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

项目摘要 心肌肌钙蛋白的高灵敏度广泛检测是诊断急性心肌梗死的主要需要。 心肌梗死。每年有1500万名有急性心肌梗死症状的患者到急诊科就诊 脑梗塞。快速识别可以显著改善患者的预后，并通过排除那些没有心肌梗死的患者 对于脑梗塞，它每年可以为医院节省数十亿美元。高敏感性心肌肌钙蛋白已成为公认的 实践，但它仅限于拥有复杂中心实验室的医院。这个测试没有任何关注点，它是 在院前环境和没有中心实验室的医院中迫切需要。我们建议开发一种新的适体- 基于POC的肌钙蛋白检测，使用高效适配子而不是抗体，简单而可靠，低成本， 微流控装置，可在20分钟内从血液中实现低于0.1pg/ml的检测限。在第一阶段，我们将制定一项 DNA适配子对，对cTnI具有超高的亲和力和特异性，减少了非特异性结合，对 异嗜性抗体干扰，提高了稳定性和批次间的一致性。我们将利用这些适配子 在电化学微流控装置中，将捕获适配子固定在传感器电极上， 检测适配子形成的DNA串联链体具有快速动力学和超高灵敏度，并验证了技术 临床样品的可行性。在第二阶段，我们将创建一个类似于葡萄糖测试试纸的原型，它的性能优于 目前的标准护理点系统，通过对健康和急性心肌梗死患者的回顾性临床研究验证，在 与商业化产品进行比较。我们希望从合作伙伴那里获得私人资本或战略投资。 公司将通过与行业合作伙伴的合作，通过临床阶段和FDA的批准。

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.