Biomarkers of sick sinus syndrome

描述(申请人提供)：在老龄化社会，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，早期诊断是至关重要的。人们对血浆生化标记物预测易感性和辅助患者管理的兴趣已经增强。心肌肌钙蛋白I(CTnI)是目前应用最广泛的生物标志物，因其具有几乎完全的心肌组织特异性。据报道，cTnI浓度升高与SSS有关。CTnI和肌红蛋白是最早释放到血液循环中的生物标志物之一，联合检测可以在ED出现后90分钟内达到97%的诊断敏感性和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对黄金时段的诊断构成了挑战，因为繁琐的分析和将样本处理物流到中心实验室造成了时间延迟。因此，该项目的目标是采取多学科的方法来开发一种创新的生物芯片，用于在患者护理点对这些蛋白质进行快速和同步的生物传感。具体地说，将开发一种基于金纳米棒探针的纳米颗粒表面等离子体共振(NanSPR)生物芯片。我们将系统地研究磁性纳米颗粒对纳米SPR敏感性和特异性增强的影响。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，开发出一种创新的、完全可操作的芯片上实验室生物传感器。这些基础研究将为MNP介导的纳米SPR机制开发超灵敏、多路生物传感提供创新性的见解。纳米SPR生物芯片与便携式光学探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段医疗诊断的护理格式，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.