Defense Date

7-7-2021

Graduation Date

Summer 8-7-2021

Availability

Immediate Access

Submission Type

thesis

Degree Name

MS

Department

Biomedical Engineering

School

Rangos School of Health Sciences

Committee Chair

Bin Yang

Committee Member

Kimberly Williams

Committee Member

Melikhan Tanyeri

Keywords

Viscoelastic hemostatic Assays, Microfluidics, blood coagulation

Abstract

Blood coagulation disorders are malfunctions in the body’s ability to control blood clotting. It can result in either insufficient clotting causing an increased risk of bleeding or excessive clotting obstructing blood flow. The rapid and accurate diagnosis of coagulopathies is an important, unmet need in the clinical setting. Rapidly identifying the source of bleeding, either acquired or inherited, is critical to reduce the risk of major blood loss and deliver personalized hemostatic therapies. Viscoelastic hemostatic assays, or VHAs, deliver an effective solution to the diagnosis of coagulopathies by evaluating global hemostatic function using whole blood rather than plasma. VHAs are functional blood tests that monitor all phases of coagulation by measuring the viscoelastic properties of blood during clot formation and degradation to help determine the root cause of bleeding. Presently, the two major commercialized VHA techniques are the thromboelastometry (TEM) and the thromboelastography (TEG). These two instruments, however, have a high acquisition cost, bulky benchtop size, and are mostly limited to use in surgical procedures. Here, we aim to develop a microfluidic viscoelastic hemostatic assay (µVHA) to facilitate point-of-care hemostatic tests based on digital microfluidics where whole blood samples are partitioned into nanoliter sized emulsion droplets. These devices have been fabricated using soft lithography techniques and are capable of determining viscoelastic properties of coagulating blood as a function of time. We employ digital microfluidics where blood samples are split into nanoliter sized droplets within a microchannel under constant pressure, and viscoelastic properties of blood are deduced from droplet properties such as droplet length and inter-droplet distance. The length of the droplets is correlated with aqueous phase viscosity at high ratios of aqueous-to-oil inlet pressure. Here, we demonstrate a proof-of-concept blood coagulation analysis device that can potentially deduce viscoelastic properties of whole blood under low shear conditions, thereby providing information about global hemostatic function from the beginning of clot formation through clot retractions and fibrinolysis. These portable and low cost µVHAs would ultimately reduce the footprint and overall cost, broaden potential applications beyond emergency and surgical procedures and enable adoption by military medics for field diagnosis of combat trauma patients.

Language

English

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