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）是大多数种族和族裔群体中人死亡的主要原因 美国。急性心肌梗塞（AMI）（也称为心脏病发作）是CVD死亡的主要原因。 AMI的早期检测转化为早期干预并提高生存率。当心肌细胞是 受损的心肌肌钙蛋白（CTN）被释放到循环中。动态和 血液CTN水平的增量升高表明急性心脏损伤的持续事件 心肌细胞损伤。这是通过商业CTN免疫测定法常规测量的血液CTN水平 怀疑患有AMI的患者。但是，当前的CTN免疫测定在灵敏度和速度方面受到限制。 由于当前CTN免疫测定中使用了两种抗体（一种是捕获，另一种作为检测 代理），当前的CTN免疫测定需要多个步骤反应，灵敏度有限。另外， 测定不是实时进行的，通常需要大约30分钟才能获得可能错过早期的结果 CTN水平或其变化率上升，从而延迟诊断。 EZ-LAB，与研究人员合作 奥克兰大学，韦恩州立大学和大学。密苏里州 - 哥伦比亚的，提议开发一种新型的CTN生物传感器 这允许高度敏感（pg/ml）和根据我们多年的研究和 1）唯一设计的肽模拟物生物传感界面，用于基于标签的亲和力 电化学生物传感器； 2）微型，低成本和实时电化学传感器平台。尖锐 与当前使用两种抗体的CTN免疫测定对比，我们成功证明了胡椒 当通过自组装单层（SAM）固定在表面上时，模仿抗体可以代替抗体 显着降低结构可变性，保留生物学活性，并最小化或消除非特异性 干扰蛋白质并提供实时，高度敏感和选择性检测蛋白质的吸附 人血清样品中的抗原。促进这种新颖的辣椒模仿生物传感技术的早期 用于临床应用的AMI检测和监测，我们将合理设计肽以形成强大的CTN 电化学CTN传感器的生物传感界面允许人类中CTN的一步和实时检测 血清和血液样本具有三个研究目的：1。发展高度敏感的肽敏感性界面 用于检测CTN； 2。使用人类验证基于SAM 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敏感性。提出的肽模拟物CTN 预计生物传感器高度敏感和定量，比电流CTN免疫测定更快 诊所，以量化现实世界中的CTN生物标志物的成本明显降低，允许对AMI进行早期诊断 临床样品。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，例如紧急医疗服务团队，以获取有关心脏损伤或AMI的关键数据 患者立即有助于制定紧急和挽救生命的治疗和管理计划。