СИНХРОНИЗИРОВАННАЯ КЛАСТЕРНАЯ ВИЗУАЛИЗАЦИЯ БИБЛИОТЕКИ АМПЛИФИЦИРОВАННЫХ ФРАГМЕНТОВ ГЕНОМНОЙ ДНК С СОХРАНЕННОЙ НЕПРЕРЫВНОСТЬЮ

Настоящее изобретение относится к области биотехнологии, в частности к способу идентификации образца, из которого был сгенерирован конкретный набор матричных цепей, включающий генерирование серии синхронизированных кластерных изображений для множества фрагментов библиотеки с сохраненной непрерывностью из образца генома, причем каждое синхронизированное кластерное изображение в серии генерируют последовательно. Также раскрыта система для осуществления указанного способа. Изобретение эффективно для идентификации образца, из которого был сгенерирован конкретный набор матричных цепей. 3 н. и 23 з.п. ф-лы, 11 ил., 2 пр.

ПРИВЕДЕНИЕ В ДЕЙСТВИЕ ИМПУЛЬСНЫМ МАГНИТНЫМ ПОЛЕМ ДЛЯ ЧУВСТВИТЕЛЬНЫХ АНАЛИЗОВ

Группа изобретений относится к медицине, а именно к лабораторной диагностике, и может быть использована для управления перемещением магнитных или намагничиваемых объектов в картридже биосенсора. Для этого проводят следующие этапы, на которых: (a) предоставляют картридж биосенсора с проходящей в боковом направлении поверхностью сенсора и, по меньшей мере, средство формирования магнитного поля для формирования магнитного поля с градиентом поля, перпендикулярным к поверхности сенсора; (b) попеременно приводят в действие средство формирования магнитного поля таким образом, чтобы сформированное магнитное поле попеременно направляло магнитные или намагничиваемые объекты перпендикулярно к поверхности сенсора от поверхности сенсора и к ней, причем длины импульсов попеременного приведения в действие подбираются таким образом, чтобы во время упомянутого попеременного приведения в действие не допускалось бокового перемещения намагничиваемых объектов вдоль проходящей в боковом направлении поверхности ...

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.

СИСТЕМЫ И СПОСОБЫ ПРИМЕНЕНИЯ МАГНИТОЧУВСТВИТЕЛЬНЫХ ДАТЧИКОВ ДЛЯ ОПРЕДЕЛЕНИЯ ГЕНЕТИЧЕСКОЙ ХАРАКТЕРИСТИКИ

УСТРОЙСТВО "ОРГАН НА ИНТЕГРАЛЬНОЙ СХЕМЕ"

... 1. Автономное устройство «орган на интегральной схеме» (1), содержащее: ! (a) по меньшей мере, один резервуар для подачи среды (2); и ! (b) по меньшей мере, одну секцию роста органов (3), содержащую, по меньшей мере, одну полость для органов (4, 4а, 4b); и ! где резервуар для подачи среды (2) соединяется, по меньшей мере, с одной секцией роста органов (3) посредством микрожидкостного канала подачи (6) и, по меньшей мере, с одной полостью для органов (4, 4а, 4b). ! 2. Автономное устройство «орган на интегральной схеме» (1) по п.1, где секция роста органов (3) содержит полость для стволовых клеток (9). !3. Автономное устройство «орган на интегральной схеме» (1) по п.1, дополнительно содержащее, по меньшей мере, один резервуар для сброса среды (5), где, по меньшей мере, одна полость для органов (4, 4а, 4b) соединяется, по меньшей мере, с одним резервуаром для сброса среды (5) посредством микрожидкостного канала сброса (7). ! 4. Автономное устройство «орган на интегральной схеме» (1) по п.1 ...

МИКРОЖИДКОСТНОЕ УСТРОЙСТВО

... 1. Микрожидкостное устройство, содержащее: ! множество камер (3, 4, 5, 6), выполненных с возможностью осуществления химических, биохимических или физических процессов; ! путь (9) прохождения, соединяющий множество камер (3, 4, 5, 6), выполненных с возможностью размещения, по меньшей мере, одной магнитной частицы (7), проходящей одну за другой множество камер; ! множество камер (3, 4, 5, 6), разделенных, по меньшей мере, одной структурой (10), подобной клапану, выполненной с возможностью разрешение прохождения, по меньшей мере, одной магнитной частицы (7) из одной из множества камер в другую из множества камер; и ! по меньшей мере, одну замедляющую структуру (11, 111), выполненную с возможностью замедления перемещения, по меньшей мере, одной магнитной частицы (7) вдоль пути прохождения посредством остановки управляемым способом перемещения, по меньшей мере, одной магнитной частицы (7) и посредством возобновления перемещения управляемым способом, по меньшей мере, одной магнитной частицы ( ...

УСТРОЙСТВО ДЛЯ АНАЛИЗОВ И СПОСОБ ВЫПОЛНЕНИЯ БИОЛОГИЧЕСКИХ АНАЛИЗОВ

... 1. Анализирующее устройство, содержащее реакционное пространство и, по меньшей мере, два набора индивидуально закодированных микроносителей (2), в которомреакционное пространство является микроканалом (1);при этом микроносители (2) имеют форму относительно сечения микроканала (1), которая позволяет иметь по всей длине микроканала (1), по меньшей мере, два каких-либо микроносителя (2), расположенных бок о бок без соприкосновения друг с другом и без соприкосновения с периметром микроканала (1);при этом устройство (1) содержит средство (4) для ограничения перемещения микроносителей (2) в продольном направлении микроканала (1), наряду с тем, что жидкости все еще могут протекать; акод микроносителей является указывающим на функцию.2. Анализирующее устройство по п.1, в котором микроканал (1) прозрачен, по меньшей мере, с одной стороны и/или, по меньшей мере, на одном участке есть возможность оптического наблюдения за микроносителями (2).3. Анализирующее устройство, по п.1, в котором сечение микроканала ...

КОРРЕКЦИЯ ФАЗИРОВАНИЯ

УСТРОЙСТВО ДЛЯ УХОДА ЗА ПОЛОСТЬЮ РТА

... 1. Устройство для ухода за полостью рта, содержащее:головку;ручку; ипо меньшей мере одну конусовидную щетинку, отходящую от передней поверхности головки, при этом конусовидная щетинка имеет продольную ось и профиль поперечного сечения, имеющий большую ось и малую ось, причем большая ось длиннее малой оси,при этом профиль поперечного сечения конусовидной щетинки представляет собой ромб,при этом устройство для ухода за полостью рта содержит множество конусовидных щетинок, расположенных в пучке щетинок, который отходит от передней поверхности головки,множество конусовидных щетинок в пучке щетинок содержит первую щетинку из конусовидных щетинок и вторую щетинку из конусовидных щетинок, при этом большая ось первой щетинки из конусовидных щетинок не параллельна большой оси второй щетинки из конусовидных щетинок.2. Устройство для ухода за полостью рта по п. 1, в котором отношение большой оси к малой оси больше или равно 1,2:1.3. Устройство для ухода за полостью рта по п. 1, в котором отношение ...

Mikrofluidische Glykananalyse

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

Screening-Testsystem mit hohem Durchfluss durch mikrofluidische Vorrichtungen

Procedure for carrying out PCR in DNA molecules, in a microreaction chamber, comprises continuous supply of nanoparticle compositions into the microreaction chamber through supply channels

The procedure for carrying out PCR in DNA molecules, in a microreaction chamber, involves continuous supply of nanoparticle compositions into the microreaction chamber through supply channels (15a, 15b, 15c). Different nanoparticle compositions react with one another to form nanoparticle reaction product (25). The formed products are continuously taken from the microreaction cell of the reactor. The first supplied nanoparticle composition is functionalized at the surface before its supply into the chamber. The functionalization is formed on the first nanoparticle composition by a layer. The procedure for carrying out PCR in DNA molecules, in a microreaction chamber, comprises continuous supply of nanoparticle compositions into the microreaction chamber through supply channels (15a, 15b, 15c). Different nanoparticle compositions react with one another to form nanoparticle reaction product (25). The formed reaction products are continuously taken from the microreaction cell of the reactor ...

Manipulation device for sample, particularly for biological sample, has sample carrier for receiving sample, and magnet element, which is moved with sample carrier by external magnetic field

The manipulation device has a sample carrier (2) for receiving a sample (1), and a magnet element (3), which is moved with the sample carrier by an external magnetic field. The magnet element is structurally separated from the sample carrier and is coupled mechanically with the sample carrier.

Lab on a chip device

Viscosity measurements

Sequencer

Method and apparatus for manipulating particles

Microfluidic photoporation

Microfluidic chip with conic bead trapping cavities and fabrication thereof

Fluid flow control in a microfluidic device

The invention relates to controlling a flow of fluids in a microfluidic device (10), the microfluidic device (10) having a fluid channel (140), comprising applying a magnetic field to at least a part of the fluid channel (141, 142) to force at least a portion of a first fluid to retain in at least a portion of the fluid channel (140).

Particle sorting in a tailored landscape

Optical sorting

Additive channels

Method

Biosensor conditioning method and system

A method of detecting a target biological entity 100 in a biofluid using a sensor, wherein the biofluid comprises the biological entity and nanoparticles 122. The sensor comprises a substrate bearing a pair of electrodes 110, 112 having an affinity with the nanoparticles. The region between the electrodes defines a sensing region 104. The method comprises treating the biofluid with the nanoparticles to obtain bound nanoparticle assemblies. The bound nanoparticle assemblies are introduced to the sensor while applying an electric field to concentrate the bound nanoparticles in the sensing region. The sensor is conditioned in the presence of the bound nanoparticle assemblies by applying an activation voltage between the electrodes 110, 112. The activation voltage increases a degree of connection between the surface of the electrodes and at least one bound nanoparticle assembly. The activation voltage is sufficient to fuse the bound nanoparticle assemblies into a link or chain linking the pair ...

Removing bubbles in a microfluidic device

Particle manipulation and trapping in microfluidic devices using two-dimensional material

Flow cell liquid degassing systema and method

Microfluidic device and apparatus

Fluidic array systems and testing for cells, organoids, organs culture

Microfluidic particle sorter

Microfluidic device for detection of analytes

method of producing polyclonal antibodies, and testing methods and apparatus using such antibodies, application to differentiation of gram positive and gram

Devices and methods for detection of biomarkers

Systems and methods for automated single cell cytological classification in flow

A specific, rapid test differentiating gram positive and gram negative bacteria

Fluidic array systems and testing for cells, organoids, organs culture

A culture system comprises a fluidic plate 1 comprising at least one plurality of wells 100; a plurality of fluidic channels 101 connected to the wells. Using the culture system comprises inserting a fluid comprising a plurality of cells, organs, organoids, and cell media into the wells, and tilting (figure 1D and 2C) to create flow through the wells and channels. The wells may be connected to form a recirculation loop 103, and these loops may be connected by side channels. A lid may be present with containers for holding additional fluids (e.g. reagent, cell media, drugs, toxins etc.) The fluidic plate may be simultaneously tilted and viewed by a microscope (figure 3C). The environment may be controlled using air, nitrogen, oxygen, or carbon dioxide. Instead of tilting, a further embodiment recirculates the fluid through the wells and channels using pumps.

Compound distribution in microfluidic devices

The present invention is related to the field of microfluidics and compound distribution within microfluidic devices and their associated systems. In one embodiment, present invention aims to solve the problem of molecule and compound absorbency into the materials making up laboratory equipment, microfluidic devices and their related infrastructure, without unduly restricting gas transport within microfluidic devices.

Compositions and methods of using partial gel layers in a microfluidic device

NANO-PCR: Methods and devices for nucleic acid amplification and detection

Nano-pcr: methods and devices for nucleic acid amplification and detection

Nano-pcr: methods and devices for nucleic acid amplification and detection

Nano-pcr: methods and devices for nucleic acid amplification and detection

INDIVIDUALLY ADDRESSIERBARER MICRO-ELECTROMAGNETIC UNIT MATRIX CHIP

LIGHT-ADJUSTED, ELECTRICALKINETIC COMPOSITION OF PARTICLES AT SURFACES

DEVICE AND PROCEDURE FOR THE PROOF OF ANALYTEN BY SICHTBARMACHUNG AND SEPARATION OF AGGLUTINATION

PROCEDURE FOR THE EFFECT OF MEANS OF THERMALCAPILLARY CONVECTION ON A FLUID IN A MICRO-FLUID CIRCUIT

MANIPULATION AND TRANSPORT DEVICE FOR MAGNET BALLS

BIOCHEMISTRY ON DROPLET BASIS

MEDICINE PRODUCT FOR THE ANALYTENÜBERWACHUNG AND DRUG DELIVERY

MANIPULATION OF MICRO PARTICLES IN MICRO-FLUID SYSTEMS

PYROSEQUENZIERUNG ON DROPLET BASIS

INTEGRATED FLUID DEVICES WITH MAGNETIC ASSORTMENT

SEQUENZIERUNG BY INCORPORATION

PROCEDURE AND DEVICE FOR THE ASSORTMENT OF MICROSCOPIC PARTICLES.

MICRO-PRODUCED DEVICE TO THE ANALYSIS OF CELLS

ELECTRODE ARRANGEMENT FOR DIELEKTROPHORETI PARTICLE DIVERSON

PROCEDURE FOR CONCENTRATING ANALYTEN IN SAMPLES

MICRO-PRODUCED DEVICE FOR ANALYSIS OF CELLS

CHANNEL LOTS SEPARATION FROM BIO PARTICLES ON AN BIOELECTRONIC CHIP THROUGH DIELEKTROPHORESIS

MICRO-FLUID SYSTEM AND PROCEDURE FOR ITS ENTERPRISE

MICRO FLUID DEVICES FOR THE STEERED HANDLING OF KLEINSTVOLUMEN

Selection and cloning of T lymphocytes in a microfluidic device

Methods of expanding T lymphocytes in a microfluidic device are provided. The methods can include introducing one or more T lymphocytes into a microfluidic device; contacting the one or more T lymphocytes with an activating agent; and perfusing culture medium through the microfluidic device for a period of time sufficient to allow the one or more T lymphocytes to undergo at least one round of mitotic cell division. The expansion can be non-specific or antigen-specific. T lymphocytes produced according to the disclosed methods are also provided, along with methods of treating cancer in a subject. The methods of treating cancer can include isolating T lymphocytes from a tissue sample obtained from the subject; expanding the isolated T lymphocytes in a microfluidic device; exporting the expanded T lymphocytes from the microfluidic device; and reintroducing the expanded T lymphocytes into the subject.

