii) a process system, wherein the process system comprises a partitioner to generate a plurality of partitions in a continuous phase from each of the samples; and(iii) an injector positioned between the intake system and the process system, wherein the injector is configured to be in fluid communication with the intake system, or to be in fluid communication with the process system, but not both simultaneously.2. The system of further comprising a reactor fluidly connected to the partitioner to initiate or modulate one or more reactions in one or more of the partitions.3. The system of wherein the reactor comprises a conduit fluidly connected to the partitioner through which partitions flow claim 2 , wherein the reactor comprises at least two different thermal zones claim 2 , and wherein the conduit repeatedly contacts the at least two different thermal zones.4. The system of further comprising a detector fluidly connected to the reactor to detect a characteristic of one or more of the partitions.5. The system of wherein the detector comprises at least one of(a) an optical restriction that limits the amount of electromagnetic radiation that reaches a detection element in the detector from an interrogation region in the detector where partitions are detected to less than 10% of the electromagnetic radiation that would reach the detection element without the optical restriction;(b) an interrogation region comprising a conduit wherein partitions flow in single file through the conduit, and wherein the cross-sectional area of the conduit is less than 90% of the average spherical cross-sectional area of the partitions;(c) an ...

Enzyme quantification

The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing an enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the subset. The amount of target can be determined based on the detected number.

Droplet-Generating Microfluidic Chips and Related Methods

Disclosed are microfluidic chips and methods of loading the same. Some microfluidic chips include a microfluidic network that has an inlet port, a channel configured to receive liquid from the inlet port, and a droplet-generating region that includes an end of the channel having a transverse dimension, a constant portion extending from the end of the channel and having a constant transverse dimension that is larger than the traverse dimension of the end of the channel, and an expanding portion extending from the constant portion, wherein the transverse dimension of the end of the channel, the transverse dimension of the constant portion, and a length of the constant portion are configured such that, when an aqueous liquid is flowed through the droplet-generating region in the presence of a non-aqueous liquid, droplets of the aqueous liquid are completely formed in the constant portion. 1. A microfluidic chip comprising a microfluidic network that includes:an inlet port;a channel configured to receive liquid from the inlet port; and an end of the channel having a transverse dimension;', a length; and', 'a constant transverse dimension along the length of the constant portion, measured parallel to the transverse dimension of the end of the channel, that is larger than the transverse dimension of the end of the channel; and, 'a constant portion extending from the end of the channel, the constant portion having, a length; and', 'a transverse dimension, measured parallel to the transverse dimension of the constant portion, that increases along the length of the expanding portion, including from a first value that is greater than the transverse dimension of the constant portion to a second value that is greater than the first value;, 'an expanding portion extending from the constant portion, the expanding portion having, 'wherein the transverse dimension of the end of the channel, the length of the constant portion, and the transverse dimension of the constant portion are ...

DEVICE FOR GENERATING DROPLETS

A system, including method and apparatus, for generating droplets suitable for droplet-based assays. The disclosed systems may include either one-piece or multi-piece droplet generation components configured to form sample-containing droplets by merging aqueous, sample-containing fluid with a background emulsion fluid such as oil, to form an emulsion of sample-containing droplets suspended in the background fluid. In some cases, the disclosed systems may include channels or other suitable mechanisms configured to transport the sample-containing droplets to an outlet region, so that subsequent assay steps may be performed. 120-. (canceled)21. A method of emulsion formation and modification , the method comprising:flowing an oil in an oil channel and a first aqueous fluid in an aqueous channel, wherein the oil channel, the aqueous channel, and an emulsion channel intersect at a first intersection;forming an emulsion including the first aqueous fluid at the first intersection;flowing the emulsion in the emulsion channel to a second intersection; andmodifying the emulsion at the second intersection, wherein modifying comprises generating droplets including a second aqueous fluid, wherein the modified emulsion comprises a first population of droplets including the first aqueous fluid and a second population of droplets including the second aqueous fluid, and wherein the first population and the second population have different compositions.22. The method of claim 21 , further comprising thermally cycling the first and second populations of droplets.23. The method of claim 21 , further comprising amplifying a nucleic acid target in each population of droplets.24. The method of claim 21 , further comprising detecting fluorescence from the first and second populations of droplets.25. The method of claim 21 , further comprising placing the first aqueous fluid into a vessel; and removably connecting the vessel to the first intersection.26. The method of claim 25 , further ...

DIFFERENTIAL PRESSURE ASSISTED DRAINAGE SYSTEM

A drainage system and method for diagnostic systems and the like. The system comprises a base with a hinged lid. A plenum chamber is formed either in the base or the lid. When formed in the lid, the plenum chamber is configured to receive a positive pressure from a pneumatic pump. When formed in the base, the plenum chamber is configured to receive a negative pressure from a pneumatic pump. The base has an elevated table, from which an array of posts project. A semipermeable layer is placed on the truncated tips of the posts, and a microfluidic plate is set over the semipermeable layer. The lid is then closed to apply compression against the sandwiched plate and semipermeable layer. The pump is activated to establish a differential pressure through the plenum chamber, however the semipermeable layer provides pneumatic resistance to air flowing through the microfluidic channel(s) in the plate. 1. A drainage system for prompting movement of at least one liquid plug through a microfluidic channel toward an outlet , said system comprising:a base, a lid operatively connected to said base, a plenum chamber associated with one of said base and lid, anda semipermeable layer disposed between said base and said lid, said semipermeable layer configured to provide pneumatic resistance to air flowing through the microfluidic channel.2. The system of wherein the pneumatic resistance is variable as a function of compression to thereby selectively establish a pressure differential.3. The system of wherein said semipermeable layer has thickness between about 0.1 mm and 25 mm.4. The system of wherein said semipermeable layer includes at least one dense porous region surrounded by a loose porous region.5. The system of wherein said semipermeable layer includes a plurality of dense porous regions surrounded by loose porous regions.6. The system of wherein said semipermeable layer is absorbent.7. The system of wherein said semipermeable layer is non-absorbent.8. The system of wherein ...

