EAGER: Demonstrating the Physics of Novel Solution-Phase Electrochemical Aptamer Sensors

EAGER：展示新型溶液相电化学适体传感器的物理原理

• 批准号: 2125056
• 负责人: Jason Heikenfeld
• 金额: $ 25.1万
• 依托单位: University of Cincinnati Main Campus
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2125056&HistoricalAwards=false
• 关键词: EAGER; Demonstrating; Physics; Novel; Solution

Continuous glucose monitoring for diabetes is a historical achievement in modern diagnostics, but unfortunately is an isolated success despite numerous acute needs across the broader field of human medicine. Glucose monitoring remains an isolated success because glucose sensors are based on enzymes which can be challenging to develop for analytes other than metabolites (e.g. glucose, lactate, ethanol). An alternate class of sensors called electrochemical aptamer sensors are simpler to develop for analytes beyond glucose (hormones, drugs, proteins), but aptamer sensors have not yet demonstrated the longevity of use required for most medical applications and often have limits in their sensitivity. These longevity and sensitivity challenges, at least in part, exist because a perfect layer of aptamer must be assembled and retained on an electrode surface. This project will demonstrate and explore the physics of a new sensor approach based on solution-phase electrochemical aptamer sensors. Simply, the aptamers are allowed to float freely in solution, and when an analyte binds with an aptamer the aptamer changes in shape in a way that is measurable by an electrode. Solution-phase electrochemical aptamer sensors will provide significant advantages in terms of (1) breakthrough longevity and robustness due to their simplicity, and (2) improved sensitivity due to their highly tunable physics. This project aligns with the goal of enabling personalized medicine, by creating a new approach for biosensors that allow continuous biosensing of hormones, peptides, therapeutic drugs, and other markers across human health and medicine. Building upon preliminary work, this project pursues two specific aims. Aim 1 - demonstrate the underlying physics of solution-phase electrochemical aptamer sensors using existing aptamer designs developed for optically measured aptamers. The rationale for pursuing this aim is that leveraging fully characterized and modeled aptamers will allow a rapid theoretical understanding of new experimental data in this project. The product of this aim will be at least one aptamer that can then be redesigned in Aim 2. Aim 2 - create a rationale toolset for modifying aptamer design for achieving maximum changes in electrochemical signal. By demonstrating this fundamental design toolset before pursuing application-specific work, this second aim will enable all researchers to more rapidly advance a new field of solution-phase electrochemical aptamer sensors. The product of this aim will be both new knowledge of the physics of solution-phase electrochemical aptamer sensors, and a launch-pad for follow-on work in both fundamental and applied proposals to create continuous biosensors that can be worn on the body or implanted in the body.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

糖尿病的连续血糖监测是现代诊断学的一项历史性成就，但不幸的是，尽管更广泛的人类医学领域存在大量迫切需求，但这只是一次孤立的成功。 血糖监测仍然是一个孤立的成功，因为葡萄糖传感器基于酶，而开发代谢物以外的分析物（例如葡萄糖、乳酸、乙醇）可能具有挑战性。 另一种传感器称为电化学适体传感器，对于葡萄糖以外的分析物（激素、药物、蛋白质）更容易开发，但适体传感器尚未证明大多数医疗应用所需的使用寿命，并且其灵敏度通常受到限制。 这些寿命和灵敏度挑战的存在，至少部分是因为必须在电极表面组装并保留完美的适体层。 该项目将演示和探索基于溶液相电化学适体传感器的新传感器方法的物理原理。简单地说，让适体在溶液中自由漂浮，当分析物与适体结合时，适体以可通过电极测量的方式改变形状。 溶液相电化学适体传感器将在以下方面提供显着优势：（1）由于其简单性而具有突破性的寿命和鲁棒性；（2）由于其高度可调的物理特性而提高了灵敏度。 该项目通过创建一种新的生物传感器方法来实现个性化医疗的目标，该方法允许对人类健康和医学领域的激素、肽、治疗药物和其他标记物进行连续生物传感。在前期工作的基础上，该项目追求两个具体目标。 目标 1 - 使用为光学测量适体开发的现有适体设计来演示溶液相电化学适体传感器的基础物理原理。追求这一目标的理由是，利用完全表征和建模的适体将有助于快速理论上理解该项目中的新实验数据。 这一目标的产物将是至少一个适体，然后可以在目标 2 中重新设计。目标 2 - 创建一个基本原理工具集，用于修改适体设计，以实现电化学信号的最大变化。 通过在进行特定应用的工作之前展示这一基本设计工具集，第二个目标将使所有研究人员能够更快地推进溶液相电化学适体传感器的新领域。 这一目标的产品将是溶液相电化学适体传感器物理学的新知识，也是基础和应用提案后续工作的启动台，以创建可佩戴在身体上或植入的连续生物传感器该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Opportunities and challenges in the diagnostic utility of dermal interstitial fluid

真皮间质液诊断应用的机遇和挑战

• DOI: 10.1038/s41551-022-00998-9
• 发表时间: 2022-12
• 期刊: Nature Biomedical Engineering
• 影响因子: 28.1
• 作者: Friedel, Mark;Thompson, Ian A.;Kasting, Gerald;Polsky, Ronen;Cunningham, David;Soh, Hyongsok Tom;Heikenfeld, Jason
• 通讯作者: Heikenfeld, Jason

Solution-Phase Electrochemical Aptamer-Based Sensors

基于溶液相电化学适体的传感器

• DOI: 10.1109/tbme.2022.3203026
• 发表时间: 2023-03
• 期刊: IEEE Transactions on Biomedical Engineering
• 影响因子: 4.6
• 作者: Yuan, Yuchan;Bali, Ahilya;White, Ryan J.;Heikenfeld, Jason
• 通讯作者: Heikenfeld, Jason

Week-Long Operation of Electrochemical Aptamer Sensors: New Insights into Self-Assembled Monolayer Degradation Mechanisms and Solutions for Stability in Serum at Body Temperature

电化学适体传感器的为期一周的运行：对自组装单层降解机制和体温血清稳定性解决方案的新见解

• DOI: 10.1021/acssensors.2c02403
• 发表时间: 2023-03
• 期刊: ACS Sensors
• 影响因子: 8.9
• 作者: Watkins, Zach;Karajic, Aleksandar;Young, Thomas;White, Ryan;Heikenfeld, Jason
• 通讯作者: Heikenfeld, Jason

Voltammetry Peak Tracking for Longer-Lasting and Reference-Electrode-Free Electrochemical Biosensors

伏安法峰值跟踪，实现更持久且无参比电极的电化学生物传感器

• DOI: 10.3390/bios12100782
• 发表时间: 2022-10
• 期刊: Biosensors
• 作者: McHenry, Adam;Friedel, Mark;Heikenfeld, Jason
• 通讯作者: Heikenfeld, Jason