Wearable Microchip for Assessing Global Hemostatsis

项目总结 出血和血栓形成是许多疾病的常见和致命的并发症。然而，回答 简单的问题是“这位病人是否有异常出血或凝血的危险？”及时地留下来 挑战现有的临床测试，这些测试既耗时又容易出错，因为引入 分析前变量。重要的是，没有测试评估血管收缩或整体止血反应， 它由血小板、细胞、凝血蛋白和组织/血管之间的协同作用组成 很复杂。此外，每个人的反应都是独一无二的，很难预测。因此，考虑到延误和 信息有限，医生依赖专家意见而不是现有的专家小组也就不足为奇了 在复杂的临床情况下进行测试。这项提议的研究目标是将新兴的领域 灵活的电子设备和微流控技术，可实现可穿戴、多参数、护理点(POC)、快速和 帮助医生诊断和管理止血的全面止血评估 并发症。我假设一种基于微芯片的可穿戴设备可以完全自动化出血 时间分析和添加现有测试的POC模拟将创建一个定量的、可靠的和全面的 止血测量。我将应用先进的工程工具来自动采集和测量 典型的糖尿病柳叶刀前臂掌侧表面形成的标准化小伤口的血液。 具体目标1集中在体外和体内的自动伤口止血测试的临床测试， 测量整体和完整的止血反应，包括血管收缩。具体目标2略微 重新配置目标1中的平台，以实现1)凝血功能的定量测量 类似于凝血酶原时间(PT)；2)活化的部分凝血活酶时间(APTT)；以及3)血小板功能 这类似于血小板功能分析仪(PFA)。特定目标3测试新版本的可接受性 技术，并检查POC aPTT对 基于实验室的aPTT，适用于肝素抗凝的患者。这里概述的目标为 一种将通过提供关键信息来诊断和指导 止血并发症的处理，最终将降低改变的显著发病率和成本 止血。此外，职业发展活动是对应聘者微观工程的补充 翻译研究基础方面的正规课程和有指导培训的背景， 凝固术，以及利用新型生物医学设备进行临床研究。这种培训发生在一个高度 具有微工程优势的机构创造的跨学科和创新环境 (佐治亚理工学院)和医学(埃默里大学)。完成后，考生将能够独立完成 将微型设备从洁净室搬到诊所。

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.