公开(公告)号：US10732172B1

公开(公告)日：2020-08-04

申请号：US15576235

申请日：2016-05-22

Applicant: President and Fellows of Harvard College ,  Children's Medical Center Corporation

Inventor： Donald E. Ingber ,  Abhishek Jain ,  Andries D. van der Meer ,  Alan David Michelson ,  Andrew L. Frelinger, III ,  Riccardo Barrile

IPC: G01N33/50 ,  B01L3/00 ,  G01N33/86

Abstract: A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.

公开(公告)号：US20160258968A1

公开(公告)日：2016-09-08

申请号：US15028667

申请日：2014-10-16

Applicant: PRESIDENT AND FELLOWS OF HARVARD COLLEGE

Inventor： Abhishek Jain ,  Anna Waterhouse ,  Mike Super ,  Donald E. Ingber ,  Daniel C. Leslie

IPC: G01N33/86 ,  B01L3/00 ,  G06F19/24

CPC classification number: B01L3/50273 ,  B01L3/502746 ,  B01L2200/146 ,  B01L2300/0627 ,  B01L2300/08 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2400/0478 ,  B01L2400/084 ,  G01N33/4905 ,  G01N33/86 ,  G06F19/24

Abstract: In accord with one aspect, a microfluidic coagulation assessment device defining a plurality of microchannels is provided, wherein a blood sample is driven through the microchannels at a substantially constant flow rate and a controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom. In another aspect, the blood sample is driven through the microchannels at a substantially constant pressure and a controller is configured to, in combination with a timer and a flow sensing device make the determination based on flow rate.

Abstract translation: 根据一个方面，提供了限定多个微通道的微流体凝固评估装置，其中血液样本以基本恒定的流速被驱动通过微通道，并且控制器被配置为结合定时器和压力感测 装置，在流动开始时确定第一压力值（或流量值），其中第二压力值大约是所确定的第一压力值的两倍的第一时间（Tpg），以及第二时间（Tpf） 压力值约为所确定的第一压力值的（1 + e）倍，并建立预测通道阻塞的对象凝固模型。 在另一方面，血液样本以基本上恒定的压力驱动通过微通道，并且控制器被配置为结合定时器和流量检测装置基于流量进行确定。

公开(公告)号：US20180185839A1

公开(公告)日：2018-07-05

申请号：US15862621

申请日：2018-01-04

Applicant: President and Fellows of Harvard College

Inventor： Abhishek Jain ,  Anna Waterhouse ,  Mike Super ,  Donald E. Ingber ,  Daniel C. Leslie

IPC: B01L3/00 ,  G06F19/24 ,  G01N33/49 ,  G01N33/86

CPC classification number: B01L3/50273 ,  B01L3/502746 ,  B01L2200/146 ,  B01L2300/0627 ,  B01L2300/08 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2400/0478 ,  B01L2400/084 ,  G01N33/4905 ,  G01N33/86 ,  G16B40/00

Abstract: A microfluidic coagulation assessment device includes a plurality of microchannels, with a blood sample driven through the microchannels at a substantially constant flow rate. A controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom.

公开(公告)号：US20170100714A1

公开(公告)日：2017-04-13

申请号：US15393596

申请日：2016-12-29

Applicant: President and Fellows of Harvard College

Inventor： Abhishek Jain ,  Anna Waterhouse ,  Mike Super ,  Donald E. Ingber ,  Daniel C. Leslie

IPC: B01L3/00 ,  G01N33/49 ,  G06F19/24 ,  G01N33/86

CPC classification number: B01L3/50273 ,  B01L3/502746 ,  B01L2200/146 ,  B01L2300/0627 ,  B01L2300/08 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2400/0478 ,  B01L2400/084 ,  G01N33/4905 ,  G01N33/86 ,  G16B40/00

Abstract: A microfluidic coagulation assessment device includes a plurality of microchannels, with a blood sample driven through the microchannels at a substantially constant flow rate. A controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom.

公开(公告)号：US20200292531A1

公开(公告)日：2020-09-17

申请号：US15929387

申请日：2020-04-29

Applicant: President and Fellows of Harvard College ,  The Children's Medical Center Corporation

Inventor： Donald E. Ingber ,  Abhishek Jain ,  Andries D. van der Meer ,  Alan David Michelson ,  Andrew L. Frelinger, III ,  Riccardo Barrile

IPC: G01N33/50 ,  B01L3/00 ,  G01N33/86

Abstract: A method is directed to determining a thrombosis function and includes flowing a fluid sample over a surface having a fixed endothelial cell monolayer. The method further includes stimulating the fixed endothelial cell monolayer to induce formation of a clot, the clot being formed via interaction between the fixed endothelial cell monolayer and the fluid sample. In response to the clot formation, the method further includes determining a thrombosis function associated with the fluid sample and the fixed endothelial cell monolayer.

公开(公告)号：US20180024110A1

公开(公告)日：2018-01-25

申请号：US15694577

申请日：2017-09-01

Applicant: President and Fellows of Harvard College

Inventor： Daniel Levner ,  Christopher David Hinojosa ,  Andries D. van der Meer ,  Marinke van der Helm ,  Abhishek Jain ,  Donald Elliot Ingber ,  Marjon Zamani

IPC: G01N33/483 ,  G01N15/08 ,  B01L3/00

CPC classification number: G01N33/4833 ,  B01L3/502715 ,  B01L3/50273 ,  B01L3/502746 ,  B01L2300/0654 ,  B01L2300/0877 ,  B01L2300/0883 ,  B01L2400/0457 ,  B01L2400/0487 ,  B01L2400/082 ,  B01L2400/084 ,  B01L2400/086 ,  G01N15/0826 ,  G01N33/50 ,  G01N33/5005 ,  G01N2015/0065

Abstract: Systems and methods for measuring dynamic hydraulic conductivity and permeability associated with a cell layer are disclosed. Some systems include a microfluidic device, one or more working-fluid reservoirs, and one or more fluid-resistance element. The microfluidic device includes a first microchannel, a second microchannel, and a barrier therebetween. The barrier includes a cell layer adhered thereto. The working fluids are delivered to the microfluidic device. The fluid-resistance elements are coupled to one or more of the fluid paths and provide fluidic resistance to cause a pressure drop across the fluid-resistance elements. Mass transfer occurs between the first microchannel and the second microchannel, which is indicative of the hydraulic conductivity and/or dynamic permeability associated with the cells.

