公开(公告)号：US08845914B2

公开(公告)日：2014-09-30

申请号：US13894296

申请日：2013-05-14

Applicant: Fluidigm Corporation

Inventor： Hany Nassef ,  Geoffrey Richard Facer ,  Marc Unger

IPC: C03C25/68 ,  G01N1/10 ,  B01L3/00 ,  G01N27/00 ,  G01N27/60

CPC classification number: C03C25/68 ,  B01L3/502707 ,  B01L2300/0645 ,  B01L2300/0816 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  G01N15/1031 ,  G01N15/12 ,  G01N27/00 ,  G01N27/60 ,  G01N33/48707 ,  G01N33/48721 ,  G01N2015/1087 ,  Y10T436/2575

Abstract: The presence of a detectable entity within a detection volume of a microfabricated elastomeric structure is sensed through a change in the electrical or magnetic environment of the detection volume. In embodiments utilizing electronic detection, an electric field is applied to the detection volume and a change in impedance, current, or combined impedance and current due to the presence of the detectable entity is measured. In embodiments utilizing magnetic detection, the magnetic properties of a magnetized detected entity alter the magnetic field of the detection volume. This changed magnetic field induces a current which can reveal the detectable entity. The change in resistance of a magnetoresistive element may also reveal the passage of a magnetized detectable entity.

Abstract translation: 通过检测体积的电气或磁环境的变化来检测在微制造弹性体结构的检测体积内的可检测实体的存在。 在利用电子检测的实施例中，对检测体积施加电场，并且测量由于可检测实体的存在引起的阻抗，电流或组合阻抗和电流的变化。 在利用磁检测的实施例中，磁化检测实体的磁性改变了检测体积的磁场。 这种改变的磁场诱发可以揭示可检测实体的电流。 磁阻元件的电阻变化也可以揭示磁化的可检测实体的通过。

公开(公告)号：US08828663B2

公开(公告)日：2014-09-09

申请号：US11912502

申请日：2006-03-20

Applicant: Marc Unger ,  Lincoln McBride ,  Geoffrey Facer ,  Michael Lucero ,  Hany Ramez Nassef

Inventor： Marc Unger ,  Lincoln McBride ,  Geoffrey Facer ,  Michael Lucero ,  Hany Ramez Nassef

IPC: C12Q1/68 ,  C12P19/34 ,  G01N27/453 ,  B01L3/00

CPC classification number: C12Q1/686 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/147 ,  B01L2300/0636 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/0887 ,  B01L2300/0893 ,  B01L2300/123 ,  B01L2300/1805 ,  B01L2300/1827 ,  B01L2400/0481 ,  B01L2400/0655 ,  G01N27/453 ,  C12Q2565/629

Abstract: Devices and methods for performing the relative concentration of a target in a sample, the sample containing both target and non-target components, the method performed by partitioning the sample into a large number of reaction volumes such that the target is concentrated relative to the non-target, and performing a detection assay upon each reaction volume to detect the target.

Abstract translation: 用于执行样品中靶标相对浓度的装置和方法，含有靶和非目标成分的样品，通过将样品分成大量反应体积进行的方法，使得靶相对于非目标成分集中 并且在每个反应体积上进行检测测定以检测目标。

公开(公告)号：US08808640B2

公开(公告)日：2014-08-19

申请号：US13755754

申请日：2013-01-31

Applicant: Fluidigm Corporation

Inventor： Emerson Chueng Quan ,  Colin Jon Taylor ,  Michael Lee ,  Christopher Ceasar ,  Greg Harris ,  Gang Sun

IPC: G01N33/00

CPC classification number: G01N33/00 ,  B01L3/5025 ,  B01L3/502707 ,  B01L2200/025 ,  B01L2200/12 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/087 ,  B01L2300/0887 ,  B01L2400/0481 ,  B01L2400/0655 ,  Y10T436/11

Abstract: A biological substrate, e.g., microfluidic chip. The substrate includes a rigid substrate material, which has a surface region capable of acting as a handle substrate. The substrate also has a deformable fluid layer coupled to the surface region. One or more well regions are formed in a first portion of the deformable fluid layer and are capable of holding a fluid therein. The one or more channel regions are formed in a second portion of the deformable fluid layer and are coupled to one or more of the well regions. An active region is formed in the deformable fluid layer. At least three fiducial markings are formed within the non-active region and disposed in a spatial manner associated with at least one of the well regions. A control layer is coupled to the fluid layer.

