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

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，尽管在人类医学的更广泛领域有许多迫切的需求，但这是一个孤立的成功。葡萄糖监测仍然是一个孤立的成功，因为葡萄糖传感器是基于酶的，除了代谢物（例如葡萄糖，乳酸盐，乙醇）之外，开发分析物可能具有挑战性。另一类称为电化学适体传感器的传感器更容易开发用于葡萄糖以外的分析物（激素，药物，蛋白质），但适体传感器尚未证明大多数医疗应用所需的使用寿命，并且通常在灵敏度上有限制。这些寿命和灵敏度方面的挑战，至少在一定程度上是因为必须在电极表面组装并保留一层完美的适体。该项目将展示和探索一种基于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，允许适配体在溶液中自由漂浮，当分析物与适配体结合时，适配体以电极可测量的方式改变形状。液相电化学适体传感器将在以下方面提供显著优势：(1)由于其简单性而具有突破性的寿命和稳健性；(2)由于其高度可调的物理特性而提高了灵敏度。该项目与实现个性化医疗的目标一致，通过创建一种新的生物传感器方法，允许对人类健康和医学中的激素、肽、治疗药物和其他标记物进行连续的生物传感。在前期工作的基础上，本项目追求两个具体目标。目的1 -演示使用现有的光学测量适体设计的溶液相电化学适体传感器的基本物理原理。追求这一目标的基本原理是利用充分表征和建模的适体将允许在这个项目中对新的实验数据进行快速的理论理解。这个目标的产物将至少是一个适配体，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，用于修改适合体设计，以实现电化学信号的最大变化。通过在从事特定应用工作之前展示这种基本设计工具集，第二个目标将使所有研究人员能够更快地推进液相电化学适体传感器的新领域。这一目标的产物将是液相电化学适体传感器物理学的新知识，以及在基础和应用建议方面的后续工作的发射台，以创建可穿戴在身体上或植入体内的连续生物传感器。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.