Microactuated Rheometer for Point of Care Coagulopathy Applications

描述（由申请方提供）：我们提议开发一种新技术，以满足对定量和灵敏的床旁（POC）粘弹性止血测定（VHA）能力的需求，从而表征对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磁致动微观表面附着的职位（SAP），其动态力学响应流体条件提供了一个定量的测量流变参数的阵列。SAP在大小和纵横比上类似于生物纤毛，并且可以在Hz至10 s的大振幅下“跳动”， Hz频率范围。SAP在设备的有源表面上排列成阵列;它们由外部磁场驱动，并且它们的振幅被光学监控。可以监测从凝血时间到凝块溶解的凝血过程的时间进展。近年来，越来越多的证据表明创伤诱导的凝血病（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，创伤可以通过抑制凝血和放大溶解来损害健康的凝血。诊断测试，可以快速评估止血相关的参数，从凝血溶解是至关重要的发展有效的治疗策略，TIC。同样至关重要的是，这些诊断可用于最需要的地方：在患者移动之前和移动过程中靠近事故。传统的实验室凝血试验，如凝血酶原时间（PT）和活化部分凝血活酶时间（APTT），在提供这些诊断都是不切实际和无效的。这些基于血浆的测试仅评估凝血过程的最开始（没有关于溶解的信息），需要血液处理，并且不提供机械信息（凝块强度）。在本项目的背景下，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。我们将专注于开发一种新的方法来解决在现场和运送病人期间服务不足的TIC问题。我们已经成功地开发了SAP的制造方案，证明了它们在流体中的致动，并有初步数据证明它们在凝血过程中测量凝块特性的能力。在这个项目的第一年，我们将使用参考粘性和粘弹性流体来表征我们的系统。在第二年，我们将使用SAP系统演示可重现的凝血测量，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）相关联进行验证。将对正常和因子缺乏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。

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.