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Development of microfluidic devices to measure and model hemostasis
Sorrells, Matthew G.
Sorrells, Matthew G.
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2022
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Abstract
Hemostasis is the sum and interplay of the biophysical and biochemical mechanisms that lead to cessation of blood loss of a compromised blood vessel. For disorders like trauma-induced coagulopathy and genetic bleeding disorders there is a lack of knowledge in the mechanisms that lead to dysregulation of hemostasis under different injury types and within different vascular beds, which in turn hampers the ability to predict bleeding risk and choose effective interventions. Whole blood microfluidic flow assays have emerged as an approach to measure the underlying global and disease-specific mechanisms in hemostasis in vitro. In this thesis dissertation, we review the current state of the field of these flow assays and present work by the author that mark contributions towards improving and using them to discover of novel mechanisms. Chapters 1 provides a general overview of hemostasis and the different methods used to measure and model it. Chapter 2 is a literature review of flow assays with an emphasis on hemostasis and fibrinolysis. In Chapter 3, we present data from mathematical modeling and flow assays that led to the discovery of coagulation factor V as a strong modifier of clot formation in hemophilia A. In Chapter 4, we present several image processing libraries written for the quantification of fluorescent microscopy images from flow assays. In Chapter 5, we describe how collage related peptides absorb into common materials used for microfluidic channels and implications of this phenomenon in micropatterning peptides. Finally, in Chapter 6, we present a new approach to studying the spatial presentation of prothrombotic substrates that mimics the segmented structure of blood vessel walls.
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