We propose development of a new technology that addresses the need for quantitative and sensitive point of care (POC) viscoelastic hemostatic assay (VHA) capability to characterize coagulation parameters that are crucial to guiding therapies for traumatic hemorrhage. Our proposed technique employs an array of magnetically actuated microscopic surface attached posts (SAPs), whose dynamic mechanical response to fluid conditions provides a quantitative measure of rheological parameters. The SAPs resemble biological cilia in size and aspect ratio and can be """"""""beat"""""""" at large amplitudes in the Hz to 10s of Hz frequency range. The SAPs are arranged in an array on the device's active surface;they are actuated with an external magnetic field and their amplitude is monitored optically. The temporal progression of the clotting process, from clotting time to clot lysis, can be monitored. In recent years increasing evidence has pointed to trauma induced coagulopathy (TIC) as a major factor in complications leading to hemorrhage related death;25-35% of trauma cases involve TIC. Mechanisms of TIC are still an active area of research, but it is clear that trauma can compromise healthy coagulation both by inhibiting clotting and amplifying lysis. Diagnostic tests that can rapidly evaluate hemostasis-related parameters from clotting to lysis are critical in developing effective therapeutic strategies for TIC. It is also crucial that these diagnostics are available where the need is greatest: near the accident prior to and during movement of the patient. Traditional laboratory coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (APTT) are both impractical and ineffective at providing these diagnostics. These plasma-based tests assess only the very beginning of the coagulation process (no information on lysis), require blood processing, and provide no mechanical information (clot strength). Within the context of this project, we will validate the ability the SP based viscoelastic measurements to provide information relevant to medical decisions. We will focus on developing a new approach to the underserved TIC problem in the field and during transportation of patients. We have successfully developed a fabrication protocol for SAPs, demonstrated their actuation in fluids, and have preliminary data demonstrating their ability to measure clot properties during coagulation. In the first year of this project we will characterize our system using reference viscous and viscoelastic fluids. In the second year we will demonstrate reproducible blood clotting measurements using the SAP system and validation by correlating these measurements with standard clinical and laboratory tests (using laboratory-based TEG instruments). Measurements on normal and factor deficient canine plasmas and whole blood will be performed including clotting time, clot stiffness, and clot lysis time.
We will development a new technology that addresses the need for quantitative and sensitive point of care viscoelastic haemostatic assay capability to guide therapies in cases of traumatic hemorrhage. Deaths due to traumatic injury account for 9% of global deaths annually, and of deaths due to trauma, more than 40% are due to hemorrhage or hemorrhagic shock. Our proposed technique employs an array of magnetically actuated microscopic surface attached posts that can provide the full spectrum of clotting parameters from clotting time to clot lysis in a compact hand held device deployable in the field.
|Judith, Robert M; Fisher, Jay K; Spero, Richard Chasen et al. (2015) Micro-elastometry on whole blood clots using actuated surface-attached posts (ASAPs). Lab Chip 15:1385-93|
|Evans, Benjamin A; Fiser, Briana L; Prins, Willem J et al. (2012) A Highly Tunable Silicone-Based Magnetic Elastomer with Nanoscale Homogeneity. J Magn Magn Mater 324:501-507|