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

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

Fluidic system and related methods

Fluidic systems including cartridges with modular components (cassettes) and/or microfluidic channels for performing chemical and/or biological analyses are provided. The systems described herein include a cartridge comprising, in some embodiments, a frame, one or more cassettes which may be inserted into the frame, and a channel system for transporting fluids. In certain embodiments, the one or more cassettes comprise one or more reservoirs or vessels configured to contain and/or receive a fluid (e.g., a stored reagent, a sample). In some cases, the stored reagent may include one or more lyospheres. The systems and methods described herein may be useful for performing chemical and/or biological reactions including polymerase chain reactions (PCR) such as those performed within a laboratory, clinical (e.g., hospital), or research setting.

DEVICES, SYSTEMS AND METHODS FOR EVALUATION OF HEMOSTASIS

Provided are devices, systems and methods for evaluation of hemostasis. Also provided are sound focusing assemblies.

Methods, systems and kits for in-pen assays

Methods, systems and kits are described herein for detecting the results of an assay. In particular, the methods, systems and devices of the present disclosure rely on a difference between the diffusion rates of a reporter molecule and an analyte of interest in order to quantify an amount of analyte in a microfluidic device. The analyte may be a secreted product of a biological micro-object.

Oriented Loading Systems And Method For Orienting A Particle Loaded In A Well

An oriented loading system is provided. The oriented loading system includes a substrate, a plurality of wells formed in the substrate, each well having a bottom and sidewalls, a plurality of particles loaded in the wells, wherein the particle comprises a core structure and an inner layer comprising magnetic material partially covering the core structure such that a part of the core structure uncovered by the inner layer is exposed, and a metal layer comprising magnetic material deposited partially in the sidewalls of the wells, wherein the inner layer is attracted by the metal layer such that the exposed core structure is oriented towards the bottom of the well or the inner layer is oriented towards the bottom of the well.

Detection and analysis of cells

The invention provides a version of fluorescent in situ hybridization (FISH) in which all the steps are performed at physiological temperatures, i.e., body temperature, to detect and identify pathogenic bacteria in clinical samples. Methods of the invention use species-specific fluorescent probes to label clinically important infectious bacteria. A sample such as a urine sample is loaded into a cartridge, fluorescently labeled, and imaged with a microscope. Labelled bacteria are pulled down onto an imaging surface and a dye cushion is used to keep unbound probes off of the imaging surface. A microscopic image of the surface shows whether and in what quantities the infectious bacteria are present in the clinical sample.

DEVICES, SYSTEMS AND METHODS FOR EVALUATION OF HEMOSTASIS

Provided are devices, systems and methods for evaluation of hemostasis. Also provided are sound focusing assemblies. WO 2013/105986 PCT/US2012/025270 __~~ ~FG IF '~1y_ Bi il 116 114 112 110 FI.1 -ill.

Individually addressable micro-electromagnetic unit array chips

Concentration and dispersion of small particles in small fluid volumes using acousting energy

APPARATUS FOR MOVING PARTICLES FROM A FIRST FLUID TO A SECOND FLUID

Microfluidic platforms for multi-target detection

Micro channel array

Nano-PCR: methods and devices for nucleic acid amplification and detection

Devices and method for enrichment and alteration of cells and other particles

SUBSTRATES, DEVICES, AND METHODS FOR CELLULAR ASSAYS

Microfluidic nucleic acid analysis

Method and device for isolating cells from heterogeneous solution using microfluidic trapping vortices

A method of isolating cells includes providing a microfluidic device having at least one microfluidic channel coupled to an inlet and an outlet, the at least one microfluidic channel comprises at least one expansion region disposed along the length thereof. The at least one expansion region is an abrupt increase in a cross-sectional dimension of the at least one microfluidic channel configured to generate a vortex within the at least one expansion region in response to fluid flow. A solution containing a population of cells at least some of which have diameters 10 µm flows into the inlet. A portion of cells is trapped within vortex created within the at least one expansion region. The trapped cells may then released from the expansion region.

Medical device for analyte monitoring and drug delivery

MEDICAL DEVICE FOR ANALYTE MONITORING AND DELIVERY 5 Disicosed is an ingestible, implantable or wearable medical device comprising a microarray which comprises a bioactive agent capable of interacting with a disease marker biological analyte; a reservoir which comprises at least one therapeutic agent and is capable of releasing the therapeutic agent(s) from the medical device; and a plurality of microchips comprising a microarray scanning device capable of obtaining physical 10 parameter data of an interaction between the disease marker biological analyte with the bioactive agent; a biometric recognition device capable of comparing the physical parameter data with an analyte interaction profile; optionally a therapeutic agent releasing device capable of controlling release of the therapeutic agent from the reservoirs; an interface device capable of facilitating communications between the microarray scanning 15 device, biometric recognition device and the therapeutic agent releasing device ...

Microstructure for particle and cell separation, identification, sorting, and manipulation

MICROFLUIDIC SYSTEM INCLUDING A BUBBLE VALVE FOR REGULATING FLUID THROUGH A MICROCHANNEL

MEMS-based integrated magnetic particle identification system

Imaging analyzer for testing analytes

Abstract The invention provides analyzers that improve tests for detecting specific cellular, viral, and molecular targets in clinical, industrial, or environmental samples. The invention permits efficient and specific selection and sensitive imaging detection of individual microscopic targets at low 5 magnification. Automated embodiments allow efficient walk-away, on-demand, random-access high-throughput testing. The analyzers perform tests without requiring wash steps thus streamlining engineering and lowering costs. Thus, the invention provides analyzers that can deliver rapid, accurate, and quantitative, easy-to-use, and cost-effective tests for analytes. 7004816_1 (GHMatters) P86909.AU.1 SARAHVV 14/10/2015 mC C c o p 0) wT ...

Imaging analyzer for testing analytes

Abstract The invention provides analyzers that improve tests for detecting specific cellular, viral, and molecular targets in clinical, industrial, or environmental samples. The invention permits efficient and specific selection and sensitive imaging detection of individual microscopic targets at low 5 magnification. Automated embodiments allow efficient walk-away, on-demand, random-access high-throughput testing. The analyzers perform tests without requiring wash steps thus streamlining engineering and lowering costs. Thus, the invention provides analyzers that can deliver rapid, accurate, and quantitative, easy-to-use, and cost-effective tests for analytes. 7004816_1 (GHMatters) P86909.AU.1 SARAHVV 14/10/2015 mC C c o p 0) wT ...

Passive separation of whole blood

Described are systems, methods, and kits for compression sedimentation and whole blood separation. For example, a compression sedimentation system may include a compression stage configured to accept a flexible reservoir configured to contain a liquid mixture. The compression stage may include a base substrate and a compression substrate configured to apply a force to the flexible reservoir effective to create a pressure in the liquid mixture. An apparatus for whole blood separation may include a sedimentation system that separates whole blood into a supernatant including platelet rich plasma and a subnatant including red blood cells. At least one platelet-concentrating device may be included to receive the supernatant including the PRP and to separate a platelet concentrate and a platelet poor plasma from the supernatant.

Microfluidic devices and methods for use thereof in multicellular assays of secretion

Methods and devices are provided herein for identifying a cell population comprising an effector cell that exerts an extracellular effect. In one embodiment the method comprises retaining in a microreactor a cell population comprising one or more effector cells, wherein the contents of the microreactor further comprise a readout particle population comprising one or more readout particles, incubating the cell population and the readout particle population within the microreactor, assaying the cell population for the presence of the extracellular effect, wherein the readout particle population or subpopulation thereof provides a direct or indirect readout of the extracellular effect, and determining, based on the results of the assaying step, whether one or more effector cells within the cell population exerts the extracellular effect on the readout particle. If an extracellular effect is measured, the cell population is recovered for further analysis to determine the cell or cells responsible ...

Microfluidics sorter for cell detection and isolation

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

A method and a system for quantitative or qualitative determination of a target component

The invention relates to a method and a system for quantitative or qualitative determination of a target component in a liquid sample. The method comprises i) providing a plurality of magnetic particle comprising one or more capture sites for the target component on their respective surfaces; ii) providing a plurality of fluorophores configured to bind to the capture sites of the magnetic particles; iii) bringing the liquid sample into contact with the fluorophores and the magnetic particles in a flow channel of a micro fluidic device comprising a transparent window; and iv) at least temporally immobilizing the magnetic particles adjacent to the transparent window using a magnet, emitting exciting electromagnetic beam towards the immobilized magnetic particles, reading signals emitted from fluorophores captured by the immobilized magnetic particles and performing a quantitative or qualitative determination of the target component based on the read signal. The invention also relates to a ...

A method and a system for quantitative or qualitative determination of a target component

The invention relates to a method and a system for quantitative or qualitative determination of a target component in a liquid sample. The method comprises i) providing a plurality of magnetic particle comprising one or more capture sites for the target component on their respective surfaces; ii) providing a plurality of fluorophores configured to bind to the capture sites of the magnetic particles; iii) bringing the liquid sample into contact with the fluorophores and the magnetic particles in a flow channel of a micro fluidic device comprising a transparent window; and iv) at least temporally immobilizing the magnetic particles adjacent to the transparent window using a magnet, emitting exciting electromagnetic beam towards the immobilized magnetic particles, reading signals emitted from fluorophores captured by the immobilized magnetic particles and performing a quantitative or qualitative determination of the target component based on the read signal. The invention also relates to a ...

Method for producing microcarriers

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

Biomolecule isolation

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

Freezing and archiving cells on a microfluidic device

A method of processing and storing biological cells includes introducing a flowable medium into a microfluidic device, the flowable medium including biological cells; sequestering one or more biological cells from the flowable medium in one or more isolation regions of the microfluidic device; and freezing the microfluidic device including the one or more biological cells sequestered therein.

Method and device for isolating cells from heterogeneous solution using microfluidic trapping vortices

A method of isolating cells includes providing a microfluidic device having at least one microfluidic channel coupled to an inlet and an outlet, the at least one microfluidic channel 5 comprises at least one expansion region disposed along the length thereof. The at least one expansion region is an abrupt increase in a cross-sectional dimension of the at least one microfluidic channel configured to generate a vortex within the at least one expansion region in response to fluid flow. A solution containing a population of cells at least some of which have diameters > 10 pm flows into the inlet. A portion of cells is trapped within vortex created within 0 the at least one expansion region. The trapped cells may then released from the expansion region.

A System and Method for Particle Filtration

Embodiments of the present disclosure feature a filtration system comprising a filtration module for particle filtration and methods of using the device for the isolation of particles (e.g., viable cells). Advantageously, embodiments of the device provide for the high throughput filtration of large volumes of sample while preserving cell viability and. providing high yields.

Separation and analysis of samples bymicrofluidic free-flow electrophoresis

A microfluidic device (11) is provided for separation and analysis of microfluidic samples. The device comprises: a separation channel (10); a first electrolyte channel (12) configured to provide a flow of high conductivity electrolyte solution, in use; and provided with a positive electrode (13) at a downstream outlet of the channel; a second electrolyte channel (14) configured to provide a flow of high conductivity electrolyte solution, in use, and provided with a negative electrode (15) at a downstream outlet of the channel; and wherein the flow of electrolyte through the first and second electrolyte channels removes electrophoresis products and gas bubbles from the device; and wherein the presence of the electrolyte provides a substantially homogenous electric field across the separation channel.

Open-top microfluidic devices and methods for simulating a function of a tissue

A device for simulating a function of a tissue includes a first structure, a second structure, and a membrane. The first structure defines a first chamber. The first chamber includes a matrix disposed therein and an opened region. The second structure defines a second chamber. The membrane is located at an interface region between the first chamber and the second chamber. The membrane includes a first side facing toward the first chamber and a second side facing toward the second chamber. The membrane separates the first chamber from the second chamber.

High throughput, feedback-controlled electroporation microdevice for efficient molecular delivery into single cells

Systems and methods for cell electroporation and molecular delivery using an intelligent, feedback controlled, microscale electroporation system for transfecting single cells.

Microfluidic device for detection of analytes

A microfluidic device for detection of an analyte in a fluid is described. The microfluidic device comprises a substrate having a first surface defining entrances to one or more chambers defined in the substrate, surfaces of the chambers defining a second surface of the substrate, the first surface being modified for selective targeting and capture of at least one analyte to operably effect a blocking of the entrance to at least one of the chambers, and wherein a response characteristic of the microfluidic device is operably varied by the blocking of the entrance to the at least one of the chambers, thereby providing an indication of the presence of the analyte within the fluid.

Microfluidic system including a bubble valve for regulating fluid flow through a microchannel

A microfluidic system includes a bubble valve for regulating fluid flow through a microchannel. The bubble valve includes a fluid meniscus interfacing the microchannel interior and an actuator for deflecting the membrane into the microchannel interior to regulate fluid flow. The actuator generates a gas bubble in a liquid in the microchannel when a sufficient pressure is generated on the membrane.

Platelet aggregation using a microfluidics device

A microfluidics device to provide real time monitoring of platelet aggregation of a biological sample obtained from a subject. The device comprises a channel configured for passage of the biological sample, the channel comprising a protrusion configured to induce an upstream region of shear acceleration coupled to a downstream region of shear deceleration and defining there-between a region of peak rate of shear, the downstream region of shear deceleration defining a zone of platelet aggregation. The device further comprises a platelet detection means for detecting aggregation of platelets in the zone of aggregation as a result of passage of the biological sample through the channel. Methods to assess real time platelet aggregation of a biological sample obtained from a subject are further described.

Electromagnetic multiplex assay biosensor

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

Channel and method of forming channels

A device is made by forming sacrificial fibers on a substrate mold. The fibers and mold are covered with a first material. The substrate mold is removed, and the covered fibers are then removed to form channels in the first material.

Multi-Shell Microspheres With Integrated Chromatographic And Detection Layers For Use In Array Sensors

The development of miniaturized chromatographic systems localized within individual polymer microspheres and their incorporation into a bead-based cross-reactive sensor array platform is described herein. The integrated chromatographic and detection concept is based on the creation of distinct functional layers within the microspheres. In this first example of the new methodology, complexing ligands have been selectively immobilized to create “separation” layers harboring an affinity for various analytes. Information concerning the identities and concentrations of analytes may be drawn from the temporal properties of the beads' optical responses, Varying the nature of the ligand in the separation shell yields a collection of cross-reactive sensing elements well suited for use in array-based micro-total-analysis systems.

Multiple laminar flow-based particle and cellular separation with laser steering

The invention provides a method, apparatus and system for separating cellular components, and can be combined with holographic optical trapping manipulation or other forms of optical tweezing. One exemplary method includes providing a first flow having a plurality of components; providing a second flow; contacting the first flow with the second flow to provide a first separation region; and differentially sedimenting a first cellular component of the plurality of components into the second flow while concurrently maintaining a second cellular component of the plurality of components in the first flow. The second flow having the first cellular component is then differentially removed from the first flow having the second cellular component. Holographic optical traps may also be utilized in conjunction with the various flows to move selected components from one flow to another, as part of or in addition to a separation stage.

