Biomarkers of sick sinus syndrome

描述（由申请人提供）：在老龄化社会中，病窦综合征（SSS）正迅速成为主要的心律失常问题之一。在适当的医疗护理下，高存活率表明早期诊断至关重要。人们对血浆生化标志物预测易感性和帮助患者管理的兴趣越来越大。心肌肌钙蛋白I（cTnI）是最广泛使用的生物标志物，由于其几乎完全的心脏组织特异性。据报告，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）的组合可以在艾德出现的90分钟内实现97%的诊断灵敏度和99%的阴性预测值。然而，在目前的临床实践中，这些生物标志物的血液检测代表了对黄金时间诊断的挑战，这是由于费力的分析和将样本处理到中心实验室的物流造成的时间延迟。因此，该项目的目标是采取多学科方法开发一种创新的生物芯片，用于在患者护理点快速同时生物传感这些蛋白质。具体而言，纳米粒子表面等离子体共振（nanoSPR）生物芯片的基础上，金纳米棒探针将被开发。磁性纳米粒子对纳米SPR灵敏度和特异性增强的影响将被系统地研究。然后，纳米生物芯片将与高灵敏度的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，多路复用的生物传感。nanoSPR生物芯片与便携式光学检测器的系统集成将临床环境中的生物分析转变为用于黄金时间医学诊断的护理点格式，以改善临床结果。

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.