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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要心血管疾病（CVD）是世界上大多数种族和族裔群体的首要死因。在美国，急性心肌梗塞 (AMI)（也称为心脏病发作）是 CVD 死亡的首要原因。早期发现 AMI 意味着早期干预并提高心肌细胞的存活率。受损的心肌肌钙蛋白 (cTn) 会被释放到循环系统中。血液 cTn 水平逐渐升高表明急性心脏损伤正在发生因此，通常使用商业 cTn 免疫测定法测量血液 cTn 水平。疑似患有 AMI 的患者然而，当前的 cTn 免疫测定的灵敏度和速度有限。由于当前的 cTn 免疫测定使用两种抗体（一种作为捕获，另一种作为检测）剂），目前的 cTn 免疫测定需要多步反应，灵敏度有限。检测不是实时进行的，通常需要大约 30 分钟才能获得结果，可能会错过早期检测结果 EZ-Lab 与研究人员合作，发现 cTn 水平或其变化率上升，从而延迟诊断。奥克兰大学、韦恩州立大学和密苏里哥伦比亚大学提议开发一种新型 cTn 生物传感器基于我们多年的研究和经验，可实现高度灵敏 (pg/ml) 和实时的 cTn 检测 1) 独特设计的肽模拟表位生物传感接口，用于基于无标记亲和力的创新电化学生物传感器；2）小型化、低成本、实时电化学传感器平台。与目前使用两种抗体的 cTn 免疫测定相比，我们成功证明了肽当通过自组装单层 (SAM) 固定在表面时，模拟表位可以代替抗体显着减少结构变异性，保留生物活性，并最大限度地减少或消除非特异性吸附干扰蛋白质并提供实时、高灵敏度和选择性的蛋白质检测推进这种新型肽模拟表位生物传感技术的早期应用。 AMI的检测和监测用于临床应用，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，可一步实时检测人体 cTn 血清和血液样本的三个研究目标： 1. 开发高灵敏度的肽传感接口用于检测 cTn；2. 使用人体验证基于肽 SAM 的 cTn 生物传感器分析性能血清和血液样本；3.血液样本中的实时cTn传感。生物传感器预计将具有高灵敏度和定量性，比目前用于检测的 cTn 免疫测定法更快。诊所，可以以显着较低的成本早期诊断 AMI，以量化现实世界中的 cTn 生物标志物临床样本预计我们易于使用的 cTn 生物传感器可用于监测患者的心脏。受伤状况，例如由紧急医疗服务团队从以下机构获取有关心脏损伤或 AMI 的关键数据立即帮助患者制定紧急且挽救生命的治疗和管理计划。