Novel Broad-Spectrum Point-of-Care Coagulometer

项目摘要/摘要 根据该提案开展的工作支持通过以下方式开发广谱护理点(POC)凝血仪 永辉科技(永辉科技POC凝固仪)，意在创造和提供 手动Lee/White凝血时间法的自动化微流控版本。该设备是基于小说 技术，并利用无试剂，一次性使用的硅和玻璃制成的微流控试管进行测量 血样。凝血激活发生在内在凝血途径的开始阶段，通过接触 血样和试管的内部玻璃和硅表面。该设备通过以下方式检测血栓形成 监测通过试管和血液样本传输的近红外光的强度，并检测纤维蛋白 在共同的凝血途径的末端组装。血栓检测方案提供了两个开发 主要化验，一种凝血时间化验，衡量血栓形成的时间，目前 在凝血仪平台上实施，以及血栓溶解时间分析，测量发病时间 随后的凝块破裂，正在开发中。研究表明，该设备对 跨药物类别的抗凝剂、其逆转剂和溶栓药物的作用。初始营销 努力将重点放在使用具有凝血时间分析的设备来监测直接口腔 抗凝剂(DOAC)和低分子肝素(LMWHs)。这项提案下的研究目标 利伐沙班对健康志愿者和患者凝血时间参考范围的建立 Apixaban、dabigatran和edoxaban，直接支持最初的营销目标。以支持未来的设备 除了应用程序，这项研究还旨在评估设备检测遗传或后天遗传的能力 基于异常凝血时间的凝血病，以及对设备对 阿贝拉西单抗是一种新型的抗凝血剂和直接凝血因子XI/XIA抑制剂，目前正在临床开发中。 Perlobe Technologies打算通过营销、销售和分销将该设备商业化 与一家全球医疗设备公司合作。该装置同样适合在紧急情况下使用 (例如急诊室、急救车)以及住院和门诊环境中的常规护理(医院， 诊所、外科套房、医生办公室、药房)，由可以表演或订购新鲜食品的医疗专业人员提供 静脉全血抽出。该设备承诺解决几个未得到满足的医疗需求，包括接入点 对DOAC的护理监测，并有可能定义新的护理标准。预计该设备将 通过为医生提供手段，改善患者护理、临床结果并降低医疗成本 做出更快、更知情的治疗决定。显影凝血时间和血栓溶解时间 化验将提供一种新的方法来描述患者的凝血状态，并使基础 疾病机制和治疗方法的研究。

Project Summary/Abstract Work under this proposal supports development of a broad-spectrum point-of-care (POC) coagulometer by Perosphere Technologies (The Perosphere Technologies POC Coagulometer) with the intent to create and offer an automated, microfluidic version of the manual Lee/White clotting time method. The device is based on novel technology and utilizes reagent-less, single-use microfluidic cuvettes made of silicon and glass for measurement of blood samples. Clot activation occurs at the beginning of the intrinsic clotting pathway through contact of a blood sample with the inner glass and silicon surfaces of the cuvette. The device detects clot formation by monitoring the intensity of near-infrared light, transmitted through cuvette and blood sample, and sensing of fibrin assembly at the end of the common clotting pathway. The clot detection scheme affords development of two main assays, a Clotting Time Assay, that measures the time to onset of clot formation and is currently implemented on the coagulometer platform, and a Clot Lysis Time assay, that measures the time to onset of subsequent clot breakdown and is in development. Research indicates that the device is broadly sensitive to the effects of anticoagulants across drug class, their reversal agents and thrombolytic drugs. Initial marketing efforts will focus on use of the device with implemented Clotting Time assay for monitoring of the direct oral anticoagulants (DOACs) and low molecular weight heparins (LMWHs). Research under this proposal targets establishment of clotting time reference ranges for healthy volunteers and patients on the DOACs rivaroxaban, apixaban, dabigatran and edoxaban, in direct support of initial marketing goals. In support of future device applications, the research also targets assessment of the device’s ability to detect inherited or acquired coagulopathies, based on abnormal clotting times, as well as assessment of the device’s sensitivity to abelacimab, a novel anticoagulant and direct factor XI/XIa inhibitor, currently in clinical development. Perosphere Technologies intends to commercialize the device through a marketing, sales and distribution partnership with a global medical device company. The device is similarly suited for use in emergency situations (e.g. emergency room, emergency vehicle) and for routine care in the inpatient and outpatient settings (hospitals, clinics, surgical suites, doctor’s offices, pharmacies) by healthcare professionals who can perform or order fresh venous whole blood draws. The device promises to address several unmet medical needs, including point-of- care monitoring of DOACs, and has the potential to define new standards of care. The device is expected to improve patient care, clinical outcome and to reduce healthcare costs, by providing physicians with the means to make faster and better-informed treatment decisions. The developed Clotting Time and Clot Lysis Time assays will present a new way to describe a patient’s coagulation state and enable opportunities for fundamental research of disease mechanisms and therapeutic approaches.