The MICELI Aggregometer: a Point-of-Care Platelet Function Analyzer

MICELI 聚合仪：即时血小板功能分析仪

基本信息

批准号：
10011463
负责人：
Frank LaDuca
金额：
$ 22.5万
依托单位：
PLAKDX, LLC
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10011463
关键词：
3D Print ADP Receptors Acute Address Adenosine Diphosphate Agonist Algorithms Antiplatelet Drugs Area Under Curve Aspirin Biological Assay Blood Blood Cells Blood Platelets Blood Vessels Blood Volume Blood coagulation Blood flow Blood specimen Cardiovascular system Cessation of life Clinical Coagulation Process Collaborations Collagen Collection Competence Complication Consumption Data Decision Making Detection Devices Diagnostic Discipline Disease Effectiveness Electrodes Electronics Equilibrium Error Sources Event Fostering Freeze Drying Functional disorder Future Generations Goals Healthcare Hematocrit procedure Hemorrhage Hemostatic Agents Hemostatic function Housing Human Human Resources Immobilization In Vitro Infarction Intervention Ischemia Laboratories Liquid substance Maintenance Manuals Measures Mediating Methods Mexico Microfluidics Operative Surgical Procedures Optics Organ Outcome Pathway interactions Patients Pharmaceutical Preparations Pharmacology Phase Physicians Plasma Platelet Activation Platelet Aggregation Inhibition Platelet Count measurement Platelet Membrane Glycoprotein IIb Platelet Transfusion Platelet aggregation Polymers Population Procedures Process Protocols documentation Reaction Regimen Reproducibility Resistance Risk Sampling Services Silicon Silver Standardization Stents System Technology Testing Therapeutic Thrombosis Thromboxanes Time Transfusion Translating Trauma Treatment Efficacy Validation Whole Blood Work blood product clinical decision-making clinical development clinical practice clinical research site clinically relevant commercialization computerized data processing cost cost effective design electric impedance improved novel operation platelet function point of care point-of-care diagnostics portability prevent prototype public health relevance real time monitoring success thienopyridine thrombogenesis tissue repair tool total artificial heart user-friendly

项目摘要

PROJECT SUMMARY: While platelets are vital blood cells to maintain vascular integrity and foster tissue repair, unfortunately they may become “inappropriately” activated in a wide range of disease states. To reduce this activation risk anti- thrombotic drugs are routinely prescribed to an ever increasing variety of patients, in fact being leading agents prescribed by physicians today. While these drugs are therapeutically effective they unfortunately increase the bleeding risk of the patient as a result of drug-induce platelet dysfunction. This is particularly problematic in the setting of acute illness and trauma with bleeding, when physicians need to make rapid decisions as to the effectiveness of a patient’s platelets as to coagulation competency; and the need for emergent platelet transfusions. Platelet aggregation is the tool to aid in this decision making, yet remains underutilized due to present device limitations. What is missing is a rapid, proximate, inexpensive means of assessing platelet function. Here we present a solution to this need. The UA consortium PI has led the development of clinical technologies including drug eluting stents, polymer paving, biodegradable electronics, and total artificial heart, and is a pioneer in the study of platelet mechanobiology and thrombotic mechanisms providing valuable expertise in the cardiovascular device diagnostics and therapeutics. Our described “MICELI” (MICrofluidic, ELectrical, Impedance) aggregometer improves on current technology to measure aggregation by decreasing the footprint and complexity of the assay, its cost and overall time to perform. Current aggregometers are large, expensive and require large blood volumes and multiple processing steps. The MICELI platform works via impedance measured across 2 electrodes, submerged in platelet sample within a closed cartridge. Impedance between electrodes increases in correspondence to platelet aggregation; the impedance data are converted into aggregation values: magnitude (Ω), velocity (Ω /min), and area under the curve (Ω∙min). A small blood volume is required (250 uL) and time between blood collection and results is under 10 minutes. The accuracy and precision of the MICELI has been successfully verified against standard aggregometers with whole blood and platelet-rich plasma. The feasibility of the MICELI aggregometer has been established at a proof-of-concept level; our goal is to translate the MICELI into a clinically relevant, point-of-care device. We will achieve this objective using a disciplined design control process with specific successful completion of aims. (SA1) We will validate the MICELI using human whole blood with collagen & TRAP-6 as aggregation agonists, verifying its sensitivity and detection limits for platelet count, hematocrit and conventional antithrombotic therapies. Current impedance aggregometry methods require highly-accurate, manual adding of liquid agonist and platelet sample to the reaction chamber, introducing source of error and lack of standardization between users. Therefore, we will design an improved MICELI cartridge that allows for (SA2) lyophilization and stability of aggregation agonists and (SA3) completely enclosed reaction chamber cartridge for volume-controlled blood sample filling and precision manufactured electrodes. A successful outcome of this proposal is an inexpensive, rapid, precise, disposable, bio-stable, MICELI cartridge prototype. Commercialization of the complete MICELI aggregometer system (housing for cartridge, electronics, data processing algorithm, and user interface) is the subject of a future Phase II submission.