Cell concentration, capture and lysis devices and methods of use thereof

The present invention provides a microfluidic devices and methods of use thereof for the concentration and capture of cells. A pulsed non-Faradic electric field is applied relative to a sample under laminar flow, which results to the concentration and capture of charged analyte. Advantageously, pulse timing is selected to avoid problems associated with ionic screening within the channel. At least one of the electrodes within the channel is coated with an insulating layer to prevent a Faradic current from flowing in the channel. Under pulsed application of a unipolar voltage to the electrodes, charged analyte within the sample is moved towards one of the electrodes via a transient electrophoretic force.

Devices and method for enrichment and alteration of cells and other particles

The invention features devices and methods for the deterministic separation of particles. Exemplary methods include the enrichment of a sample in a desired particle or the alteration of a desired particle in the device. The devices and methods are advantageously employed to enrich for rare cells, e.g., fetal cells, present in a sample, e.g., maternal blood and rare cell components, e.g., fetal cell nuclei. The invention further provides a method for preferentially lysing cells of interest in a sample, e.g., to extract clinical information from a cellular component, e.g., a nucleus, of the cells of interest. In general, the method employs differential lysis between the cells of interest and other cells (e.g., other nucleated cells) in the sample.

Minimally invasive cytometry system with qcl inspection of single cells for cancer detection

This disclosure concerns a minimally invasive cytometry system including a handling system that presents single cells to at least one QCL laser source. The QCL laser source is configured to deliver light to a cell within the cells in order to induce vibrational bond absorption in one or more analytes within the cell. The cytometry system also includes a detection facility that detects the mid-infrared wavelength light transmitted by the cell and identifies the cell as either cancerous or non-cancerous.

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.

Devices and methods for interfacing microfluidic devices with macrofluidic devices

The present disclosure is directed generally to devices and methods with the purpose of interfacing microfluidic devices with macrofluidic devices. Specifically, the present disclosure includes the de-

Microfluidic system and method for automated processing of particles from biological fluid

A microfluidic system for automatically depleting particles not of interest from a biological sample, comprising: a sampling module configured to receive the sample; and one or more microfluidic protein and nucleic acid depletion modules fluidically coupled to the sampling module and comprising binding agents configured to selectively bind to abundant plasma proteins or nucleic acids. A method for automatically depleting particles not of interest from a sample, comprising: receiving the sample; subjecting the sample to a force that separates at least a portion of the particles not of interest from the sample, thereby isolating at least a portion of the target component; passing the isolated target copmonent into a chamber; circulating the isolated target component in the chamber; and selectively capturing proteins or nucleic acids with binding agents within the chamber.

Magnetic sample purification

The invention relates to means for extracting magnetic particles (M) from a sample (S). The sample (S) is arranged adjacent to a liquid carrier (C), which is immiscible with it, in a configuration stable under the influence of gravity, and the magnetic particles (M) are moved by a magnetic field (B) from the sample (S) into the carrier (C). Preferably, the magnetic particles (M) are non-wetting with respect to the carrier (C) and will therefore form agglomerates in the carrier (C).

Microfluidic device and method of manufacturing the microfluidic device

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

Flow through metallic nanohole arrays

The present invention presents a device and methods of use thereof in combined electrohydrodynamic concentration and plasmonic detection of a charged species of interest using a flow-through nanohole array. The device comprises microchannels, which are linked to a substrate with arrays of through nanoholes, wherein the substrate comprises two layers, wherein one of the layers is made of insulator material and one of the layers is made of metal, whereby induction of an electric field across the nanohole array results in the species of interest concentrating inside the nanoholes and in the vicinity of the nanohole arrays. The induction of an electric field is achieved by means of an external electric field source, which is applied to the fluid containing the species of interest, resulting in electroosmotic (EO) flow. An additional pressure driven fluid flow in the microchannels, co-directional to the EO flow is applied by external means. The resulting fluid flow from the combination of the EO and pressure driven flow results in a total bulk fluid flow hereafter referred to as bulk flow (BF). The local electric field strength across the insulator layer of the nanoholes is high and the charged species in the fluid may exhibit a high electrophoretic (EP) velocity, opposing the BF. The local field strength in the metallic portion of the nanoholes is null, due to the conducting nature of the metal, and the charged species in the fluid exhibits a null EP velocity in this region. The BF and the EP velocity of the charged species may be balanced which may result in the concentration of the charged species inside the nanoholes and at both sides of the nanohole array. An incident light over one side of the nanohole array may result in the formation of surface plasmons (SP) at the interface of the metal and the surrounding liquid containing the concentrated species. The signal from the SP may be detected by optical means, including surface plasmon resonance (SPR) imaging and SPR ...

Sheath flow devices and methods

The invention relates generally to fluid processing and, in particular aspects, processing fluids for detection, selection, trapping and/or sorting of particulate moieties. Sheath flow devices described allow isolation of target species from fluid samples while avoiding non-specific binding of unwanted species to the surfaces of the separation device. Biological fluid processing, detection, sorting or selection of cells, proteins, and nucleic acids is described. The invention finds particular use in diagnostic settings, analyzing a patient's medical condition, monitoring and/or adjusting a therapeutic regimen and producing cell based products.

Particle Analysis in an Acoustic Cytometer

The present invention is a method and apparatus for acoustically manipulating one or more particles.

Multi-Sample Particle Analyzer and Method for High Throughput Screening

Embodiments of the present invention provide a system and method for analyzing a plurality of samples comprising obtaining with an autosampler a plurality of samples from a first plate having a plurality of sample wells wherein the autosampler has a plurality of probes for sampling a set of samples and wherein each probe of the plurality of probes is in communication with a separate flow cytometer via a separate conduit. The plurality of samples comprising particles is moved into a fluid flow stream for each separate conduit. Adjacent ones of the plurality of samples are separated from each other in the fluid flow stream by a separation gas, thereby forming a gas-separated fluid flow stream. The gas-separated fluid flow stream is independently guided to and through each separate flow cytometer.

Method and system for transferring and/or concentrating a sample

A method of controlling the concentration of a sample flowing through a microchannel is provided. The method includes flowing a sample carrier fluid from a sample carrier channel and into an upstream portion of a microchannel such that the sample carrier fluid flows from the upstream portion and toward a downstream portion of the microchannel, and flowing a sheathing fluid from a sheathing fluid channel and into the upstream portion of the microchannel such that the sheathing fluid flows from the upstream portion and toward the downstream portion of the microchannel, and generally parallel to the sample carrier fluid. The method further includes detecting a concentration of a sample in the sample carrier fluid in the downstream portion of the microchannel, and adjusting a flow rate of at least one of the sample carrier fluid and the sheathing fluid based upon the detected concentration of the sample.

Bioprinting station, assembly comprising such bioprinting station and bioprinting method

Bioprinting station (1) comprising:—a Bioprinting device (4) adapted to deposit a pattern of biological material (2) onto an area of interest (3 a ) of a substrate (3),—an imaging system (15) adapted to acquire an image of the substrate (3) and to reveal on the acquired image the area of interest (3 a ) with respect to a remaining part (3 b ) of the substrate (3), the acquired image of the substrate (3) being processed so as to detect the revealed area of interest (3 a ) on the acquired image and to determine the pattern corresponding to the area of interest (3 a ) detected on the acquired image.

Sample processing device and method

A sample processing device is disclosed, which sample processing device comprises a first substrate and a second substrate, where the first substrate has a first surface comprising two area types, a first area type with a first contact angle with water and a second area type with a second contact angle with water, the first contact angle being smaller than the second contact angle. The first substrate defines an inlet system and a preparation system in areas of the first type which two areas are separated by a barrier system in an area of the second type. The inlet system is adapted to receive a sample liquid comprising the sample and the first preparation system is adapted to receive a receiving liquid. In a particular embodiment, a magnetic sample transport component, such as a permanent magnet or an electromagnet, is arranged to move magnetic beads in between the first and second substrates.

Chamber free nanoreactor system

Aspects of the invention include methods for improving the accuracy and read length of sequencing reactions by utilizing unlabeled unincorporable nucleotides, or by rephasing colony based sequencing reactions. Other aspects include systems and devices for improved measurement of biological reactions associated with bead which may be removed, utilizing current measurement methods through the counter ions associated with said beads due to the presence of reactants bound or associated with said bead, wherein electrodes for generating and measuring said current may be within the Debye length of said bead. Other aspects of the invention include methods for determining concentrations of input samples, means for reuse of an array, methods and apparatus for separating beads with different charge levels from each other.

Method and Apparatus for a Microfluidic Device

An microfluidic device and methods for its use, where the microfluidic device comprises: (a) a porous membrane, (b) a gradient layer defining a plurality of gradient micro-channels, where the gradient layer is coupled to a top surface of the membrane, (c) a distributor layer defining a plurality of distributor micro-channels, where the distributor micro-channels are coupled to the plurality of gradient micro-channels, where the distributor layer defines at least one inlet opening and at least one outlet opening, each inlet opening and outlet opening are coupled to the plurality of distributor micro-channels, and (d) self-supporting means coupled to one or more of the porous membrane, the gradient layer and the distributor layer.

Flow Step Focusing

Flow step focusing isolates and concentrates a molecule of interest by flowing a liquid comprising a molecule of interest through a main channel having an inlet and an outlet with application of a first pressure at the inlet; applying a voltage along the channel during the flowing, wherein the voltage is configured to have a polarity such that it drives the molecule of interest in a direction opposite the flow of the liquid; controlling the first pressure and/or the voltage in a manner so as to trap and concentrate the molecule of interest in a region of the main channel; and removing the concentrated molecule of interest from the channel by recovering a portion of the liquid from a side channel diverging from the main channel, wherein the side channel is maintained at a pressure lower than the first pressure. Also disclosed is an apparatus for such.

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

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

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

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

Device and method of manipulating particles

Provided is a device and method of manipulating particles. The device includes: a channel for accommodating an electrolyte solution including particles to be manipulated; an anode and cathode for imposing a direct current (DC) electric field on the channel; metal strip(s) attached to an inner wall of the channel and resulting in induced-charge electroosmosis near a surface of the channel; a DC power supply unit for supplying a DC voltage to the anode and the cathode of the channel; control electrodes on both sides of the metal strip(s) to locally tune the induced-charge electroosmosis on the metal strip(s) regardless of the global electric field across the channel; and a DC power supply unit for supplying a DC voltage to the control electrodes.

Methods of and devices for capturing circulating tumor cells

A device and methods are provided for efficient and quick capture of target cells through a main microchannel having capture elements immobilized thereon and manipulating a velocity profile of a sample as it passes through the main microchannel. The cell capture device may have a main microchannel with a depth slightly larger than the diameter of the target cells and a plurality of side microchannels. The side microchannels may have a depth smaller than the diameter of the target cells. The device and methods may be used for early cancer detection.

Microfluidic platform for discrete cell assay

A microfluidic chamber for use in individual cell assays. The microfluidic chamber includes a cell microchamber having an interior region and front and rear valves, each of which are separately controllable so that they can be selectively opened and closed to thereby permit the transference of an individual cell into and out of the interior region. Cell secretion and contact interaction studies can be carried out using the microchambers, with the valves permitting either complete isolation or perfusion media flow through the microchambers. An internal perfusion wall can be included to partition the microchamber for non-contact perfusion studies of secretion interactions between cells.

Method and device for isolating cells from heterogeneous solution using microfluidic trapping vortices

A method of isolating cells includes providing a microfluidic device having at least one microfluidic channel coupled to an inlet and an outlet, the at least one microfluidic channel comprises at least one expansion region disposed along the length thereof. The at least one expansion region is an abrupt increase in a cross-sectional dimension of the at least one microfluidic channel configured to generate a vortex within the at least one expansion region in response to fluid flow. A solution containing a population of cells at least some of which have diameters ≧10 μm flows into the inlet. A portion of cells is trapped within vortex created within the at least one expansion region. The trapped cells may then released from the expansion region.

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.

Apparatus for separating fine particles using magnetophoresis, and method for separating fine particles using same

The present invention relates to an apparatus for separating fine particles using magnetophoresis, and to a method for separating fine particles using same, and particularly, to an apparatus for separating fine particles using magnetophoresis, which includes a fine, patterned magnetic structure capable of quickly and efficiently separating even particles that are weakly magnetized and coupled to fine particles, and to a method for separating fine particles using same.

Microfluidic cartridge for processing and detecting nucleic acids

A microfluidic cartridge, configured to facilitate processing and detection of nucleic acids, comprising: a top layer comprising a set of cartridge-aligning indentations, a set of sample port-reagent port pairs, a shared fluid port, a vent region, a heating region, and a set of Detection chambers; an intermediate substrate, coupled to the top layer comprising a waste chamber; an elastomeric layer, partially situated on the intermediate substrate; and a set of fluidic pathways, each formed by at least a portion of the top layer and a portion of the elastomeric layer, wherein each fluidic pathway is fluidically coupled to a sample port-reagent port pair, the shared fluid port, and a Detection chamber, comprises a turnabout portion passing through the heating region, and is configured to be occluded upon deformation of the elastomeric layer, to transfer a waste fluid to the waste chamber, and to pass through the vent region.

Acoustic waves in microfluidics

Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.

Method and device for high-throughput solution exchange for cell and particle suspension

A method of exchanging fluids with suspended particles includes providing a microfluidic device with a first inlet channel operatively coupled to a source of particles and a second inlet channel operatively coupled to an exchange fluid. A transfer channel is connected at a proximal end to the first inlet channel and the second inlet channel. First and second outlet channels are connected to a distal end of the transfer channel. The source of particles is flowed at a first flow rate into the first inlet channel while the exchange fluid is flowed at a second flow rate into the second inlet channel wherein the ratio of the second flow rate to the first flow rate is at least 1.5. Particles are collected in one of the first and second outlet channels while fluid substantially free of particles is collected in the other of the first and second outlet channels.

Methods and apparatus for particle introduction and recovery

Particles may be injected into a matrix for concentration by scodaphoresis using a quadrupole injection field. Particles may be injected from two or more sample chambers simultaneously. Particle injection may be performed simultaneously with performing scodaphoresis. In some embodiments the particles are concentrated into a well containing fluid. The well can extend out of a plane of the matrix. Altering the relative phases of components of a scodaphoresis field permits concentration of selected particles and exclusion of other particles. Scodaphoresis methods may be applied to DNA, other bio-molecules and other particles.

