Microactuated Rheometer for Point of Care Coagulopathy Applications

适用于护理点凝血病应用的微驱动流变仪

基本信息

批准号：
8301848
负责人：
RICHARD SUPERFINE
金额：
$ 21.67万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8301848
关键词：
Accidents Accounting Activated Partial Thromboplastin Time measurement Address Area Biological Biological Assay Blood Blood Clot Blood Coagulation Disorders Blood Coagulation Factor Blood Platelets Blood coagulation Blood coagulation tests Canis familiaris Cessation of life Cilia Clinical Coagulation Process Cytolysis Data Development Devices Diagnostic Diagnostic tests Elasticity Factor VIII Fibrinogen Frequencies Gel Glycerol Hand Hemorrhage Hemorrhagic Shock Hemostatic Agents Hemostatic function Human Hyaluronic Acid Injury Laboratories Liquid substance Measurement Measures Mechanics Medical Methods Microscopic Molecular Weight Monitor Movement Operative Surgical Procedures Optical Methods Patients Phase Plasma Preparation Process Production Property Prothrombin time assay Protocols documentation Research Rheology Sampling Simulate Solutions Surface System Techniques Technology Testing Therapeutic Thrombelastography Time Transportation of Patients Trauma Traumatic Hemorrhage Validation Viscosity Water Whole Blood aqueous base blood product improved instrument magnetic field new technology novel strategies point of care prototype research study response

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：我们建议开发一种新技术，以满足定量和敏感的护理点（POC）粘弹性止血测定（VHA）能力的需求，以表征对于指导创伤性出血治疗至关重要的凝血参数。我们提出的技术采用了一系列磁驱动的微观表面附着柱（SAP），其对流体条件的动态机械响应提供了流变参数的定量测量。 SAP 在大小和纵横比上类似于生物纤毛，并且可以以 Hz 至 10 秒的大幅度“跳动”。 Hz 频率范围。 SAP 在设备的活动表面上以阵列形式排列；它们由外部磁场驱动，并通过光学方式监控它们的振幅。可以监测凝血过程的时间进程，从凝血时间到凝块溶解。近年来，越来越多的证据表明创伤诱发的凝血病（TIC）是导致出血相关死亡的并发症的主要因素。 25-35% 的创伤病例涉及 TIC。 TIC 的机制仍然是一个活跃的研究领域，但很明显，创伤会通过抑制凝血和放大裂解来损害健康的凝血。能够快速评估从凝血到裂解的止血相关参数的诊断测试对于制定有效的 TIC 治疗策略至关重要。同样重要的是，在最需要的地方提供这些诊断：在患者移动之前和移动期间靠近事故的地方。凝血酶原时间 (PT) 和活化部分凝血活酶时间 (APTT) 等传统实验室凝血测试在提供这些诊断方面既不实用又无效。这些基于血浆的测试仅评估凝血过程的最开始（没有裂解信息），需要血液处理，并且不提供机械信息（凝块强度）。在该项目的背景下，我们将验证基于 SP 的粘弹性测量提供与医疗决策相关的信息的能力。我们将重点开发一种新方法来解决现场和患者转运过程中服务不足的 TIC 问题。我们已经成功开发了 SAP 的制造协议，展示了它们在流体中的驱动，并拥有初步数据证明它们在凝血过程中测量凝块特性的能力。在该项目的第一年，我们将使用参考粘性和粘弹性流体来表征我们的系统。第二年，我们将使用 SAP 系统演示可重复的凝血测量，并通过将这些测量与标准临床和实验室测试（使用基于实验室的 TEG 仪器）关联起来进行验证。将对正常和缺乏因子的犬血浆和全血进行测量，包括凝血时间、凝块硬度和凝块溶解时间。公共健康相关性：我们将开发一种新技术，满足定量和敏感的护理点粘弹性止血测定能力的需求，以指导创伤性出血病例的治疗。每年因创伤导致的死亡占全球死亡人数的9%，而在因创伤导致的死亡中，40%以上是由于失血或失血性休克。我们提出的技术采用一系列磁驱动的微观表面附着柱，可以在可现场部署的紧凑手持设备中提供从凝血时间到凝血溶解的全谱凝血参数。