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

用于快速综合评估创伤患者凝血功能的近患者低血容量平台

• 批准号: 10697216
• 负责人: VAMSEE K. PAMULA
• 金额: $ 30万
• 依托单位: BAEBIES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-10 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10697216
• 关键词: Accident and Emergency department; Activated Partial Thromboplastin Time measurement; Acute; Address; Adult; American; Anemia; Automation; Award; Biological Assay; Biological Markers; Blood; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Platelets; Blood Transfusion; Blood Volume; Businesses; Cause of Death; Cessation of life; Clinical; Clinical Chemistry; Coagulation Process; Complex; Data; Development; Devices; Diagnosis; Diagnostic; Disparate; Drops; Endothelium; Engineering; Ensure; Evaluation; Fibrinogen; Funding; Generations; Goals; Guidelines; Hematologist; Hemorrhage; Hemostatic function; Hour; Iatrogenesis; Inflammation; Injury; International Normalized Ratio; Journals; Laboratories; Left; Legal patent; Manuscripts; Marketing; Measurement; Measures; Methods; Microfluidics; Monitor; Monitoring for Recurrence; Morbidity - disease rate; Operating Rooms; Operative Surgical Procedures; Optics; Organ failure; Patient-Focused Outcomes; Patients; Performance; Perioperative; Phase; Plasma; Platelet Count measurement; Postoperative Period; Procedures; Prothrombin time assay; Protocols documentation; Publishing; Recommendation; Recurrence; Research; Risk; Running; Sampling; Scientist; Shock; Small Business Innovation Research Grant; System; Technology; Testing; Therapeutic; Time; Training; Transfusion; Trauma; Trauma patient; Traumatic Hemorrhage; Triage; Update; Whole Blood; assay development; blood product; cellular imaging; clinically actionable; design; detection platform; digital; experience; feasibility testing; imaging capabilities; immune system function; improved; innovation; innovative technologies; instrument; microfluidic technology; military trauma; mortality; multidisciplinary; multiplex assay; operation; pediatric patients; point of care; point of care testing; portability; post-trauma; preventable death; prototype; rapid detection; risk minimization; trauma induced coagulopathy; viscoelasticity

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.

摘要 一种用于快速综合评价的近患者、低血容量平台 创伤患者的凝血 （快速通道SBIR） 创伤是世界范围内死亡的主要原因，出血是最常见的原因。 可预防的受伤后死亡三分之一的创伤患者会出现凝血功能障碍， 凝血和炎症，需要紧急输血以降低器官衰竭的可能性， mortality.患有创伤后凝血病的患者经历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，这使得难以使用 单一生物标志物。传统的凝血试验是有用的，但大多数不足以用于急性 由于结果周转时间长（> 45分钟），出血控制。粘弹性凝血试验， 或者，可以快速检测异常凝血的存在，但需要较长的测试时间（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 对于出血性创伤患者，建议使用10%的止血时间，然而， 中心实验室凝血试验（每次试验1-2 mL）会增加医源性贫血的风险。最优 用于创伤患者凝血的快速、反复评估的凝血组尚不存在。 为了满足快速、低容量检测的关键需求，以诊断和治疗管理 在创伤患者的凝血功能障碍，我们将开发一个四测定面板和相应的近病人的数字 微流控（DMF）平台，将提供临床可操作数据，以指导全血给药 输血和其他血液制品。我们的创新技术将同时测量凝血酶原 时间/国际标准化比值（PT/INR）、活化部分凝血活酶时间（aPTT）、纤维蛋白原和 血小板计数< 50 µL全血。所有分析操作，包括从全血中分离血浆， 将自动执行，便于接受过最低限度培训的用户在患者附近环境中使用，例如 急诊室和手术室。通过将四种基本检测结合在一个方案中， 到10分钟内的结果，我们的系统将更好地告知输血要求，减少医源性血液 从复发性凝血监测损失，并改善临床工作流程，在忙碌创伤设置。 该快速通道SBIR项目的第一阶段将通过开发DMF来确定测试小组的可行性 能够在单个一次性检测盒上同时测量PT/INR、aPTT和纤维蛋白原的仪器。 我们还将验证血小板计数测量所需光学系统的DMF兼容硬件。 第二阶段将把光学系统和补充墨盒整合到我们现有的DMF平台上， 血小板计数测定的全自动化。然后，我们将在单次运行中多重检测，并评估 每项试验的分析和临床性能。我们的最终产品将在市场上用于一般和军事用途 分类和围手术期的创伤环境，二级市场包括成人和儿科 正在接受手术或其他程序的患者，这些程序会增加出血和休克的风险。