Encoded microcarriers, assay system using them and method for performing an assay

The present invention relates to an encoded microcarrier comprising a readable code attached to it for identification, said encoded microcarrier comprising a body having at least a detection surface to detect a chemical and/or biological reaction, the microcarrier further comprising at least a spacing element projecting from the body and shaped to ensure that, when the encoded microcarrier is laid on a flat plane with the detection surface facing said flat plane, a gap exists between said flat plane and the detection surface. The invention also relates to an assay device designed to use a plurality of said encoded microcarriers to perform assays. The invention relates finally to a method for monitoring a chemical or biological reaction.

Magnetic flow cytometry for high sample throughput

In a measuring device, a production thereof, and a use thereof for magnetic flow cytometry, a microfluidic channel is disposed along an enrichment route such that a magnetically marked cell sample flowing through the microfluidic channel is aligned to magnetic guide strips, enriched by the magnetic field of a magnet at the floor of the channel, and guided past a sensor. The enrichment route is thereby implemented with the microfluidic channel on the packaging of the semiconductor chip carrying the sensor. This construction ensures a long enrichment route for high throughput of large sample volumes.

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.

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

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

TWO-STAGE MICROFLUIDIC DEVICE FOR ACOUSTIC PARTICLE MANIPULATION AND METHODS OF SEPARATION

Exemplary embodiments of the present disclosure provide for two-stage microfluidic devices using surface acoustic waves, methods of use thereof, methods of making, methods of focusing and separating particles, and the like. 1. A two-stage microfluidic device , comprising: at least a first pair of surface acoustic wave generators, wherein the first pair of surface acoustic wave generators are positioned opposite one another, and', 'a first channel disposed between the first pair of surface acoustic wave generators;, 'a particle focusing stage including a second pair of surface acoustic wave generators, wherein the pair of surface acoustic wave generators are positioned opposite one another, and', 'a second channel disposed between the second pair of surface acoustic wave generators;', 'wherein the first channel and the second channel are in fluidic communication with one another., 'a particle separating stage including2. The two-stage microfluidic device of claim 1 , wherein each surface acoustic wave generator of the first pair produces a surface acoustic wave claim 1 , wherein the first pair of surface acoustic waves interfere with one another to form a periodic distribution of one or more pressure nodes and anti-nodes on the first channel.3. The two-stage microfluidic device of claim 1 , wherein the first pair of surface acoustic wave generators produce a single pressure node.4. The two-stage microfluidic device of claim 1 , wherein the interference of the surface acoustic waves generated by the first pair of surface acoustic wave generators focus particles to a first area of the first channel as the particles flow through the first channel.5. The two-stage microfluidic device of claim 4 , wherein the first area is in a center area of the first channel.6. The two-stage microfluidic device of claim 4 , wherein the flow is a non-sheath flow.7. The two-stage microfluidic device of claim 1 , wherein the first channel is interfaced with the second channel so that a ...

LATERAL CAVITY ACOUSTIC TRANSDUCER BASED MICROFLUIDIC SWITCH

A microfluidic switching device that includes an upstream microfluidic channel configured to contain a liquid having particles therein and a plurality of outlet channels coupled to the upstream microfluidic channel at a junction. A dead-end side channel or LCAT is oriented generally perpendicular to the upstream microfluidic channel and coupled to the upstream microfluidic channel at the junction, the dead-end side channel having a gas contained therein. The device includes a transducer configured to apply an external source of acoustic energy. Actuation of the transducer effectuates symmetrical oscillation of a gas/liquid boundary at the junction. Preferably, the junction comprises a bifurcation with two outlets. Further, the LCAT has a leading edge and a trailing edge and wherein the trailing edge of the LCAT is substantially aligned with the bifurcation. 1. A microfluidic switching device comprising:an upstream microfluidic channel configured to contain a liquid having particles therein;a plurality of outlet channels coupled to the upstream microfluidic channel at a junction;a dead-end side channel oriented generally perpendicular to the upstream microfluidic channel and coupled to the upstream microfluidic channel at the junction, the dead-end side channel having a gas contained therein;a transducer; andwherein actuation of the transducer effectuates symmetrical oscillation of a gas/liquid boundary at the junction.2. The microfluidic switching device of claim 1 , wherein the plurality of outlet channels comprise two outlet channels originating at a bifurcation and wherein the dead-end side channel comprises a leading edge and a trailing edge and wherein the trailing edge of the dead-end side channel is substantially aligned with the bifurcation.3. The microfluidic switching device of claim 1 , wherein a upstream microfluidic channel claim 1 , the plurality of outlet channels claim 1 , and the dead-end side channel are formed in a PDMS substrate.4. The ...

Micro-devices for disease detection

Among others, the present invention provides micro-devices for detecting or treating a disease, each comprising a first micro sensor for detecting a property of the biological sample at the microscopic level, and an interior wall defining a channel, wherein the micro sensor is located in the interior wall of the micro-device and detects the property of the biological sample in the microscopic level, and the biological sample is transported within the channel.

Apparatus for detecting tumor cells

Among others, the present invention provides apparatus for detecting circulating tumor cells, comprising a system delivery biological subject and a probing and detecting device, wherein the probing and detecting device includes a first micro-device and a first substrate supporting the first micro-device, the first micro-device contacts a biologic material to be detected and is capable of measuring at the microscopic level an electrical, magnetic, electromagnetic, thermal, optical, acoustical, biological, chemical, electro-mechanical, electro-chemical, electro-optical, electro-thermal, electro-chemical-mechanical, bio-chemical, bio-mechanical, bio-optical, bio-thermal, bio-physical, bio-electro-mechanical, bio-electro-chemical, bio-electro-optical, bio-electro-thermal, bio-mechanical-optical, bio-mechanical thermal, bio-thermal-optical, bio-electro-chemical-optical, bio-electro-mechanical-optical, bio-electro-thermal-optical, bio-electro-chemical-mechanical, physical or mechanical property, or a combination thereof, of the biologic subject.

Microfluidic and nanofluidic devices, systems, and applications

The present invention discloses the integration of programmable microfluidic circuits to achieve practical applications to process biochemical and chemical reactions and to integrate these reactions. In some embodiments workflows for biochemical reactions or chemical workflows are combined. Microvalves such as programmable microfluidic circuit with Y valves and flow through valves are disclosed. In some embodiments microvalves of the present invention are used for mixing fluids, which may be part of an integrated process. These processes include mixing samples and moving reactions to an edge or reservoir for modular microfluidics, use of capture regions, and injection into analytical devices on separate devices. In some embodiments star and nested star designs, or bead capture by change of cross sectional area of a channel in a microvalve are used. Movement of samples between temperature zones are further disclosed using fixed temperature and movement of the samples by micropumps.

Device with controlled fluid dynamics, for isolation of an analyte from a sample

Devices for use in extracting an analyte of interest from a sample are described. In one embodiment, a device is comprised of a first plurality of chambers, where one or more chambers in the plurality of chambers has a deep end and a shallow end with a depth d 1 . A channel disposed between at least two adjacent chambers in the plurality of chambers has a depth greater than d 1 . The dimensions of the chamber and channel provide control of fluid movement in the device, particularly when introducing fluid into the device for its use and during use of the device.

Microstructure for Particle and Cell Separation, Identification, Sorting, and Manipulation

The invention relates to microscale cell separating apparatus which are able to separate cells on the basis of size of the cells, interaction of the cells with surfaces of the apparatus, or both. The apparatus comprises a stepped or sloped separation element ( 16 ) interposed between an inlet region ( 20 ) and an outlet region ( 22 ) of a void that can be tilled with fluid. The void can be enclosed within a cover ( 12 ) and fluid flow through the void engages cells with the separation element. Only cells which have (or can deform to have) a characteristic dimension smaller than or equal to the distance between a step and the cover or body can pass onto or past a step. Modifications of surfaces within the apparatus can also inhibit passage of cells onto or past a step.

Microfluidic photoporation

A cell permeabilizing micro fluidic system for permeabilizing one or more cells in a fluid flow. The system has a micro fluidic channel for channeling at least one cell in a fluid flow and an optical source for generating a beam of light for permeabilizing the at least one cell, wherein the channel and the source are arranged so that the light beam and fluid flow are collinear in a permeabilization part of the channel and cells are permeabilized within the permeabilization part.

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

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

Flow control method and apparatuses

Aspects of the present disclosure are directed to the flow of analytes, particles or other materials. As consistent with one or more embodiments described herein, an apparatus includes a membrane having one or more pores in a membrane. First and second electrodes facilitate electrophoretic flow of analytes through the pore, and a third electrode controls movement of the particles in the pore by modulating the shape of an electric double layer adjacent sidewalls of pore. This modulation controls the strength of an electroosmotic field that opposes the electrophoretic flow of the analytes via the pore

Non-adherent cell support and manufacturing method

A non-adherent cell support for use as a substrate in fluidic chambers used for cell culturing and assays. The non-adherent cell support allows for the formation of sphere cultures from single cells, which can better mimic primary tumor-like behavior in the study of cancer stem cells. The non-adherent cell support can allow for adhesive culturing and may include a hydrophobic substrate having a lower body and a raised support structure extending upwardly from an upper surface of the body. The support structure comprises one or more vertically extending support members that extend from a proximal portion at the upper surface of the body to a distal end spaced from the upper surface of the body. The support structure may be formed from a biocompatible material such as poly-2-hydroxyethyl methacrylate, polydimethylsiloxane, polymethyl methacrylate, polystyrene, or a polyethylene glycol diacrylate-based hydrogel.

Mems based filter and catalizer

The present invention provides a filter for separating particles and/or catalyzer for particle reaction in a fluid. The device comprising array of passageways fabricated on a die wherein the passageway size is controlled by actuators. The passageway size is monitored and the actuators controlling the passageway size are activated conditionally upon the passageway size monitoring. Using movable actuators the passageway can achieve passageway size that is less then the fabrication minimal resolution. Proper locating, setting and/or activation of the actuators create passageways that can perform filtration of particles, trapping of particles and catalyzing particles reaction.

Novel Micropores and Methods of Making and Using Thereof

Disclosed herein are methods of making micropores of a desired height and/or width between two isotropic wet etched features in a substrate which comprises single-level isotropic wet etching the two features using an etchant and a mask distance that is less than 2× a set etch depth. Also disclosed herein are methods using the micropores and microfluidic devices comprising the micropores. 122.-. (canceled)27. The apparatus of claim 23 , wherein the at least one micropore has a zero thickness.28. The apparatus of claim 23 , wherein the width of the at least one micropore is about two times the height of the micropore.29. The apparatus of claim 23 , wherein the at least one micropore is less than about 7 μm in height.30. The apparatus of claim 23 , wherein the at least one micropore is operable as a hydrodynamic confinement claim 23 , particle trap.31. The apparatus of claim 23 , wherein the at least one micropore is operable as a picoliter droplet.32. The apparatus of claim 23 , wherein the plurality of features comprise a plurality of microchannels which are interconnected by the plurality of micropores which are ordered by decreasing pore size along a direction of a fluid. This application claims the benefit of U.S. Patent Application Ser. No. 61/062,401, filed 24 Jan. 2008, U.S. Patent Application Ser. No. 61/062,545, filed 24 Jan. 2008, and U.S. Patent Application Ser. No. 61/142,780, filed 6 Jan. 2009, all of which are herein incorporated by reference in their entirety.Employees of Sandia National Laboratories made this invention. The government has certain rights in the invention.1. Field of the InventionThe present invention generally relates to methods for embedding micropores in microchannels and devices thereof using a single-level etching process and to tailoring the physical characteristics of these micropores for biological and chemical analysis.2. Description of the Related ArtThe concept of micro total analysis systems (microTAS) introduced for ...

Microvessels, microparticles, and methods of manufacturing and using the same

A plurality of isolated microvessels including a plurality of encoded microvessels each having a microbody and a reservoir core. The microbody is configured to separate a biological or chemical substance in the reservoir core from an ambient environment surrounding the microbody. The microbody includes a transparent material that at least partially surrounds the reservoir core and facilitates detection of an optical characteristic of the substance within the reservoir core. The microbody of each microvessel includes an identifiable code that distinguishes individual microvessels of the plurality of encoded microvessels from each other. The plurality of isolated microvessels also includes a plurality of compartments each configured to separate individual microvessels of the plurality of encoded microvessels from each other.

COLUMN-BASED DEVICE AND METHOD FOR RETRIEVAL OF RARE CELLS BASED ON SIZE, AND USES THEREOF

A device and method for retrieving cells of interest, in particular rare cells, were disclosed. Tumor-derived endothelial cell clusters (TECCs) retrieved using the disclosed device and method can be used for the diagnosis and prognosis of cancer. 1. A method for detecting a tumor-derived endothelial cell cluster (TECC) in a blood sample of a subject , the method comprising:(a) obtaining a blood sample from a subject;(b) filtering the sample by passing the sample at a flow-rate selected from the group consisting of at least about 0.05 mL/min, at least about 0.10 mL/min, at least about 0.15 mL/min, at least about 0.20 mL/min, at least about 0.25 mL/min, at least about 0.30 mL/min, at least about 0.40 mL/min, and at least about 0.50 mL/min through a sieve that comprises a plurality of pores having a diameter selected from the group consisting of at least about 6 μm, at least about 7 μm, at least about 8 μm, at least about 9 μm, at least about 10 μm, at least about 12 μm, at least about 14 μm, at least about 16 μm, at least about 18 μm and at least about 20 μm;(c) lysing the cells retained on a surface of the sieve;(d) contacting the lysed cell sample from step (c) with a reverse primer from a first primer pair, the reverse primer from the first primer pair being directed to a target RNA region, and a reverse transcriptase to effect reverse transcription of the RNA into cDNA; (i) a forward primer from the first primer pair, the forward primer from the first primer pair being directed to a target cDNA region,', '(ii) a reverse primer and a forward primer from a second primer pair, the reverse primer and forward primer from the second primer pair being directed to a target DNA region, and', '(iii) a DNA polymerase to simultaneously amplify the target cDNA region and the target DNA region in a pre-amplification step; and, '(e) subsequently contacting the sample from step (d) with(f) analyzing the amplified target cDNA region and/or the amplified target DNA region;wherein ...

Microfluidic device for measuring the enzymatic activity of thiopurin s-methyltransferase

A test microfluidic strip or cartridge comprising a blood sample collection zone, red blood cell isolation zone, lysis zone, reagents mixing zone, and sensing zone for measuring the enzymatic activity thiopurine methyltransferase is disclosed. The test strip or cartridge is disclosed to be operably connected to a metering device comprising a processor, a display and a memory card.