MICROFLUIDIC DEVICES AND METHODS FOR BIOASSAYS

A microfluidic device includes a substrate and a cover. The substrate has an inlet port, a first microchannel, one or more parking loops, a second microchannel and an outlet port for each microchannel network. The first microchannel is connected to the inlet port, the second microchannel is connected to the outlet port, the parking loops are connected between the first and second microchannels. Each parking loop includes a parking loop inlet, a parking loop output, a fluidic trap connected between the parking loop inlet and the parking loop outlet, and a bypass microchannel connected to the parking loop inlet and the parking loop outlet. The cover is attached to a top of the substrate and has an inlet opening and an outlet opening through the cover for each microchannel network. The inlet and outlet openings of the cover are disposed above the inlet and outlet ports in the substrate. 1. A microfluidic device having one or more microchannel networks comprising:a substrate having an inlet port, a first microchannel, one or more parking loops, a second microchannel and an outlet port for each microchannel network, wherein the first microchannel is connected to the inlet port, the second microchannel is connected to the outlet port, the one or more parking loops are connected between the first microchannel and the second microchannel, and each parking loop comprises a parking loop inlet, a parking loop output, a fluidic trap connected between the parking loop inlet and the parking loop outlet, and a bypass microchannel connected to the parking loop inlet and the parking loop outlet; anda cover attached to a top of the substrate, the cover having an inlet opening and an outlet opening through the cover for each microchannel network, wherein the inlet opening of the cover is disposed above the inlet port in the substrate and the outlet opening is disposed above the outlet port in the substrate.2. The microfluidic device as recited in claim 1 , wherein the fluidic trap ...

Monolithic magnets with magnetic field domains for diamagnetic levitation

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

Biological Detection System and Method of Use

Provided herein is a biological detection system and method of use wherein the biological detection system comprises at least one mixer or liquid bridge for combining at least two liquid droplets and an error correction system for detecting whether or not proper mixing or combining of the two component droplets have occurred.

CARTRIDGE FOR PERFORMING ASSAYS IN A CLOSED SAMPLE PREPARATION AND REACTION SYSTEM

In one embodiment, a multiplex fluid processing cartridge includes a sample well, a deformable fluid chamber, a mixing well with a mixer disposed therein, a lysis chamber including a lysis mixer, an electrowetting grid for microdroplet manipulation, and electrosensor arrays configured to detect analytes of interest. An instrument for processing the cartridge is configured to receive the cartridge and to selectively apply thermal energy, magnetic force, and electrical connections to one or more discrete locations on the cartridge and is further configured to compress the deformable chamber(s) in a specified sequence. 1. A fluid sample processing cartridge comprising: i) a substrate;', 'ii) a sample well formed in said substrate and configured to receive a volume of fluid sample;', 'iii) a closure configured to be selectively placed over said sample well;', 'iv) a first deformable fluid chamber supported on said substrate and configured to hold a fluid therein when in an undeformed state and to collapse upon application of an external compression force to expel at least a portion of the fluid from the first fluid chamber, said first deformable fluid chamber being in fluid communication with said sample well via a channel formed in said substrate;', 'v) a mixing well formed in said substrate, said mixing well being in fluid communication with said sample well via a channel formed in said substrate;', 'vi) a driven mixing apparatus disposed within said mixing well and constructed and arranged to mix the contents of said mixing well; and', 'vii) a first fluid exit port formed in the substrate, said first fluid exit port being in fluid communication with said mixing well via a channel formed in said substrate; and, 'a) a sample preparation module comprising [ 1) a top surface;', '2) a raised wall at least partially circumscribing said top surface and in fluid sealing contact with a surface of said sample preparation module to form an interstitial space between the top ...

MICROFLUIDIC PROCESS FOR TREATING AND ANALYSING A SOLUTION CONTAINING A BIOLOGICAL MATERIAL AND CORRESPONDING MICROFLUIDIC CIRCUIT

The subject matter of the present invention is a microfluidic process for treating and analysing a solution containing a biological material, comprising a step of introducing the solution into microchannels of a microfluidic circuit (), a step of forming drops of this solution, under the effect of modifications of the surface tension of the solution, a step of moving the drops to one or more drop storage zones(s) (), under the effect of modifications of the surface tension of the drops, a step of treating the drops and a step of analysing the drops. 2. The microfluidic process according to claim 1 , wherein the microfluidic process further comprises:d. moving at least a portion of the plurality of droplets to the at least one storage zone in the microfluidic circuit, thereby concentrating the at least a portion of the plurality of droplets in said at least one storage zone.3. The microfluidic process according to claim 1 , wherein the at least one storage zone is a zone wherein the droplets have a lower surface energy than in the adjacent zones.4. The microfluidic process according to claim 1 , wherein the carrier fluid is substantially static.5. A microfluidic process for analyzing a solution comprising at least one biological material claim 1 , wherein said process comprises the steps of:{'claim-ref': {'@idref': 'CLM-00002', 'claim 2'}, 'a. generating a plurality of droplets of said solution by partitioning the solution according to the microfluidic process of ;'}c. analyzing the plurality of droplets located in the at least one storage zone.6. The microfluidic process according to claim 5 , wherein the at least one storage zone comprises claim 5 , at least in part claim 5 , a transparent material suitable for analyzing the plurality of droplets located in said at least one storage zone claim 5 , from outside the microfluidic circuit.7. The microfluidic process according to claim 5 , wherein analyzing the plurality of droplets is performed by fluorescence analysis ...

