In Pursuit of Zero 2.0: Recent Developments in Nonfouling Polymer Brushes for Immunoassays

“Nonfouling” polymer brush surfaces can greatly improve the performance of in vitro diagnostic (IVD) assays due to the reduction of nonspecific protein adsorption and consequent improvement of signal‐to‐noise ratios. The development of synthetic polymer brush architectures that suppress adventitious protein adsorption is reviewed, and their integration into surface plasmon resonance and fluorescent sandwich immunoassay formats is discussed. Also, highlighted is a novel, self‐contained immunoassay platform (the D4 assay) that transforms time‐consuming laboratory‐based assays into a user‐friendly and point‐of‐care format with a sensitivity and specificity comparable or better than standard enzyme‐linked immunosorbent assay (ELISA) directly from unprocessed samples. These advancements clearly demonstrate the utility of nonfouling polymer brushes as a substrate for ultrasensitive and robust diagnostic assays that may be suitable for clinical testing, in field and laboratory settings. The development of nonfouling polymer brush surfaces has ushered in a new wave of in vitro diagnostic (IVD) tests. Polymer brushes eliminate nonspecific protein adsorption to the surface and thus enable ultrasensitive detection of proteins directly from complex biological milieu. Diagnostic platforms capable of point‐of‐care testing are highlighted.