ASSESSMENT OF MICRO-ORGANISM PRESENCE

The present disclosure relates to a consumable sample partition device and it assembly and use. The sample partition device can be used to test a sample for absence of microorganisms (sterility) and/or for concentration of said organisms (bio-burden). The sample partition device partitions the sample input volume into multiple discrete measurement zones with little or no loss of sample (e.g., zero-loss) and with little operator involvement, thereby reducing operator- and environment-based false positives. 1. A sample partition device , comprising: a well plate structure comprising a plurality of wells and a plurality of mesofluidic channels linking each well to at least one other well;', 'a compliant layer positioned over at least the wells and mesofluidic channels; and', 'a cover plate positioned over the compliant layer so as to secure the compliant layer to the well plate so as to create a sealed environment within the plurality of wells and the plurality of mesofluidic channels., 'one or more components that, when assembled, comprise2. The sample partition device of claim 1 , wherein the well plate comprises a microtiter plate.3. The sample partition device of claim 1 , wherein the compliant layer comprises a membrane having a thickness between 50 μm and 500 μm μm.4. The sample partition device of claim 1 , wherein the cover plate claim 1 , the compliant layer claim 1 , and the well plate comprise complementary alignment features which engage to align the cover plate claim 1 , the compliant layer claim 1 , and the well plate when assembled.5. The sample partition device of claim 1 , further comprising an inlet through which a sample may be introduced to the well plate and an outlet through which air may exit as the well plate is filled with the sample.6. The sample partition device of claim 1 , further comprising:an engagement layer comprising a plurality of protruding structures corresponding to locations of at least the wells within the well plate and ...

Particle separation

An example system includes an input channel having a first end and a second end to receive particles through the first end, a separation chamber, at least two output channels, and an integrated pump to facilitate flow through the separation chamber. The separation chamber is in fluid communication with the second end of the input channel. The separation chamber has a passive separation structure, the passive separation structure including an array of columns spaced apart to facilitate separation of particles in a flow based on a size of the particles. Each output channel is in fluid communication with the separation chamber to receive separated particles. The integrated pump is positioned within at least one of the input channel or one of the at least two output channels.

Microparticle separation method, microparticle separation program, microparticle separation system

A method of extracting microparticles by detecting target microparticles for extraction in a main flow path which communicates with a pressure chamber, generating for each of the detected target microparticles a change in a negative pressure in the pressure chamber communicating with the main flow path to separate and extract each of the detected target microparticles flowing in the main flow path into the pressure chamber, wherein generating the change of the negative pressure to extract the detected target microparticles comprises generating a negative change in pressure by a different amount in accordance with a separation between the detected target microparticles.

SYSTEM AND METHOD FOR DETECTION AND SORTING OF CELLS

A system and method for detection of cells and sorting of cells are disclosed. Target cells, such as circulating tumor cells (CTCs) or antigen-specific antibody producing circulating memory B cells from COVID-19 patients, may be of interest. Magnetic beads may be bound to the target cells. After which, the bead-bound target cells may be identified using an applied magnetic field. In one example, magnetic sensors may be used to detect movement of the bead-bound target cells responsive to an applied magnetic field. In another example, an optical sensor may be used to detect movement of the bead-bound target cells responsive to an applied magnetic field. Further, separate from identification of the target cells, the bead-bound target cells may be sorted using an applied magnetic field. In this way, a magnetic field may be used for target cell identification and target cell sorting in order to detect and collect target cells of interest at the single-cell resolution. 1. An apparatus configured to determining whether a magnetic bead-labeled target cell is present in a fluid , the apparatus comprising:a well configured to house the fluid containing particles and including at least one outlet;at least one magnetic field generator configured to generate a magnetic field to at least a part of the well;one or more sensors configured to generate sensor data; and control the magnetic field generator to generate the magnetic field to the at least a part of the well;', 'identify, based on the sensor data responsive to the magnetic field, the magnetic bead-labeled target cell and an associated location within the well; and', 'control the magnetic field generator, based on the associated location within the well of the magnetic bead-labeled target cell and the at least one outlet, in order to move the magnetic bead-labeled target cell toward the at least one outlet, thereby sorting the magnetic bead-labeled target cell, in order to remove the magnetic bead-labeled target cell from ...

REAL-TIME CELL-SURFACE MARKER DETECTION

Cell-separation systems and methods utilizing cell-specific microbubble tags and ultrasound-based separation are described. The methods are useful for simplification of time-consuming and costly cell purification procedures and real time apoptosis detection. 1. A cell-sorting system comprising:a flow cell for flowing a sample comprising microbubble-labeled cells and unlabeled cells, wherein the flow cell comprises one or more inlet channels, a flow channel having an upstream portion and a downstream portion, and one or more outlet channels; andone or more acoustic transducers acoustically coupled with the flow cell, wherein the one or more acoustic transducers is positioned and configured to deliver a traveling acoustic wave through the flow channel to apply an acoustic radiation force to a sample flowing through the flow channel such that the microbubble-labeled cells are displaced relative to unlabeled cells.2. The cell-sorting system of claim 1 , wherein a downstream portion of the flow channel splits into two or more outlet channels for separating the portion of the flow enriched in microbubble-labeled cells from the portion of the flow depleted of microbubble-labeled cells.3. The cell-sorting system of claim 1 , wherein the flow cell comprises a recirculating channel connecting the upstream portion and the downstream portion of the flow channel and configured to return the portion of the flow depleted of microbubble-labeled cells back into the flow cell.4. The cell-sorting system of claim 1 , wherein the portion of the sample comprising the displaced microbubble-labeled cells is flown out of at least one outlet channel.5. The cell-sorting system of claim 5 , wherein the portion of the sample comprising the displaced microbubble-labeled cells is collected into a cell collector.6. The cell-sorting system of claim 1 , wherein system comprises two or more transducers.7. The cell-sorting system of claim 6 , where the two or more transducers are configured to produce ...

MICROFLUIDIC DEVICE, SYSTEM, AND METHOD

The present invention relates to a micro-fluidic device for use in a micro-fluidic system. A rigid base structure is provided with a flexible membrane. An external magnetic driver moves from a first position to a second position underneath the micro-fluidic device whilst applying a magnetic field. A droplet containing magnetic particles will be attracted to the external magnetic driver. The flexible membrane is thin, and therefore the micro-fluidic device can be brought closer to the external magnetic driver, thus increasing the magnetic force incident on the fluid drop. A force will be exerted on the flexible membrane, so deflecting the flexible membrane, thus bringing the droplet containing magnetic particles closer to the external magnetic driver. The effect of the increased magnetic field is to increase the packing density of the magnetic droplet. Therefore, a droplet with higher integrity, and less susceptible to splitting, may be moved through the micro-fluidic device. 1. A micro-fluidic device for fluidic sample analysis , arranged to be positioned in a micro-fluidic controller comprising an external magnetic driver , comprising:a base structure;a flexible membrane;a micro-fluidic transition path limited by, at a bottom side, at least a portion of the base structure and by, at a top side, at least a portion of the flexible membrane, and extending between at least one inlet to be in communication with a first region and at least one outlet to be in communication with a second region; and 'wherein the micro-fluidic device further comprises:', 'wherein the microfluidic device is adapted such that, once in position in the micro-fluidic controller, the flexible membrane is placed in proximity to said external magnetic driver;'}a plurality of magnetic particles (i) arranged to be put in contact and included thereafter in a fluid included in the microfluidic device or (ii) already included in the fluid and the micro-fluidic device further comprises this fluid; ...

MICROFLUIDIC BASED INTEGRATED SAMPLE ANALYSIS SYSTEM

A portable microfluidic system capable of rapid diagnosis is described, which is able to analyze genetic, protein and cell composition of a sample in parallel for specific diseases from a relatively small sample. The method uses a single microfluidic chip integrated into a unique portable microfluidic platform and provides improved diagnostic accuracy, allows for frequent monitoring and is suitable for easy use in clinical settings. 1. A sample analysis system comprising: a sample input for applying a sample to the chip;', 'a separator connected to the sample input by a separation channel;', 'one or more reaction channels, each reaction channel being connected to the separator and being of varying length,', 'each said reaction channel being further connected to a respective outlet; and', 'a reagent inlet;, 'a microfluidic chip comprisinga thermoelectric semiconductor arranged to heat or cool one or more of said channels;an LED array arranged to emit radiation at a specific wavelength to the microfluidic chip;a detector arranged to detect fluorescence from said microfluidic chip; anda control unit arranged to control the valves and analyze results from the detector.2. The system according to wherein flow of the sample through the microfluidic chip is regulated by differential pressure.3. The system according to wherein the differential pressure is generated by the respective channels being of different lengths claim 2 , at least one of the channels including a valve for regulating flow along said one of the channels.4. The system according to wherein the separator is a gravity trap for separating blood into cells and plasma.5. The system according to including a cell reaction channel.6. The system according to including a PCR reaction chamber.7. The system according to including a protein detection channel.8. A microfluidic chip which comprises:a sample input for applying a sample to the microfluidic chip;a separator connected to the sample input by a separator ...

NON-INVASIVE MONITORING CANCER USING INTEGRATED MICROFLUIDIC PROFILING OF CIRCULATING MICROVESICLES

A microfluidic exosome profiling platform integrating exosome isolation and targeted proteomic analysis is disclosed. This platform is capable of quantitative exosomal biomarker profiling directly from 30 μL plasma samples within approximately 100 minutes with markedly enhanced sensitivity and specificity. Identification of distinct subpopulation of patient-derived exosomes is demonstrated by probing surface proteins and multiparameter analyses of intravesicular biomarkers in the selected subpopulation. The expression of IGF-1R and its phosphorylation level in non-small cell lung cancer (NSCLC) patient plasma is assessed, as a non-invasive alternative to the conventional biopsy and immunohistochemistry. The microfluidic chip, which may be fabricated of a glass substrate and a layer of poly(dimethylsiloxane), can include a first capture chamber, a second capture chamber, a serpentine microchannel, a first microchannel, a second microchannel, a sample inlet, a buffer inlet, a bead inlet, at least a first connector channel, and a reagent inlet. 1. A microfluidic chip comprising:a first capture chamber configured to enable immunomagnetic isolation;a second capture chamber configured to enable protein analysis;a serpentine microchannel connecting the first capture chamber and the second capture chamber;a first microchannel connecting the first capture chamber and the serpentine microchannel;a second microchannel connecting the serpentine microchannel and the second capture chamber;a sample inlet connected to the first capture chamber;a buffer inlet connected to the first capture chamber;a bead inlet;at least a first connector channel connected to the bead inlet and the first microchannel, wherein the first connector channel is connected to the first microchannel upstream of the serpentine microchannel and downstream of the first capture chamber; anda reagent inlet connected to the second microchannel upstream of the second capture chamber and downstream of the serpentine ...

MAGNETIC SEPARATION DEVICE AND METHOD OF USE

The current invention relates to the method and apparatus to magnetically separate biological entities with magnetic labels from a fluid sample. The claimed magnetic separation device removes biological entities with magnetic labels from its fluidic solution by using a soft-magnetic center pole with two soft-magnetic side poles. The claimed device further includes processes to dissociate entities conglomerate after magnetic separation. 1. A device for separating biological entities comprising:a magnetic field source having a first surface and a second surface;a soft magnetic center pole having a first end contacting said first surface, and a tip end tapering away from said first end, thereby concentrating magnetic flux from said first surface towards said tip end;a first soft magnetic side pole having a first base end and a second end;a second soft magnetic side pole having a second base end and a third end;a channel contacting said tip end contains a fluidic sample comprising said biological entities, thereby causing separation of said biological entities bound with magnetic labels towards said tip end;wherein said first and second base ends contact said second surface;wherein said second and third ends are located on opposing sides of said tip end;wherein said magnetic flux from said tip end divides into each of said second and third ends, thereby forming a flux closure within said center pole and said first and second side poles; andwherein said biological entities bound with magnetic labels are removed from said channel after separating said channel from said tip end.2. The device according to claim 1 , wherein said magnetic field source comprises a permanent magnet having a first polarization surface contacting a top surface of a soft magnetic shield claim 1 , and a second polarization surface opposing said first polarization surface claim 1 , wherein said first surface is said second polarization surface and said second surface is said top surface.3. The ...

OPTICAL READER SYSTEMS AND LATERAL FLOW ASSAYS

Systems and methods for determining the presence and/or amount of analytes in a fluid sample are described. 1. A method of performing a diagnostic test , comprising:positioning a cassette in an optical reader, the cassette comprising at least one lateral flow strip;directing a single flash of excitation energy toward an exposed portion of the at least one lateral flow strip in the cassette; andcapturing an image from a viewing area using an imaging system, the viewing area comprising the exposed portion.2. The method of claim 1 , wherein the excitation energy is directed from a flashlamp and the method further comprises blocking at least a portion of the excitation energy directed by the flashlamp using an optical filter.3. A cassette for holding a lateral flow strip through which a test sample fluid flows in a direction of flow through the lateral flow strip claim 1 , comprising:a housing comprising a top member and a bottom member; anda lateral flow strip receiving area located between the top and bottom members;wherein the housing comprises one or more cantilevered flow control springs formed in the bottom member that each have a fixed end and a free end, wherein the fixed end is coupled to the bottom member, and the free end comprises a protuberance that is configured to extend toward and contact at least a portion of a lateral flow strip to provide a force against the lateral flow strip when the lateral flow strip is positioned in the lateral flow strip receiving area.4. The cassette of claim 3 , wherein the one or more flow control springs comprise two flow control springs.5. The cassette of claim 4 , wherein the two flow control springs extend along the length of the cassette in the direction of flow and are generally in-line with one another.6. The cassette of claim 3 , wherein the flow control springs exert a force of between about 30 and 400 grams on a back of the lateral flow strip.7. The cassette of claim 3 , wherein the housing comprises a plurality of ...

FLUIDIC DEVICE, SYSTEM, AND METHOD

A fluidic device includes: 1. A fluidic device , comprising:a first flow path in which two or more solutions are mixed; anda second circulation flow path in which a solution mixed in the first flow path is circulated and which has a capture part configured to capture a sample substance included in the solution and/or a detection part configured to detect a sample substance included in the solution.2. The fluidic device according to claim 1 , comprising:a connection flow path that directly or indirectly connects the first flow path and the second circulation flow path.3. The fluidic device according to claim 2 , whereinthe second circulation flow path has two or more circulation flow path valves, andthe connection flow path is connected to the circulation flow path at one partition, which is partitioned by closing any two of the circulation flow path valves, of the second circulation flow path.4. The fluidic device according to claim 1 , whereinthe second circulation flow path has two or more circulation flow path valves, and each of the circulation flow path valves is arranged such that each of circulation flow path partitions compartmentalized by a circulation flow path valve has a predetermined volume, and whereinat least one introduction flow path and at least one discharge flow path are connected to the second circulation flow path, and the introduction flow path and the discharge flow path are configured such that a different solution is capable of being introduced to each of the second circulation flow path partitions.5. The fluidic device according to claim 1 , whereina volume inside the second circulation flow path is smaller than a volume inside the first flow path.6. The fluidic device according to claim 1 , whereinthe first flow path is a first circulation flow path.7. The fluidic device according to claim 6 , whereinvolumes of a plurality of solutions are quantitatively determined in the first circulation flow path, and the quantitatively determined ...

