SBIR Phase I: Automated DOAC assay to determine coagulation status in emergent care

小型企业创新研究(SBIR)第一阶段项目的更广泛影响/商业影响潜力是一种诊断性产品，旨在为管理服用直接口服抗凝剂(DOAC)的患者的医生解决患者安全和临床决策问题。DOAC正在成为降低血栓风险的首选药物，这些血栓可能会导致严重的不良事件，如中风。然而，DOAC是与不良事件相关的急诊科就诊涉及的主要药物类别的一部分。这些不良事件以输血、血液制品暴露、血小板补充、逆转治疗以及其他并发症(如感染、败血症、多器官衰竭)的形式给医疗系统带来重大负担，导致住院时间延长、死亡率上升和医疗成本上升。在紧急情况下，在计划手术、严重创伤、药物过量、紧急手术或监测肾功能衰竭和肝功能衰竭时的药物积聚时，需要快速检测DOAC抗凝。这个项目提出了一种在护理点进行诊断的方法。据估计，全球有2100万患者在服用DOAC，这项技术可以大大减少与治疗和纠正因紧急护理情况下缺乏DOAC信息而导致的不良事件相关的25亿美元的成本。这一小型企业创新研究(SBIR)第一阶段项目将为急诊室临床医生展示护理点(POC)诊断芯片的可行性，以管理出血风险并避免过度使用药物逆转疗法，从而在降低医疗成本的同时改善患者预后。目前还没有批准的快速诊断POC测试，可以准确地识别患者正在使用的DOAC药物的类型，也不能准确识别患者的血液中有多少药物。提出了一种集成的微流体色谱柱，用于管理设备内的血液分布，将血液与DOAC检测试剂混合，并提供评估凝块形成中三个重要凝血因子(纤维蛋白/凝血酶/血小板)的综合分析结果。这项技术的独特之处在于，与其他凝血测试不同，它重新创造了体内发生的血液凝结生理和特有的血液流动。有了DOAC逆转药物，诊断可以确定DOAC类型(因子Xa或因子IIa)，以及血液中DOAC的水平，使急诊室医生能够做出更知情的护理决定。这一奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial impact potential of this Small Business Innovation Research (SBIR) Phase 1 project is a diagnostic product that addresses patient safety and clinical decision-making for physicians managing patients taking Direct Oral Anticoagulants (DOACs). DOACs are becoming the preferred drugs to reduce the risk of blood clots that can lead to significant adverse events, such as stroke. However, DOACs are part of the leading class of drugs implicated in adverse event-related emergency department visits. These adverse events place a significant burden on the healthcare system in the form of transfusions, exposure to blood products, platelet repletion, reversal therapies, and additional complications (e.g. infection, sepsis, multiple organ failure) driving longer hospitalizations, higher mortality rates, and escalating healthcare costs. In emergency situations, the rapid detection of DOAC anticoagulation is needed when planning for urgent care for surgery, serious trauma, drug overdose, emergency procedures, or monitoring for drug accumulation in cases of renal and liver failure. This project proposes a diagnostic at the point of care. With an estimated 21 M patients globally taking DOACs, this technology could significantly reduce the $2.5 B in costs related to treating and correcting adverse events caused by the absence of DOAC information in emergency care situations. This Small Business Innovation Research (SBIR) Phase I Project will demonstrate the feasibility of a point-of-care (POC) diagnostic chip for emergency room clinicians to manage bleeding risk and avoid overuse of drug reversal therapies, thereby improving patient outcomes while reducing healthcare costs. Currently there is no approved rapid diagnostic POC test that accurately identifies the type of DOAC drug a patient is using, nor how much of the drug is in the patient’s blood. An integrated microfluidic cartridge is proposed developed to manage blood distribution within the device, mix the blood with DOAC detection reagents, and provide an integrated assay result that evaluates the three important clotting factors in clot formation (fibrin/thrombin/platelets). The technology is unique in that, unlike other coagulation tests, it re-creates the blood clotting physiology, and characteristic blood flow, that happens within the body. With DOAC-reversing drugs, the diagnostic can determine DOAC type (Factor Xa or Factor IIa), and the level of DOAC in the blood, allowing emergency room physicians to make more informed care decisions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.