项目概要：虽然血小板是维持血管完整性和促进组织修复的重要血细胞，但不幸的是，它们可能在多种疾病状态下变得“不适当”激活，以降低这种激活风险。血栓药物经常被开给越来越多的患者，实际上是主要药物虽然这些药物在治疗上有效，但不幸的是，它们会增加医生的处方。由于药物引起的血小板功能障碍而导致患者出血的风险，这在患者中尤其成问题。当发生急性疾病和出血性创伤时，医生需要快速做出决定患者血小板的凝血能力的有效性以及对紧急血小板的需求；输血是帮助做出这一决策的工具，但由于以下原因仍未得到充分利用。目前设备的局限性在于缺乏一种快速、直接、廉价的血小板评估方法。在这里，我们提出了针对这一需求的解决方案。 UA 联盟 PI 引领了临床的发展。技术包括药物洗脱支架、聚合物铺路、可生物降解电子产品和全人工心脏，他是血小板力学生物学和血栓形成机制研究的先驱，为研究提供了宝贵的信息我们所描述的“MICELI”（MICrofluidic，电气、阻抗）聚合计改进了当前技术，通过减少测量聚合检测的占地面积和复杂性、其成本和执行的总时间都很大， MICELI 平台的工作原理是昂贵且需要大量血液和多个处理步骤。通过 2 个电极测量阻抗，电极浸入封闭式阻抗盒内的血小板样本中。电极之间的阻抗增加对应于血小板聚集；聚合值：幅度 (Ω)、速度 (Ω /min) 和曲线下面积 (Ω∙min)。需要 (250 uL)，并且采血和结果之间的时间少于 10 分钟准确性和精密度。 MICELI 的功能已成功通过全血和富含血小板的标准聚集计进行验证 MICELI 聚合计的可行性已达到我们的目标；的目标是将 MICELI 转化为临床相关的即时护理设备，我们将使用 (SA1) 我们将验证 MICELI 使用含有胶原蛋白和TRAP-6的人全血作为聚集激动剂，验证其灵敏度和检测血小板计数、血细胞比容和传统抗血栓治疗的限制。方法需要高度准确地手动将液体激动剂和血小板样品添加到反应室中，引入误差源和用户之间缺乏标准化，因此，我们将设计一个改进的。 MICELI 试剂盒可实现 (SA2) 冻干和聚集激动剂的稳定性，以及 (SA3) 完全用于体积控制的血样填充和精密制造的封闭室反应盒该提案的成功成果是一种廉价、快速、精确、一次性、生物稳定、 MICELI 墨盒原型完整的 MICELI 聚合计系统（外壳）的商业化墨盒、电子设备、数据处理算法和用户界面）是未来第二阶段的主题提交。