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

MICELI 聚合仪：即时血小板功能分析仪

• 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
• 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

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， 在广泛的疾病状态下被“不适当地”激活。为了降低这种激活风险， 血栓形成药物被常规地开给越来越多的患者，实际上是主要的药物 由今天的医生开的处方。虽然这些药物在治疗上是有效的，但不幸的是，它们增加了 药物诱导的血小板功能障碍导致患者出血风险。这一点在欧洲尤其成问题。 急性疾病和创伤出血的情况下，当医生需要迅速作出决定， 患者血小板对凝血能力的有效性;以及紧急血小板输注的需要。 输血血小板聚集是辅助这一决策的工具，但由于以下原因， 存在设备限制。目前缺少的是一种快速、近距离、廉价的评估血小板的方法 功能在这里，我们提出了满足这一需求的解决方案。UA联盟PI领导了临床的发展， 包括药物洗脱支架、聚合物铺路、生物可降解电子产品和全人工心脏在内的技术， 是血小板机械生物学和血栓形成机制研究的先驱， 心血管器械诊断和治疗方面的专业知识。我们描述的“MICELI”（微流体， 电（阻抗）聚集计改进了现有技术，通过减少 测定的占地面积和复杂性、其成本和执行的总时间。目前的聚集计很大， 昂贵且需要大量血液和多个处理步骤。MICELI平台通过 在2个电极上测量阻抗，浸没在封闭盒内的血小板样本中。阻抗 电极之间的阻抗增加对应于血小板聚集;阻抗数据被转换为 聚集值：幅度（Ω）、速度（Ω /min）和曲线下面积（Ω/min）。一个小的血容量是 需要（250 uL），采血和结果之间的时间在10分钟内。准确度和精密度 的MICELI已成功地验证了标准凝集仪与全血和血小板丰富的 等离子体MICELI聚合仪的可行性已经在概念验证层面上得到确立;我们的目标是 是将MICELI转化为临床相关的床旁设备。我们将通过以下方式实现这一目标： 有纪律的设计控制过程，具体成功完成目标。(SA1)我们将验证MICELI 以人全血和胶原蛋白及TRAP-6作为聚集激动剂，验证其灵敏度和检测性 血小板计数、红细胞压积和常规抗血栓治疗的限度。电流阻抗聚集法 这些方法需要高度精确地、手动地将液体激动剂和血小板样品添加到反应室， 引入了用户之间的错误来源和缺乏标准化。因此，我们将设计一个改进的 MICELI药筒，允许（SA 2）冻干和稳定聚集激动剂，（SA 3）完全 封闭式反应室盒，用于体积控制的血液样本填充和精密制造 个电极该建议的成功结果是廉价、快速、精确、一次性、生物稳定， MICELI药筒原型。完整的MICELI聚集度计系统的商业化（用于 药筒、电子器件、数据处理算法和用户界面）是未来第二阶段的主题 成绩.

项目成果

Electrical impedance vs. light transmission aggregometry: Testing platelet reactivity to antiplatelet drugs using the MICELI POC impedance aggregometer as compared to a commercial predecessor.

电阻抗与光透射聚集测量：使用 MICELI POC 阻抗聚集测量仪测试血小板对抗血小板药物的反应性，并与商业前身进行比较。

• DOI: 10.1016/j.thromres.2021.05.021
• 发表时间: 2021
• 期刊: Thrombosis research
• 影响因子: 7.5
• 作者: Mencarini,Tatiana;Roka-Moiia,Yana;Bozzi,Silvia;Redaelli,Alberto;Slepian,MarvinJ
• 通讯作者: Slepian,MarvinJ