A Near-Patient, Low Blood Volume Platform for Rapid Comprehensive Evaluation of Coagulation in Trauma Patients

摘要 一种近距离、低输血量的快速综合评估平台 创伤患者的凝血功能 (快速通道SBIR) 创伤是世界范围内主要的死亡原因，其中出血是最常见的原因 受伤后可预防的死亡。三分之一的创伤患者出现凝血障碍，其特征是异常 凝血和炎症，需要紧急输血以降低器官衰竭和 死亡率。创伤后凝血障碍患者经历了许多由内皮促进的变化， 血小板、循环凝血因子和免疫系统功能，这使得使用 单一生物标志物。常规的凝血试验是有用的，但大多数不适用于急性 由于结果周转时间较长(&gt；45分钟)，因此可控制出血。粘弹性凝血试验， 或者，可以快速检测异常凝血的存在，但需要更长的检测时间(30-45 分钟)，以提供可用于确定治疗中的具体变化的结果。重复监测 建议对出血创伤患者进行止血，然而， 中心实验室凝血试验(每次1-2毫升)会增加医源性贫血的风险。最优的 用于创伤患者凝血功能快速、反复评估的凝血系统尚不存在。 为了满足对诊断和治疗管理的快速、低容量测试的关键需求 创伤患者的凝血障碍，我们将开发一个四项化验小组和相应的近患者数字 微流控(DMF)平台，将提供临床可操作的数据来指导全血给药 输血和其他血液制品。我们的创新技术将同时检测凝血酶原 时间/国际标准化比率(PT/INR)、活化部分凝血活酶时间(APTT)、纤维蛋白原和 50微克L全血中的血小板计数。所有化验操作，包括从全血中分离血浆， 将自动执行，便于受过最低程度培训的用户在接近患者的环境中使用 急诊科和手术室。通过将四种基本化验结合在一个单一的方案中，在一个时间内- 由于在10分钟内，我们的系统将更好地通知输液要求，减少医源性血液 减少反复凝血监测的损失，并在繁忙的创伤环境中改善临床工作流程。 该快速通道SBIR项目的第一阶段将通过开发DMF来确定测试面板的可行性 能够同时测量PT/INR、aPTT和纤维蛋白原的仪器，可在单个一次性试剂盒上使用。 我们还将为血小板计数测量所需的光学系统验证与DMF兼容的硬件。 第二阶段将把光学系统和补充墨盒集成到我们现有的DMF平台中，以支持 全自动化的血小板计数分析。然后，我们将在一次运行中对多个分析进行多路传输，并评估 每项测试的分析和临床表现。我们的最终产品将投放市场，用于一般和军事用途 分诊和围手术期的创伤设置，二级市场包括成人和儿童 接受手术或其他程序会增加出血和休克风险的患者。

ABSTRACT A Near-Patient, Low Blood Volume Platform for Rapid Comprehensive Evaluation of Coagulation in Trauma Patients (Fast-Track SBIR) Trauma is a leading cause of death worldwide, with hemorrhage constituting the most common cause of preventable death after injury. A third of trauma patients develop coagulopathy, characterized by abnormal coagulation and inflammation, and require urgent transfusion to decrease the likelihood of organ failure and mortality. Patients with post-traumatic coagulopathy experience many changes facilitated by the endothelium, platelets, circulating coagulation factors, and immune system function, which make it difficult to assess using a single biomarker. Conventional coagulation tests are informative, but most are not adequate for acute hemorrhage control due to long result turnaround times (> 45 minutes). Viscoelastic coagulation tests, alternatively, can rapidly detect the presence of abnormal clotting, but necessitate longer test times (30-45 minutes) to provide results that may be used to determine specific changes in treatment. Repeated monitoring of hemostasis is recommended for bleeding trauma patients, however, the cumulative blood loss required for central laboratory coagulation tests (1-2 mL per test) increases the risk of iatrogenic anemia. The optimal coagulation panel for rapid, recurrent assessment of coagulation in trauma patients does not yet exist. To address the critical unmet need for rapid, low volume tests for the diagnosis and therapeutic management of coagulopathy in trauma patients, we will develop a four-assay panel and corresponding near-patient digital microfluidic (DMF) platform that will provide clinically actionable data to guide the administration of whole blood transfusion and other blood products. Our innovative technology will simultaneously measure prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), fibrinogen, and platelet count from < 50 µL of whole blood. All assay operations, including plasma separation from whole blood, will be performed autonomously, facilitating use by minimally trained users in near-patient settings such as the emergency department and operating room. By combining four essential assays in a single protocol with a time- to-result of under 10 minutes, our system will better inform transfusion requirements, reduce iatrogenic blood loss from recurrent coagulation monitoring, and improve clinical workflow in busy trauma settings. Phase I of this Fast-Track SBIR project will establish feasibility of the testing panel by developing a DMF instrument capable of simultaneously measuring PT/INR, aPTT, and fibrinogen on a single disposable cartridge. We will also validate DMF-compatible hardware for the optical system required for platelet count measurement. Phase II will integrate the optical system and complementary cartridge into our existing DMF platform to support full automation of the platelet count assay. We will then multiplex the assays in a single run and evaluate the analytical and clinical performance of each test. Our final product will be marketed for use in general and military trauma settings during triage and perioperative periods, with secondary markets including adult and pediatric patients undergoing surgery or other procedures that raise the risk for hemorrhage and shock.