MICROFLUIDIC DEVICE AND METHODS

This disclosure provides devices and methods for the isolation of single cells or particles of interest from a solution comprising a plurality of cells or a solution composed of a homogenous population of particles. Specifically, the present disclosure is directed to microfluidic devices and methods for analyzing cells in a sample. More specifically, the present disclosure provides droplet microfluidic devices and methods for using the same to obtain (trap), encapsulate, and retrieve (isolate) single cells or particles from a sample with improved efficiency. 119.-. (canceled)20. A method for encapsulating a single cell in a droplet comprising: a first region comprising', 'a microfluidic channel, wherein said microfluidic channel comprises at least one displacement element on a first inner sidewall surface of said microfluidic channel, wherein said at least one displacement element extends into the microfluidic channel toward an second inner sidewall surface of the microfluidic channel that is opposite said first inner sidewall surface, wherein said at least one displacement element comprises between three and nine tapered displacement elements, wherein each of said tapered displacement elements are aligned in series on said first inner sidewall surface of said microfluidic channel, and', 'at least one trapping chamber coupled to the microfluidic channel downstream of said at least one displacement element, wherein said at least one trapping chamber comprises a first opening in said second inner sidewall of said microfluidic channel that allows the flow of fluid into said at least one trapping chamber, wherein said at least one trapping chamber comprises at least two parallel sidewalls, wherein said at least one trapping chamber comprises a second opening opposite said first opening, and wherein said second opening is connected to a trapping channel, wherein said trapping channel connects said first microfluidic channel and said second microfluidic channel, and ...

MANIPULATION OF FLUIDS, FLUID COMPONENTS AND REACTIONS IN MICROFLUIDIC SYSTEMS

Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply. 179.-. (canceled)80. A method for partitioning a fluid sample , the method comprising:providing a microfluidic device having a substrate comprising a plurality of microwells in fluid communication with an inlet;introducing a first fluid into the inlet of the microfluidic device, the first fluid comprising a biological sample and a plurality of beads, each bead comprising a reactive component for binding a target molecule from the biological sample to the bead;introducing a second fluid immiscible with the first fluid into the microfluidic device and flowing the second fluid towards each of the plurality of microwells so as to form partitions of fluid in corresponding microwells, each partition of fluid comprising a subvolume of the first fluid, including at least the biological sample and a single bead, wherein each partition of fluid is separated from one another by the second fluid; andmaintaining each partition of fluid in corresponding microwells for detection of contents in each partition of fluid.81. The method of claim 80 , wherein each partition of fluid is at least partially surrounded by the second fluid.82. The method of claim 80 , wherein the second fluid is an oil.83. The method of claim 80 , further comprising monitoring each partition of fluid and detecting claim 80 , with a detector claim 80 ...

Microfluidic method for handling microdrops

Method for handling at least one first microdrop and at least one second microdrop in a microfluidic system including a capillary trap that has a first trapping zone and a second trapping zone, the method including steps consisting of: (i) trapping the first microdrop in the first trapping zone, and (ii) trapping the second microdrop in the second trapping zone, the first and the second trapping zone being arranged such that the first and the second microdrops are in contact with each other, the first and the second trapping zones being adapted such that the trapping forces returned to one of the microdrops are different.

MASSIVELY PARALLEL INTEGRATED CIRCUIT-BASED DNA SYNTHESIS DEVICES, SYSTEMS, AND METHODS

DNA synthesis devices, systems, and methods are disclosed. An apparatus can include a synthesizer chip having an array of reaction units in a predetermined pattern, each reaction unit including a reaction surface and a reaction electrode of an IC array of reaction electrodes, and a synthesizer chip controller coupled to the IC array of reaction electrodes configured to address each reaction electrode individually. The apparatus can also include a reagent delivery chip positionable above the synthesizer chip, comprising an array of reagent delivery units arranged in the predetermined pattern, each reagent delivery unit including a reagent electrode of an IC array of reagent electrodes and each reagent delivery unit configured to receive and deliver a droplet of reagent fluid having a volume of 1 picoliter or less, and a reagent delivery chip controller coupled to the IC array of reagent electrodes configured to address each reagent electrode individually. 1. A deoxyribonucleic acid (DNA) synthesis apparatus , comprising: an array of reaction units arranged in a predetermined pattern, each reaction unit including a reaction surface;', 'an integrated circuit (IC) array of reaction electrodes arranged in the predetermined pattern such that each reaction unit includes a reaction electrode; and', 'a synthesizer chip controller coupled to the IC array of reaction electrodes and configured to address and control each of the reaction electrodes individually; and, 'a synthesizer chip, further comprising an array of reagent delivery units arranged in the predetermined pattern, each reagent delivery unit configured to receive and deliver a droplet of reagent fluid having a volume of 1 picoliter (pL) or less;', 'an IC array of reagent electrodes arranged in the predetermined pattern such that each reagent delivery unit includes a reagent electrode; and', 'a reagent delivery chip controller communicatively coupled to the IC array of reagent electrodes and configured to address ...

METHOD AND APPARATUS FOR PROCESSING TISSUE AND OTHER SAMPLES ENCODING CELLULAR SPATIAL POSITION INFORMATION

Provided herein is a system comprising: a) spatial sampler system configured to collect and transmit one or a plurality of cells or nuclei from a tissue specimen, the system comprising: i) a lower carrier having an array of conduits passing therethrough, each conduit comprising an opening on a first side and communicating with an opening on a second side, wherein the opening on the second side either (1) terminates in a capillary or (2) opens onto a well of a multiwell plate; ii) positioned, above the lower carrier, a perforated specimen holder configured to support a frozen tissue specimen, wherein the specimen holder comprises a plurality of perforations having a size sufficient to permit the passage of single cells or nuclei; and iii) positioned, above the specimen holder, a multifunctional head comprising an upper array of upper conduits, optionally, each aligned with a conduit opening of the lower carrier. 1. A system comprising: i) a lower carrier having an array of conduits passing therethrough, each conduit comprising an opening on a first side of the lower carrier and communicating with an opening on a second side, wherein the opening on the second side of the lower carrier either (1) terminates in a capillary or (2) opens onto a well of a multiwell plate;', 'ii) positioned, above the lower carrier, a perforated specimen holder configured to support a frozen tissue specimen, wherein the specimen holder comprises a plurality of perforations having a size sufficient to permit the passage of cells or nuclei; and', 'iii) positioned, above the specimen holder, a multifunctional head comprising an upper array of upper conduits, optionally, each aligned with a conduit opening of the lower carrier., 'a) spatial sampler system configured to collect and transmit one or a plurality of cells or nuclei from a tissue specimen, the system comprising2. The system of claim 1 , wherein the openings on the top side of the lower carrier are configured as wells that communicate ...

