Novel Device for Sensitive, Small Sample Volume Assessment of Clot Elasticity

用于对血块弹性进行灵敏、小样本量评估的新型装置

• 批准号: 8305499
• 负责人: Amy L Oldenburg
• 金额: $ 17.03万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8305499
• 关键词: Acoustics; Address; Animal Model; Antibodies; Benchmarking; Blood; Blood Clot; Blood Coagulation Disorders; Blood Platelets; Blood coagulation; Blood specimen; Calibration; Cardiovascular Diseases; Cardiovascular system; Clinic; Clinical; Clinical Research; Clinical Trials; Coagulants; Coagulation Process; Coronary Arteriosclerosis; Data; Detection; Development; Devices; Diabetes Mellitus; Diagnosis; Diagnostic; Disease; Dose; Elasticity; Exhibits; Factor IX; Factor VIII; Fibrin; Fibrinogen; Frequencies; Future; Gases; Gel; Genetic; Health; Hemophilia A; Human; Hyperglycemia; Ions; Lasers; Lead; Measurement; Measures; Mechanics; Methods; Metric; Microspheres; Monitor; Mus; Myocardial Infarction; Noise; Operative Surgical Procedures; Optics; Perioperative; Pharmaceutical Preparations; Phase; Physiological; Positioning Attribute; Procedures; Property; Research; Resources; Risk Management; Sample Size; Sampling; Sepharose; Simulate; Specimen; Spectrum Analysis; Speed; Stroke; System; Techniques; Technology; Temperature; Testing; Thrombin; Thromboembolism; Time; Transducers; Translations; Venous; Viscosity; Whole Blood; Work; base; clinical application; cost; expectation; improved; miniaturize; mouse model; novel; parallel processing; point of care; tool; viscoelasticity

DESCRIPTION (provided by applicant): We propose to develop a novel device for the measurement of blood clot elasticity with improved accuracy and speed, and requiring smaller sample volumes. In the long term, this may enable better point- of-care management and diagnoses of coagulopathies arising from a wide array of cardiovascular disorders including myocardial infarction, stroke, coronary artery disease, venous thromboembolism, and hyperglycemia. This expectation arises from the fact that the clot elastic modulus (CEM) or related clot structural properties have been shown to be strongly correlated with hypofibrinolysis (decreased ability to break up clots) in these diseases. We hypothesize that a more accurate device will provide a better predictive ability for CEM as a relevant diagnostic parameter, that the increased speed of analysis may be especially important for preoperative monitoring of anti-coagulant therapies, and that the decreased sample volume will enable studies of genetic murine animal models for cardiovascular disease. Our proposal entails the development of an emerging technique for small sample elasticity measurement based upon resonant acoustic spectroscopy with optical vibrometry-based detection (RASOV). In RASOV, the fundamental acoustic resonance modes of a blood sample are measured by sweeping the excitation frequency on a microbead transducer that imparts negligible inertia to the sample. Because the resonance modes are an intrinsic property of the specimen directly related to the CEM, the measurement requires no calibration procedures. Furthermore, there is no limitation to sample size, and measurement speeds <0.2s are anticipated. While preliminary data indicates the utility of RASOV for fibrin clot analysis, resources are needed for further improvements in order to position this technology for clinical translation. Our first aim is to incorporate several hardware improvements into the RASOV, including a smaller optical interferometer for improved displacement sensitivity, and a microbead transducer with smaller inertial mass. Also, we will validate CEM measurements with a commercial mechanical analyzer. Our second aim is to apply the robust RASOV technology to the analysis of whole blood samples from healthy donors. To investigate the capabilities of RASOV, additional fibrinogen or antibodies will be added to blood to simulate hyperfibrinogenemia and hemophilia, respectively, which we expect to result in increased and decreased CEM, respectively. Furthermore, we will compare the time-dependent CEM results during coagulation with that from a commercial clot analyzer, to understand the particular strengths of RASOV. By the conclusion of this study the RASOV technology will have been tested over the physiological range of expected CEM in whole blood and fully validated against a standard mechanical analyzer. This will poise the technology for clinical trials in a wide variety of cardiovascular diseases to establish the diagnostic relevance of CEM, and will lead to rapid clinical translation.

描述（由申请人提供）：我们建议开发一种新型设备，以提高准确性和速度，并需要较小的样品体积来测量血凝块弹性。从长远来看，这可能使得更好地护理管理和由多种心血管疾病引起的凝血病的诊断，包括心肌梗塞，卒中，冠状动脉疾病，静脉血栓栓塞和高血糖。这种预期源于以下事实：已经证明，凝块弹性模量（CEM）或相关的凝块结构特性与这些疾病中的低纤维蛋白溶解（分解凝块的能力降低）密切相关。我们假设一个更准确的设备将为CEM提供更好的预测能力，作为相关的诊断参数，提高的分析速度对于术前监测抗凝治疗疗法尤其重要，并且减少的样品体积减少将促进对心血管疾病的遗传动物模型的研究。 我们的建议需要开发基于基于光振动测定的检测（RASOV）的谐振声学光谱，以开发针对小样品弹性测量的新兴技术。在拉索夫（Rasov），血液样本的基本声共振模式是通过在微珠传感器上扫描的激发频率来测量的，从而使样品毫无含量可以忽略不计。由于共振模式是与CEM直接相关的样品的固有特性，因此测量不需要校准程序。此外，样本量没有限制，预计测量速度<0.2s。虽然初步数据表明RASOV用于纤维蛋白血块分析的实用性，但需要进行进一步改进的资源，以便将该技术定位为临床翻译。我们的第一个目的是将一些硬件改进纳入RASOV，包括较小的光学干涉仪，以提高位移灵敏度，以及具有较小惯性质量的Microbead发音器。此外，我们将使用商业机械分析仪验证CEM测量值。我们的第二个目标是将强大的Rasov技术应用于对健康捐助者的全血样品的分析。为了研究RASOV的能力，将在血液中添加其他纤维蛋白原或抗体，以分别模拟高纤维蛋白原血症和血友病，我们期望这会导致CEM增加和减少CEM。此外，我们将将凝结过程中时间依赖性的CEM结果与商业凝块分析仪进行比较，以了解Rasov的特定优势。 通过这项研究的结论，RASOV技术将在全血的预期CEM的生理范围内进行测试，并针对标准的机械分析仪进行了全面验证。这将使在各种心血管疾病中的临床试验中为建立CEM诊断相关性的临床试验增强，并将导致快速的临床翻译。