Wearable Microchip for Assessing Global Hemostatsis

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PROJECT SUMMARY Bleeding and thrombosis are common and lethal complications of many disease states. However, answering the simple question “Is this patient in danger of abnormal bleeding or clotting?” in a timely manner remains challenging with the existing clinical tests, which are time consuming and prone to error via the introduction of pre-analytical variables. Importantly, no test assess vasoconstriction or the overall entire hemostatic response, which is composed of concerted actions between platelets, cells, coagulation proteins, and the tissue/vessel complex. In addition, the response is unique to each individual and difficult to predict. Hence, given delays and limited information, it is unsurprising that physicians rely on expert opinion rather than the existing panel of tests in complicated clinical situations. The research objective of this proposal is to apply the nascent fields of flexible electronics and microfluidics to create a wearable, multi-parameter, point of care (POC), rapid, and comprehensive assessment of hemostasis that helps physicians diagnose and manage hemostatic complications. I hypothesize that a wearable microchip-based device that completely automates the bleeding time assay and adds POC analogs of existing tests will create a quantitative, reliable, and comprehensive measurement of hemostasis. I will apply advanced engineering tools to automatically collect and measure blood from a standardized, small wound created on the volar forearm surface with a typical diabetic lancet. Specific Aim 1 focuses on in vitro and in vivo clinical testing of an automated wound hemostasis assay that measures the overall and complete hemostatic response, including vasoconstriction. Specific Aim 2 slightly reconfigures the platform in aim 1, to enable quantitative measurements of 1) coagulation function which is analogous to prothrombin time (PT), 2) activated partial thromboplastin time (aPTT); and 3) platelet function which is analogous to a platelet functional analyzer (PFA). Specific Aim 3 tests the acceptability of the new technology in pediatric patients and examines the reliability (or degree of agreement) of the POC aPTT to the lab based aPTT for patients being anticoagulated with heparin. The aims outlined here lay the groundwork for a device that will transform clinical practice by providing critical information to diagnose and guide the management of hemostatic complications that ultimately will reduce the significant morbidity and cost of altered hemostasis. In addition, the career development activities complement the candidate’s micro-engineering background with formal coursework and supervised training in translational research fundamentals, coagulation, and conducting clinical research with novel biomedical devices. This training occurs in a highly interdisciplinary and innovative environment created by institutions with strengths in micro-engineering (Georgia Tech) and medicine (Emory University). Upon completion, the candidate will able to independently translate microdevices from the cleanroom to the clinic.