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

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

METHOD OF CONCENTRATING ANALYTES, AND SYSTEM FOR CONCENTRATING AND DETECTING ANALYTES

A method for concentrating at least one analyte including the following steps: preparing a first phase including at least one analyte; depositing a drop of the first phase on a substrate; depositing on the drop of first phase a drop of a second liquid phase including at least one surfactant, the second phase being non-miscible with the first phase; evaporating the drop of the second phase; and evaporating the drop of the first phase. Also relates to a method for detecting at least one analyte using the concentration method; and a system using the detection method. 113-. (canceled)14. A method for concentrating at least one analyte comprising the following steps:preparing a first phase comprising at least one analyte;depositing a drop of said first phase on a substrate;depositing on said drop of first phase a drop of a second liquid phase comprising at least one surfactant, said second phase being non-miscible with said first phase;evaporating the drop of the second phase; andevaporating the drop of the first phase.15. The method for concentrating at least one analyte according to claim 14 , wherein the at least one surfactant is non-miscible with the first phase.16. The method for concentrating at least one analyte according to claim 14 , wherein the at least one surfactant is non-volatile.17. The method for concentrating at least one analyte according to claim 16 , wherein the at least one non-volatile surfactant is fluorinated claim 16 , for example selected from the following surfactants claim 16 , but without being limited thereto: 1H claim 16 ,1H claim 16 ,2H claim 16 ,2H-perfluoro-1-octanol; 1H claim 16 ,1H-perfluoro-1-tetradecanol; perfluorodecanoic acid; 2-(Perfluorooctyl) ethyl alcohol; 2 claim 16 ,2 claim 16 ,3 claim 16 ,3 claim 16 ,4 claim 16 ,4 claim 16 ,4 claim 16 ,4-heptafluoro-1-butanol; or indeed a compound of the same family.18. The method for concentrating at least one analyte according to claim 14 , wherein the first phase does not comprise ...

HIGH THROUGHPUT SEQUENCING OF MULTIPLE TRANSCRIPTS

The present disclosure generally relates to sequencing two or more genes expressed in a single cell in a high-throughput manner. More particularly, the present disclosure relates to a method for high-throughput sequencing of pairs of transcripts co-expressed in single cells (e.g., antibody VH and VL coding sequence) to determine pairs of polypeptide chains that comprise immune receptors. 1. A method comprising:a) sequestering single cells and an mRNA capture agent into individual compartments;b) lysing the cells and collecting mRNA transcripts with the mRNA capture agent;c) isolating the mRNA from the compartments using the mRNA capture agent;d) performing reverse transcription followed by PCR amplification on the captured mRNA; ande) sequencing at least two distinct cDNA products amplified from a single cell.2. The method of claim 1 , further defined as a method for obtaining a plurality of paired antibody VH and VL sequences wherein the cells are B-cells.3. The method of claim 1 , wherein the mRNA capture agent is a bead.4. The method of claim 3 , wherein the beads are magnetic.5. The method of claim 3 , wherein the bead comprises oligonucleotides which hybridize mRNA.6. The method of claim 5 , wherein the oligonucleotides comprise at least one of poly(T) and primers specific to a transcript of interest.7. The method of claim 2 , further defined as a method for obtaining paired antibody VH and VL sequences for an antibody that binds to an antigen of interest.8. The method of claim 3 , wherein the beads are conjugated to the antigen of interest and the oligonucleotides are only conjugated to the beads in the presence of an antibody that binds to the antigen of interest.913-. (canceled)14. The method of claim 1 , wherein steps (a) and (b) comprise isolating single cells and an mRNA capture agent into individual microvesicles in an emulsion and in the presence of a cell lysis solution.1516-. (canceled)17. The method of claim 1 , wherein step (e) comprises linking ...

SINGLE NUCLEOTIDE DETECTION METHOD

A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterised by the steps of (1) generating a stream of single nucleotide bases from the analyte by pyrophosphorolysis; (2) producing captured molecules by reacting each single nucleotide base with a capture system labelled with detectable elements in an undetectable state; (3) releasing the detectable elements from each captured molecule in a detectable state and (4) detecting the detectable elements so released and determining the sequence of nucleotide bases therefrom. The method can be used advantageously in sequencers involving the use of microdroplets. 124-. (canceled)25. A method for identifying the nucleotide base in a single nucleoside triphosphate molecule , the method comprising the steps of: (a) producing a captured molecule by reacting the nucleoside triphosphate molecule with a capture system comprising an oligonucleotide selective for the nucleotide base and labelled with at least one characteristic fluorophore in an undetectable state; (b) releasing the fluorophore(s) from the captured molecule in a detectable state; (c) detecting characteristic fluorescence from the fluorophore(s) so released; and (d) inferring therefrom the identity of the nucleoside triphosphate molecule.26. The method of claim 25 , wherein the capture system is comprised of two oligonucleotide components; (a) a first oligonucleotide comprising a double-stranded region and a single-stranded nucleotide region and (b) a second single-stranded oligonucleotide whose nucleotide base sequence is at least partially complimentary to that of the single-stranded region of the first oligonucleotide.27. The method of claim 25 , wherein the capture system comprises a single oligonucleotide component comprising a single-stranded nucleotide region complementary to the nucleotide base of the nucleoside triphosphate molecule the 3′ and 5′ ends of which are attached to two different double- ...

