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: 10400164
• 负责人: VAMSEE K. PAMULA
• 金额: $ 87.88万
• 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/10400164
• 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; design verification; 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; 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; design verification; 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 改善小儿患者的抗凝监测：使用微流体平台测试低体积 高跟鞋收集获得的血液样本 （HL140662 IIB SBIR） 针对患有先天性心脏缺陷，血栓形成或谁的儿童表示抗凝治疗 有患血栓形成的风险。在过去的十年中，使用的使用急剧增加 小儿患者的抗凝治疗，多达15％的住院儿童接受肝素或 肝素。这些疗法的使用经常进行实验室测试（每4小时）多次测试 分析物 - 抗凝血酶功能（ATIII），因子XA活性（XA）和激活的部分血栓形成时间（APTT） - 避免服用不足（血栓性事件）或过量（出血）。现有的肝素治疗诊断 在新生儿和儿童中存在问题，因为它们通常是成人样本标准化的，并且需要 全面板每天分析物的全血全血或每天高达12毫升的累积血容量。 有一个迫切需要开发小体积，微创和快速转向诊断测试的需求 用于监测儿童肝素疗法的面板，这些面板在单个平台上具有多个分析物测试。 通过该项目的第一阶段和第二阶段完成的工作（R44HL140662）已确定可行性 三个关键测定法（ATIII，XA和APTT）的面板，用于实验室质量监测抗凝剂（肝素，， 肝素）在我们近病人的数字微流体平台（Finder）上。该平台最近被标记为 用于6-磷酸葡萄糖脱氢酶（G6PD）测试，并正在从FDA中清除510（k）。这 拟议的IIB期项目将支持根据CLSI指南的完整分析验证和严格的临床 为我们的肝素测定面板获得FDA清除所需的验证。我们正在准备进行预先 与FDA提交有关我们的验证协议和验证研究的设计，以满足510（k） 基于每个分析物的单个测试谓词设备的要求。我们正在与临床紧密合作 波士顿儿童医院的合作伙伴优化肝素测试平台工作流程，以进行无缝集成 商业化后进入医院实验室。 通过此阶段的IIB机制资金将完成我们的发现者肝素的发展道路 监视平台，从概念到市场，通过预期的FDA清除率。目前没有单一 可用的即时测试平台支持ATIII，XA和APTT的快速测试。小体积 格式继承了我们的数字微流体技术，使所有三个测定都能以少于50的 通过脚后跟或静脉穿刺收集的全血或血浆，非常适合小儿使用 经常吸收​​血液的环境大大增加了息肉性贫血的风险。通过结合三个 技术复杂的测定在一个自动化平台中，我们可以提高技术性能 肝素监测测定法（减少样品到答案时间，三个分析物测试来自单个血液 样本）并通过减少肝素反复测试所需的血量来改善临床结果 和其他抗凝剂。