Biomarkers of sick sinus syndrome

病态窦房结综合征的生物标志物

• 批准号: 8869030
• 负责人: Liang Tang
• 金额: $ 25.29万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-07 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8869030
• 关键词: Age; Arrhythmia; Biochemical Markers; Biological Assay; Biological Markers; Biological Models; Bioprobe; Biosensing Techniques; Biosensor; Blood; Blood Circulation; Blood Tests; Blood specimen; Cardiac; Caring; Clinic; Clinical; Complex; Coupled; Development; Devices; Diagnosis; Diagnostic; Diagnostic Sensitivity; Early Diagnosis; Electrocardiogram; Environment; Enzyme-Linked Immunosorbent Assay; Functional disorder; Gold; Health Care Costs; Healthcare; Heart Diseases; High Pressure Liquid Chromatography; Holter Electrocardiography; Hospitals; Hour; Image; Immunoassay; Lead; Logistics; Magnetic nanoparticles; Mediating; Medical; Myoglobin; Optics; Outcome; Pathogenesis; Patient Care; Patients; Plasma; Polymerase Chain Reaction; Predictive Value; Predisposition; Procedures; Proteins; Reporting; Resources; Route; Sampling; Semiconductors; Sensitivity and Specificity; Sick Sinus Syndrome; Sinus; Societies; Solid; Specificity; Spottings; Sudden Death; Surface Plasmon Resonance; Survival Rate; System; Systems Integration; Techniques; Test Result; Testing; Time; Tissues; Translational Research; Triage; Troponin I; United States; base; biochip; clinical practice; design; detector; improved; innovation; insight; instrument; interdisciplinary approach; interest; metal oxide; micro-total analysis system; nano; nanobiosensor; nanobiotechnology; nanoparticle; nanorod; point of care; rapid diagnosis; sensor; sudden cardiac death; technology development

DESCRIPTION (provided by applicant): In the ageing society, sick sinus syndrome (SSS) is rapidly becoming one of the major arrhythmia problems. High survival rate with appropriate medical care indicates the paramount importance of early diagnosis. Interests have intensified in plasma biochemical markers to predict susceptibility and aid in patient management. Cardiac troponin I (cTnI) is the most widely used biomarker, due to its nearly complete cardiac tissue specificity. An elevated cTnI concentration was reported to be associated with SSS. A combination of cTnI and myoglobin, one of the earliest biomarkers released into blood circulation, can achieve diagnostic sensitivity of 97% with a 99% negative predictive value within 90 mins of ED presentation. However, blood testing of these biomarkers in current clinical practice represents a challenge for prime time diagnosis due to the time delay caused by laborious analysis and the logistics of sample handling to central labs. Therefore, the objective of this project is to take a multidisciplinary approach to develop an innovative biochip for rapid and simultaneous biosensing of these proteins at point of patient care. Specifically, a nanoparticle surface plasmon resonance (nanoSPR) biochip based on gold nanorod probes will be developed. Effect of the magnetic nanoparticles on the nanoSPR sensitivity and specificity enhancement will be systematically studied. The nano-biochip will then be integrated with a highly sensitive CMOS (complementary metal oxide semiconductor) image sensor and nanohole array to develop an innovative, fully operational lab-on-a-chip biosensor. The fundamental studies will provide innovative insights into MNP mediated nanoSPR mechanism to develop an ultra-sensitive, multiplexed biosensing. System integration of nanoSPR biochip with portable optical detector will transform bio-analysis in clinical environment to a point of care format for prime time medical diagnostics to improve clinical outcome.

描述（申请人提供）：在老龄化社会中，病态窦房结综合征（SSS）正迅速成为主要的心律失常问题之一。高存活率和适当的医疗护理表明早期诊断的重要性。人们对血浆生化标记物的兴趣日益浓厚，以预测易感性并帮助患者管理。心肌肌钙蛋白 I (cTnI) 因其几乎完全的心脏组织特异性而成为最广泛使用的生物标志物。据报道，cTnI 浓度升高与 SSS 相关。 cTnI 和肌红蛋白（最早释放到血液循环中的生物标志物之一）的组合可在 ED 出现后 90 分钟内实现 97% 的诊断灵敏度和 99% 的阴性预测值。然而，在当前的临床实践中，由于繁琐的分析和样本处理到中心实验室的物流造成的时间延迟，这些生物标志物的血液检测对黄金时间诊断提出了挑战。因此，该项目的目标是采用多学科方法来开发一种创新的生物芯片，以便在患者护理时快速、同步地对这些蛋白质进行生物传感。具体来说，将开发基于金纳米棒探针的纳米颗粒表面等离子共振（nanoSPR）生物芯片。将系统地研究磁性纳米粒子对nanoSPR灵敏度和特异性增强的影响。然后，纳米生物芯片将与高灵敏度 CMOS（互补金属氧化物半导体）图像传感器和纳米孔阵列集成，以开发创新的、完全可操作的芯片实验室生物传感器。基础研究将为 MNP 介导的 nanoSPR 机制提供创新见解，以开发超灵敏、多重生物传感。 nanoSPR 生物芯片与便携式光学检测器的系统集成将把临床环境中的生物分析转变为黄金时间医疗诊断的护理点格式，以改善临床结果。