SINGLE NUCLEOTIDE DETECTION METHOD

A method for determining the sequence of nucleotide bases in a polynucleotide analyte is provided. It is characterised by the steps of (1) generating a stream of single nucleotide bases from the analyte by pyrophosphorolysis; (2) producing captured molecules by reacting each single nucleotide base with a capture system labelled with detectable elements in an undetectable state; (3) releasing the detectable elements from each captured molecule in a detectable state and (4) detecting the detectable elements so released and determining the sequence of nucleotide bases therefrom. The method can be used advantageously in sequencers involving the use of microdroplets. 124-. (canceled)25. A microfluidic device for sequencing a nucleic acid analyte comprising:(a) a pyrophosphorolysis zone including a bead-receiving location where pyrophosphorolysis of a polynucleotide attached to a bead is carried out;(b) at least one inlet for delivering a flowing aqueous medium to the bead-receiving location;(c) at least one first outlet for removing a stream of single nucleotides in the flowing aqueous medium from the bead-receiving location via a first microfluidic pathway;(d) a microdroplet-generating chamber comprising a carrier solvent inlet, a first microdroplet head attached to the first outlet and a second outlet for removing a stream of microdroplets in the carrier solvent therefrom;(e) a second microfluidic pathway attached to the second outlet and provided with at least one microdroplet injector and/or at least one second microdroplet coalescence zone for introducing enzymes and biological probes into the first microdroplets;(f) a storage zone comprising locations at which the microdroplets issuing from the second microfluidic pathway are stored;(g) a light source for interrogating microdroplet locations; and(h) a photodetector for detecting fluorescence at the microdroplet locations and generating an output signal characteristic of the sequence of the nucleic acid analyte.26. ...

ADDRESSABLE MICRO-REACTION CHAMBER ARRAY

The present invention provides a micro-reactor () adapted to host chemical reactions having at least one microfluidic layer, said micro-reactor () comprising a fluid inlet () and a fluid outlet (); a plurality of micro-reaction chambers () arranged in rows () and columns (), each micro-reaction chamber comprising a chamber inlet () and a chamber outlet (); a plurality of supply channels () for supplying fluid to from said fluid inlet () to said micro-reaction chambers () and further arranged for draining said micro-reaction chambers () to said fluid outlet (), said supply channels () extending in a first direction (D) along the columns () of micro-reaction chambers () and arranged such that there is one supply channel () between adjacent columns (). The micro-reaction chambers () in the columns () are arranged such that the chamber inlets () of a column are in fluid contact with the same supply channel () and the chamber outlets () are in fluid contact with the supply channel () adjacent to the supply channel () arranged in fluidic contact with the chamber inlets (). Further, the plurality of supply channels () comprises a first end supply channel () arranged for supplying fluid to a first end column () of the micro-reaction chambers () and a second end supply channel () arranged for draining fluid from the second, opposite, end column () of said micro-reaction chambers (); and wherein the micro-reactor () further comprises at least one reagent inlet () in fluid contact with the first end supply channel and a reagent outlet () in fluid contact with the second end supply channel such that reagents introduced to the at least one reagent inlet () fill the plurality of micro-reaction chambers () in a second direction (D) along the rows () of micro-reaction chambers () to the reagent outlet ().

METHOD FOR PURIFYING PARTICLES, METHOD FOR DISPENSING A SINGLE PARTICLE, METHOD FOR ANALYZING CELL CLUSTER, AND APPARATUS USING THE SAME

One object of the present invention is to provide a method or apparatus for purifying target particles from high-concentration particles in a short time. The above problem can be solved by a method for purifying target particles, characterized in that the method comprises a step of sorting the target particles from a high concentration of non-target particles, wherein the sorting step is repeated for three times or more.

DROPLET-TRAPPING DEVICES FOR BIOASSAYS AND DIAGNOSTICS

In alternative embodiments, provided are high-throughput, multiplexed systems or methods for detecting a chemical, biological, a physiological or a pathological analyte, or a single molecule or a single cell in droplets using the floating droplet array system, whereby droplets are trapped in an array of trapping structures. In alternative embodiments, high-throughput, multiplexed systems as provided herein are integrated with portable imaging systems such as CCD, CMOS, digital camera, or cell phone-based imaging. 1: A high throughput , multiplexed system or device , or method , for detecting and/or quantifying a chemical , biological , physiological or pathological analyte , or a single molecule or a single cell , or a chemical or a biochemical reaction; or recognition of a cell or molecule , using a floating droplet array (FDA) system integrated with use of a sensing element or reporter or a fluorogenic reaction , comprising:(a) providing a sensor or sensing reaction that involves a small molecule, peptide, protein, nucleic acid, enzyme, antibody, cell, or chemical agent capable of detecting a target of interest and producing a signal readout;(b) providing a floating droplet array system, droplet microfluidics system or microdroplet-manipulating device or system;(c) providing a chemical, biological or an environmental sample containing a target of interest such as a small molecule, an aptamer, a metabolite, peptide, protein, nucleic acid, or cell; and(d) encapsulating the chemical, biological or environmental sample into a plurality of positive microdroplets, trapping the positive microdroplets into trapping structures, and processing the positive microdroplets comprising the encapsulated chemical, biological or environmental sample in the positive droplet microfluidics system or microdroplet-manipulating device, and detecting the presence of a fluorophore signal, or fluorescence, in each positive microdroplet in the device,wherein detection of a fluorophore signal ...

DEVICE FOR GENERATING DROPLETS

A system, including method and apparatus, for generating droplets suitable for droplet-based assays. The disclosed systems may include either one-piece or multi-piece droplet generation components configured to form sample-containing droplets by merging aqueous, sample-containing fluid with a background emulsion fluid such as oil, to form an emulsion of sample-containing droplets suspended in the background fluid. In some cases, the disclosed systems may include channels or other suitable mechanisms configured to transport the sample-containing droplets to an outlet region, so that subsequent assay steps may be performed. 1. A device for generating droplets , the device comprising:a body including a substrate and a plurality of protrusions, the substrate having a bottom side defining a channel network including a first channel, a second channel, and a third channel that meet one another at a droplet-generation region, the plurality of protrusions being formed integrally with the substrate and projecting from a top side of the substrate; anda sealing member attached to the bottom side of the substrate in a fluid-tight seal and providing a bottom wall for each channel of the channel network;wherein the device includes a carrier port configured to receive carrier fluid that flows from the carrier port to the droplet-generation region via the first channel;wherein the device includes a sample well configured to receive sample-containing fluid that flows to the droplet-generation region via the second channel;wherein the device includes a droplet well configured to receive sample-containing droplets and carrier fluid that flow from the droplet-generation region to the droplet well via the third channel; andwherein each of the sample well and the droplet well has an upper portion created by a protrusion of the plurality of protrusions.2. The device of claim 1 , wherein the carrier port is provided by a carrier well.3. The device of claim 2 , wherein the carrier well has ...

