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

基本信息

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
项目类别：
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

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

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项目摘要

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：个性化医学的全部影响只能通过快速便捷的访问来实现单个生物标志物数据在家中和诊所中。生物传感器可以按需定量长期以来，已承诺将药物，激素和其他临床相关分析作为下一个突破促进精度医学。虽然护理点和连续的葡萄糖监测器已大大改善糖尿病患者的结果，几乎没有针对其他靶标的临床采用生物传感器分析物尽管在治疗药物监测等领域产生了巨大影响，但术后术。监视和连续激素监测。除了酶促葡萄糖传感器之外，电化学基于适体的（EAB）传感器是唯一已广泛验证的其他生物传感方式体内。尽管在动物模型中表明了超过十几种不同分析物的连续传感，否 EAB传感器由于缺乏将可部署设备的整合而对人类受试者进行了验证。因此，存在主要需求，以弥合生物传感器研究与所需设备类型之间的差距为了真正的患者影响。我们假定最初的影响特别良好，直接需要产科和小儿种群中药物和激素浓度的高频监测，尽管这些患者的生理变异可以导致分析物浓度的严重室内变异性。我们的中心假设是，通过以设备为导向和新颖的信号转导创新，EAB 传感器可以实现将它们从研究工作台转换为格式所需的性能可以在临床上部署，以进行护理和/或连续生物传感。具体来说，我们假设货架存储，现成稳定性，传感器询问和传感器保护的进步将允许EAB 在适合人类受试者测试的集成设备中进行表征和验证的传感器。我们计划通过（1）在AT-中运行的EAB传感器对我们的中心假设进行验证家庭测试带格式，（2）在可穿戴设备中演示EAB传感器的连续操作> 1 一周和（3）验证人类受试者中的这些集成设备的模型EAB传感器针对的模型EAB传感器狭窄的治疗指数抗生素万古霉素。该提议将迎来已久的EAB的验证用于对人类受试者分析物进行按需监测的传感器，这是进一步的基础随着此处开发的技术的临床采用，这种传感方式已扩展到其他分析物和个性化医学的应用。