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Breakthrough Blocking-Layer Stability for Broader Clinical Utility of Continuous Aptamer Biosensors

突破性的阻断层稳定性使连续适体生物传感器具有更广泛的临床应用

基本信息

批准号：
10705842
负责人：
Jason Heikenfeld
金额：
$ 24.78万
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：
2022-09-19 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705842
关键词：
Achievement Acute Adoption Biosensor Body Temperature Cardiac Cardiac health Chemistry Clinical Clinical Research Complex Continuous Glucose Monitor Data Defect Dermal Devices Diagnostic Disease Management Dose Electrodes Electron Transport Enzymes Fertility Film Glucose Gold Growth Hour Industry Intercellular Fluid Kinetics Knowledge Letters Longevity Measures Modernization Molecular Monitor Outcome Oxidation-Reduction Pharmaceutical Preparations Positioning Attribute Property Research Research Personnel Resistance Serum Signal Transduction Silanes Sulfhydryl Compounds Surface System Techniques Technology Thick Time United States National Institutes of Health aptamer bioelectronics clinical application clinically relevant density diabetes management drug metabolism fabrication glucose monitor glucose sensor human disease improved in vivo insight monolayer nanomolar nuclease operation prevent real time monitoring self assembly sensor success

项目摘要

PROJECT SUMMARY The use of 10-14 day continuous glucose monitors for diabetes management is a historical achievement in modern diagnostics, but unfortunately it remains an isolated success despite acute needs for the real-time monitoring of many other molecules across the broader field of human disease management (cardiac, drug dosing, fertility, etc.). The limitation is that glucose sensors are enzymatic, limiting their generalizability to other analytes (i.e., enzymes oxidize/reduce the target molecule). Unlike enzymatic sensors, electrochemical aptamer-based (EAB) sensors are broadly generalizable, demonstrated by several examples of real-time, in- vivo molecular monitoring at nanomolar to micromolar concentrations. Unfortunately, in-vivo device longevity remains a significant challenge for the clinical adoption of EAB sensors. EAB sensors conventionally use a monolayer of redox-tagged aptamers and alkylthiol blocking molecules on a gold working electrode. These self-assembled monolayers (SAMs) rapidly degrade on gold electrodes in real biofluids at body temperature of 37 °C. The mechanisms of degradation of EAB SAMs have not been well- understood in complex biofluids, which then limits the ability to pursue techniques to improve longevity. Our preliminary data now provides major insights into the true mechanisms of SAM degradation. With this improved understanding of degradation, its is now feasible to pursue stable operation for at least 5 days. Multi-day operation would then allow EABs to be credibly pursued for applications beyond glucose, and for the first time, proper research could begin on resolving the next expected longevity bottlenecks that would likely prevent 1-2 week operation (e.g. fouling, nuclease attack, etc.). The central hypothesis is that at minimum 5 day EAB sensor operation can be achieved through a blocking layer with superior stability achieved by either (1) electrochemically stabilizing an alkylthiol blocking layer during sensor fabrication, or (2) replacing an alkylthiol blocking layer with a inorganic dielectric film that has a similar density of defects supporting efficient electron transfer. 5 day operation would provide a leap forward in clinical relevance, and is 10-20X greater the typical limit of 6-12 hours. 5 day operation would then position the PI Heikenfeld to pursue clinical research, and would ignite critically-needed partnerships with industry leaders in glucose sensors. The PI Heikenfeld is a new NIH investigator, but is well-prepared to pursue this longevity breakthrough given his deep expertise in biosensors, and his co-PI’s White and Porter’s expertise in EAB sensors and electrochemical blocking layers.

项目总结