DEVICES AND METHODS FOR GENERATING AND RECOVERING DROPLETS

The invention provides kits, devices, methods, and systems for forming droplets or particles and methods of their use. The devices may be used to form droplets of a size suitable for utilization as microscale chemical reactors, e.g., for genetic sequencing. In general, droplets are formed in a device by flowing a first liquid through a channel and into a droplet formation region including a second liquid, i.e., the continuous phase. The invention allows for more efficient recovery of droplets or processed droplets. 2. The kit of claim 1 , wherein the lumen has an angle of between ±45 degrees from surface normal.3. The kit of wherein the collection device comprises a pipette tip or a tube having a proximal end and a distal end claim 1 , wherein the proximal end is in fluid communication with the lumen and the distal end is in fluid communication with an external container.4. (canceled)5. The kit of claim 1 , wherein the device further comprises a second channel having a second depth claim 1 , a second width claim 1 , a second proximal end claim 1 , and a second distal end claim 1 , wherein the second channel intersects the first channel between the first proximal and first distal ends.6. (canceled)7. The kit of claim 1 , wherein the droplet formation region comprises a shelf having a third depth claim 1 , a third width claim 1 , at least one inlet claim 1 , and at least one outlet claim 1 , wherein the shelf is configured to allow the first liquid to expand in at least one dimension and a step having a fourth depth.8. (canceled)9. The kit of claim 1 , wherein the device further comprises a reservoir configured to be controllably in fluid communication with the collection reservoir.10. The kit of claim 9 , wherein the reservoir comprises an immiscible displacement fluid.11. A method of producing droplets of a first liquid in a second liquid claim 9 , the method comprising:{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'a) providing the device of for producing ...

Microfluidic Chips Including a Gutter to Facilitate Loading Thereof and Related Methods

A microfluidic chip can comprise a body and a microfluidic network defined by the body. The network can include one or more inlet ports, a test volume, and one or more flow paths extending between the inlet port(s) and the test volume. Along each of the flow path(s), fluid is permitted to flow from one of the inlet port(s), through at least one droplet-generating region in which a minimum cross-sectional area of the flow path increases along the flow path, and to the test volume. The network can include a gutter disposed along at least a portion of a periphery of the test volume such that fluid from the flow path(s) is not permitted to flow into the gutter without flowing through the test volume, wherein, along the gutter, a depth of the gutter is at least 10% larger than the depth of the test volume at the periphery. 1. A microfluidic chip comprising:a body; and one or more inlet ports;', 'a test volume;', 'one or more flow paths extending between the inlet port(s) and the test volume, wherein, along each of the flow path(s), fluid is permitted to flow from one of the inlet port(s), through at least one droplet-generating region in which a minimum cross-sectional area of the flow path increases along the flow path, and to the test volume; and', 'a gutter disposed along at least a portion of a periphery of the test volume such that fluid from the flow path(s) is not permitted to flow into the gutter without flowing through the test volume, wherein, along the gutter, a depth of the gutter is at least 10% larger than the depth of the test volume at the periphery., 'a microfluidic network defined by the body, the network including'}2. The chip of claim 1 , wherein the gutter is disposed along at least a majority of the periphery of the test volume.3. The chip of claim 1 , wherein claim 1 , along the gutter claim 1 , a depth of the gutter is at least 90% larger than the depth of the test volume at the periphery.4. The chip of claim 1 , wherein the network includes one ...

METHODS AND APPARATUS FOR GENERATING DROPLETS

Methods and apparatus for generating droplets are disclosed. In one arrangement a peristaltic screw pump is configured to drive pulsatile flows of fluids in different conduits which are phased relative to each other such that a sequence of droplets are formed at a junction downstream from the pump. 1. An apparatus for generating droplets , comprising:a first conduit for transporting a first fluid;a second conduit for transporting a second fluid; anda pumping mechanism comprising a first rotatable member having one or more radially peripheral portions that engage against the first and second conduits and apply a dynamic deformation to the first and second conduits on rotation of the first rotatable member, the dynamic deformation being such as to drive a pulsatile motion of the first and second fluids in the first and second conduits, whereinthe pulsatile motions of the first and second fluids are phase shifted relative to each other at a first junction between the first and second conduits downstream of the pumping mechanism resulting in the formation of droplets of the second fluid in the first fluid at the first junction.2. An apparatus according to claim 1 , wherein longitudinal axes of the first and second conduits are parallel to the axis of rotation of the first rotatable member in a region where the one or more radially peripheral portions engage against the first and second conduits.3. An apparatus according to claim 1 , wherein the one or more radially peripheral portions comprises a thread winding around the axis of the first rotatable member.4. An apparatus according to claim 1 , wherein a longitudinal axis of each of the first and second conduits is non-parallel to the axis of rotation of the first rotatable member in a region where the one or more radially peripheral portions engage against the first or second conduit.5. An apparatus according to claim 4 , wherein:the one or more radially peripheral portions engage against the first conduit exclusively ...

