Development of a microfluidic device for the assessment of hemostatic function

开发用于评估止血功能的微流体装置

• 批准号: 8804026
• 负责人: FRANCESCO VIOLA
• 金额: $ 22.48万
• 依托单位: HEMOSONICS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-12 至 2016-09-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8804026
• 关键词: Address; Adult; Anticoagulation; Blood; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Platelets; Blood Volume; Blood coagulation; Blood specimen; Cardiac Surgery procedures; Caring; Child; Childhood; Clinical; Coagulation Process; Congenital Heart Defects; Craniocerebral Trauma; Defect; Development; Devices; Economics; Equilibrium; Fibrinogen; Fibrinolysis; Focused Ultrasound Therapy; Freeze Drying; Geometry; Goals; Healthcare; Hemostatic Agents; Hemostatic function; Hospitals; Incidence; Infection; Injury; Left; Legal patent; Length of Stay; Liquid substance; Literature; Live Birth; Malignant Neoplasms; Marketing; Measurement; Measures; Mechanical ventilation; Methods; Microfluidic Microchips; Microfluidics; Monitor; Morbidity - disease rate; Neonatal; Outcome; Output; Patients; Performance; Phase; Population; Prevalence; Procedures; Reagent; Retrospective Studies; Risk Factors; Sampling; Savings; Severities; Small Business Innovation Research Grant; Solutions; System; Technology; Testing; Thromboembolism; Thrombosis; Transfusion; Trauma; Venous; Whole Blood; Work; base; cancer therapy; congenital heart disorder; design; improved; instrument; mortality; neonate; novel; pediatric trauma; point of care; point-of-care diagnostics; prototype; public health relevance; rapid detection; trauma care

DESCRIPTION (provided by applicant): The monitoring and management of the hemostatic balance in neonatal and pediatric patients remains challenging. Although several conditions/procedures are known to have great impact in altering hemostatic function in this population, the differences between "childhood" and "adulthood" hemostasis make it challenging to determine and monitor the appropriate treatment(s). Furthermore, the systems that are available are mostly tailored for use in adult patients (they require large sample volumes for testing). Cardiac surgery for children with congenital heart defects represents an important indication where hemostatic monitoring is essential to determine the need for transfusion or anticoagulation. Congenital heart disease occurs in 0.8% of live births and the prevalence of transfusion during these procedures remains as high as 80%. However, several studies have shown that the liberal use of transfusions is associated with increased mortality, morbidity, infection and longer duration of mechanical ventilation/hospital stays in the ICU. In trauma, a retrospective study of 803 pediatric trauma patients showed that early coagulopathy was present in 37.9% of the patients and that it was greatly associated with mortality (13.4%) based on injury severity, increasing as high as 4X for patients with traumatic head injuries. Children with cancer comprise 8 to 22% of the pediatric patients with thrombosis. Aside from changes in the coagulation cascade due to the presence of the cancer, the incidence of venous thromboembolism associated with cancer therapy administration through central venous lines remains one of the biggest risk factor for thrombosis in children (60% of all pediatric blood clots and up to 90% in neonates). While there is a great need to monitor hemostasis in these patients, no true point-of-care (POC) device exists that can deliver global coagulation results quickly using a minimal amount of blood. HemoSonics' Proposed Solution: HemoSonics is developing a novel POC diagnostic instrument, the Global Hemostasis Analyzer (GHA), which has the capability of measuring the hemostatic profile from a sample of whole blood. The GHA is based on sonorheometry (SR), a patented technology able to assess the function of the coagulation factors, fibrinogen, platelets, and fibrinolysis. These outputs are tied to available treatments. Stand-alone prototypes have been designed that demonstrate the functionality of the technology. Proposed SBIR work: This Phase I proposal will determine the technical feasibility of a test chamber that utilizes sample volumes of 50ul (hence amenable for pediatric and neonate patients) and the viability of utilizing lyophilized reagents. In Phase II we will buil a compact prototype of our microfluidic chip and evaluate its performance in cardiac surgery, in order to test the hypothesis that SR can be implemented in a portable, easy to use, easy to interpret instrument suitable for use with these patients and that the information provided will ai in minimizing unnecessary transfusions, reducing overall healthcare spending and improving patients outcomes.

描述（由申请人提供）：新生儿和儿科患者的止血平衡监测和管理仍然具有挑战性。尽管已知几种情况/程序对改变该人群的止血功能有很大影响，但“儿童”和“成年”止血之间的差异使得确定和监测适当的治疗方法具有挑战性。此外，可用的系统大多是为成年患者量身定制的（它们需要大量样本进行测试）。先天性心脏缺陷儿童的心脏手术是一个重要的适应症，其中止血监测对于确定是否需要输血或抗凝至关重要。 0.8% 的活产婴儿患有先天性心脏病，而这些手术期间的输血患病率仍高达 80%。然而，一些研究表明，大量使用输血与死亡率、发病率、感染率的增加以及机械通气/重症监护病房住院时间的延长有关。在创伤方面，一项针对 803 名儿童创伤患者的回顾性研究表明，37.9% 的患者存在早期凝血功能障碍，并且根据损伤严重程度，其与死亡率 (13.4%) 密切相关，对于头部外伤患者而言，死亡率增加高达 4 倍受伤。患有癌症的儿童占血栓形成儿科患者的 8% 至 22%。除了由于癌症的存在而导致的凝血级联变化之外，与通过中心静脉导管进行癌症治疗相关的静脉血栓栓塞的发生率仍然是儿童血栓形成的最大危险因素之一（占所有儿童血栓的 60%） 新生儿中高达 90%）。虽然非常需要监测这些患者的止血情况，但目前还没有真正的即时护理 (POC) 设备能够使用最少量的血液快速提供整体凝血结果。 HemoSonics 提出的解决方案：HemoSonics 正在开发一种新型 POC 诊断仪器，即全局止血分析仪 (GHA)，它能够测量全血样本的止血情况。 GHA 基于声流变测量 (SR)，这是一项专利技术，能够评估凝血因子、纤维蛋白原、血小板和纤维蛋白溶解的功能。这些产出与可用的治疗方法相关。独立原型的设计可以展示该技术的功能。拟议的 SBIR 工作：该第一阶段提案将确定使用 50ul 样本量（因此适合儿科和新生儿患者）的测试室的技术可行性以及使用冻干试剂的可行性。在第二阶段，我们将构建我们的微流控芯片的紧凑原型并评估其在心脏手术中的性能，以测试 SR 可以在适合这些患者使用的便携式、易于使用、易于解释的仪器中实施的假设所提供的信息将有助于最大限度地减少不必要的输血、减少总体医疗支出并改善患者的治疗结果。