Enhancing the Flow Dynamics and Sensitivity of Paper-Based Lateral Flow Immunoassays Through Zwitterionic Antifouling Modification

This study achieved anti-biofouling properties for cellulose/nitrocellulose through zwitterionization, enabling more antigen to reach the detection site in lateral flow immunoassay (LFIA) technology and significantly improving sensing efficiency. An epoxylated zwitterionic copolymer, poly(glycidyl methacrylate-<i>co</i>-sulfobetaine methacrylate) (PGS), which exhibits excellent and stable anti-biofouling properties, was selected to modify the surface of cellulose paper (CP) and reveal anti-biofouling properties and biocompatibility. Through the characterization of chemical functional groups and element distribution in FT-IR and XPS analysis, the surface modification of P(GS) on the CP was proven successfully. As a result, the zwitterionization-cellulose paper (Z-CP) was more hydrophilic than CP so that the vertical climb time was sped up by an average of 35 s. Through the zwitterionic modification, it can resist on average 55% of the protein adsorption capacity. In addition, red blood cell (RBC), bacteria, and tissue cells attachment were tested, and the results showed that the Z-CP can reduce the adhesion of RBC by about 89%, the adhesion of <i>Escherichia coli</i> by about 77%, and the adhesion of tissue cells by about 84%. Based on the dynamic protein transportation segmentation flow test, it was proved that the modified Z-CP can improve the fluidity efficiency of protein by 6.96 times. The sensitivity results of lateral flow immunoassays showed that the detection sensitivity of Z-CP achieved 2-fold enhancement compared to the CP. In addition, in commercial nitrocellulose papers (NCP), the detection sensitivity of Z-NCP achieved 10-fold enhancement compared to the NCP in the nanogold immunoassay lateral flow sensor.