Non-specific adsorption (NSA) is a persistent problem that negatively affects biosensors, decreasing sensitivity, specificity, and reproducibility. Passive and active removal methods exist to remedy this issue, by coating the surface or generating surface forces to shear away weakly adhered biomolecules, respectively. However, many surface coatings are not compatible or effective for sensing, and thus active removal methods have been developed to combat this phenomenon. This review aims to provide an overview of methods of NSA reduction in biosensing, focusing on the shift from passive methods to active methods in the past decade. Attention is focused on protein NSA, due to their common use in biosensing for biomarker diagnostics. To our knowledge, this is the first review to comprehensively discuss active NSA removal methods. Lastly, the challenges and future perspectives of NSA reduction in biosensing are discussed.
Keywords: biofouling; biosensors; non-specific adsorption; proteins; surface functionalization.