Implantable real-time troponin biosensor for early diagnosis of silent cardiac injuries

植入式实时肌钙蛋白生物传感器用于早期诊断无症状心脏损伤

• 批准号: 10932735
• 负责人: ZHENGUO LIU
• 金额: $ 42.3万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10932735
• 关键词: Implantable; real; time; troponin; biosensor

Project Summary Cardiovascular disease is the leading cause of death in the United States. Among them, silent heart attack, also known as silent myocardial infarction (SMI) that occurs without apparent symptoms, accounts for approximately half of the total number of heart attacks. When cardiac myocytes are damaged, cardiac troponin (cTn), a component of the heart muscle, is released into circulation. Currently, blood cTn is routinely measured in patients suspected of having Acute Myocardial Infarction (AMI). However, SMI is often undiagnosed until it is too late, although SMI causes similar level of damage to the heart as symptomatic typical AMI. We hypothesize that an implantable cTn sensor providing a real-time and continuous data on the blood levels of cTn will allow a timely diagnosis at the very time when a SMI occurs to a subject, enabling timely treatment. For an in vivo biosensor, the sensing reactions not only need to be sensitive and selective to the analyte but also need to be self-sustaining for a long time in complex physiological conditions. This requires that the sensing reactions can be self- regenerating while at the same time developing a signal related to the analytes. Currently there is no cTn sensors that can be operated in real-time and continuously. We propose to use a radically new biosensor approach to develop highly sensitive, specific, and self-sustaining biosensors based on our years of research and innovations in 1) uniquely designed peptide mimotope biosensing interface for label-free affinity based electrochemical biosensor; 2) the unique properties of bifunctional Pd/Au bimetallic substrate electrode for sensing interface self- regeneration; and 3) miniaturized, low cost and real-time electrochemical sensor platform. Peptide mimotopes, in lieu of antibodies, when immobilized on the surface via self-assemble monolayer (SAM) can significantly reduce the structural variability, retain biological activity, and minimize or eliminate non-specific adsorption from interfering proteins and provide real-time, highly sensitive and selective detection of protein antigens in human blood samples. In addition, our multifunctional bimetallic nanostructured Pd/Au electrode will allow the formation of stable and robust peptide SAM on gold (Au) as well as controlled rapid regeneration of the protein complex using palladium (Pd) chemistry to induce rapid local pH change. We have two research Aims to develop and validate this novel biosensing technology: 1. Develop self-regenerable electrochemical cTn biosensor for real-time detection of cTn; 2. Develop miniaturized implantable cTn biosensor and validate its in vivo sensing using rat cardiac ischemia model. Successful completing these Aims will validate the capability of our cTn biosensor for real-time, sensitive and selective sensing of cTn in vivo for early detection and monitoring of SMI. The sensor will have great potential in the diagnosis and monitoring of a variety of other forms of heart injuries including (but not limited to) viral myocarditis (such as myocardial injury related to COVID-19 infection), drug-induced cardiac toxicities, and radiation-induced cardiac injuries. The biosensor methods developed can also be applied to many other implantable real-time sensing applications.

项目摘要 心血管疾病是美国死亡的主要原因。其中，沉默的心脏病发作也 被称为无明显症状的沉默心肌梗塞（SMI） 心脏病发作总数的一半。当心肌细胞受损时，心脏肌钙蛋白（CTN）， 心肌的成分被释放到循环中。目前，血液CTN通常在患者中测量 怀疑急性心肌梗塞（AMI）。但是，SMI通常一直无法诊断直到为时已晚， 尽管SMI与典型的AMI造成类似的心脏损害水平。我们假设 可植入的CTN传感器提供有关CTN血液水平的实时和连续数据，将允许及时 在受试者发生SMI的时候诊断，可以及时治疗。对于体内生物传感器， 传感反应不仅需要对分析物具有敏感和选择性，而且还需要自我维持 长期以来在复杂的生理条件下。这要求感应反应可以是自我的 再生，同时开发与分析物相关的信号。目前没有CTN传感器 这可以实时，连续地进行操作。我们建议使用一种根本新的生物传感器方法 根据我们多年的研究和创新，开发高度敏感，具体和自我维持的生物传感器 在1）基于无标签亲和力的电化学的独特设计的肽模拟物生物传感界面 生物传感器； 2）双功能PD/AU双金属底物电极的独特特性用于感应界面自我 再生; 3）小型，低成本和实时电化学传感器平台。肽二霉素， 代替抗体，当通过自组装单层（SAM）固定在表面上时 降低结构可变性，保留生物学活性，并最大程度地减少或消除非特异性吸附 干扰蛋白质并提供人类蛋白质抗原的实时，高度敏感和选择性检测 血液样本。此外，我们的多功能双金属纳米结构PD/AU电极将允许形成 稳定和稳健的肽SAM在金上（AU）以及蛋白质复合物的受控快速再生 使用钯（PD）化学诱导局部pH快速变化。我们有两个研究目的是开发和 验证这种新颖的生物传感技术：1。开发可自我获得的电化学CTN生物传感器 CTN的实时检测； 2。开发微型植入CTN生物传感器并验证其体内 使用大鼠心脏缺血模型感测。成功完成这些目标将验证能力 我们的CTN生物传感器的实时，敏感和选择性感测，用于早期检测和监测 smi。传感器将在诊断和监测各种形式的心脏中具有巨大潜力 损伤包括（但不限于）病毒心肌炎（例如，与1900次感染有关的心肌损伤）， 药物诱导的心脏毒性和辐射引起的心脏损伤。开发的生物传感器方法可以 也适用于许多其他可植入的实时感应应用。