MAGNETIC PARTICLE SEPARATOR

The magnetic particle separator uses an induced magnetic field to separate magnetic particles held in solution by magnetophoresis. The magnetic particles may be, for example, inherently paramagnetic or superparamagnetic, may be magnetically tagged or the like. First and second magnetic particles initially flow along a longitudinal direction. An external magnetic field along a lateral direction, orthogonal (or near orthogonal) to the longitudinal direction, is applied to an externally magnetizable wire, which extends along a transverse direction orthogonal to both the longitudinal and lateral directions. The external magnetic field generates an induced magnetic field in the externally magnetizable wire, and the induced magnetic field generates repulsive magnetic force on the first and second magnetic particles. Due to differing magnetic susceptibility, size and/or mass between the first and second magnetic particles, they are separated by following separate paths generated by the respective magnetic forces thereon. 1. A magnetic particle separator , comprising:an elongate hollow channel extending along a longitudinal axis, the hollow channel having opposed inlet and outlet ends;a mixture port disposed at the inlet end of the hollow channel for injecting a mixture of first and second magnetic particles into the hollow channel, the first and second magnetic particles having separate and distinct properties with respect to one another, the properties being at least one property selected from the group consisting of magnetic susceptibility, size, and mass;a buffer port disposed at the inlet end of the hollow channel for injecting a buffer solution into the hollow channel, such that the mixture of the first and second magnetic particles in the buffer solution flow through the hollow channel along the longitudinal axis from the inlet end toward the outlet end;a first outlet channel disposed at the outlet end of the hollow channel;a second outlet channel disposed at the ...

MICROFLUIDIC CHIP FOR ANALYSIS OF CELL MOTILITY AND METHODS FOR USING SAME

The present invention describes an integrated apparatus that enables identification of migratory cells directly from a specimen. The apparatus only requires a small number of cells to perform an assay and includes novel topographic features which can reliably differentiate between migratory and non-migratory cell populations in a sample. Both the spontaneous and chemotactic migration of cancer cells may be measured to distinguish between subpopulations within a tumor sample. The migratory cells identified using the apparatus and methods of the present invention may be separated and further analyzed to distinguish factors promoting metastasis within the population. Cells in the apparatus can be treated with chemotherapeutic or other agents to determine drug strategies to most strongly inhibit migration. The use of optically transparent materials in some embodiments allows a wide range of imaging techniques to be used for in situ imaging of migratory and non-migratory cells in the apparatus. The apparatus and methods of the present invention are useful for predicting the metastatic propensity of tumor cells and selecting optimal drugs for personalized therapies. 1. A method for analysis of the motility of a population of cells in a sample comprising:a) adding to the inlet reservoir of the second channel of microchannel migration device a suspension of a population of cells from the sample;b) incubating the cells for a period time to allow the cells to fill the second channel;c) washing the inlet of the second channel;d) adding cell media to the one or more reservoirs of the one or more inlets of the first channel;e) imaging the cells in the apparatus for a period of time; andf) comparing the images of the cells in the device over time and identifying a cell or subpopulation of cells in the sample as migratory when the cell or subpopulation of cells migrates to the bifurcation of any of the migratory channels and/or enters one or more of the branch channels, and/or ...

Devices And Method For Enrichment And Alteration Of Cells And Other Particles

The invention features devices and methods for the deterministic separation of particles. Exemplary methods include the enrichment of a sample in a desired particle or the alteration of a desired particle in the device. The devices and methods are advantageously employed to enrich for rare cells, e.g., fetal cells, present in a sample, e.g., maternal blood and rare cell components, e.g., fetal cell nuclei. The invention further provides a method for preferentially lysing cells of interest in a sample, e.g., to extract clinical information from a cellular component, e.g., a nucleus, of the cells of interest. In general, the method employs differential lysis between the cells of interest and other cells (e.g., other nucleated cells) in the sample. 1150-. (canceled)151. A method of enriching a sample in fetal cells relative to maternal cells , the method comprising:(a) introducing a maternal blood sample into a microfluidic device capable of enriching fetal nucleated cells relative to maternal cells based on size, shape, deformability, or affinity to produce an enriched sample;(b) lysing fetal nucleated cells in the enriched sample to release fetal nuclei; and(c) detecting fetal nuclei.152. The method of claim 151 , wherein step (b) comprises lysing all cells in the enriched sample and collecting fetal nuclei.153. The method of claim 151 , wherein step (b) comprises selectively lysing fetal nucleated cells relative to maternal cells.154. The method of claim 151 , wherein the microfluidic device comprises a channel having a structure that deterministically directs fetal nucleated cells in a first direction and at least some maternal cells in a second direction based on deterministic lateral displacement.155. The method of claim 154 , wherein the microfluidic device is a duplex device comprising a channel comprising a first section comprising first and second outer regions claim 154 , each outer region comprising a structure that deterministically directs particles ...

MANIPULATING DROPLET SIZE

The invention generally relates to methods and systems for manipulating droplet size. In certain aspects, the invention provides methods for manipulating droplet size that include forming droplets of aqueous fluid surrounded by an immiscible carrier fluid, and manipulating droplet size during the forming step by adjusting pressure exerted on the aqueous fluid or the carrier fluid. 117-. (canceled)18. A system for forming droplets , the system comprising:a microfluidic substrate comprising a sample channel and a carrier fluid channel that connects to the sample channel at a junction;a manifold in fluid communication with the microfluidic substrate, the manifold configured to deliver an aqueous fluid to the sample channel and an immiscible carrier fluid to the carrier channel to thereby form droplets of aqueous fluid surrounded by carrier fluid at the junction; anda pump in fluid communication with the microfluidic substrate, the pump configured to regulate pressure of the aqueous fluid at the junction.19. The system of claim 18 , further comprising a fluid interface comprising a plurality of interconnects each aligned with and forming a seal with an inlet of one of the plurality of microfluidic channels.20. The system of claim 19 , wherein the manifold is in fluid communication with the microfluidic substrate via the fluid interface.21. The system of claim 18 , wherein the microfluidic substrate comprises a top plate and a bottom plate.22. The system of claim 18 , wherein the channels are etched into one or both of the top plate and the bottom plate.23. The system of claim 18 , further comprising an outlet channel downstream of the junction.24. The system of claim 18 , wherein the pump is coupled to an electronic pressure regulator.25. The system of claim 18 , wherein the pump is an external compressor comprising a reservoir of nitrogen claim 18 , argon claim 18 , or air.26. The system of claim 18 , wherein the pump is an internal air cylinder with a linear actuator. ...

Manipulation of Beads in Droplets and Methods for Manipulating Droplets

The invention provides a method of circulating magnetically responsive beads within a droplet in a droplet actuator. The invention also provides methods for splitting droplets. The invention, in one embodiment, makes use of a droplet actuator with top and bottom substrates, a plurality of magnetic fields respectively present proximate the top and bottom substrates, wherein at least one of the magnet fields is selectively alterable, and a plurality of droplet operations electrodes positioned along at least one of the top and bottom surfaces. A droplet is positioned between the top and bottom surfaces and at least one of the magnetic fields is selectively altered.

METHODS AND SYSTEMS FOR DIAGNOSING DISEASES

The present disclosure provided methods and systems for diagnosing diseases and monitoring their progression and therapeutic responses by detecting a presence or absence, or an increase or decrease, of one or more substances in a sample. 1. A method for detecting a presence of a plurality of biomarkers in a biological sample of a subject , comprising:(a) providing a microfluidic device including at least one fluid channel in fluid communication with at least one emitter having a plurality of nozzles that are operatively coupled to a detector, wherein said fluid channel includes a separation medium that is adapted to separate said plurality of biomarkers into subsets of biomarkers along said fluid channel, and wherein said detector is adapted to generate signals that are indicative of each of said subsets of biomarkers;(b) directing said biological sample having a volume less than or equal to about 50 microliters through said fluid channel to said at least one emitter under conditions that permit said plurality of biomarkers to be separated into said subsets of biomarkers along said fluid channel;(c) directing at least a portion of said biological sample from said plurality of nozzles to said detector, wherein said detector generates signals upon exposure to said at least said portion of said biological sample; and(d) detecting a presence of said subsets of biomarkers based on said signals generated in (c) to detect said presence of said plurality of biomarkers in said biological sample.2. The method of claim 1 , wherein said microfluidic device is part of a disposable chip.3. (canceled)4. The method of claim 1 , wherein said nozzles extend from a base tube having a larger cross-sectional dimension than said nozzles claim 1 , and wherein said base tube is in fluid communication with said fluid channel.5. (canceled)6. The method of claim 4 , wherein said nozzles and said base tube are monolithic.7. The method of claim 4 , wherein said nozzles have a cross-sectional ...

Method for detecting different properties in a microorganism population by optically induced dielectrophoretic force

A method for detecting different properties in a microorganism population by ODEP force includes obtaining a microorganism sample solution having a plurality of microorganisms to be tested; pre-processing the microorganism sample solution to obtain a microorganism sample solution to be tested including the microorganisms having electrical properties differences; placing the microorganism sample solution to be tested in a channel of an ODEP device and activating an optical projection device to form at least one optical projection directed to the ODEP device; flowing the microorganism sample solution to be tested from one end of the channel to the other end thereof, and exerting an ODEP force on the optical projection device to generate a force having a direction different from a flowing direction of the microorganism sample solution to be tested; and detecting heterogeneity of the microorganisms based on strength differences of the ODEP force exerted on the respective microorganisms.

High-Throughput Microfluidic Isolation of Single Particles

The present invention provides microfluidic devices capable of sequestering single particles in individual microchambers and isolating the particles from one another. The devices provide a plurality of channels fluidly connected to a plurality of microchambers. A fluid suspension comprising particles of interest can be passed through the devices in a first direction to sequester single particles in each microchamber. An isolating fluid can be passed through the devices in a second, reverse direction to isolate the particles from one another. The devices can selectively isolate several particles in each microchamber. 1. A microfluidic device for isolation of single particles , comprising:a planar substrate having an anterior end, a posterior end, a top surface, a bottom surface, and a thickness in-between the top and bottom surface;at least one anterior port and at least one posterior port extending from the top surface into the substrate;at least one channel embedded within the substrate; and 'wherein each anterior port is fluidly connected to a posterior port by the at least one channel; and wherein the at least one microchamber is connected to a channel by an anterior opening and at least one posterior opening.', 'at least one microchamber embedded within the substrate;'}2. The device of claim 1 , wherein the at least one microchamber comprises a shape that tapers posteriorly towards the at least one posterior opening.3. The device of claim 1 , wherein the at least one channel has a segment for each microchamber that is in direct alignment with the anterior opening of each microchamber.4. The device of claim 1 , wherein the at least one channel has a segment with a channel opening connected to each posterior opening of each microchamber by a channel branch.5. The device of claim 4 , wherein the segment with the channel opening is aligned along a first axis and the channel branch is aligned along a second axis claim 4 , such that the first axis and the second axis ...

Microfluidic Sensing

A device including a microfluidic channel structure formed on a substrate and including a first channel and a fluid actuator within the microfluidic channel structure. A sense region within the first channel is to receive a fluid flow of target biologic particles for counting in a single file pattern, with the sense region having a volume on a same order of magnitude as a volume of a single one of the target biologic particles. 1. A biologic test chip comprising:a substrate;a microfluidic channel structure formed on the substrate and including a first channel;a fluid actuator within the microfluidic channel structure.a sense region within the first channel to receive a fluid flow of biologic particles on a one-at-a-time basis via operation of the fluid actuator, the sense region having a volume on a same order of magnitude as a volume of a single respective one of the biologic particles.2. The chip of claim 1 , wherein the sense region operates according to a volume fraction in which a ratio of the volume of each single biologic particle relative to the volume of the sense region is on an order of tenths.3. The chip of claim 2 , comprising:at least one impedance sensor generally coextensive within the sense region to count biologic particles passing through the sense region.4. The chip of claim 3 , wherein the biologic particles are subject to a dilution factor on the order of tens.5. The chip of claim 4 , wherein the channel structure provides a non-uniform flow portion to align the biological particles into a single file flow pattern through the sense region claim 4 , the non-uniform flow portion including at least one of:an exclusion structure upstream from the sense region to exclude biologic particles larger than the volume of the sense region; andan inlet including a progressively narrowing cross-sectional area in the downstream orientation.6. The chip of claim 5 , wherein the first channel generally defines a first cross-sectional area and the first channel ...

DETECTION APPARATUS AND DETECTION METHOD

Disclosed is a detection apparatus that transfers magnetic particles through a plurality of chambers in a cartridge which includes the plurality of chambers and a channel connecting between the plurality of chambers, and that causes the magnetic particles to carry a complex of a test substance and a labelling substance, to detect the test substance on the basis of the labelling substance in the complex. The detection apparatus includes: a rotation mechanism configured to rotate the cartridge about a rotation shaft; a magnet configured to collect the magnetic particles in the chambers; a movement mechanism configured to move the magnet in a direction different from a circumferential direction of a circle in which the rotation shaft is centered; a detector configured to detect the test substance; and a controller programmed to control the rotation mechanism and the movement mechanism so as to transfer the magnetic particles from one of the chambers to another one of the chambers. 1. A detection apparatus that transfers magnetic particles through a plurality of chambers in a cartridge which comprises the plurality of chambers and a channel connecting between the plurality of chambers , and that causes the magnetic particles to carry a complex of a test substance and a labelling substance , to detect the test substance on the basis of the labelling substance in the complex , the detection apparatus comprising:a rotation mechanism configured to rotate the cartridge about a rotation shaft;a magnet configured to collect the magnetic particles in the chambers;a movement mechanism configured to move the magnet in a direction different from a circumferential direction of a circle in which the rotation shaft is centered;a detector configured to detect the test substance; anda controller programmed to control the rotation mechanism and the movement mechanism so as to transfer the magnetic particles from one of the chambers to another one of the chambers.2. The detection ...