METHODS AND APPARATUS FOR INTRODUCING A SAMPLE INTO A SEPARATION CHANNEL FOR ELECTROPHORESIS

Methods and apparatus for introducing a sample into a separation channel for electrophoresis are disclosed. In one arrangement sample droplets having a membrane that encapsulates a sample are formed and brought to an injection position in contact with a transport medium of a separation channel. An electric field is applied to rupture the sample droplets and cause the sample to enter the separation channel and undergo electrophoresis. 1. A method of introducing a sample into a separation channel for electrophoresis , comprising:encapsulating the sample within a sample droplet, the sample droplet having a spatially continuous sample droplet membrane that surrounds the sample within the sample droplet;bringing the sample droplet to an injection position in which a first region of the sample droplet membrane is in contact with a portion of a first surface and a second region of the sample droplet membrane, different from the first region, is in contact with a portion of a second surface, wherein:the first and second surfaces are configured so that the material forming the sample droplet membrane will not pass through the surfaces and is capable of stably isolating the sample from the first and second surfaces while the droplet is intact;the method further comprises applying an electric field to the sample droplet via the first and second surfaces, the electric field being such as to cause the sample droplet membrane to rupture and the sample to be brought into contact with the first and second surfaces; andthe second surface is a surface of a transport medium defining the separation channel, the transport medium being configured such that the sample passes through the second surface and into the separation channel when the sample droplet membrane is ruptured.2. A method according to claim 1 , wherein the first surface is also a surface of a transport medium.3. A method according to claim 1 , wherein the sample droplet membrane comprises a surfactant.4. A method ...

FLUIDIC AUTOSAMPLER AND INCUBATOR

Provided are devices for automated analysis of one or more samples in single or multi-well plates or vessels, wherein the process of automated analysis comprises automated flow, wherein the samples comprise liquid or particles in a sample vessel, and wherein the devices comprise an assembly of components that enable processing of a sample for analytical assessment by fluidic and/or particle based instruments. Automated flow may comprise systems for moving samples including vacuum systems, pressure-based systems, pneumatic systems, pumps, peristaltic pumps, diaphragms, or syringes. The devices may comprise an assembly of components that enable movement in X, Y, and Z dimensions, as well as switches, microfluidic tubing, well plate block, electronic pressure controllers, pneumatic or fluidic mixing devices, components for fluid handling, sampling vessels, and mechanical components for translating or transporting system components. 1. A device for automated analysis of one or more samples ,wherein the process of automated analysis comprises automated flow,wherein the samples comprise liquid or particles in a sample vessel, andwherein the device comprises an assembly of components that enable processing of a sample for analytical assessment by fluidic and/or particle based instruments.2. The device of claim 1 , wherein automated flow comprises systems for moving samples including vacuum systems claim 1 , pressure-based systems claim 1 , pneumatic systems claim 1 , pumps claim 1 , peristaltic pumps claim 1 , diaphragms claim 1 , or syringes.3. The device of claim 1 , wherein the samples comprise polymer claim 1 , metal claim 1 , glass claim 1 , or alloy based particles claim 1 , biological cells claim 1 , plant cells (algal cells or others) claim 1 , prokaryotic cells (bacteria) claim 1 , eukaryotic cells claim 1 , yeast claim 1 , fungus claim 1 , mold cells claim 1 , red blood cells claim 1 , neurons claim 1 , egg cell (ovum) claim 1 , spermatozoa claim 1 , white blood ...

DEVICE AND METHOD FOR DETECTING TUMOR MUTATION BURDEN (TMB) BASED ON CAPTURE SEQUENCING

A device and a method for detecting tumor mutation burden (TMB) based on capture sequencing are disclosed. The device includes: a panel design module configured to uniformly add population single-nucleotide polymorphism (SNP) sites to a genome and screen out gene regions that show the highest consistency with whole exome sequencing (WES); a data acquisition module configured to acquire tissue and plasma samples of a target object and acquire sequencing data of the samples; an alignment module configured to align the sequencing data with a reference genome to acquire mutation data results; a somatic mutation analysis module configured to perform somatic analysis on the mutation data results to obtain somatic mutation results; a filtering module configured to remove unreal mutation sites from the somatic mutation results; and a calculation module configured to calculate the TMB. 1. A device for detecting tumor mutation burden (TMB) based on a capture sequencing , comprising:a panel design module, wherein the panel design module is configured to uniformly add population single-nucleotide polymorphism (SNP) sites to a genome and screen out genome regions, and the genome regions show a highest consistency with whole exome sequencing (WES);a data acquisition module, wherein the data acquisition module is configured to acquire tissue and plasma samples of a target object and acquire sequencing data of the tissue and plasma samples based on the genome regions screened out by the panel design module;an alignment module, wherein the alignment module is configured to align the sequencing data acquired by the data acquisition module with a reference genome to acquire mutation data results;a somatic mutation analysis module, wherein the somatic mutation analysis module is configured to perform a somatic analysis on the mutation data results obtained by the alignment module to obtain somatic mutation results;a filtering module, wherein the filtering module is configured to remove ...

High Definition Microdroplet Printer

Methods for delivering discrete entities including, e.g., cells, media or reagents to substrates are provided. In certain aspects, the methods include manipulating and/or analyzing qualities of the entities or biological components thereof. In some embodiments, the methods may be used to create arrays of microenvironments and/or for two and three-dimensional printing of tissues or structures. Systems and devices for practicing the subject methods are also provided. 1. A method of delivering discrete entities to a substrate , the method comprising:flowing a plurality of discrete entities through a microfluidic device in a carrier fluid, wherein the discrete entities are insoluble and/or immiscible in the carrier fluid;directing the carrier fluid and one or more of the plurality of discrete entities through a delivery orifice to the substrate; andaffixing the one or more of the plurality of discrete entities to the substrate.2. The method of claim 1 , wherein the one or more of the plurality of discrete entities are affixed to the substrate via a force claim 1 , wherein the force is selected from a gravitational force claim 1 , an electrical force claim 1 , a magnetic force claim 1 , and combinations thereof.3. The method of claim 2 , comprising storing the affixed entity under controlled environmental conditions for a storage period claim 2 , wherein the force is maintained during the storage period.4. The method of claim 3 , wherein the controlled environmental conditions comprise a constant temperature and/or pressure.5. The method of any one of - claim 3 , wherein the force is an electrical force.6. The method of claim 5 , wherein the electrical force is a dielectrophoretic force.7. The method of any one of - claim 5 , wherein the discrete entities are droplets.8. The method of claim 7 , wherein the droplets are affixed to the substrate via wetting.9. The method of claim 7 , wherein the droplets comprise an aqueous fluid claim 7 , which is immiscible with the ...

