Label-free electrochemical biosensing leverages the advantages of label-free techniques, low cost, and fewer user steps, with the sensitivity and portability of electrochemical analysis. In this review, we identify four label-free electrochemical biosensing mechanisms: (a) blocking the electrode surface, (b) allowing greater access to the electrode surface, (c) changing the intercalation or electrostatic affinity of a redox probe to a biorecognition unit, and (d) modulating ion or electron transport properties due to conformational and surface charge changes. Each mechanism is described, recent advancements are summarized, and relative advantages and disadvantages of the techniques are discussed. Furthermore, two avenues for gaining further diagnostic information from label-free electrochemical biosensors, through multiplex analysis and incorporating machine learning, are examined.
Keywords: analytical chemistry; biosensing; diagnostics; disease detection; electrochemistry; label-free.