Multi-plexed Cardiac Biomarker Detection Using Electrochemically Active Aptamers

描述（由申请人提供）：“心脏病”超过癌症成为美国的主要死因。为了更好地诊断心血管疾病并准确评估患者发生此类危及生命的疾病的风险，ISL的I期工作将重点关注用三分子SAM修饰的微电极的表征以及修饰电极提供超灵敏检测C反应蛋白（CRP）的能力。项目目标包括（1）证明修饰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在开发用于心血管疾病相关生物标志物的新型适体，以及用于一组重要心血管疾病生物标志物的适体修饰微电极阵列的表征和构建。 拟议的研究将在诊断学中产生广泛的影响，通过证明：（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品;（2）微电极阵列格式作为光学方法的成本效益替代品;（3）使用微电极阵列与适体组合的蛋白质生物标志物的超灵敏和选择性检测;（4）核酸适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患病率可能会直接或间接影响美国的每个人。更方便、准确、可及的诊断技术的发展将对未来控制和预防心血管疾病的方向起着直接的作用。 公共卫生相关性：在美国，“心脏病”超过癌症成为死亡的主要原因。为了更好地诊断心血管疾病并准确评估患者发生此类危及生命的疾病的风险，I期工作将重点关注用三分子SAM修饰的微电极的表征以及修饰电极提供超灵敏检测C反应蛋白（CRP）的能力。这种设备的开发在医疗保健行业中具有多种应用，用于医生、护理人员、疗养院护理人员和急诊室的预后和诊断用途。该设备的开发将使急救人员能够准确地确定治疗过程，并允许医生筛选有风险的患者，以确定他们即将发生心脏病发作的风险。

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.