Abstract translation: 生物底物，例如微流体芯片。 衬底包括刚性衬底材料，其具有能够用作手柄衬底的表面区域。 衬底还具有耦合到表面区域的可变形流体层。 一个或多个阱区域形成在可变形流体层的第一部分中并且能够在其中保持流体。 一个或多个通道区域形成在可变形流体层的第二部分中并且耦合到一个或多个阱区域。 在可变形流体层中形成有源区。 在非有源区域内形成至少三个基准标记，并以与至少一个阱区域相关联的空间方式设置。 控制层耦合到流体层。

公开(公告)号：US08802368B2

公开(公告)日：2014-08-12

申请号：US12708153

申请日：2010-02-18

Applicant: Stanley N. Lapidus

Inventor： Stanley N. Lapidus

IPC: C12Q1/68

CPC classification number: C12Q1/68 ,  C12Q1/6869 ,  C12Q1/6874 ,  C12Q2565/518 ,  C12Q2563/107 ,  C12Q2533/101

Abstract: The invention provides methods and devices for detecting, enumerating or identifying target nucleic acid molecules using immobilized capture probes and single molecule sequencing techniques.

Abstract translation: 本发明提供了使用固定的捕获探针和单分子测序技术来检测，列举或鉴定靶核酸分子的方法和装置。

公开(公告)号：US20140087973A1

公开(公告)日：2014-03-27

申请号：US14029676

申请日：2013-09-17

Applicant: Fluidigm Corporation

Inventor： Yusuf D. Amin

IPC: B01J19/00

CPC classification number: B01J19/0046 ,  B01L3/502707 ,  B01L9/527 ,  B01L2200/027 ,  B01L2200/04 ,  B01L2200/10 ,  B01L2200/12 ,  B01L2300/043 ,  B01L2300/123 ,  B01L2300/1805

Abstract: An injection molding method of fabricating a carrier for holding a microfluidic device can form all of the desired features of such a carrier, including wells, channels and ports having smaller dimensions and greater density than previously achieved, while reducing or avoiding fracturing and the need for drilling the substrate to form certain features, in particular the ports. The carrier includes a substrate with a plurality of wells, each well defining a volume of between 0.1 μl and 100 μl; a plurality of channels within the substrate wherein each well is in fluid communication with at least one of the plurality of channels; a plurality of ports within the carrier substrate wherein each port is for coupling with regions in the carrier substrate adapted to receive fluids or pressure; and a receiving portion for receiving a microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells. The carrier has a polymeric composition and/or an array of structural features achieved via the injection molding fabrication technique that enhance its performance and compatibility with existing instrumentation.

Abstract translation: 用于制造用于保持微流体装置的载体的注射成型方法可以形成这种载体的所有期望特征，包括具有比以前实现的更小尺寸和更大密度的孔，通道和端口，同时减少或避免压裂和 钻基板以形成某些特征，特别是端口。 载体包括具有多个孔的底物，每个孔限定0.1μl和100μl之间的体积; 衬底内的多个通道，其中每个阱与所述多个通道中的至少一个流体连通; 载体衬底内的多个端口，其中每个端口用于与适于接收流体或压力的载体衬底中的区域耦合; 以及用于接收微流体装置并将微流体装置与多个孔流体连通的接收部分。 载体具有聚合物组合物和/或通过注射成型制造技术实现的结构特征阵列，其增强其性能和与现有仪器的兼容性。

公开(公告)号：US20140045184A1

公开(公告)日：2014-02-13

申请号：US13784736

申请日：2013-03-04

Applicant: Fluidigm Corporation

Inventor： Martin Pieprzyk ,  Geoff Facer ,  Timothy Woudenberg ,  Brian Fowler

IPC: C12Q1/68

CPC classification number: G01N1/28 ,  B01L3/502738 ,  B01L7/52 ,  B01L2200/16 ,  B01L2300/0867 ,  B01L2300/0874 ,  B01L2300/123 ,  B01L2400/0481 ,  B01L2400/0655 ,  B33Y80/00 ,  C12Q1/686 ,  G01N21/05 ,  G01N21/6452 ,  G01N2021/0346 ,  Y10T137/7793 ,  Y10T436/2575

Abstract: Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices.