公开(公告)号：US20180008980A1

公开(公告)日：2018-01-11

申请号：US15694557

申请日：2017-09-01

Applicant: President and Fellows of Harvard College

Inventor： Daniel Levner ,  Christopher David Hinojosa ,  Andries D. van der Meer ,  Marinke van der Helm ,  Abhishek Jain ,  Donald Elliot Ingber ,  Marjon Zamani

IPC: B01L3/00 ,  G01N33/483 ,  G01N33/50

CPC classification number: G01N33/4833 ,  B01L3/502715 ,  B01L3/50273 ,  B01L3/502746 ,  B01L2300/0654 ,  B01L2300/0877 ,  B01L2300/0883 ,  B01L2400/0457 ,  B01L2400/0487 ,  B01L2400/082 ,  B01L2400/084 ,  B01L2400/086 ,  G01N15/0826 ,  G01N33/50 ,  G01N33/5005 ,  G01N2015/0065

Abstract: Systems and methods for measuring dynamic hydraulic conductivity and permeability associated with a cell layer are disclosed. Some systems include a microfluidic device, one or more working-fluid reservoirs, and one or more fluid-resistance element. The microfluidic device includes a first microchannel, a second microchannel, and a barrier therebetween. The barrier includes a cell layer adhered thereto. The working fluids are delivered to the microfluidic device. The fluid-resistance elements are coupled to one or more of the fluid paths and provide fluidic resistance to cause a pressure drop across the fluid-resistance elements. Mass transfer occurs between the first microchannel and the second microchannel, which is indicative of the hydraulic conductivity and/or dynamic permeability associated with the cells.

公开(公告)号：US09562914B2

公开(公告)日：2017-02-07

申请号：US15028667

申请日：2014-10-16

Applicant: President and Fellows of Harvard College

Inventor： Abhishek Jain ,  Anna Waterhouse ,  Mike Super ,  Donald E. Ingber ,  Daniel C. Leslie

IPC: G01N33/49 ,  G01N33/86 ,  B01L3/00 ,  G06F19/24

CPC classification number: B01L3/50273 ,  B01L3/502746 ,  B01L2200/146 ,  B01L2300/0627 ,  B01L2300/08 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2400/0478 ,  B01L2400/084 ,  G01N33/4905 ,  G01N33/86 ,  G06F19/24

Abstract: In accord with one aspect, a microfluidic coagulation assessment device defining a plurality of microchannels is provided, wherein a blood sample is driven through the microchannels at a substantially constant flow rate and a controller is configured to, in combination with a timer and a pressure sensing device, determine a first pressure value (or flow value) at an initiation of flow, a first time (Tpg) at which a second pressure value is about twice the determined first pressure value, and a second time (Tpf) at which a third pressure value is about (1+e) times the determined first pressure value and establish a subject coagulation model predictive of channel occlusion therefrom. In another aspect, the blood sample is driven through the microchannels at a substantially constant pressure and a controller is configured to, in combination with a timer and a flow sensing device make the determination based on flow rate.

Abstract translation: 根据一个方面，提供了限定多个微通道的微流体凝固评估装置，其中血液样本以基本恒定的流速被驱动通过微通道，并且控制器被配置为结合定时器和压力感测 装置，在流动开始时确定第一压力值（或流量值），其中第二压力值大约是所确定的第一压力值的两倍的第一时间（Tpg），以及第二时间（Tpf） 压力值约为所确定的第一压力值的（1 + e）倍，并建立预测通道阻塞的对象凝固模型。 在另一方面，血液样本以基本上恒定的压力驱动通过微通道，并且控制器被配置为结合定时器和流量检测装置基于流量进行确定。

公开(公告)号：US11085911B2

公开(公告)日：2021-08-10

申请号：US16534255

申请日：2019-08-07

Applicant: President and Fellows of Harvard College

Inventor： Daniel Levner ,  Christopher David Hinojosa ,  Andries D. van der Meer ,  Marinke van der Helm ,  Abhishek Jain ,  Donald Elliot Ingber ,  Marjon Zamani

IPC: G01N33/483 ,  G01N33/50 ,  B01L3/00 ,  C12M1/00 ,  G01N15/08 ,  G01N15/00

Abstract: Systems and methods for measuring dynamic hydraulic conductivity and permeability associated with a cell layer are disclosed. Some systems include a microfluidic device, one or more working-fluid reservoirs, and one or more fluid-resistance element. The microfluidic device includes a first microchannel, a second microchannel, and a barrier therebetween. The barrier includes a cell layer adhered thereto. The working fluids are delivered to the microfluidic device. The fluid-resistance elements are coupled to one or more of the fluid paths and provide fluidic resistance to cause a pressure drop across the fluid-resistance elements. Mass transfer occurs between the first microchannel and the second microchannel, which is indicative of the hydraulic conductivity and/or dynamic permeability associated with the cells.