Integrated Electrochemical Aptamer Based Platforms for the Point-of-Care and Continuous Monitoring of Clinically Relevant Analytes

项目摘要/摘要： 个性化医疗的全面影响只有通过快速方便地获取 在家中和临床中的个体生物标记物数据。支持按需量化的生物传感器 长期以来，药物、激素和其他与临床相关的分析方法一直被承诺为下一个突破 促进精准医疗。虽然医疗点和连续血糖监测仪已经大幅改进 对于糖尿病患者的预后，几乎没有临床采用用于其他靶点的生物传感器 尽管在治疗药物监测、手术后等领域有巨大的影响潜力，但分析人员 监测和持续的激素监测。超越酶葡萄糖传感器，电化学 基于适配子的(EAB)传感器是唯一一种已在 活着。尽管在动物模型中证明了对十几种不同的分析物进行连续传感，但没有 由于缺乏与可部署设备的集成，EAB传感器已在人类受试者中得到验证。 因此，需要弥合生物传感器研究和所需设备类型之间的差距 给病人带来真正的影响。我们假设，最初的影响特别符合以下方面的迫切需求 产科和儿科人群中药物和激素浓度的高频监测，如 关于这些患者的临床试验数据通常很稀少，尽管有各种生理变化可以 导致患者间分析物浓度的剧烈变化。 我们的中心假设是，通过面向设备和新颖的信号转导创新，EAB 传感器可以实现所需的性能，将它们从研究台转换为 临床上可部署用于护理点和/或连续生物传感。具体来说，我们假设 在货架存储、现成稳定性、传感器询问和传感器保护方面的进步将使EAB 传感器应在适用于人体受试者测试的集成设备中进行表征和验证。 我们计划通过以下方式来验证我们的中心假设：(1)在体外验证工作在At-At中的EAB传感器- 家用测试条格式，(2)演示EAB传感器在可穿戴设备中的连续操作 周和(3)在人体受试者中验证这些集成设备的模型EAB传感器靶向 治疗指数窄的抗生素万古霉素。这项提案将迎来期待已久的EAB的确认 用于按需监测人类受试者中分析物的传感器，作为进一步研究的基础 临床采用这种传感模式，因为这里开发的技术扩展到其他分析物和 在个性化医疗中的应用。

Project Summary/Abstract: The full impact of personalized medicine can only be realized through rapid and convenient access to individual biomarker data both at home and in the clinic. Biosensors that enable on-demand quantification of drugs, hormones, and other clinically relevant analytes have long been promised as the next breakthrough for facilitating precision medicine. While point-of-care and continuous glucose monitors have drastically improved outcomes for diabetic patients, there has been virtually no clinical adoption of biosensors for other target analytes despite tremendous potential for impact in areas such as therapeutic drug monitoring, post-operative surveillance, and continuous hormone monitoring. Beyond enzymatic glucose sensors, electrochemical aptamer based (EAB) sensors comprise the only other biosensing modality that has been broadly validated in vivo. Despite demonstration of continuous sensing for over a dozen different analytes in animal models, no EAB sensor has seen validation in human subjects due to lack of integration into deployable devices. Therefore, a major need exists to bridge the gap between biosensor research and the type of devices needed for real patient impact. We postulate that initial impact is particularly well-aligned with immediate needs for high-frequency monitoring of drug and hormone concentrations in obstetric and pediatric populations, as clinical trial data are often sparse with regard to these patients despite various physiological variations that can lead to drastic interpatient variability in analyte concentrations. Our central hypothesis is that through both device-oriented and novel signal-transduction innovations, EAB sensors can achieve the performance needed to translate them from the research bench to a format that is clinically deployable for point-of-care and/or continuous biosensing. Specifically, we postulate that advancements in shelf storage, off-the-shelf stability, sensor interrogation, and sensor protection will allow EAB sensors to be characterized and validated in integrated devices suitable for human subject testing. We plan to pursue validation of our central hypothesis by (1) in vitro validating EAB sensors operating in an at- home test strip format, (2) demonstrating the continuous operation of EAB sensors in a wearable device for >1 week and (3) validating these integrated devices in human subjects for model EAB sensors targeting the narrow therapeutic index antibiotic vancomycin. This proposal will usher in the long-awaited validation of EAB sensors for the on-demand monitoring of analytes in human subjects, serving as a foundation for further clinical adoption of this sensing modality as the technology developed here is expanded to other analytes and applications in personalized medicine.