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.

抽象的 一个接近患者的低血量平台，用于快速综合评估 创伤患者的凝血 （Fast-Track Sbir） 创伤是全球死亡的主要原因，出血构成了最常见的原因 受伤后可预防的死亡。三分之一的创伤患者患有凝血病，其特征是异常 凝结和炎症，需要紧急输血以减少器官衰竭的可能性和 死亡。创伤后凝血病的患者经历了原始疗法促进的许多变化， 血小板，循环凝血因子和免疫系统功能，这使得很难使用 单个生物标志物。常规的凝血测试是有益的，但大多数不足以适合急性 由于很长的结果周转时间（> 45分钟）而导致的出血控制。粘弹性凝血测试， 另外，可以迅速检测出异常结束的存在，但必要的测试时间更长（30-45 分钟）提供可能用于确定治疗特定变化的结果。重复监视 建议用于出血的创伤患者的止血，但是， 中央实验室凝血测试（每次测试1-2毫升）增加了息肉性贫血的风险。最佳 凝血面板可快速，反复评估创伤患者的凝血量。 解决对快速，低容量测试的关键需求，用于诊断和治疗管理 创伤患者的凝血病，我们将开发一个四顺式面板和相应的接近病人数字 微流体（DMF）平台将提供临床可行的数据以指导全血的给药 输血和其他血液产品。我们的创新技术将仅测量凝血酶原 时间/国际归一化比率（PT/INR），激活的部分血栓形成时间（APTT），纤维蛋白原和 <50 µl全血的血小板计数。所有测定操作，包括与全血的血浆分离， 将自动执行，以支持最少培训的用户在近乎患者的设置中的使用，例如 急诊室和手术室。通过将四个基本测定在单个协议中结合到一个时间 - 不到10分钟的时间，我们的系统将更好地告知传输要求，减少医源性血液 复发性凝血监测的损失，并改善繁忙创伤环境中的临床工作流程。 这个快速轨道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 能够简单地在单个一次性弹药筒上测量PT/INR，APTT和纤维蛋白原的仪器。 我们还将为血小板计数所需的光学系统验证与DMF兼容的硬件。 第二阶段将将光学系统和互补墨盒集成到我们现有的DMF平台以支持 血小板计数测定的完全自动化。然后，我们将在一次运行中多重测定并评估 每个测试的分析和临床性能。我们的最终产品将在一般和军事中销售 分类和周期期间的创伤设置，包括成人和小儿在内的二级市场 接受手术或其他程序的患者增加出血和休克的风险。