SYSTEM, METHOD, AND MODULE FOR BIOMARKER DETECTION

Systems, methods, and modules for detecting a biomarker in a sample are described. A system for detecting presence or absence of a biomarker in a sample includes: a light source for producing electromagnetic radiation for interrogating the sample; a biosensor module including: a waveguide for guiding the electromagnetic radiation, the waveguide exposed to the sample; and a recognition element affixed to the waveguide and configured to bind to the biomarker; a detector for receiving the electromagnetic radiation from the waveguide and detecting a signal corresponding to an interaction of the electromagnetic radiation with the biomarker bound to the recognition element, in accordance with at least one detection modality; and a computing device for analyzing data related to the signal in order to detect presence or absence of the biomarker in the sample. 1. A system for detecting presence or absence of a biomarker in a sample comprising:a light source for producing electromagnetic radiation for interrogating the sample; a waveguide for guiding the electromagnetic radiation, the waveguide exposed to the sample; and', 'a recognition element affixed to the waveguide and configured to bind to the biomarker;, 'a biosensor module comprisinga detector for receiving the electromagnetic radiation from the waveguide and detecting a signal corresponding to an interaction of the electromagnetic radiation with the biomarker bound to the recognition element, in accordance with at least one detection modality; anda computing device, having one or more processors, for analyzing data related to the signal in order to detect presence or absence of the biomarker in the sample.2. The system of claim 1 , further comprising a microfluidic device for effecting movement of the sample through the biosensor module.3. The system of claim 1 , further comprising a filtration system for filtering the sample according to at least one physical characteristic.4. The system of claim 3 , wherein at ...

SYSTEM AND METHOD FOR RETRIEVING AND ANALYZING PARTICLES

A system and method for isolating and analyzing single cells, including: a substrate having a broad surface; a set of wells defined at the broad surface of the substrate, and a set of channels, defined by the wall, that fluidly couple each well to at least one adjacent well in the set of wells; and fluid delivery module defining an inlet and comprising a plate, removably coupled to the substrate, the plate defining a recessed region fluidly connected to the inlet and facing the broad surface of the substrate, the fluid delivery module comprising a cell capture mode. 1. A system for material processing at a capture substrate comprising a set of wells distributed across a broad face of the capture substrate , the system comprising: a tip, a terminal opening, and a void defined between the tip and the terminal opening, and', 'a positioning device coupled to the tip and providing a range of motion for positioning the terminal opening of the tip with respect to one or more wells of the set of wells of the capture substrate;, 'an aspiration and delivery subsystem comprising an illumination source, an optical sensor, an optical pathway from the illumination source to the capture substrate and from the capture substrate to the optical sensor; and', 'a processor in communication with the aspiration and delivery subsystem and the imaging subsystem;, 'an imaging subsystem comprising the imaging subsystem to generate an image dataset from the set of wells of the capture substrate, wherein the image dataset is captured from a direction perpendicular to the broad surface of the substrate,', 'the processor to generate an analysis characterizing a set of states of the set of wells and contents of the set of wells, and', 'the aspiration and delivery subsystem to, responsive to the analysis, perform at least one of an aspiration operation and a delivery operation with transmission of the tip to individual wells of the set of wells., 'wherein the processor comprises a non-transitory ...

METHODS, SYSTEMS AND COMPOSITIONS FOR FUNCTIONAL IN VITRO CELLULAR MODELS OF MAMMALIAN SYSTEMS

The present invention comprises methods, systems and compositions comprising cell culture analog systems, comprising components which optionally comprise biologically functional cells, and the components and systems function similarly to in vivo conditions. 137-. (canceled)38. A method of assessing one or more effects of varying an input variable or a cell culture characteristic on a microfluidic cell culture analog system , the method comprising:varying an input variable or a cell culture characteristic to which a microfluidic cell culture analog system is exposed, the microfluidic cell culture analog system comprising one or more organ components, each organ component comprising one or more chambers, and each organ component (i) being microfluidically coupled to one another, and (ii) comprising cells cultured on a surface;recording, over a duration of time, changes in measured electrophysiological properties, contractile properties or both in response to the varying input variable or cell culture characteristic;in which the electrophysiological properties, if measured, are measured from a first population of cells cultured on a surface comprising a microelectrode array housed in a first chamber and the contractile properties, if measured, are measured from a second population of cells cultured on a surface comprising a cantilever array housed in a second chamber;the recorded changes providing an assessment of the one or more effects of varying an input variable or a cell culture characteristic.39. The method of claim 38 , wherein the duration of time is a time period of days.40. The method of claim 38 , wherein the multiple microfluidically coupled organ components include a cardiac component claim 38 , and the method further comprises measuring at least one electrophysiological property from cardiomyocyte cells cultured on a microelectrode array of the cardiac component and simultaneously measuring at least one contractile property from cardiomyocyte cells ...

MULTIOMIC ANALYSIS OF CELL ANALYTES USING MICROFLUIDIC SYSTEMS

A method for isolating one or more distinct analyte component from a cell sample is disclosed, as well as processes for testing and analyzing the distinct analyte components. The distinct analyte components include: (i) a total protein fraction; (ii) a plasma membrane protein fraction; (iii) a total RNA fraction; (iv) a cytosolic RNA fraction; (v) a cytosolic protein fraction; (vi) a nuclear RNA fraction; (vii) a nuclear protein fraction; (viii) a chromatin fraction comprising genomic DNA (gDNA); (ix) a gDNA markers fraction. This method involves the use of microfluidic device having a cell capture component and a nucleic acid entanglement component, where the cell capture component includes a cell capture array having a plurality of cell capture micropillars, where the nucleic acid entanglement component includes a nucleic acid entanglement array having a plurality of nucleic acid entanglement micropillars, and where the microfluidic device operates under continuous flow conditions. 1. A method for isolating one or more distinct analyte component from a cell sample , said method comprising the steps of:(a) providing a microfluidic device comprising a cell capture component and a nucleic acid entanglement component, wherein said cell capture component comprises a cell capture array comprising a plurality of cell capture micropillars, wherein said nucleic acid entanglement component comprises a nucleic acid entanglement array comprising a plurality of nucleic acid entanglement micropillars, and wherein the microfluidic device operates under continuous flow conditions;(b) capturing one or more cell in the cell capture array of the microfluidic device while being subjected to a continuous flow rate, said capturing step comprising introducing the one or more cell sample into the microfluidic device under sufficient hydrodynamic flow to entrap, by size exclusion, the one or more cell within the cell capture component; (i) a total protein fraction;', '(ii) a plasma ...

BRIDGING LIQUID BETWEEN MICROFLUIDIC ELEMENTS WITHOUT CLOSED CHANNELS

According to a first aspect, the present invention is embodied as a method of processing a filtered liquid with a microfluidic device. The method includes positioning a porous filtering medium with respect to the microfluidic device, so as to allow a flow path between the filtering medium and a channel of the microfluidic device. The method further includes introducing a liquid in the porous filtering medium for the liquid to advance along the filtering medium and be filtered by the medium. The method further includes applying compression to the filtering medium to extract a given volume of the filtered liquid from the filtering medium, where the extracted liquid volume reaches said channel via the flow path. The method further includes processing the extracted volume with the microfluidic device. 1. A method of processing a liquid with a microfluidic device , the method comprising:positioning a porous filtering medium with respect to the microfluidic device, so as to allow a flow path between the filtering medium and a channel of the microfluidic device;introducing a liquid in the porous filtering medium for the liquid to advance along and be filtered by the filtering medium;applying compression to the filtering medium to extract a given liquid volume of the filtered liquid from the filtering medium, whereby the extracted liquid volume reaches said channel via the flow path; andprocessing the extracted liquid volume with the microfluidic device.2. The method according to claim 1 , wherein the porous filtering medium is positioned so as to contact one or more of an entity selected from the group consisting of: a holder and the microfluidic device.3. The method according to claim 2 , wherein:the microfluidic device comprises a substrate structured so as to form said channel and a cover layer covering a first portion of a top surface of the structured substrate; andthe porous filtering medium is positioned so as for:a bottom surface of the filtering medium to contact ...

TRAPPING AT LEAST ONE MICROPARTICLE

A device for trapping at least one microparticle in a fluid flow is suggested. The device comprises a trapping element and an electrode. The trapping element is configured for trapping the at least one microparticle and has at least one recess for receiving the at least one microparticle. The electrode is configured for generating an asymmetric electric field. In operation, at least one microparticle of a plurality of microparticles passing through the asymmetric electric field is forced into the at least one recess of the trapping element. 1. A device for trapping at least one microparticle in a fluid flow , comprising:a trapping element for trapping the at least one microparticle, the trapping element having at least one recess for receiving the at least one microparticle; andan electrode for generating an asymmetric electric field;wherein, in operation, at least one microparticle of a plurality of microparticles passing through the asymmetric electric field is forced into the at least one recess of the trapping element.2. The device of claim 1 , whereinthe trapping element has a front face directing in an upstream direction of the fluid flow and a rear face directing in a downstream direction of the fluid flow; andthe at least one recess is formed in a side face of the trapping element, the side face connecting the front and rear faces.3. The device of claim 2 , whereinthe front face of the trapping element is convex.4. The device of claim 2 , whereinthe front face and the rear face are symmetrically shaped with respect to an axis perpendicular to a fluid flow direction.5. The device of claim 2 , whereinthe front face is configured to divert the fluid flow from the recess.6. The device of claim 1 , whereinthe trapping element has two side faces comprising a recess, respectively.7. The device of claim 1 , whereinthe trapping element has at least two recesses; andthe at least two recesses are dimensioned differently for receiving microparticles of different sizes.8 ...

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.

SYSTEM AND METHOD FOR CAPTURING AND ANALYZING CELLS

A system and method for capturing and analyzing cells comprising: a fluid delivery module; a reservoir configured to receive a biological sample including a target cell population and at least one fluid from the fluid delivery module; a manifold configured to receive and distribute the biological sample and at least one fluid from the reservoir into a cell capture device; a waste chamber configured to couple to the manifold; and a pump configured to couple to the waste chamber. In embodiments of the system configured to promote further purification of captured cells, the system can further comprise a magnet that enables further separation of captured cells from undesired sample materials. The system can additionally further comprise a heater configured to heat at least one fluid and/or biological sample, and a cell capture device configured to couple to the manifold, in order to facilitate capture of the target cell population. 1. A system for capturing and analyzing a target in a biological sample , comprising:a fluid delivery module including 1) cartridge having a set of chambers, angularly displaced about a rotational axis of the cartridge, that hold at least one fluid for processing the biological sample and 2) an actuator coupled to a piercer configured to access at least one chamber of the set of chambers; 'wherein the cartridge is rotatable about the rotational axis to align a chamber of the set of chambers with the piercer, to facilitate flow of contents of the chamber into the reservoir inlet;', 'a reservoir, including a reservoir inlet and a reservoir outlet, configured to receive the biological sample and to receive at least one fluid from the fluid delivery module at the reservoir inlet,'}a manifold coupled to the reservoir outlet and configured to receive and deliver the biological sample and at least one fluid from the reservoir into a sample-processing device during operation; anda heater including a heating element and a heating substrate that ...

COLUMN-BASED DEVICE AND METHOD FOR RETRIEVAL OF RARE CELLS BASED ON SIZE, AND USES THEREOF

A column-based device and method for retrieving cells of interest were enclosed. The said device comprises a column comprising (i) an inner wall defining an inner chamber with inlet and outlet openings, (ii) a perforated plug disposed adjacent to the outlet opening, (iii) a sleeve insert with a channel and disposed within the chamber and adjacent to the perforated plug, and (iv) a filtering means housed within sleeve insert sandwiched between two sealing means. In particular, Tumor-derived endothelial cell clusters (TECCs) as characterized multiple nuclei, expression of endothelial markers (PECAM1, VWF and CDH5), and non-expression of leukocyte, megakaryocyte and platelets markers, may be retrieved using the disclosed device. Also encompassed are methods, reagents and kits for the diagnosis and prognosis of cancers by detecting for the presence of TECCs isolated from blood samples using the claimed device. 1. An apparatus for capturing and retrieving a cell from a sample , comprising at least one column , the column comprising:(i) an inner wall defining an inner chamber, the inner chamber having an inlet opening at a first end of the column for receiving the sample, and an outlet opening at a second end of the column;(ii) a perforated plug disposed within the inner chamber adjacent to the second end of the column;(iii) a sleeve insert having an opening at a first end and an opening at a second end, the sleeve insert comprising a channel tapered at the second end and disposed within the inner chamber with its second end adjacent to the perforated plug; and(iv) a filtering means housed within the sleeve insert, the filtering means comprising a sieve sandwiched between two sealing means.2. The apparatus of claim 1 , wherein the apparatus has one or more of the following properties:(A) comprising a number of columns selected from a group consisting of (a) one column and (b) two or more columns,(B) the second end of the column is adapted for connection to one or more ...

DIAGNOSTIC CHIP

A microfluidic diagnostic chip may comprise a main fluid channel comprising a main pump, a secondary fluid channel branching off from the main fluid channel, and a secondary pump within the secondary fluid channel wherein the secondary pump is to pull a particle of analyte of a first size from a fluid passing through the main channel, the fluid comprising particles of analyte of the first size and of a number of larger sizes. A method of analyzing an analyte on a microfluidic chip may comprise pumping, with a main microfluidic pump, a fluid comprising an analyte particle through a main microfluidic channel fluidly coupled to a fluid slot and sorting the analyte particle within the fluid through a secondary microfluidic channel by pulling the analyte particle into the secondary microfluidic channel with a secondary microfluidic pump. 1. A microfluidic diagnostic chip , comprising:a main fluid channel comprising a main pump;a secondary fluid channel branching off from the main fluid channel; anda secondary pump within the secondary fluid channel wherein the secondary pump is to pull a particle of analyte of a first size from a fluid passing through the main channel, the fluid comprising particles of analyte of the first size and of a number of larger sizes.2. The microfluidic diagnostic chip of claim 1 , wherein the secondary fluid channel comprises a smaller diameter than the main fluid channel.3. The microfluidic diagnostic chip of claim 2 , wherein the secondary fluid channel comprises a first sensor to count a number of the particles of the first size passing therethrough.4. The microfluidic diagnostic chip of claim 2 , wherein the diameter of the secondary fluid channel excludes the number of larger sizes of particles.5. The microfluidic diagnostic chip of claim 3 , wherein the main fluid channel comprises a second sensor to count particles of the analyte of the first size and larger sizes passing therethrough.6. The microfluidic diagnostic chip of claim 5 , ...

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 ...

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.

Cell capture in microfluidic devices

A capturing of target cells from a biological sample is achieved by inducing a flow of the biological sample in a flow channel (30, 60) of an upstream microfluidic device (1). Target cells present in the biological sample are captured in cell channels (20) of the upstream microfluidic device(1). Once at least a minimum number of target cells are captured in the cell channels (20), the flow of the biological sample in the flow channel is reduced and are verse flow is applied at the upstream microfluidic device (1) to release the target cells captured in the cell channels (20) of the upstream microfluidic device (1) and enable transfer the target cells into cell channels (120) of a downstream microfluidic device (100).

