Microfluidic chip-based, universal coagulation assay
Inventors
Bakhru, Sasha • Laulicht, Bryan • Zappe, Stefan • Steiner, Solomon
Assignees
Perosphere Technologies Inc • Perosphere Pharmaceuticals Inc
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Publication Number
US-10534006-B2
Publication Date
2020-01-14
Expiration Date
Abstract
A microfluidic, chip-based assay device has been developed for measuring physical properties of an analyte (particularly, whole blood or whole blood derivatives). The technologies can be applied to measure clotting times of whole blood or blood derivatives, determine the effects of anticoagulant drugs on the kinetics of clotting/coagulation, as well as evaluate the effect of anticoagulant reversal agents. These technologies can additionally be used to optimize the dosage of anticoagulation drugs and/or their reversal agents. The assay is independent of the presence of anticoagulant; clotting is activated by exposure of the blood sample in the device to a glass (or other negatively charged material such as oxidized silicon) surface, which activates the intrinsic pathway and can be further hastened by the application of shear flow across the activating materials surface. The absence of chemical activating agents and highly controlled and reproducible micro-environment yields a point of care universal clotting assay.
Core Innovation
The invention relates to a test microchip for measurement of clotting time in a blood or plasma sample. The test microchip includes an inlet communicating with one or more microchannels and one or more test chambers, and each microchannel has a defined volume configured to draw the blood or plasma sample into the one or more test chambers by passive capillary action.
The microchannels and/or the entry into the test chambers include at least one anionically charged surface at the inlet into the microchannel and/or the entry into the test chamber. The anionically charged surface activates clotting of the blood or plasma sample upon entry, while not including chemical agents activating clotting, and the anionically charged surfaces described include glass and negatively charged/oxidized silicon surfaces such as SiO2 and silicon nitride/thermally oxidized silicon.
Clot formation is detected by measurable changes in properties indicative of clot formation in the test chamber. The measurable changes include changes in viscosity, impedance, acoustic properties, or optical properties, and the invention further supports point-of-care use with a reader that measures clotting time from activation-to-detection change timing using electrical and/or optical sensing and temperature control.
Claims Coverage
The independent claims cover a test microchip that passively draws a blood or plasma sample into microchambers, activates clotting using anionically charged surfaces without chemical clotting activators, and detects clot formation using measurable property changes. The main inventive features are centered on microfluidic capillary transport, anionically charged clot activation surfaces lacking chemical activators, and multi-parameter readout of viscosity, impedance, acoustic, or optical property changes.
Passive capillary microchannel drawing into micro test chambers
A test microchip having an inlet communicating with one or more microchannels, where each microchannel comprises one or more test chambers with a defined volume and is configured to draw the blood or plasma sample into the test chambers by passive capillary action.
Anionically charged clot-activating surface without chemical agents
Each microchannel comprises at least one anionically charged surface at the inlet into the microchannel and/or the entry into the test chamber, wherein the anionically charged surface activates clotting upon entry and does not include chemical agents activating clotting.
Clotting-indicative property measurement in the test chamber
Changes in viscosity, impedance, acoustic properties, or optical properties indicative of clot formation can be measured in the test chamber.
Overall, the claim coverage requires passive capillary microfluidic delivery into test chambers, clotting activation by anionically charged surfaces that excludes chemical clotting activators, and detection based on measurable viscosity, impedance, acoustic, or optical changes in the test chamber.
Stated Advantages
Provides measurement of clotting time in a blood or plasma sample using an anionically charged surface that activates clotting without chemical agents activating clotting.
Enables detecting clot formation by measuring changes in viscosity, impedance, acoustic properties, or optical properties in the test chamber.
Documented Applications
Point-of-care microfluidic, chip-based coagulation assay for measuring clotting time.
Use with anticoagulant drugs where clotting time measurement is supported in contexts described in the document (e.g., anticoagulated blood/plasma, including cases tied to aPTT measurability constraints as referenced by dependent claim context).
Experimental example demonstrating impedance and IR correlation for sham control versus delayed clotting and reversal using a reversal agent (PER977/ciraparantag).
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