Bio-electrochemical detectors for in vivo continuous monitoring

用于体内连续监测的生物电化学检测器

基本信息

批准号：
9238429
负责人：
Kevin W Plaxco
金额：
$ 57.31万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9238429
关键词：
Affinity Amino Acids Aminoglycoside Antibiotics Aminoglycosides Animal Model Anticoagulation Biological Markers Biomedical Research Biosensor Bladder Blood Brain Caliber Chemistry Circadian Rhythms Clinical Coagulation Process Complex DNA Detection Development Disease Dose Doxorubicin Drug Controls Drug Delivery Systems Drug Kinetics Drug Targeting Feedback Future Goals Half-Life Health Health Status Healthcare Hour In Vitro Individual Intercellular Fluid Kanamycin Knowledge Laboratories Laboratory Animals Measurement Measures Membrane Metabolic Metabolism Methods Molecular Molecular Target Monitor Oryctolagus cuniculus Outcome Patients Pharmaceutical Preparations Physiological Physiology Rattus Reporter Research Resolution Running Sampling Sensitivity and Specificity Specificity Technology Testing Therapeutic Therapeutic Index Time Tissues Tobramycin Translating Urine Validation Variant Veins Whole Blood aptamer awake base biomaterial compatibility brain tissue clinical application clinical practice clinically relevant detector improved in vivo novel therapeutics operation pre-clinical programs sensor specific biomarkers stability testing temporal measurement tool

项目摘要

Summary. Our goal is the development and validation of a technology that can measure a wide range of drugs, metabolites, and biomarkers in the blood, urine, and interstitial fluids of living subjects continuously and in real time, an ability that would revolutionize many aspects of biomedical research and healthcare. To achieve this goal we will combine electrochemical aptamer-based sensors (which are reagentless and wash-free and can operate directly in complex samples without fouling) with biocompatible anti-coagulation membranes and advanced drift correction methods to achieve continuous, real-time, multi-day measurements directly in vivo. As preliminary results supporting this goal we demonstrate the continuous, real-time measurement of four different drugs directly in the jugulars of anesthetized rats for periods of more than five hours with 20-second time resolution and sub-micromolar precision. Leveraging these initial results we propose here three further advancements: First, we will expand the platform to the in vivo measurement of nine additional drugs and metabolites, which will demonstrate the platform's versatility. Second, we will improve the platform's stability such that we can perform high-precision in vivo measurements over the course of days, which will enable continuous measurements of long-lived drugs and capture clinically important circadian metabolic variations. Finally, we will expand the platform to the simultaneous measurement of multiple molecules and/or across multiple body compartments (e.g., blood, tissues, brain, bladder), rendering it a powerful new tool for understanding pharmacokinetics and physiology. By creating an unprecedented window into a patient's molecular-level physiological state, the proposed technology would enable many transformative clinical applications, including the high-precision measurement of patient-specific pharmacokinetics, the continuous monitoring of health status via the real-time measurement of specific biomarkers, and, ultimately, feedback- controlled drug delivery.

概括。我们的目标是开发和验证一种可以测量多种药物的技术，连续真实地采集活体血液、尿液和组织液中的代谢物和生物标志物时间，这种能力将彻底改变生物医学研究和医疗保健的许多方面。为了实现这一目标我们的目标是结合基于电化学适体的传感器（无需试剂、无需清洗，并且可以直接在复杂样品中操作（无污染），具有生物相容性抗凝膜和先进的漂移校正方法，可直接在体内实现连续、实时、多天的测量。作为支持这一目标的初步结果，我们展示了四个连续、实时的测量将不同的药物直接注射到麻醉大鼠的颈静脉中，持续时间超过 5 小时，持续 20 秒时间分辨率和亚微摩尔精度。利用这些初步结果，我们在此提出三个进一步的建议进展：首先，我们将把平台扩展到另外九种药物的体内测量，代谢物，这将展示该平台的多功能性。二、我们将提高平台的稳定性这样我们就可以在几天内进行高精度的体内测量，这将使连续测量长效药物并捕获临床上重要的昼夜代谢变化。最后，我们将将该平台扩展到同时测量多个分子和/或跨分子多个身体隔室（例如血液、组织、大脑、膀胱），使其成为一种强大的新工具了解药代动力学和生理学。通过创建一个前所未有的窗口来了解患者的情况分子水平的生理状态，所提出的技术将使许多变革性的临床应用，包括患者特异性药代动力学的高精度测量、连续通过实时测量特定生物标志物来监测健康状况，并最终反馈- 受控药物输送。