Department of Electrical Engineering, Stanford University, Stanford, CA, 94305, USA.
Department of Radiology, Stanford University, Stanford, CA, 94305, USA.
Adv Sci (Weinh). 2021 Dec;8(23):e2102495. doi: 10.1002/advs.202102495. Epub 2021 Oct 19.
Electrochemical biosensors hold the exciting potential to integrate molecular detection with signal processing and wireless communication in a miniaturized, low-cost system. However, as electrochemical biosensors are miniaturized to the micrometer scale, their signal-to-noise ratio degrades and reduces their utility for molecular diagnostics. Studies have reported that nanostructured electrodes can improve electrochemical biosensor signals, but since the underlying mechanism remains poorly understood, it remains difficult to fully exploit this phenomenon to improve biosensor performance. In this work, electrochemical aptamer biosensors on nanoporous electrode are optimized to achieve improved sensitivity by tuning pore size, probe density, and electrochemical measurement parameters. Further, a novel mechanism in which electron transfer is physically accelerated within nanostructured electrodes due to reduced charge screening, resulting in enhanced sensitivity is proposed and experimentally validated. In concert with the increased surface areas achieved with this platform, this newly identified effect can yield an up to 24-fold increase in signal level and nearly fourfold lower limit of detection relative to planar electrodes with the same footprint. Importantly, this strategy can be generalized to virtually any electrochemical aptamer sensor, enabling sensitive detection in applications where miniaturization is a necessity, and should likewise prove broadly applicable for improving electrochemical biosensor performance in general.
电化学生物传感器具有将分子检测与信号处理和无线通信集成在一个小型化、低成本系统中的巨大潜力。然而，随着电化学生物传感器缩小到微米级，其信噪比降低，限制了它们在分子诊断中的应用。研究表明，纳米结构电极可以改善电化学生物传感器的信号，但由于其潜在机制仍未得到充分理解，因此仍然难以充分利用这一现象来提高生物传感器的性能。在这项工作中，通过调整孔径、探针密度和电化学测量参数，对纳米多孔电极上的电化学适体生物传感器进行了优化，以实现灵敏度的提高。此外，还提出并实验验证了一种新的机制，即在纳米结构电极中，由于电荷屏蔽的减少，电子转移在物理上得到加速，从而提高了灵敏度。与具有相同足迹的平面电极相比，这种新的效应可以使信号水平提高 24 倍，检测限降低近 4 倍，而平台表面积的增加则可以实现这一效果。重要的是，这种策略可以推广到几乎任何电化学适体传感器，从而能够在需要小型化的应用中进行灵敏检测，并且同样可以普遍适用于提高一般电化学生物传感器的性能。
