Aptamer-Enabled High-sensitivity Troponin assay for rapid POC diagnosis of myocardial infarction

适配体高灵敏度肌钙蛋白检测可快速诊断心肌梗死

• 批准号: 9163615
• 负责人: Brian Scott Ferguson
• 金额: $ 22.31万
• 依托单位: APTITUDE MEDICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9163615
• 关键词: Accident and Emergency department; Acute myocardial infarction; Affect; Affinity; Antibodies; Bedside Testings; Binding; Biological Assay; Blood; Buffers; Capital; Cardiac; Clinical; Clinical Research; Collaborations; Computers and Advanced Instrumentation; Concatenated DNA; Cryopreservation; DNA; Data; Detection; Devices; Diagnosis; Diagnostic; Electrodes; Enzyme-Linked Immunosorbent Assay; Glucose; Hospitals; Hour; Immunoassay; Individual; Investments; Kinetics; Label; Lead; Measurement; Measures; Methods; Microfluidic Microchips; Microfluidics; Myocardial Infarction; Oxidation-Reduction; Patient-Focused Outcomes; Patients; Performance; Phase; Point-of-Care Systems; Population; Pre-hospital setting; Process; Reagent; Resistance; Retrospective Studies; Sampling; Serum; Small Business Innovation Research Grant; Specificity; Speed; Staging; Symptoms; System; Technology; Testing; Time; Triage; Troponin; Troponin I; Variant; Whole Blood; Work; aptamer; base; chemical stability; cost; effective therapy; experience; improved; industry partner; mortality; novel; particle; point of care; prototype; rapid diagnosis; screening; sensor; single molecule

PROJECT ABSTRACT There is a major need for the widespread measurement of cardiac troponin at high sensitivity in the diagnosis of myocardial infarction. Yearly, 15 M patients present to the emergency department with symptoms of acute myocardial infarction. Rapid identification can significantly improve patient outcomes, and by ruling out those without myocardial infarction, it can save hospitals billions of dollars per year. High sensitivity cardiac troponin has become an accepted practice, but it is limited to hospitals with sophisticated centrals labs. There is no point of care version of this test which is urgently needed in pre-hospital settings and in hospitals without a central lab. We propose to develop a novel aptamer- based POC troponin assay that utilizes high-performance aptamers instead of antibodies, in a simple and robust, low cost, microfluidic device to achieve detection limit of less than 0.1 pg/ml in 20 min from blood. In phase I, we will develop a DNA aptamer pair, with ultra-high affinity and specificity against cTnI, reduced non-specific binding, resistance to heterophilic antibody interference, and increased stability and batch-to-batch consistency. We will exploit these aptamers in an electrochemical microfluidic device, with the capture aptamer immobilized on the sensor electrode, and the detection aptamer forming a DNA concatemer yielding rapid kinetics and ultra-high sensitivity, and verified the technical feasibility with clinical samples. In phase II, we will create a prototype similar to a glucose test strip, which outperforms the current standard point of care systems, validated by a retrospective clinical study in healthy and AMI patients, in comparison with commercial products. We expect to follow on with private capital or strategic investment from a partner company to proceed through clinical stage and FDA clearance via collaboration with industry partners.

项目摘要 目前主要需要以高灵敏度广泛测量心肌肌钙蛋白，以诊断心肌梗死。 心肌梗死每年有1500万名患者因急性心肌梗死症状到急诊室就诊， 梗塞快速识别可以显着改善患者的预后，并通过排除那些没有心肌梗死的患者， 它每年可以为医院节省数十亿美元。高敏心肌肌钙蛋白已成为公认的 实践，但它仅限于拥有先进中心实验室的医院。该检测没有即时版本， 在院前环境和没有中心实验室的医院中迫切需要。我们打算开发一种新的适体- 基于POC的肌钙蛋白测定，其利用高性能适体代替抗体，以简单和稳健，低成本， 微流控装置在20分钟内从血液中实现小于0.1 pg/ml的检测限。在第一阶段，我们将开发一个 DNA适体对，对cTnI具有超高亲和力和特异性，减少非特异性结合， 异嗜性抗体干扰，并增加稳定性和批次间一致性。我们将利用这些适体 在电化学微流体装置中，捕获适体固定在传感器电极上， 形成DNA多联体的检测适体产生快速动力学和超高灵敏度，并验证了该技术 临床样本的可行性。在第二阶段，我们将创建一个类似于葡萄糖试纸的原型， 通过对健康和AMI患者的回顾性临床研究验证的当前标准护理点系统， 与商业产品相比。我们希望通过私人资本或合作伙伴的战略投资来跟进 通过与行业合作伙伴的合作，公司将继续通过临床阶段和FDA批准。