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

项目概要/摘要： 个性化医疗的全面影响只能通过快速便捷地获得 在家里和诊所的个人生物标志物数据。生物传感器能够按需定量 药物、激素和其他临床相关分析物长期以来一直被认为是下一个突破， 促进精准医疗。虽然即时和连续血糖监测仪已经大大改善， 对于糖尿病患者，几乎没有临床采用生物传感器用于其他目标 尽管在治疗药物监测、手术后监测等领域具有巨大的影响潜力， 监测和持续的激素监测。除了酶促葡萄糖传感器，电化学 基于适体（EAB）的传感器包括唯一的其他生物传感模式，其已经在生物传感领域得到广泛验证。 vivo.尽管在动物模型中证明了对十几种不同分析物的连续感测， EAB传感器已在人类受试者中进行了验证，原因是无法集成到可部署设备中。 因此，主要需要弥合生物传感器研究与所需设备类型之间的差距 对真实的病人的影响。我们假设，最初的影响与以下方面的迫切需要特别一致： 对产科和儿科人群的药物和激素浓度进行高频监测， 关于这些患者的临床试验数据通常很少， 导致患者间分析物浓度剧烈变化。 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，将它们从研究工作台转换为 临床上可用于护理点和/或连续生物感测。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允许EAB 传感器将在适合人体测试的集成设备中进行表征和验证。 我们计划通过（1）在体外验证EAB传感器在at- 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>1 （3）在人类受试者中验证这些集成装置，用于EAB型传感器， 窄治疗指数抗生素万古霉素。这一提议将迎来期待已久的EAB验证 用于按需监测人类受试者中分析物的传感器，作为进一步 这种传感模式的临床采用，因为这里开发的技术扩展到其他分析物， 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.