Exploring Differential Electron Transfer Kinetics of Electrochemical Aptamer-Based Sensors to Achieve Calibration-Free Measurements

Abstract

Due to fabrication variation (i.e., device-to-device differences in the total number of probes immobilized on their electrode), electrochemical aptamer-based (EAB) sensors generally require calibration, reducing their convenience. In response, here, we describe an approach for achieving calibration-free EAB measurement relying on the differential electron transfer kinetics between target-bound and -unbound states using a square wave voltammetry technique. Specifically, by adjusting the amplitude and frequency of the potential wave, we generate a voltammetric output with two distinct current peaks, which are representative of signals probed from different electron transfer kinetics. The ratio of these two peaks provides a means of correcting the sensor-to-sensor fabrication variation. Using this approach, we demonstrate accurate, calibration-free measurements of multiple small molecules (e.g., kanamycin, ATP, and doxorubicin) and proteins (e.g., thrombin) in whole blood.