Abstract translation: 本发明的实施例提供了改进的微流体装置和相关装置，系统和方法。 提供了减少使用微流体装置期间的混合时间的方法。 微流控装置和相关的制造方法具有提高的制造产率。 提供改进的装置和相关系统用于向微流体装置提供受控的压力。 提供了方法和相关的微流体装置，用于在使用过程中减少微流体装置的脱水。 微流控装置和相关方法提供了改进的样品与试剂混合比控制。 微流体装置和系统具有改进的抗压缩夹具压力引起的故障的阻力。 提供了使用微流体装置进行温度控制反应的方法和系统，其减少微流体装置内的冷凝水平。 提供了用于改进微流体装置的荧光成像的方法和系统。

公开(公告)号：US20140024559A1

公开(公告)日：2014-01-23

申请号：US14031972

申请日：2013-09-19

Applicant: Fluidigm Corporation

Inventor： Marc A. Unger ,  Geoffrey Richard Facer ,  Barry Clerkson ,  Christopher G. Cesar ,  Neil Switz

IPC: G01N21/64

CPC classification number: C12Q1/686 ,  B01J2219/00576 ,  B01J2219/00704 ,  B01L3/5027 ,  B01L7/52 ,  G01N21/64 ,  G01N21/6452 ,  G01N21/6456 ,  G01N21/6486 ,  G01N21/75 ,  G01N21/8483 ,  G01N27/44721 ,  G01N2021/6421 ,  G01N2201/061 ,  G02B21/16 ,  G02B21/36

Abstract: An apparatus for imaging one or more selected fluorescence indications from a microfluidic device. The apparatus includes an imaging path coupled to least one chamber in at least one microfluidic device. The imaging path provides for transmission of one or more fluorescent emission signals derived from one or more samples in the at least one chamber of the at least one microfluidic device. The chamber has a chamber size, the chamber size being characterized by an actual spatial dimension normal to the imaging path. The apparatus also includes an optical lens system coupled to the imaging path. The optical lens system is adapted to transmit the one or more fluorescent signals associated with the chamber.

Abstract translation: 一种用于从微流体装置成像一个或多个选定的荧光指示的装置。 该装置包括耦合到至少一个微流体装置中的至少一个腔室的成像路径。 成像路径提供从至少一个微流体装置的至少一个室中的一个或多个样品衍生的一个或多个荧光发射信号的传输。 腔室具有腔室尺寸，腔室尺寸的特征在于与成像路径垂直的实际空间尺寸。 该装置还包括耦合到成像路径的光学透镜系统。 光学透镜系统适于透射与腔室相关联的一个或多个荧光信号。

公开(公告)号：US08600168B2

公开(公告)日：2013-12-03

申请号：US13253857

申请日：2011-10-05

Applicant: Simant Dube ,  Gang Sun ,  Lian-She Zhao

Inventor： Simant Dube ,  Gang Sun ,  Lian-She Zhao

IPC: G06K9/36 ,  G06K9/40 ,  G06T7/00

CPC classification number: G01N21/64 ,  G06T7/0012 ,  G06T7/74 ,  G06T2207/10064 ,  G06T2207/30004

Abstract: A method of processing data associated with fluorescent emissions from a microfluidic device. The method includes performing an auto-focus process associated with a first image of the microfluidic device and performing an auto-exposure process associated with the first image of the microfluidic device. The method also includes capturing a plurality of images of the microfluidic device. The plurality of images are associated with a plurality of thermal cycles. The method further includes performing image analysis of the plurality of captured images to determine a series of optical intensities and performing data analysis of the series of optical intensities to provide a series of change in threshold values.

