Development of a microfluidic device for the assessment of hemostatic function

描述(申请人提供)：监测和管理新生儿和儿科患者的止血平衡仍然具有挑战性。虽然已知有几种条件/程序对改变这一人群的止血功能有很大影响，但“儿童”和“成人”止血之间的差异使确定和监测适当的治疗具有挑战性(S)。此外，可用的系统大多是为成人患者量身定做的(它们需要大量样本进行测试)。先天性心脏病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是必不可少的。先天性心脏病发生在0.8%的活产儿中，在这些过程中输血的患病率仍高达80%。然而，几项研究表明，自由使用输血与增加死亡率、发病率、感染和更长时间的机械通气/在ICU住院有关。在创伤方面，对803例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障碍，并且根据创伤的严重程度，早期凝血障碍与死亡率(13.4%)密切相关，颅脑创伤患者的死亡率高达4倍。儿童癌症患者占儿童血栓形成患者的8%至22%。除了癌症引起的凝血级联改变外，通过中心静脉给药引起的静脉血栓栓塞症的发生率仍然是儿童血栓形成的最大风险因素之一(占所有儿科血栓的60% 新生儿高达90%)。虽然非常需要监测这些患者的止血情况，但没有真正的护理点(POC)设备可以使用最少的血液快速提供全局凝血结果。HemoSonics建议的解决方案：HemoSonics正在开发一种新的POC诊断仪器--全球止血分析仪(GHA)，该仪器具有从全血样本测量止血曲线的能力。GHA基于超声流变仪(SR)，这是一项能够评估凝血因子、纤维蛋白原、血小板和纤溶功能的专利技术。这些产出与可用的治疗方法有关。已经设计了独立的原型，以展示该技术的功能。拟议的SBIR工作：这项第一阶段的提案将确定使用50ul样品体积的测试室的技术可行性(因此适合儿童和新生儿患者)，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型原型，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，以及所提供的信息将有助于最大限度地减少不必要的输血，减少整体医疗支出，并改善患者的预后。

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.