MICROFLUIDIC NUCLEIC ACID ANALYSIS

Nucleic acid from cells and viruses sampled from a variety of environments may purified and expressed utilizing microfluidic techniques. In accordance with one embodiment of the present invention, individual or small groups of cells or viruses may be isolated in microfluidic chambers by dilution, sorting, and/or segmentation. The isolated cells or viruses may be lysed directly in the microfluidic chamber, and the resulting nucleic acid purified by exposure to affinity beads. Subsequent elution of the purified nucleic acid may be followed by ligation and cell transformation, all within the same microfluidic chip. In one specific application, cell isolation, lysis, and nucleic acid purification may be performed utilizing a highly parallelized microfluidic architecture to construct gDNA and cDNA libraries. 1. A microfluidic apparatus comprising:(a) a solid substrate;(b) a cell separation and processing system embedded in the substrate that includes an arrangement of flow channels configured so that individual cells from a cell population can be singly isolated;(c) one or more inlet channels in the substrate connected with the cell separation and processing system so that a reagent can be delivered through the inlet channel(s) and combined with cells isolated by the system; and(d) one or more outlet channels in the substrate connected with the cell separation and processing system so that contents obtained by lysing isolated cells can be flowed through the outlet channel(s) and kept separate;wherein the apparatus is designed and constructed so that a user can prepare a plurality of cDNA libraries from single cells by a method that comprises:(1) receiving a sample of cells into the cell separation and processing system of the apparatus;(2) processing the sample in the cell separation and processing system such that a plurality of single cells from the sample are fluidically isolated from all other cells in the sample, thereby producing isolated single cells;(3) combining ...

Microfluidic Devices And Systems For Cell Culture And/Or Assay

Described herein are microfluidic devices and systems for high density cell culture and/or high throughput cell assays. Methods of using the same are also provided herein. In some embodiments, the microfluidic devices and systems described herein provide rapid and automated trapping of single embryos in ordered arrays. 1. A microfluidic device comprising:a main channel system having an inlet, an outlet, a central portion located between the inlet and the outlet, and a plurality of first chambers, the first chambers extending transversely to a first channel segment within the central portion, each of the first chambers having a channel opening that fluidly communicates with the first channel segment and a medium opening located away from the channel opening, each of the first chambers being sized to receive a single target biological specimen from the first channel segment; anda medium-manifold system having a medium inlet for receiving a culture medium and a plurality of first connecting channels, each of the first connecting channels distributing the culture medium to the corresponding first chamber through the medium opening of the corresponding first chamber, andwherein each of the first connecting channels is configured such that the culture medium exposed to the biological specimen received in the corresponding first chamber does not contact another biological specimen received in another first chamber.2. A microfluidic device comprising:a main channel system having an inlet, an outlet, a central portion located between the inlet and the outlet, and a plurality of first chambers, the first chambers extending transversely to a first channel segment within the central portion, each of the first chambers having a channel opening that fluidly communicates with the first channel segment and a medium opening located away from the channel opening, anda medium-manifold system that includes a medium inlet for receiving a culture medium and a plurality of first ...

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

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

A Modular Bio-Processing Unit and a Bio-Processing System Employing Plural Units

Disclosed is a modular bio-processing unit () comprising: a housing () having one or more internal fluid paths (), the housing having at least one inlet and at least one outlet (), each in fluid communication with the fluid path or one or more of the fluid paths; one or more sensor elements () operatively associated with the or each path, said sensor(s) elements including elements of one or more of: a flow sensor, a flow rate sensor, a conductivity sensor, a pressure sensor, a pH sensor, and a light absorbance sensor such as a UV spectroscopic concentration sensor; one or more fluid flow inducing components () operatively associated with the or each fluid path; and plural valves () for preventing or reducing flow in the or each path, the housing, inlet(s), outlet(s), flow inducing component(s) and valve(s) being arranged to operate together as a bio-processing unit within or substantially within the housing. 1. A modular bio-processing unit operable with like units to provide a bio-processing system , comprising:a housing having one or more internal fluid paths, the housing having at least one inlet and at least one outlet, each in fluid communication with the fluid path or one or more of the fluid paths;one or more sensor elements operatively associated with the or each path, said sensor(s) elements including elements of one or more of: a flow rate or flow direction sensor, a conductivity sensor, a pressure sensor, a pH sensor, an air trap and a light absorbance sensor such as a UV light absorbance sensor;one or more fluid flow inducing components operatively associated with the or each fluid path; andplural valves for preventing or reducing flow in the or each path, operate together as a bio-processing unit within or substantially within the housing.2. The modular bio-processing unit of claim 1 ,wherein the unit includes a selection valve for selecting input into the path(s) from plural sources.3. The modular bio-processing unit of claim 2 ,wherein the flow ...

Methods and systems for cell-based non-invasive prenatal testing

Methods and systems are provided for isolating fetal cells from a maternal blood supply in order to perform non-invasive prenatal testing. In one example, a system for non-invasive prenatal testing includes a substrate coated with a cell-capturing surface, the cell-capturing surface including an array of pillar-like structures, each pillar-like structure including a plurality of intersecting arms. 1. A system for non-invasive prenatal testing , comprising:a substrate coated with a cell-capturing surface, the cell-capturing surface including an array of pillar-like structures, each pillar-like structure including a plurality of intersecting arms.2. The system of claim 1 , wherein the cell-capturing surface comprises a polystyrene membrane claim 1 , and wherein the array of pillar-like structures are imprinted on the polystyrene membrane.3. The system of claim 1 , wherein each pillar-like structure has a diameter in a range of 8-12 μm.4. The system of claim 1 , wherein each pillar-like structure has a height in a range of 0.2-2 μm.5. The system of claim 1 , wherein each pillar-like structure is spaced apart from neighboring pillar-like structures by an equal amount.6. The system of claim 1 , wherein each pillar-like structure comprises a double-cross pillar structure including four arms that intersect at a center of the double-cross pillar structure claim 1 , each arm having a length of 10 μm.7. The system of claim 1 , wherein the substrate includes a microfluidic channel and the cell-capturing surface extends along a length and width of the microfluidic channel.8. A system for non-invasive prenatal testing claim 1 , comprising:a substrate including a first curved microfluidic channel located on a top surface of the substrate;a polymer membrane coated on the top surface of the substrate, the polymer membrane including an array of pillar-like structures; anda top piece including a second curved microfluidic channel located on a bottom surface of the top piece.9. The ...

Methods and Systems for Circulating Tumor Cell Capture

Methods and systems are provided for isolating circulating tumor cells from a peripheral blood supply in order to diagnose early stage cancer and/or evaluate tumor status. In one example, a system for capturing circulating tumor cells includes a substrate having a cell-capturing region, the cell-capturing region having a curved, switchback-like shape and including an array of micropillar structures within the curved, switchback-like shape. 1. A system for capturing circulating tumor cells , comprising:a substrate having a cell-capturing region, the cell-capturing region having a curved, switchback-like shape and including an array of micropillar structures within the curved, switchback-like shape.2. The system of claim 1 , wherein the array of micropillar structures are formed on a top surface of the substrate within the cell-capturing region.3. The system of claim 1 , wherein each micropillar structure has a diameter in a range of 0.8-1.2 μm.4. The system of claim 1 , wherein each micropillar structure has a height in a range of 0.2-2 μm.5. The system of claim 1 , wherein each micropillar structure is spaced apart from neighboring micropillar structures by an equal amount.6. The system of claim 1 , wherein the cell-capturing region is a first cell-capturing region claim 1 , and wherein the substrate has a plurality of additional cell-capturing regions arranged in parallel claim 1 , each additional cell-capturing region including an array of micropillar structures and having the curved claim 1 , switchback-like shape.7. The system of claim 6 , further comprising a top piece including a plurality of curved microfluidic channels claim 6 , each curved microfluidic channel having a shape that matches the curved claim 6 , switchback-like shape of each cell-capturing region.8. The system of claim 1 , wherein the substrate comprises a glass slide.9. The system of claim 1 , wherein the cell-capturing region includes biotin groups.10. The system of claim 9 , further ...

Biocompatible Micropillar Array Substrate and Methods for Fabricating Such Substrate

A biocompatible micropillar array substrate (MAS) and methods for preparing the biocompatible MAS are provided. In on example, the biocompatible MAS includes multiple micropillars made from a biocompatible polymer. The biocompatible MAS may be prepared using a replica fabricated based on a silicon MAS. The configuration of the multiple micropillars of the silicon MAS and a configuration of the multiple micropillars of the biocompatible MAS are the same. 1. A method for preparing a biocompatible micropillar array substrate (MAS) with multiple micropillars comprising:preparing a replica based on a silicon MAS with multiple micropillars; andpreparing the biocompatible MAS by imprinting the replica on a layer of biocompatible polymer, where a configuration of the multiple micropillars of the silicon MAS and a configuration of the multiple micropillars of the biocompatible MAS are the same.2. The method of claim 1 , wherein preparing the replica based on the silicon MAS includes treating a surface of the silicon MAS with hexamethyldisilazane (HMDS) claim 1 , and coating the treated surface of the silicon MAS with polydimethylsiloxane (PDMS).3. The method of claim 1 , wherein the replica includes a plurality of indentations claim 1 , and imprinting the replica on the layer of biocompatible polymer includes flowing the biocompatible polymer into the indentations.4. The method of claim 3 , wherein the biocompatible polymer is flowed into the indentations by applying pressure and heat to the replica and the biocompatible polymer.5. The method of claim 3 , wherein imprinting the replica on the layer of biocompatible polymer further includes polymerizing the biocompatible polymer after flowing the biocompatible polymer into the indentations claim 3 , and removing the replica from the polymerized biocompatible polymer.6. The method of claim 1 , wherein the layer of biocompatible polymer is formed by coating a flat substrate with the biocompatible polymer.7. The method of claim ...

Methods and Systems for Circulating Tumor Cell Capture

Methods and systems are provided for isolating circulating tumor cells from a peripheral blood supply in order to diagnose early stage cancer and/or evaluate tumor status. In one example, a system for capturing circulating tumor cells includes a substrate having a cell-capturing region, the cell-capturing region having a curved, switchback-like shape and including an array of micropillar structures within the curved, switchback-like shape. 1. A system for capturing circulating tumor cells , comprising:a substrate having a cell-capturing region, the cell-capturing region having a curved, switchback-like shape and including an array of micropillar structures within the curved, switchback-like shape.2. The system of claim 1 , wherein the array of micropillar structures are formed on a top surface of the substrate within the cell-capturing region.3. The system of claim 1 , wherein each micropillar structure has a diameter in a range of 0.8-1.2 μm.4. The system of claim 1 , wherein each micropillar structure has a height in a range of 0.2-2 μm.5. The system of claim 1 , wherein each micropillar structure is spaced apart from neighboring micropillar structures by an equal amount.6. The system of claim 1 , wherein the cell-capturing region is a first cell-capturing region claim 1 , and wherein the substrate has a plurality of additional cell-capturing regions arranged in parallel claim 1 , each additional cell-capturing region including an array of micropillar structures and having the curved claim 1 , switchback-like shape.7. The system of claim 6 , further comprising a top piece including a plurality of curved microfluidic channels claim 6 , each curved microfluidic channel having a shape that matches the curved claim 6 , switchback-like shape of each cell-capturing region.8. The system of claim 1 , wherein the substrate comprises a glass slide.9. The system of claim 1 , wherein the cell-capturing region includes biotin groups.10. The system of claim 9 , further ...

Methods and Systems for Cell-Based Non-Invasive Prenatal Testing

Methods and systems are provided for isolating fetal cells from a maternal blood supply in order to perform non-invasive prenatal testing. In one example, a system for non-invasive prenatal testing includes a substrate coated with a cell-capturing surface, the cell-capturing surface including an array of pillar-like structures, each pillar-like structure including a plurality of intersecting arms. 1. A system for non-invasive prenatal testing , comprising:a substrate coated with a cell-capturing surface, the cell-capturing surface including an array of pillar-like structures, each pillar-like structure including a plurality of intersecting arms.2. The system of claim 1 , wherein the cell-capturing surface comprises a polystyrene membrane claim 1 , and wherein the array of pillar-like structures are imprinted on the polystyrene membrane.3. The system of claim 1 , wherein each pillar-like structure has a diameter in a range of 8-12 μm.4. The system of claim 1 , wherein each pillar-like structure has a height in a range of 0.2-2 μm.5. The system of claim 1 , wherein each pillar-like structure is spaced apart from neighboring pillar-like structures by an equal amount.6. The system of claim 1 , wherein each pillar-like structure comprises a double-cross pillar structure including four arms that intersect at a center of the double-cross pillar structure claim 1 , each arm having a length of 10 μm.7. The system of claim 1 , wherein the substrate includes a microfluidic channel and the cell-capturing surface extends along a length and width of the microfluidic channel.8. A system for non-invasive prenatal testing claim 1 , comprising:a substrate including a first curved microfluidic channel located on a top surface of the substrate;a polymer membrane coated on the top surface of the substrate, the polymer membrane including an array of pillar-like structures; anda top piece including a second curved microfluidic channel located on a bottom surface of the top piece.9. The ...

Biocompatible Micropillar Array Substrate and Methods for Fabricating Such Substrate

A biocompatible micropillar array substrate (MAS) and methods for preparing the biocompatible MAS are provided. In on example, the biocompatible MAS includes multiple micropillars made from a biocompatible polymer. The biocompatible MAS may be prepared using a replica fabricated based on a silicon MAS. The configuration of the multiple micropillars of the silicon MAS and a configuration of the multiple micropillars of the biocompatible MAS are the same. 1. A method for preparing a biocompatible micropillar array substrate (MAS) with multiple micropillars comprising:preparing a replica based on a silicon MAS with multiple micropillars; andpreparing the biocompatible MAS by imprinting the replica on a layer of biocompatible polymer, where a configuration of the multiple micropillars of the silicon MAS and a configuration of the multiple micropillars of the biocompatible MAS are the same.2. The method of claim 1 , wherein preparing the replica based on the silicon MAS includes treating a surface of the silicon MAS with hexamethyldisilazane (HMDS) claim 1 , and coating the treated surface of the silicon MAS with polydimethylsiloxane (PDMS).3. The method of claim 1 , wherein the replica includes a plurality of indentations claim 1 , and imprinting the replica on the layer of biocompatible polymer includes flowing the biocompatible polymer into the indentations.4. The method of claim 3 , wherein the biocompatible polymer is flowed into the indentations by applying pressure and heat to the replica and the biocompatible polymer.5. The method of claim 3 , wherein imprinting the replica on the layer of biocompatible polymer further includes polymerizing the biocompatible polymer after flowing the biocompatible polymer into the indentations claim 3 , and removing the replica from the polymerized biocompatible polymer.6. The method of claim 1 , wherein the layer of biocompatible polymer is formed by coating a flat substrate with the biocompatible polymer.7. The method of claim ...