Troponin Biosensor for Early Detection and Real-time Monitoring of Myocardial Infarction

用于心肌梗死早期检测和实时监测的肌钙蛋白生物传感器

• 批准号: 10483760
• 负责人: XIANGQUN ZENG
• 金额: $ 30.13万
• 依托单位: EZ LAB LIMITED LIABILITY COMPANY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10483760
• 关键词: Acute; Acute myocardial infarction; Address; Adsorption; Affinity; Antibodies; Antigens; Binding; Biological; Biological Assay; Biological Markers; Biosensing Techniques; Biosensor; Blood; Blood Circulation; Blood specimen; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cause of Death; Chemistry; Clinic; Clinical; Collaborations; Coupled; DNA; Data; Detection; Development; Diagnosis; Early Diagnosis; Early Intervention; Electrodes; Elements; Emergency medical service; Environment; Enzymes; Ethnic group; Event; Goals; Gold; Health Care Costs; Heart Injuries; Human; Immobilization; Immunoassay; Knowledge; Label; Libraries; Life; Measurement; Measures; Mediation; Methods; Missouri; Monitor; Myocardial Infarction; Myocardium; Noise; Nucleic Acids; Patient Monitoring; Patients; Peptides; Performance; Persons; Phage Display; Phase; Productivity; Property; Proteins; Race; Reaction; Research; Research Personnel; Sampling; Savings; Sensitivity and Specificity; Serum; Small Business Technology Transfer Research; Speed; Structure; Surface; Survival Rate; Technology; Time; Transducers; Translating; Troponin; Troponin I; United States; Whole Blood; accurate diagnosis; aptamer; base; clinical application; clinical biomarkers; clinically relevant; cost; cross reactivity; design; detection limit; functional group; improved; innovation; miniaturize; monolayer; myocardial injury; novel; optimal treatments; point of care; rate of change; rational design; real time monitoring; receptor; sensor; temporal measurement

Project Summary Cardiovascular disease (CVD) is the leading cause of death for people in most racial and ethnic groups in the United States. Acute Myocardial Infarction (AMI) (also called heart attack) is the top cause of death in CVD. Early detection of AMI translates to earlier intervention and improves survival rates. When cardiac myocytes are damaged, cardiac troponin (cTn), a component of the heart muscle, is released into circulation. Dynamic and incremental elevation of blood cTn levels is indicative of an on-going event of heart injury with acute cardiomyocyte damage. Thus, blood cTn level is routinely measured with commercial cTn immunoassays in patients suspected of having AMI. However, current cTn immunoassays are limited in sensitivity and speed. Since two antibodies are used in the current cTn immunoassays (one as the capture and another as the detection agents), current cTn immunoassays require multiple step reactions with limited sensitivity. Additionally, the assays are not performed in real time and typically take about 30 mins to get results that could miss the early rises in cTn levels or its rate of change thus delaying diagnosis. EZ-Lab, in collaborations with investigators at Oakland Univ., Wayne State Univ., and Univ. of Missouri-Columbia, proposes to develop a novel cTn biosensor that allows highly sensitive (pg/ml) and real-time detection of cTn based on our years of research and innovations in 1) uniquely designed peptide mimotope biosensing interface for label-free affinity based electrochemical biosensor; 2) miniaturized, low cost and real-time electrochemical sensor platform. In sharp contrast to current cTn immunoassays using two antibodies, we successfully demonstrated that 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 serum samples. To advance this novel peptide mimotope biosensing technology for early detection and monitoring of AMI for clinical applications, we will rationally design peptides to form robust cTn biosensing interface for electrochemical cTn sensors allowing one step and real-time detection of cTn in human serum and blood samples with three research Aims: 1. Develop a highly sensitive peptide sensing interface for detection of cTn; 2. Validate peptide SAM based cTn biosensor analytical performance using human serum and blood samples; 3. Real-time cTn sensing in blood sample. The proposed peptide mimotope cTn biosensor is expected to be highly sensitive and quantitative, faster than current cTn immunoassays used in the clinics, allowing for early diagnosis of AMI at significantly lower cost for quantifying cTn biomarkers in real world clinical samples. It is expected that our easy-to-use cTn biosensor can be used to monitor patients’ cardiac injury status such as by emergency medical service team to obtain the critical data on cardiac injury or AMI from the patients instantly to help develop urgent and life-saving treatment and management plan.

项目摘要 心血管疾病（CVD）是世界上大多数种族和民族群体的主要死亡原因。 美国的急性心肌梗死（AMI）（也称为心脏病发作）是心血管疾病死亡的首要原因。 AMI的早期检测转化为早期干预并提高存活率。当心肌细胞 受损的心肌肌钙蛋白（cTn）（心肌的一种成分）被释放到循环中。动态和 血液cTn水平的递增性升高表明正在发生的心脏损伤事件， 心肌细胞损伤因此，血液cTn水平常规地用商业cTn免疫测定法测量， 疑似AMI患者。然而，目前的cTn免疫测定在灵敏度和速度方面受到限制。 由于在当前的cTn免疫测定中使用两种抗体（一种作为捕获，另一种作为检测 试剂），目前的cTn免疫测定需要灵敏度有限的多步反应。另夕h 测定不是在真实的时间内进行的，并且通常需要大约30分钟才能得到结果， cTn水平或其变化率升高，从而延迟诊断。EZ-Lab与研究人员合作， 奥克兰大学，韦恩州立大学，和密苏里-哥伦比亚大学，建议开发一种新型的cTn生物传感器 基于我们多年的研究，可实现高灵敏度（pg/ml）和实时检测cTn， 创新之处在于：1）独特设计的肽模拟表位生物传感界面， 电化学生物传感器; 2）小型化、低成本和实时电化学传感器平台。形成鲜明 与目前使用两种抗体的cTn免疫测定相比，我们成功地证明了肽 当通过自组装单层（SAM）固定在表面上时，代替抗体的模拟表位可以 显著降低结构变异性，保留生物活性，并最小化或消除非特异性 吸附干扰蛋白，并提供实时、高灵敏度和选择性的蛋白检测 人血清样品中的抗原。为了使这种新型的肽模拟表位生物传感技术在早期 检测和监测AMI的临床应用，我们将合理设计肽，以形成稳健的cTn 用于电化学cTn传感器的生物传感接口，其允许一步和实时检测人体中的cTn 血清和血液样本有三个研究目的：1。开发高灵敏度的肽传感接口 用于检测cTn; 2.人肌钙蛋白生物传感器的分析性能 血清和血液样品; 3.血液样本中的实时cTn传感。提出的肽模拟表位cTn 生物传感器预期是高度灵敏和定量的，比目前用于免疫学的cTn免疫测定更快。 在真实的世界中，以显著更低的成本定量cTn生物标志物，从而实现AMI的早期诊断 临床样本。预期我们的易于使用的cTn生物传感器可用于监测患者的心脏 损伤状态，例如由紧急医疗服务团队从以下获得关于心脏损伤或AMI的关键数据 立即帮助患者制定紧急和挽救生命的治疗和管理计划。