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: 10705637
• 负责人: Zachary L Watkins
• 金额: $ 4.08万
• 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/10705637
• 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; Continuous Glucose Monitor; 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; 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; 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.

项目摘要/摘要： 个性化医疗的全面影响只能通过快速、便捷的获取来实现 家庭和诊所的个体生物标志物数据。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。虽然护理点和连续血糖监测仪已大大改进 糖尿病患者的结果，临床上几乎没有采用生物传感器来检测其他目标 尽管分析物在治疗药物监测、术后监测等领域具有巨大的影响潜力 监测和持续激素监测。除了酶促葡萄糖传感器之外，电化学传感器 基于适配体 (EAB) 的传感器是唯一已在以下领域得到广泛验证的其他生物传感方式： 体内。尽管在动物模型中展示了对十多种不同分析物的连续感测，但没有 由于缺乏与可部署设备的集成，EAB 传感器已在人体中得到验证。 因此，迫切需要弥合生物传感器研究和所需设备类型之间的差距 对患者产生真正的影响。我们假设最初的影响与当前的需求特别吻合 高频监测产科和儿科人群的药物和激素浓度，例如 尽管这些患者存在各种生理变化，但临床试验数据往往很少。 导致分析物浓度的剧烈的患者间差异。 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 传感器可以实现将其从研究台转换为可使用的格式所需的性能 临床上可部署用于即时护理和/或连续生物传感。具体来说，我们假设 货架存储、现货稳定性、传感器询问和传感器保护方面的进步将使 EAB 成为可能 在适合人体测试的集成设备中对传感器进行表征和验证。 我们计划通过 (1) 体外验证在 at- 中运行的 EAB 传感器来验证我们的中心假设。 家庭测试条格式，(2) 演示 EAB 传感器在可穿戴设备中连续运行 >1 周和 (3) 在人类受试者中验证这些集成设备的 EAB 传感器模型 窄治疗指数抗生素万古霉素。该提案将迎来期待已久的 EAB 验证 用于按需监测人体分析物的传感器，为进一步的研究奠定了基础 随着这里开发的技术扩展到其他分析物，临床采用了这种传感方式 在个性化医疗中的应用。