Wearable Microchip for Assessing Global Hemostatsis

项目摘要 出血和血栓形成是许多疾病状态的常见和致命的并发症。然而，回答 简单的问题“病人是否有异常出血或凝血的危险”及时地， 挑战现有的临床测试，这些测试是耗时的，并且通过引入 预分析变量。重要的是，没有测试评估血管收缩或整体止血反应， 其由血小板、细胞、凝血蛋白和组织/血管之间的协同作用组成 复杂.此外，每个人的反应都是独特的，很难预测。因此，由于延误和 由于信息有限，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。这项建议的研究目标是应用新兴领域， 灵活的电子和微流体技术，以创建一个可穿戴的，多参数，护理点（POC），快速， 全面的止血评估，帮助医生诊断和管理止血 并发症我假设一个可穿戴的基于微芯片的设备完全自动出血 时间分析和增加现有测试的POC类似物将创建一个定量的，可靠的，全面的 止血的测量。我将应用先进的工程工具自动收集和测量 用典型的糖尿病刺血针在前臂掌侧表面上产生标准化的小伤口的血液。 具体目标1侧重于自动伤口止血测定的体外和体内临床测试， 测量总体和完全止血反应，包括血管收缩。具体目标2轻微 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）活化部分凝血活酶时间（aPTT）;和3）血小板功能 其类似于血小板功能分析仪（PFA）。具体目标3测试新的 技术在儿科患者中的应用，并检查POC aPTT与 肝素抗凝患者的实验室aPTT。这里概述的目标为以下方面奠定了基础： 该设备将通过提供关键信息来诊断和指导临床实践， 止血并发症的管理，最终将减少显著的发病率和成本的改变， 止血。此外，职业发展活动与考生的微工程相辅相成 具有正式课程和翻译研究基础的监督培训背景， 凝血，并使用新型生物医学设备进行临床研究。这种训练发生在一个高度 由在微型工程方面具有优势的机构创造跨学科和创新的环境 （格鲁吉亚理工）和医学（埃默里大学）。完成后，候选人将能够独立 将微型设备从洁净室转移到诊所。

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.