Wearable Microchip for Assessing Global Hemostatsis

用于评估整体止血的可穿戴微芯片

• 批准号: 10582630
• 负责人: David Richard Myers
• 金额: $ 15.75万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582630
• 关键词: Activated Partial Thromboplastin Time measurement; Agreement; Anticoagulants; Anticoagulation; Biological Assay; Bleeding time procedure; Blood; Blood Cells; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Platelets; Blood Volume; Blood flow; Blood specimen; Cells; Childhood; Clinic; Clinical; Clinical Research; Coagulation Process; Complement; Complex; Consumption; Data; Devices; Diagnosis; Diagnostic; Disease; Engineering; Environment; Expert Opinion; Forearm; Gold; Health Expenditures; Hemophilia A; Hemophilia B; Hemorrhage; Hemostatic Agents; Hemostatic function; Heparin; Hospitalization; In Situ; In Vitro; Individual; Institution; Intuition; K-Series Research Career Programs; Lead; Life; Measurement; Measures; Medicine; Mentors; Microfabrication; Microfluidics; Morbidity - disease rate; Oral; Paper; Patient Monitoring; Patients; Phenotype; Physicians; Platelet Transfusion; Platelet aggregation; Plavix; Population; Proteins; Prothrombin time assay; Research; Sampling; Skin; Standardization; Surface; System; Technology; Testing; Therapeutic; Thrombosis; Time; Tissues; Training; Translating; Translational Research; Universities; Variant; Warfarin; analog; care costs; career development; clinical practice; clinically relevant; cost; diabetic; electronic sensor; experience; experimental study; flexible electronics; fundamental research; improved; in vivo; in vivo evaluation; innovation; microchip; microdevice; microelectronics; miniaturize; mortality; new technology; novel; pediatric patients; percutaneous coronary intervention; platelet function; point of care; prototype; research clinical testing; response; screening; tool; trend; vasoconstriction; wound; wound care

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.

项目摘要 许多疾病状态的出血和血栓形成是常见的，致命的并发症。但是，回答 一个简单的问题：“这个患者有异常出血还是关闭的危险？”及时仍然存在 通过现有的临床测试挑战，这很耗时，并且很容易通过引入 预分析变量。重要的是，没有测试评估血管收缩或整个止血反应， 由血小板，细胞，凝结蛋白和组织/血管之间的协同作用组成 复杂的。此外，响应对每个人都是独特的，难以预测。因此，给定延迟和 有限的信息，医生依靠专家意见而不是现有的面板，这不足为奇 在复杂的临床情况下进行测试。该提议的研究目的是应用 柔性电子和微流体，可创建可穿戴的多参数，护理点（POC），快速和 全面评估止血的评估，可帮助医生诊断和处理止血 并发症。我假设这是一种可穿戴的基于微芯片的设备，可以完全自动化出血 时间分析并添加现有测试的POC类似物将创建定量，可靠和全面 止血的测量。我将应用高级工程工具自动收集和测量 来自标准化小伤的血液在沃拉前臂表面产生，并具有典型的糖尿病刺伤。 特定的目标1专注于自动伤口止血测定法的体外和体内临床测试 测量总体和完整的止血反应，包括血管收缩。特定的目标2稍微 重新配置AIM 1中的平台，以实现1）凝结功能的定量测量值 类似于凝血酶原时间（PT），2）激活的部分凝血活蛋白时间（APTT）； 3）血小板功能 类似于血小板功能分析仪（PFA）。特定目标3测试新的可接受性 小儿患者的技术并检查POC APTT的可靠性（或一致程度） 基于实验室的APTT，用于用肝素抗凝的患者。这里概述的目的为 通过提供关键信息来诊断和指导的设备将改变临床实践 止血并发症的管理，最终将降低明显的发病率和成本 止血。此外，职业发展活动完成了候选人的微工程 背景正式课程和翻译研究基础的监督培训， 凝血，并使用新型的生物医学设备进行临床研究。这种训练在高度发生 跨学科和创新的环境由机构创造，具有微观工程的优势 （佐治亚理工学院）和医学（埃默里大学）。完成后，候选人将能够独立 将微型电视从洁净室转换为诊所。