Anti-Fouling Polymer or Peptide-Modified Electrochemical Biosensors for Improved Biosensing in Complex Media

Electrochemical biosensing represents a highly effective technology for detecting disease biomarkers given its high sensitivity, low and clinically relevant limit of detection, and cost effectiveness. However, in complex media such as urine, blood, sweat or saliva, biosensing performance can be significantly impacted by electrode biofouling by proteins, cells, lipids, and other matrix components. Such biofouling leads to reduced signal from the target analyte coupled with an elevated background signal, resulting in poor signal-to-noise ratios (SNRs), reduced sensitivity, and lower specificity. This comprehensive review describes the design of anti-fouling polymers and peptides as a potential solution to prevent or suppress electrochemical biosensor fouling. Various anti-fouling polymers and peptides developed for improved biosensing in complex media are summarized in the context of their mechanism(s) of anti-fouling, methods of deposition, and practical applications. Recent advances and persistent challenges in the field are also reviewed to provide perspectives on new directions toward enhancing anti-fouling in electrochemical biosensors.