Digital Microfluidics - Minimizing blood volume for pediatric coagulation screening

描述（由申请方提供）：据报告，多达40%的接受心脏手术的新生儿发生严重血栓形成事件。 由于先天性或获得性高凝状态导致血栓形成风险增加的儿科患者需要个体化抗凝治疗。血栓形成倾向的存在会影响关于抗凝时间和持续时间的临床决策，特别是在静脉血栓形成的儿童中。治疗的持续时间取决于危险因素和血栓形成倾向的数量。高凝状态筛查允许治疗管理的风险分层。 高凝状态的筛查适用于有血栓形成家族史的儿科患者，或患有严重血栓形成或血栓栓塞事件的患者。然而，大量患者在不符合当前筛选标准的情况下发生血栓形成。目前可用的筛查测试是昂贵的，耗时的，单独订购，需要大量的血液样本。这些问题使得常规筛查一个完整的高凝状态面板临床上不切实际，特别是在儿科患者。因此，迫切需要一种廉价的高凝实验室面板，其需要非常小体积的血液，具有快速的周转时间，并且可以应用于大量的潜在风险患者。 这样的诊断面板通过采用数字微流体系统是可能的。在数字微流控盒上的高凝性测试将实现便携式自动化、快速周转时间和多路复用几种测定，包括每次测试使用约100 nL样品的不同类型的测定（免疫测定和功能测定）。使用数字微流控操作的用于高凝性面板测试的一次性盒 将开发的水滴。 最终目标是开发一个单一平台，可以使用手指针刺全血样本进行多重免疫测定或酶联免疫吸附测定（ELISA）和功能测定，以确定高凝风险，最初重点是接受此类检测的儿科患者。在第I阶段，我们建议将多重免疫测定（抗凝血酶III、蛋白C和纤溶酶原激活物抑制剂-1）与功能测定（抗凝血酶III、蛋白C、纤溶酶原、FVIII和凝血酶生成）集成，从而在单个一次性检测盒上实现完整的血栓形成倾向检测板。在第II阶段，将开发试剂盒上试剂储存、全面质量控制和产品商业化的其他必要活动。

DESCRIPTION (provided by applicant): It is reported that up to 40% of neonates undergoing cardiac surgery suffer a major thrombosis event. Pediatric patients who are at increased risk for thrombosis due to either congenital or acquired hypercoagulability require individualized anticoagulation management. Presence of a thrombophilia influences clinical decision making regarding timing and duration of anticoagulation, particularly in children with venous thrombosis. The duration of therapy is guided by the number of risk factors and thrombophilic conditions. Hypercoagulability panel screening allows risk stratification for therapeutic management. Screening for hypercoagulability is indicated in pediatric patients with a family history of thrombosis, or in those who have suffered a major thrombotic or thromboembolic event. However, a large number of patients develop thrombosis without meeting current criteria for screening. Currently available screening tests are expensive, time-consuming and ordered individually, requiring large volumes of blood sample. These issues make routine screening for a full hypercoagulability panel clinically impractical, especially in pediatric patients. Hence, thre is a compelling need for an inexpensive hypercoagulability laboratory panel that requires very small volumes of blood, has a rapid turn-around time and can be applied to a larger number of potentially at-risk patients. Such a diagnostic panel is possible by employing a digital microfluidic system. Hypercoagulability tests on a digital microfluidic cartridge will enable portable automation, rapid turn-around time, and multiplexing several assays, including different types of assays (immunoassays and functional) utilizing about 100 nL sample per test. A disposable cartridge for hypercoagulability panel testing using digital microfluidic manipulation of droplets will be developed. The ultimate goal is the development of a single platform that can perform multiplexed immunoassays or enzyme-linked immunosorbent assay (ELISA) and functional assays using a finger prick whole blood sample to determine hypercoagulability risk, with initial emphasis on pediatric patients undergoing such testing. In Phase I, we propose to integrate the multiplexed immunoassays (Anti-thrombin III, Protein C and Plasminogen Activator Inhibitor-1) with functional assays (Anti-thrombin III, Protein C, Plasminogen, FVIII and Thrombin generation) allowing for a complete thrombophilia panel on a single disposable cartridge. In Phase II, on-cartridge reagent storage, comprehensive quality control, and other necessary activities for commercialization of a product will be developed.