Multi-plexed Cardiac Biomarker Detection Using Electrochemically Active Aptamers

描述（由申请人提供）：在美国，“心脏病”超过癌症，成为导致死亡的主要原因。为了更好地诊断心血管疾病，并准确评估这些危及生命的疾病的患者风险，ISL的I期工作将侧重于用三分子SAM修饰的微电极的特性，以及修饰电极提供c反应蛋白（CRP）超灵敏检测的能力。该项目的目标包括(1)证明修饰的电极表面抵抗非特异性相互作用/吸附(2)CRP的检测限为0.1 mg/L，线性动态范围为0.1-10 mg/L。第二阶段的工作将集中于心血管疾病相关生物标志物的新型适配体的开发，以及一组重要心血管疾病生物标志物的适配体修饰微电极阵列的表征和构建。拟议的研究将在诊断方面产生广泛的影响，证明：(1)在蛋白质组学诊断的蛋白质微阵列设计中，使用适体作为抗体的可行和直观的替代方案；(2)微电极阵列格式作为光学方法的成本效益替代方案；(3)结合适体的微电极阵列对蛋白质生物标志物进行超灵敏和选择性检测；(4)适体与抗体在诊断医学中的优势。心血管疾病及相关疾病的严重程度和流行程度可能会直接或间接地影响到美国的每个人。更加便捷、准确、可及的诊断技术的发展，将对今后心血管疾病的控制和预防方向起到直接作用。

DESCRIPTION (provided by applicant): "Heart disease" surpasses cancer as the leading cause of death in the United States. To better diagnose cardiovascular diseases and to accurately evaluate patient risk for such life- threatening conditions, ISL's Phase I efforts will focus on the characterization of microelectrodes modified with a trimolecular SAM and the ability of the modified electrodes to provide ultrasensitive detection of C-reactive protein (CRP). The project objectives include (1) demonstration that the modified electrode surface resists non-specific interactions/adsorption (2) a limit of detection for CRP of 0.1 mg/L and a linear dynamic range from 0.1-10 mg/L. Phase II efforts will focus on the development of novel aptamers for cardiovascular disease-related biomarkers, as well as, characterization and construction of an aptamer-modified microelectrode array for a panel of important cardiovascular disease biomarkers. The proposed research will have broad impacts in diagnostics by demonstrating: (1) the use of aptamers as a viable and intuitive alternative for antibodies in the design of protein microarrays for proteomic diagnostics; (2) microelectrode array formats as a cost effective alternative to optical methods; (3) ultrasensitive and selective detection of protein biomarkers using microelectrode arrays combined with aptamers; (4) advantages of aptamers versus antibodies in diagnostic medicine. The severity and prevalence of cardiovascular disease and related conditions will likely affect every person in the United States, either directly or indirectly. The development of diagnostic technologies that are more convenient, accurate and accessible will play a direct role in the future direction of controlling and preventing cardiovascular diseases. PUBLIC HEALTH RELEVANCE: "Heart disease" surpasses cancer as the leading cause of death in the United States. To better diagnose cardiovascular diseases and to accurately evaluate patient risk for such life-threatening conditions, Phase I efforts will focus on the characterization of microelectrodes modified with a trimolecular SAM and the ability of the modified electrodes to provide ultrasensitive detection of C-reactive protein (CRP). The development of such a device has several applications in the healthcare industry for prognostic and diagnostic use by physicians, paramedics, nursing home caretakers, and in emergency rooms. Development of this device will allow first responders to accurately determine a course of treatment, and allow for physicians to screen at-risk patients to determine their risk of impending heart attacks.