Bakestani Rose Mery, Wu Yuyang, Glahn-Martínez Bettina, Kippin Tod E, Plaxco Kevin W, Kolkman Ruben W
Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, California 93106, United States.
Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense de Madrid, 28040 Madrid, Spain.
ACS Appl Mater Interfaces. 2025 Feb 5;17(5):8706-8714. doi: 10.1021/acsami.4c21790. Epub 2025 Jan 22.
Electrochemical aptamer-based (EAB) sensors are a molecular measurement platform that enables the continuous, real-time measurement of a wide range of drugs and biomarkers in situ in the living body. EAB sensors are fabricated by depositing a thiol-modified, target-binding aptamer on the surface of a gold electrode, followed by backfilling with an alkanethiol to form a self-assembled monolayer. And while the majority of previously described EAB sensors have employed hydroxyl-terminated monolayers, a handful of studies have shown that altering the monolayer headgroup can strongly affect sensor performance. Here, using 4 different EAB sensors, we show that the mixed monolayers composed of mixtures of 6-carbon hydroxyl-terminated thiols and varying amounts of either 6- or 8-carbon, carboxylate-terminated thiols lead to improved EAB sensor performance. Specifically, the use of such mixed monolayers enhances the signal gain (the relative change in the signal seen upon target addition) for all tested sensors, often by several fold, both in buffer and whole blood at room temperature or physiological temperatures. Moreover, these improvements in gain are achieved without significant changes in the aptamer affinity or the stability of the resulting sensors. In addition to proving a ready means of improving EAB sensor performance, these results suggest that exploration of the chemistry of the electrode surface employed in such sensors could prove to be a fruitful means of advancing this unique in vivo sensing technology.
基于电化学适配体的（EAB）传感器是一种分子测量平台，能够在活体中对多种药物和生物标志物进行连续、实时的原位测量。EAB传感器是通过将硫醇修饰的、与目标结合的适配体沉积在金电极表面，然后用链烷硫醇回填以形成自组装单分子层来制造的。虽然之前描述的大多数EAB传感器都采用了羟基封端的单分子层，但一些研究表明，改变单分子层的头基会强烈影响传感器性能。在这里，我们使用4种不同的EAB传感器表明，由6碳羟基封端硫醇与不同量的6碳或8碳羧酸盐封端硫醇的混合物组成的混合单分子层可提高EAB传感器性能。具体而言，使用这种混合单分子层可增强所有测试传感器的信号增益（添加目标后信号的相对变化），在室温或生理温度下的缓冲液和全血中，增益通常会提高几倍。此外，在适配体亲和力或所得传感器稳定性没有显著变化的情况下实现了增益的这些改善。除了提供一种改善EAB传感器性能的现成方法外，这些结果还表明，探索此类传感器中使用的电极表面化学可能是推进这种独特的体内传感技术的富有成效的方法。