Abstract translation: 处理与微流体装置的荧光发射有关的数据的方法。 该方法包括执行与微流体装置的第一图像相关联的自动聚焦处理，并且执行与微流体装置的第一图像相关联的自动曝光处理。 该方法还包括捕获微流体装置的多个图像。 多个图像与多个热循环相关联。 该方法还包括执行多个拍摄图像的图像分析以确定一系列光强度并执行该系列光强度的数据分析以提供一系列阈值变化。

公开(公告)号：US08591834B2

公开(公告)日：2013-11-26

申请号：US13439390

申请日：2012-04-04

Applicant: David S. Cohen ,  Robert C. Jones ,  Andrew May ,  Hany Nassef ,  Jing Wang

Inventor： David S. Cohen ,  Robert C. Jones ,  Andrew May ,  Hany Nassef ,  Jing Wang

IPC: B01L3/00

CPC classification number: B01L3/502738 ,  B01L3/5025 ,  B01L7/52 ,  B01L2200/0684 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/087 ,  B01L2300/0874 ,  B01L2300/0887 ,  B01L2300/123 ,  B01L2400/0487 ,  B01L2400/0605 ,  B01L2400/0638 ,  B01L2400/0655 ,  B33Y80/00 ,  F16K99/0001 ,  F16K99/0026 ,  F16K99/0059 ,  F16K2099/0074 ,  F16K2099/0078 ,  F16K2099/008 ,  F16K2099/0084 ,  Y10T137/0318 ,  Y10T137/85938

Abstract: New high density microfluidic devices and methods provide precise metering of fluid volumes and efficient mixing of the metered volumes. A first solution is introduced into a segment of a flow channel in fluidic communication with a reaction chamber. A second solution is flowed through the segment so that the first solution is displaced into the reaction chamber, and a volume of the second solution enters the chamber. The chamber can then be isolated and reactions within the chamber can be initiated and/or detected. High throughput methods of genetic analysis can be carried out with greater accuracy than previously available.

Abstract translation: 新的高密度微流体装置和方法提供流体体积的精确计量和计量体积的有效混合。 将第一溶液引入与反应室流体连通的流动通道的段中。 第二溶液流过该段，使得第一溶液移入反应室，并且第二溶液的体积进入该室。 然后可以分离室，并且可以启动和/或检测室内的反应。 遗传分析的高通量方法可以比以前更高的精度进行。

公开(公告)号：US20130078610A1

公开(公告)日：2013-03-28

申请号：US13429861

申请日：2012-03-26

Applicant: Jake Kimball ,  Brandon Ripley ,  Gang Sun ,  Dominique Toppani ,  Myo Thu Maung

Inventor： Jake Kimball ,  Brandon Ripley ,  Gang Sun ,  Dominique Toppani ,  Myo Thu Maung

IPC: B01L7/00 ,  C12Q3/00

CPC classification number: B01L7/52 ,  B01L3/5027 ,  B01L2200/025 ,  B01L2200/147 ,  B01L2300/0819 ,  B01L2300/0893 ,  B01L2300/1805 ,  B01L2300/1822 ,  C12P19/34 ,  C12Q3/00 ,  G01N21/6408 ,  G01N21/6428 ,  G01N21/6456 ,  G01N21/76

Abstract: A thermal cycler for a microfluidic device includes a controller operable to provide a series of electrical signals, a heat sink, and a heating element in thermal communication with the heat sink and operable to receive the series of electrical signals from the controller. The thermal cycler also includes a thermal chuck in thermal communication with the heating element. The thermal chuck comprises a heating surface operable to make thermal contact with the microfluidic device. The heating surface is characterized by a temperature ramp rate between 2.5 degrees Celsius per second and 5.5 degrees Celsius per second and a temperature difference between a first portion of the heating surface supporting a first portion of the microfluidic device and a second portion of the heating surface supporting a second portion of the microfluidic device is less than 0.25° C.

Abstract translation: 用于微流体装置的热循环仪包括控制器，其可操作以提供与散热器热连通的一系列电信号，散热器和加热元件，并可操作以从控制器接收一系列电信号。 热循环仪还包括与加热元件热连通的热卡盘。 热卡盘包括可操作以与微流体装置进行热接触的加热表面。 加热表面的特征在于每秒2.5摄氏度和5.5摄氏度/秒之间的温度升高速率，并且支撑微流体装置的第一部分的加热表面的第一部分与加热表面的第二部分之间的温度差 支撑微流体装置的第二部分小于0.25℃