Microfluidic device for real-time clinical monitoring and quantitative assessment of whole blood coagulation

Patent metadata

Field	Value
Publication number	US-9562914-B2
Application number	US-201415028667-A
Country	US
Kind code	B2
Filing date	Oct 16, 2014
Priority date	Oct 16, 2013
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

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.

First claim

What is claimed is:

1. A microfluidic coagulation device, comprising:
at least one substrate defining a plurality of microchannels;
a first port at a first end portion of the substrate, the first port connecting to first ends of the plurality of microchannels;
a second port at a second end portion of the substrate, the second port connecting to second ends of the plurality of microchannels;
a first sensing device configured to determine a pressure value in, or relating to, a pressure across the plurality of microchannels;
a timer; and
a controller configured to determine, in combination with the first sensing device and the timer, a first pressure value at an initiation of flow, a first time at which a second pressure value is determined to be about twice the determined first pressure value, and a second time at which a third pressure value is about (1+e) times the determined first pressure value, and further configured to establish a subject coagulation model predictive of channel occlusion in accord with the relation

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wherein T pf is the second time and T pg is the first time, and
wherein a differential pressure or flow rate/shear applied across the first port drives a blood sample across the plurality of microchannels at a substantially constant flow rate.

2. The microfluidic coagulation device according to claim 1 , further comprising:
an instrument that causes differential pressure or flow rate/shear applied across the first port to drive a blood sample across the plurality of microchannels at a substantially constant flow rate,
wherein the instrument that generates the differential pressure or flow is a pump.

3. The microfluidic coagulation device according to claim 2 , wherein the instrument is a syringe pump.

4. The microfluidic coagulation device according to claim 1 , wherein the at least some of the plurality of microchannels comprise a cross-sectional surface area between about 125 μm 2 -1.75 mm 2 .

5. The microfluidic coagulation device according to claim 1 , wherein the at least some of the plurality of microchannels comprise a maximal hydraulic diameter between about 25 μm-5 mm.

6. The microfluidic coagulation device according to claim 5 , wherein at least some of the plurality of microchannels have a maximal dimension between about 75 μm-200 μm.

7. The microfluidic coagulation device according to claim 1 , wherein at least one of the plurality of microchannels has a first cross-sectional area and at least one of the plurality of microchannels has a second cross-sectional area different than the first cross-sectional area.

8. The microfluidic coagulation device according to claim 1 , wherein at least a portion of a first microchannel has a first surface treatment.

9. The microfluidic coagulation device according to claim 8 , wherein at least a portion of a second microchannel has a second surface treatment different than the first surface treatment.

10. The microfluidic coagulation device according to claim 9 , wherein at least one of the first surface treatment or second surface treatment comprises one of a naturally occurring or synthetic reagent, collagen, a thrombus formation-inducing material, a thrombus formation-inhibiting material, a platelet activating material, and platelet inhibiting material, a fibrin network forming material, a fibrin network disrupting material, cells, endothelial cells, smooth muscle cells, segmented polyurethane, polyvinyl chloride, or polymethyl-methacrylate.

11. The microfluidic coagulation device according to claim 1 , wherein the shear rate is between 75 sec −1 and 5000 sec −1 .

12. The microfluidic coagulation device according to claim 1 , further comprising:
an imaging system configured to image at least one portion of at least one of the plurality of microchannels.

13. The microfluidic coagulation device according to claim 12 , wherein the imaging system comprises an automated imaging protocol.

14. The microfluidic coagulation device according to claim 13 , wherein the imaging system comprises confocal imaging or on-chip flow cytometry.

15. The microfluidic coagulation device according to claim 13 , wherein the imaging system is configured to measure platelet aggregates or to image effects of platelet activators, cellular components of blood, or cells on coagulation.

16. The microfluidic coagulation device according to claim 1 , wherein the differential pressure applied across the first port to drive a blood sample across the plurality of microchannels at a substantially constant flow rate comprises a patient's blood pressure.

17. A microfluidic coagulation device, comprising:
at least one substrate defining a plurality of microchannels;
a first port at a first end portion of the substrate, the first port connecting to first ends of the plurality of microchannels;
a second port at a second end portion of the substrate, the second port connecting to second ends of the plurality of microchannels;
a first sensing device configured to determine a flow rate in, or relating to, the plurality of microchannels,
a timer; and
a controller configured to determine, in combination with the first sensing device and the timer, (i) a first flow rate value at a first time corresponding to an initiation of flow, (ii) a second time at which a second flow rate value is determined to be about half the determined first flow rate value, (iii) a third time at which a third flow rate value is determined to be about (1+e) times lesser than the determined first flow rate value, and (iv) a blood coagulation model predictive of channel occlusion governed by the relation

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Assignees

• Harvard College

Inventors

• Jain Abhishek
• Waterhouse Anna
• Super Mike
• Ingber Donald E
• Leslie Daniel C

Classifications

• B01L2300/0861

  Configuration of multiple channels and/or chambers in a single devices · CPC title

• B01L2300/08

  Geometry, shape and general structure · CPC title

• B01L2200/146

  Employing pressure sensors · CPC title

• G01N33/4905

  Determining clotting time of blood (by chemical methods G01N33/86, C12Q1/56) · CPC title

• G06F19/24

  Physics · mapped topic