Design and testing of aptamer-based electrochemical biosensors for proteins and small molecules

The fabrication of aptamer-based electrochemical biosensors as an emerging technology has made the detection of small and macromolecular analytes easier, faster, and more suited for the ongoing transition from fundamental analytical science to the early detection of protein biomarkers. Aptamers are synthetic oligonucleotides that have undergone iterative rounds of in vitro selection for binding with high affinity to specific analytes of choice; a sensitive yet simple method to utilize aptamers as recognition entities for the development of biosensors is to transduce the signal electrochemically. In this review article, we attempt to summarize the state-of-the-art research progresses that have been published in recent years; in particular, we focus on the electrochemical biosensors that incorporate aptamers for sensing small organic molecules and proteins. Based on differences in the design of the DNA/RNA-modified electrodes, we classify aptamer-based electrochemical sensors into three categories, for which the analyte detection relies on: (a) configurational change, i.e., the analyte binding induces either an assembly or dissociation of the sensor construct; (b) conformational change, i.e., the analyte binding induces an alteration in the conformation (folding) of the surface immobilized aptamer strands; and (c) conductivity change, i.e., the analyte binding "switches on" the conductivity of the surface-bound aptamer-DNA constructs. In each section, we will discuss the performance of these novel biosensors with representative examples reported in recent literature.