Improving Anticoagulation Monitoring in Pediatric Patients: Use of a Microfluidic Platform to Test Low Volume Blood Samples Obtained by Heel-Stick Collection

改善儿科患者的抗凝监测：使用微流体平台测试通过跟棒采集获得的少量血液样本

• 批准号: 10080472
• 负责人: VAMSEE K. PAMULA
• 金额: $ 21.41万
• 依托单位: BAEBIES, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080472
• 关键词: Activated Partial Thromboplastin Time measurement; Adoption; Adult; Agreement; Anticoagulants; Anticoagulation; Antithrombin III; Awareness; Biological Assay; Blood; Blood Circulation; Blood Volume; Blood specimen; Boston; Businesses; Bypass; Caring; Child; Childhood; Clinic; Clinical; Clinical Research; Collaborations; Collection; Congenital Heart Defects; Coronary; Critical Illness; Deep Vein Thrombosis; Development; Devices; Diagnosis; Disease; Dose; Ensure; Factor Xa; Funding; Future; Guidelines; Health; Heel; Heparin; Hospitals; Hour; Individual; Instruction; Lead; Low-Molecular-Weight Heparin; Measurement; Methods; Microfluidics; Monitor; Multi-site clinical study; Neonatal Screening; Newborn Infant; Operative Surgical Procedures; Outcome; Patients; Pediatric Hospitals; Phase; Physicians; Pilot Projects; Population; Positioning Attribute; Procedures; Process; Production; Prothrombin time assay; Readiness; Reagent; Recording of previous events; Records; Research; Risk; Running; Sampling; Secure; Shipping; Site; Small Business Innovation Research Grant; Source; System; Testing; Thrombosis; Time; Traction; United States National Institutes of Health; Validation; Whole Blood; Work; appropriate dose; clinical research site; clinically actionable; clinically relevant; commercialization; cost; design; digital; dosage; dose information; drug efficacy; experience; improved; instrument; lot production; manufacturing process; manufacturing process development; nanolitre; novel; operation; optimal treatments; patient response; patient safety; patient screening; pediatric cardiologist; pediatric patients; point of care; pre-clinical; preclinical study; prevent; programs; response; success; validation studies

ABSTRACT Improving Anticoagulation Monitoring in Pediatric Patients: Use of a Microfluidic Platform to Test Low Volume Blood Samples Obtained by Heel-Stick Collection Children treated for congenital heart defects or other disorders of hypercoagulation are prescribed unfractionated heparin (UFH) or low molecular weight heparin (LMWH) throughout surgical treatment; they may be prescribed heparin for up to 2 weeks post-surgery to prevent thrombosis. UFH is a fiscally efficient, effective anticoagulant that should be closely monitored over time to ensure proper dosage and patient response; LMWH is a newer anticoagulant that is gaining traction among cardiologists. Despite the need for constant monitoring of heparin levels, sometimes every 4 hours, there are limitations to currently available systems hindering delivery of optimal heparin level results to physicians. These barriers include individual assays that use relatively large volumes of blood (~2 mL per assay) and long turnaround times between measurements (up to 2 hours) that limit the utility of these tests for appropriate dosing, especially in the beginning of anticoagulation therapy. In addition, commonly utilized assays (partial thromboplastin time (PTT), activated PTT (aPTT), and prothrombin time) show poor correlation to heparin levels infused in patients, but are still in use due to their historical value and wide adoption in the field. More rapid and accurate methods are needed to assess heparin levels that reduce the overall amount of blood and provide physicians with sufficient dosing information to deliver optimal therapy to pediatric patients. Through a previously funded NIH Fast-Track project, we developed a novel and scalable platform to assess and monitor heparin therapy administered to pediatric patients through measurement of Factor Xa (FXa) and Anti- thrombin III (ATIII) levels. In response to input from key opinion leaders, we are developing a third assay for aPTT. This assay panel is run on our near-patient digital microfluidic (DMF) platform using 50 L of whole blood input. The fluorescent assays use nanoliter volumes of sample and reagents on a disposable single-use cartridge. Although the platform has been developed and feasibility has been demonstrated with the assays, much work remains for this product to be commercially ready. Funding through this Commercialization Readiness Pilot (CRP) will support studies to establish reliable reagent and cartridge manufacturing processes, preclinical studies to validate the manufacturing processes, and development of the FDA regulatory strategy for a full multi-site clinical method comparison study. Our approach is strengthened by our continued partnership with Boston Children’s Hospital, the high potential clinical impact of the tests, and thorough analysis and global distributor relationships demonstrating a significant market gap. The DMF heparin monitoring product will fill a critical gap in pediatric care by providing an inexpensive rapid, low-blood volume system for comprehensive assessment of heparin levels in a hospital or clinic setting. The successful completion of these CRP aims will accelerate commercial development so that we are poised to immediately complete final validation studies for regulatory approval and commercial.

抽象的 改善儿科患者的抗凝监测：使用微流体平台测试低容量 通过跟棒采集获得的血液样本 接受先天性心脏病或其他高凝疾病治疗的儿童需进行普通治疗 在整个手术治疗过程中可能会使用肝素（UFH）或低分子肝素（LMWH）； 术后 2 周内使用肝素预防血栓形成是一种经济有效的抗凝剂。 应长期密切监测，以确保正确的剂量和患者的反应； 尽管需要持续监测肝素，但抗凝剂仍受到心脏病专家的关注。 水平，有时每 4 小时一次，当前可用的系统存在限制，阻碍了最佳交付 这些障碍包括使用相对大量的个体检测。 血液（每次测定约 2 mL）和测量之间的周转时间长（长达 2 小时）限制了实用性 通过这些测试确定适当的剂量，特别是在抗凝治疗开始时。 常用的检测（部分凝血活酶时间 (PTT)、活化 PTT (aPTT) 和凝血酶原时间）显示 与患者输注的肝素水平相关性较差，但由于其历史价值和广泛应用仍在使用 需要在现场采用更快速、更准确的方法来评估肝素水平，以降低肝素水平。 血液总量，并为医生提供足够的剂量信息，以提供最佳治疗 儿科患者。 通过之前资助的 NIH Fast-Track 项目，我们开发了一个新颖且可扩展的平台来评估和 通过测量 Xa 因子 (FXa) 和抗凝血因子来监测儿科患者的肝素治疗情况 根据关键意见领袖的意见，我们正在开发第三种检测方法。 aPTT 检测组使用 50 µL 全血在我们的患者附近数字微流体 (DMF) 平台上运行。 荧光分析使用一次性一次性使用的纳升体积的样品和试剂。 尽管该平台已经开发出来并且可行性已经通过检测得到证明， 该产品要通过商业化进行商业化准备还有很多工作要做。 准备试点（CRP）将支持研究建立可靠的试剂和墨盒制造工艺， 验证生产工艺的临床前研究，以及 FDA 监管策略的制定 完整的多中心临床方法比较研究。 我们与波士顿儿童医院的持续合作伙伴关系加强了我们的方法，该医院具有高潜力 测试关系、全面分析和全球分销商的临床影响证明了显着的 DMF 肝素监测产品将填补儿科护理领域的一个关键空白。 廉价的快速、低血容量系统，用于综合评估医院或医院的肝素水平 这些CRP目标的成功完成将加速商业发展，使我们能够 准备立即完成最终验证研究以获得监管批准和商业化。