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: 10214018
• 负责人: VAMSEE K. PAMULA
• 金额: $ 91.2万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214018
• 关键词: Activated Partial Thromboplastin Time measurement; Address; Adult; Anemia; Anticoagulants; Anticoagulation; Antithrombin III; Biological Assay; Blood; Blood Volume; Blood capillaries; Blood specimen; Boston; Cardiovascular system; Child; Childhood; Clinical; Coagulation Process; Collection; Community Hospitals; Complex; Computer software; Congenital Heart Defects; Critical Illness; Development; Devices; Diagnostic; Diagnostic tests; Documentation; Ensure; Equilibrium; Event; Factor Xa; Freezing; Funding; Future; Glucosephosphate Dehydrogenase; Goals; Guidelines; Heel; Hemorrhage; Hemostatic Agents; Heparin; Heparinoids; Hospitalized Child; Hospitals; Hour; Iatrogenesis; Infrastructure; Laboratories; Methods; Microfluidic Microchips; Microfluidics; Monitor; Newborn Infant; Operative Surgical Procedures; Oral; Outcome; Overdose; Patient Monitoring; Patients; Pediatric Hospitals; Performance; Phase; Plasma; Positioning Attribute; Preparation; Production; Protocols documentation; Recurrence; Reporting; Risk; Rural Hospitals; Sampling; Small Business Innovation Research Grant; Standardization; System; Test Result; Testing; Thrombin; Thrombosis; Time; Validation; Venipunctures; Venous; Whole Blood; Work; base; clinical research site; clinically actionable; commercialization; cost; design; digital; high risk population; hospital laboratories; improved; innovation; laboratory experience; microfluidic technology; minimally invasive; neonate; novel; patient safety; pediatric patients; point of care testing; prevent; product development; programs; rapid testing; real time monitoring; sample collection; thrombotic; uptake; 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 (HL140662 Phase IIB SBIR) Anticoagulation therapy is indicated for children who suffer from congenital heart defects, thrombosis, or who are at risk of developing thrombosis. Over the past decade, there has been a dramatic increase in the use of anticoagulation therapies in pediatric patients, with up to 15% of hospitalized children receiving heparin or heparinoids. The use of these therapies necessitates frequent laboratory testing (every 4 hours) of multiple analytes -- anti-thrombin function (ATIII), Factor Xa activity (Xa), and activated partial thromboplastin time (aPTT) -- to avoid underdosing (thrombotic events) or overdosing (bleeding). Existing diagnostics for heparin therapy are problematic in newborns and children as they are generally standardized for adult samples and require as much as 2 mL of whole blood per analyte or a cumulative blood volume of up to 12 mL per day for the full panel. There is a critical unmet need to develop a low-volume, minimally invasive, and rapid turn-around diagnostic test panel for monitoring heparin therapy in children that features multiple analyte testing on a single platform. Work completed through Phase I and II of this project (R44HL140662) has established feasibility to perform a panel of three critical assays (ATIII, Xa, and aPTT) for laboratory quality monitoring of anticoagulants (heparin, heparinoids) on our near patient digital microfluidic platform (FINDER). This platform was recently CE marked for glucose-6-phosphate dehydrogenase (G6PD) testing and is pending 510(k) clearance from the FDA. The proposed Phase IIB project will support full analytical validation per CLSI guidelines and a rigorous clinical validation necessary to obtain FDA clearance for our heparin assay panel. We are preparing to engage in a pre- submission with the FDA regarding our validation protocols and design of the validation studies to meet 510(k) requirements based on single test predicate devices for each analyte. We are working closely with our clinical partners at Boston Children’s Hospital to optimize the heparin testing platform workflow for seamless integration into a hospital laboratory setting upon commercialization. Funding through this Phase IIB mechanism will complete the developmental path for our FINDER heparin monitoring platform, from concept to market through anticipated FDA clearance. There is currently no single point-of-care testing platform available that supports rapid testing of ATIII, Xa, and aPTT. The small volume format inherent to our digital microfluidic technology enables all three assays to be performed with less than 50 L of whole blood or plasma, collected via heel-stick or venipuncture, and is perfectly suited for use in pediatric settings where frequent blood draws significantly increase the risk of iatrogenic anemia. By combining three technically complex assays into a single, automated platform, we can improve both technical performance of heparin monitoring assays (reduced sample-to-answer time, three analyte test results from a single blood sample) and improve clinical outcomes through reduced blood volume needed for recurrent testing of heparin and other anticoagulants.

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 (HL140662 IIB期SBIR) 抗凝治疗适用于患有先天性心脏病、血栓形成或患有先天性心脏病的儿童 在过去的十年中，血栓形成的风险急剧增加。 儿科患者接受抗凝治疗，高达 15% 的住院儿童接受肝素或 使用这些疗法需要经常进行多次实验室检测（每 4 小时一次）。 分析物——抗凝血酶功能 (ATIII)、Xa 因子活性 (Xa) 和活化部分凝血活酶时间 (aPTT) -- 避免剂量不足（血栓事件）或剂量过量（出血）。 在新生儿和儿童中存在问题，因为它们通常针对成人样本进行标准化，并且需要 每个分析物需要多达 2 mL 的全血，或者全组每天的累积血量高达 12 mL。 开发一种低容量、微创且快速周转的诊断测试存在着尚未满足的关键需求 用于监测儿童肝素治疗的面板，其特点是在单一平台上进行多种分析物测试。 该项目 (R44HL140662) 第一阶段和第二阶段完成的工作已经确定了执行 用于抗凝剂（肝素、肝素、 我们的近患者数字微流体平台 (FINDER) 上的类肝素）最近获得了 CE 标志。 用于葡萄糖-6-磷酸脱氢酶 (G6PD) 测试，正在等待 FDA 的 510(k) 许可。 拟议的 IIB 期项目将支持根据 CLSI 指南进行全面分析验证和严格的临床 我们的肝素检测小组需要进行 FDA 批准所需的验证。 向 FDA 提交有关我们的验证方案和验证研究设计的意见，以满足 510(k) 的要求 基于每种分析物的单一测试谓词设备的要求我们正在与我们的临床密切合作。 波士顿儿童医院的合作伙伴优化肝素检测平台工作流程以实现无缝集成 商业化后进入医院实验室。 通过这一 IIB 期机制提供的资金将完成我们 FINDER 肝素的发展路径 监控平台，从概念到市场，直至 FDA 的预期审批 目前还没有单一的平台。 提供即时检测平台，支持 ATIII、Xa 和 aPTT 的快速检测。 我们的数字微流控技术固有的格式使所有三种测定都可以在不到 50 L 全血或血浆，通过足跟刺针或静脉穿刺收集，非常适合儿科使用 频繁抽血的环境会显着增加医源性贫血的风险，将这三者结合起来。 将技术上复杂的检测整合到一个单一的自动化平台中，我们可以提高 肝素监测分析（减少样本到答案的时间，单份血液的三种分析物测试结果 样本）并通过减少肝素重复检测所需的血容量来改善临床结果 和其他抗凝剂。