Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94304, United States.
ACS Nano. 2023 Mar 28;17(6):5632-5643. doi: 10.1021/acsnano.2c11618. Epub 2023 Mar 13.
The development of , longitudinal, real-time monitoring devices is an essential step toward continuous, precision health monitoring. Molecularly imprinted polymers (MIPs) are popular sensor capture agents that are more robust than antibodies and have been used for sensors, drug delivery, affinity separations, assays, and solid-phase extraction. However, MIP sensors are typically limited to one-time use due to their high binding affinity (>10 M) and slow-release kinetics (<10 μM/sec). To overcome this challenge, current research has focused on stimuli-responsive MIPs (SR-MIPs), which undergo a conformational change induced by external stimuli to reverse molecular binding, requiring additional chemicals or outside stimuli. Here, we demonstrate fully reversible MIP sensors based on electrostatic repulsion. Once the target analyte is bound within a thin film MIP on an electrode, a small electrical potential successfully releases the bound molecules, enabling repeated, accurate measurements. We demonstrate an electrostatically refreshed dopamine sensor with a 760 pM limit of detection, linear response profile, and accuracy even after 30 sensing-release cycles. These sensors could repeatedly detect <1 nM dopamine released from PC-12 cells , demonstrating they can longitudinally measure low concentrations in complex biological environments without clogging. Our work provides a simple and effective strategy for enhancing the use of MIPs-based biosensors for all charged molecules in continuous, real-time health monitoring and other sensing applications.
开发能够进行纵向、实时监测的设备是实现连续、精准健康监测的重要步骤。分子印迹聚合物（MIP）是一种常用的传感器捕捉剂，其稳定性优于抗体，已被用于传感器、药物输送、亲和分离、分析和固相萃取等领域。然而，由于 MIP 传感器的高结合亲和力（>10 M）和缓慢释放动力学（<10 μM/秒），它们通常仅限于一次性使用。为了克服这一挑战，目前的研究集中在对刺激有响应的 MIP（SR-MIP）上，这些 MIP 会在外来刺激下发生构象变化，从而逆转分子结合，这需要额外的化学物质或外部刺激。在这里，我们展示了基于静电斥力的完全可重复使用的 MIP 传感器。一旦目标分析物在电极上的薄膜 MIP 中被结合，一个小的电势就可以成功释放结合的分子，从而实现重复、准确的测量。我们展示了一种基于静电再生的多巴胺传感器，其检测限为 760 pM，具有线性响应曲线，即使经过 30 次传感-释放循环，其准确性也不受影响。这些传感器可以重复检测到 PC-12 细胞释放的<1 nM 多巴胺，表明它们可以在不堵塞的情况下，在复杂的生物环境中对低浓度物质进行长期监测。我们的工作为增强基于 MIP 的生物传感器在连续、实时健康监测和其他传感应用中对所有带电分子的应用提供了一种简单而有效的策略。