Droplet creation techniques

The present invention is generally related to systems and methods for producing droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, at least one droplet is used to create a plurality of droplets, using techniques such as flow-focusing techniques. In one set of embodiments, a plurality of droplets, containing varying species, can be divided to form a collection of droplets containing the various species therein. A collection of droplets, according to certain embodiments, may contain various subpopulations of droplets that all contain the same species therein. Such a collection of droplets may be used as a library in some cases, or may be used for other purposes.

Stabilized droplets for calibration and testing

Provided herein, are droplet mixture compositions and systems and methods for forming mixtures of droplets. The system may comprise two or more droplet generation units. Each unit may include at least one first input well, a second input well, and an output well connected to the first and second input wells by channels that form a droplet generator. The combined droplet populations can be mixed, heated, and collected for multiple uses, such as for use as calibration standards for instrument testing and analysis.

Droplet producing device, droplet producing method, liposome producing method, fixture, and droplet producing kit

A droplet producing device includes an outer tube; and an inner tube that is arranged inside the outer tube and feeds a droplet raw material, in which an inner tube discharge port opens to an inner tube tip portion formed on a downstream in a fluid feed direction, an outer tube discharge port opens to an outer tube tip portion formed on the downstream in the fluid feed direction, and in which a gap is formed between the outer tube and the inner tube.

SYSTEM FOR GENERATING DROPLETS - INSTRUMENTS AND CASSETTE

System, including methods, apparatus, and kits, for forming emulsions. An exemplary system may comprise a device including a sample well configured to receive sample-containing fluid, a continuous-phase well configured to receive continuous-phase fluid, and a droplet well. The device also may include a channel network having a first channel, a second channel, and a third channel that meet one another in a droplet-generation region. The system also may comprise a holder for the device. The system further may comprise an instrument configured to operatively receive an assembly including the device and the holder and to drive sample-containing fluid from the sample well to the droplet-generation region via the first channel, continuous-phase fluid from the continuous-phase well to the droplet-generation region via the second channel, and sample-containing droplets from the droplet-generation region to the droplet well via the third channel. 1. A system for generating droplets , comprising:a device including a sample well configured to receive sample-containing fluid, a continuous-phase well configured to receive continuous-phase fluid, and a droplet well, the device also including a channel network having a first channel, a second channel, and a third channel that meet one another in a droplet-generation region;a holder for the device; andan instrument configured to operatively receive an assembly including the device and the holder and to drive sample-containing fluid from the sample well to the droplet-generation region via the first channel, continuous-phase fluid from the continuous-phase well to the droplet-generation region via the second channel, and sample-containing droplets from the droplet-generation region to the droplet well via the third channel.2. The system of claim 1 , further comprising a gasket configured to engage a rim of at least one of the wells.3. The system of claim 2 , wherein the gasket also is configured to engage the holder.4. The system of ...

THERMALLY COMPENSATED MICROFLUIDIC STRUCTURES

Exemplary liquid lenses generally include two liquids disposed within a microfluidic cavity disposed between a first window and a second window. Applying varying electric fields to these liquid lenses can vary the wettability of one of the liquids with respect to this microfluidic cavity, thereby varying the shape and/or the curvature of the meniscuses formed between the two liquids and, thus, changing the optical focal length or the optical power of the liquid lenses. These liquids can expand and/or contract as result of varying temperatures. The exemplary liquid lenses include one or more thermal compensation chambers to allow these liquids to expand and/or contract without impacting the integrity of the microfluidic cavity, for example, without bowing or deflecting the first window and/or the second window. 1. A thermally compensated fluidic device , comprising:a fluidic cavity disposed between a first window and a second window;at least one liquid disposed within the fluidic cavity;a thermal compensation chamber; anda fluidic pathway that connects the fluidic cavity and the thermal compensation chamber;wherein a volume of the thermal compensation chamber increases in response to an increase in a temperature of the thermally compensated fluidic device;wherein the volume of the thermal compensation chamber decreases in response to a decrease in the temperature of the thermally compensated fluidic device;wherein the at least one liquid is transferred from the fluidic cavity to the thermal compensation chamber in response to the increase in the volume of the thermal compensation chamber; andwherein the at least one liquid is transferred from the thermal compensation chamber to the fluidic cavity in response to the decrease in the volume of the thermal compensation chamber.2. The thermally compensated fluidic device of claim 1 , wherein the at least one liquid comprises:a first liquid; anda second liquid that is substantially immiscible with the first liquid.3. The ...

MICROFACS FOR DETECTION AND ISOLATION OF TARGET CELLS

The present invention relates to the detection and isolation of target cells based on microfluidics and cell sorting technology (MicroFACS). In this method the biological cells and microparticles are encapsulated inside hydrodynamically generated droplets and analyzed using suitable optics based on fluorescence and scattering signals. Once the target cells are detected, the optics triggers electro-coalescence for sorting of the target cells into an aqueous stream. 1. A microfluidic device for analysis , sorting and demulsification of biological cells and microparticles from a complex mixture , the device comprising:a. focusing and encapsulation moduleb. optical detection modulec. electro-coalescence modulewherein the rapid extraction of the target cells or microparticles from droplets into a co-flowing stream of aqueous phase or in single-cell format without any damage to the cells,wherein the hydrodynamic focusing and encapsulation module consists of one inlet for introducing the sample fluid, second inlet for introducing a sheath fluid for focusing cells or microparticles into a single-file stream, and third inlet for introducing an immiscible phase, wherein the flow rates of the sample, sheath and the continuous phase are adjusted in the encapsulation module such that the rate of arrival of cells or microparticles at the droplet junction matches with the droplet generation rate so the number of empty droplets is reducedwherein the optical detection module consists of a fluidic channel, a number of optical grooves placed at a predetermined angle with the fluid channel, laser source, fibres, filter and high-speed detectors, wherein the target cells or microparticles are detected by using a combination of the fluorescence, forward scatter and side scatter signatureswherein the electro-coalescence module consists of a microchannel with two inlets in which the aqueous droplets containing the cells are in continuous contact with the interface between the continuous ...