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

基于集成电化学适体的平台，用于临床相关分析物的护理点和连续监测

• 批准号: 10538257
• 负责人: Zachary L Watkins
• 金额: $ 3.97万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-06 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10538257
• 关键词: Adoption; Amino Acids; Animal Model; Animals; Antibiotics; Area; Biological Markers; Biosensing Techniques; Biosensor; Blood; Blood Glucose; Calibration; Cardiac Surgery procedures; Child; Childhood; Clinic; Clinical; Clinical Trials; Cyclosporine; Data; Device or Instrument Development; Devices; Diabetes Mellitus; Digoxin; Discipline of obstetrics; Disease; Doctor of Philosophy; Dose; Drug Monitoring; Electrodes; Enzymes; Fingers; Foundations; Frequencies; Glucose; Home; Hormones; Hour; Hydrocortisone; In Vitro; Individual; Insulin; Intercellular Fluid; LCN2 gene; Lead; Longevity; Medical; Membrane; Mentorship; Microfluidics; Modality; Modeling; Monitor; Patient-Focused Outcomes; Patients; Performance; Pharmaceutical Preparations; Phenytoin; Physiological; Population; Postoperative Period; Pregnancy; Pregnant Women; Progesterone; Research; Risk; Sampling; Signal Transduction; Technology; Testing; Therapeutic; Therapeutic Index; Time; Translating; Troponin; Validation; Vancomycin; Variant; Work; aptamer; base; catalyst; clinical development; clinically relevant; design; diabetic patient; glucose monitor; glucose sensor; home test; human subject; improved; improved outcome; in vivo; individual patient; individualized medicine; innovation; interpatient variability; lead candidate; novel; nuclease; operation; pediatric patients; personalized medicine; point of care; point of care testing; post gamma-globulins; precision medicine; programs; sensor; success; test strip; virtual; wearable device

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.

项目总结/文摘: