Microfluidic Device For Real-Time Clinical Monitoring And Quantitative Assessment Of Whole Blood Coagulation

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 (T pg ) at which a second pressure value is about twice the determined first pressure value, and a second time (T pf ) 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.

1 - 86 . (canceled) 
     
     
         87 . A method of assessing coagulation, comprising:
 a) flowing a first portion of a blood sample at a flow rate through a microchannel of a microfluidic device, wherein the microchannel comprises endothelial cells; and   b) detecting blood coagulation.   
     
     
         88 . The method of  claim 87 , wherein the detecting is done with an imaging system. 
     
     
         89 . The method of  claim 87 , wherein the detecting is done in real-time with the imaging system. 
     
     
         90 . The method of  claim 88 , wherein the imaging system comprises confocal imaging. 
     
     
         91 . The method of  claim 87 , wherein the microchannel is approximately 125 μm in diameter. 
     
     
         92 . The method of  claim 87 , wherein the coagulation causes full occlusion of the microchannel. 
     
     
         93 . The method of  claim 87 , wherein the microfluidic device comprises a first port at a first end, the first port connecting to an inlet end of the microchannel, and a second port at a second end, the second port connecting to an outlet end of the microchannel. 
     
     
         94 . The method of  claim 87 , wherein blood coagulation is detected by an increase in pressure. 
     
     
         95 . The method of  claim 87 , further comprising, prior to step a), removing a coagulation component from a first portion of the blood sample. 
     
     
         96 . The method of  claim 87 , further comprising, prior to step a), removing platelets from a first portion of the blood sample to enhance isolation of fibrin formation. 
     
     
         97 . The method of  claim 87 , further comprising:
 c) adding a modifier to a second portion of the blood sample;   d) flowing the second portion of a blood sample at a flow rate through a microchannel of a second microfluidic device; and   e) comparing the blood coagulation in the first device with the second device.   
     
     
         98 . The method of  claim 97 , wherein the modifier comprises an anti-coagulant. 
     
     
         99 . The method of  claim 97 , wherein the modifier comprises one of heparin, a low molecular weight heparin, a direct factor inhibitor, a direct thrombin inhibitor, an antithrombin protein, rivorxaban, apixaban, debigatran, a coumarin, hirudin, lepirudin, bivalirudin, argatroban, dabigatran, batroxobin, hementin. 
     
     
         100 . The method of  claim 97 , wherein the modifier comprises a food supplement derivative. 
     
     
         101 . The method of  claim 97 , wherein the modifier comprises a drug. 
     
     
         102 . The method of  claim 97 , wherein the drug is an anti-platelet drug. 
     
     
         103 . A method of assessing coagulation, comprising:
 a) flowing a first portion of a blood sample at a flow rate through a microchannel of a microfluidic device; and   c) detecting blood coagulation by detecting an increase in pressure.   
     
     
         104 . The method of  claim 103 , wherein the increase in pressure is detected by a pressure sensor.