Method and device for high throughput cell deformability measurements

    公开(公告)号:US11169078B2

    公开(公告)日:2021-11-09

    申请号:US15868025

    申请日:2018-01-11

    摘要: A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

    METHOD AND DEVICE FOR HIGH THROUGHPUT CELL DEPORMABILITY MEASUREMENTS
    2.
    发明申请
    METHOD AND DEVICE FOR HIGH THROUGHPUT CELL DEPORMABILITY MEASUREMENTS 审中-公开
    用于高通量细胞可分量测量的方法和装置

    公开(公告)号:US20160231224A1

    公开(公告)日:2016-08-11

    申请号:US14552256

    申请日:2014-11-24

    IPC分类号: G01N15/14 G01N33/487 B01L3/00

    摘要: A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

    摘要翻译: 公开了一种能够以高产量自动测量细胞机械参数的系统。 微流体装置使用相交流来产生细胞经受受控拉伸的拉伸流动区域。 在进入延伸流动区域之前,细胞被聚焦成流线。 在拉伸区域中,每个单元的变形用成像装置测量。 自动图像分析从图像中提取一系列独立的生物力学参数。 这些可能包括细胞大小,变形能力和圆形度。 然后可以以各种方式使用所获得的单细胞数据。 可以为用户开发和显示可变形性和圆形度的散射密度图。 诸如可变形性和圆形度的机械参数可以被门控或阈值化以识别感兴趣的某些细胞或感兴趣的亚群。 类似地,使用该设备获得的机械数据可以用作单元签名。

    SYSTEM AND METHOD FOR DEFORMING AND ANALYZING PARTICLES
    3.
    发明申请
    SYSTEM AND METHOD FOR DEFORMING AND ANALYZING PARTICLES 有权
    用于变形和分析颗粒的系统和方法

    公开(公告)号:US20140315287A1

    公开(公告)日:2014-10-23

    申请号:US14058028

    申请日:2013-10-18

    IPC分类号: G01N15/14

    摘要: A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.

    摘要翻译: 用于变形和分析载体在样品体积中的多个颗粒的系统包括限定入口的衬底,其构造成接收样品体积和出口; 以及流体连接到入口和出口的流体通路。 流体通道包括配置成从入口接收多个颗粒并将多个颗粒从随机分布聚焦到聚焦状态的输送区域,限定位于输送区域下游并且耦合到出口的交叉的变形区域, 并且其中所述变形区域被配置为从所述递送区域接收所述多个颗粒并且将多个颗粒中的每个颗粒从单个方向传播到所述交叉点,所述第一分支流体耦合到所述变形区域并且被配置为传输第一 流入所述十字路口的第二分支和流体耦合到所述变形区域并被配置为将基本上与所述第一流相对的第二流传送到所述交叉点的第二分支,其中所述第一流和所述第二流被配置为诱导一个或多个 多个颗粒中的颗粒。

    SYSTEM AND METHOD FOR DEFORMING AND ANALYZING PARTICLES
    4.
    发明申请
    SYSTEM AND METHOD FOR DEFORMING AND ANALYZING PARTICLES 有权
    用于变形和分析颗粒的系统和方法

    公开(公告)号:US20140113324A1

    公开(公告)日:2014-04-24

    申请号:US14057942

    申请日:2013-10-18

    IPC分类号: G01N33/50

    摘要: A system for deforming and analyzing particles includes a substrate defining an inlet, and an outlet; a fluidic pathway fluidly coupled to the inlet and the outlet and defining a delivery region upstream of a deformation region configured to deform particles, wherein the fluidic pathway comprises a first branch configured to generate a first flow, and a second branch configured to generate a second flow that opposes the first flow, wherein an intersection of the first flow and the second flow defines the deformation region; a detection module including a sensor configured to generate a morphology dataset characterizing deformation of the particles, and a photodetector configured to generate a fluorescence dataset characterizing fluorescence of the particles; and a processor configured to output an analysis of the plurality of particles based at least in part on the deformation dataset and the fluorescent dataset for the plurality of particles.

    摘要翻译: 用于变形和分析颗粒的系统包括限定入口的基板和出口; 流体路径,流体地联接到入口和出口,并且限定被配置为变形颗粒的变形区域上游的输送区域,其中流体路径包括被配置为产生第一流量的第一分支和被配置为产生第二流量的第二分支 所述第一流与所述第一流相对,其中所述第一流和所述第二流的交点限定所述变形区; 检测模块,其包括被配置为生成表征所述粒子的变形的形态学数据集的传感器,以及被配置为产生表征所述粒子的荧光的荧光数据集的光电检测器; 以及处理器,被配置为至少部分地基于所述多个粒子的所述变形数据集和所述荧光数据集来输出所述多个粒子的分析。

    System and method for deforming and analyzing particles
    9.
    发明授权
    System and method for deforming and analyzing particles 有权
    颗粒变形和分析的系统和方法

    公开(公告)号:US09151705B2

    公开(公告)日:2015-10-06

    申请号:US14058028

    申请日:2013-10-18

    IPC分类号: G01N15/14 G01N33/50

    摘要: A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.

    摘要翻译: 用于变形和分析载体在样品体积中的多个颗粒的系统包括限定入口的衬底,其构造成接收样品体积和出口; 以及流体连接到入口和出口的流体通路。 流体通道包括配置成从入口接收多个颗粒并将多个颗粒从随机分布聚焦到聚焦状态的输送区域,限定位于输送区域下游并且耦合到出口的交叉的变形区域, 并且其中所述变形区域被配置为从所述递送区域接收所述多个颗粒并且将多个颗粒中的每个颗粒从单个方向传播到所述交叉点,所述第一分支流体耦合到所述变形区域并且被配置为传输第一 流入所述十字路口的第二分支和流体耦合到所述变形区域并被配置为将基本上与所述第一流相对的第二流传送到所述交叉点的第二分支,其中所述第一流和所述第二流被配置为诱导一个或多个 多个颗粒中的颗粒。

    System and method for deforming and analyzing particles

    公开(公告)号:US10295455B2

    公开(公告)日:2019-05-21

    申请号:US15471851

    申请日:2017-03-28

    摘要: A system for deforming and analyzing a plurality of particles carried in a sample volume includes a substrate defining an inlet, configured to receive the sample volume, and an outlet; and a fluidic pathway fluidly coupled to the inlet and the outlet. The fluidic pathway includes a delivery region configured to receive the plurality of particles from the inlet and focus the plurality of particles from a random distribution to a focused state, a deformation region defining an intersection located downstream of the delivery region and coupled to the outlet, and wherein the deformation region is configured to receive the plurality of particles from the delivery region and to transmit each particle in the plurality of particles into the intersection from a single direction, a first branch fluidly coupled to the deformation region and configured to transmit a first flow into the intersection, and a second branch fluidly coupled to the deformation region and configured to transmit a second flow, substantially opposing the first flow, into the intersection, wherein the first flow and the second flow are configured to induce extension of one or more particles in the plurality of particles.