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Enhancing the Flow Dynamics and Sensitivity of Paper-Based Lateral Flow Immunoassays Through Zwitterionic Antifouling
Mei-Lian Yao1, Fan-Chih Wen2, Ya-Ting Chang3
1Department of Chemical and Materials Engineering, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan.
Analytical Chemistry
|March 18, 2026
Summary
Zwitterionization of cellulose and nitrocellulose papers creates advanced anti-biofouling surfaces. This modification significantly enhances lateral flow immunoassay sensitivity and reduces non-specific binding for improved diagnostic applications.
Area of Science:
- Materials Science
- Biomedical Engineering
- Analytical Chemistry
Background:
- Biofouling impedes the efficiency of biosensing technologies, particularly lateral flow immunoassays (LFIA).
- Non-specific adsorption of biological molecules and cells reduces assay sensitivity and accuracy.
- Developing surfaces with robust anti-biofouling properties is crucial for improving LFIA performance.
Purpose of the Study:
- To impart anti-biofouling properties to cellulose and nitrocellulose papers using zwitterionization.
- To enhance antigen accessibility and improve sensing efficiency in lateral flow immunoassay technology.
- To evaluate the impact of zwitterionic modification on protein adsorption, cell adhesion, and immunoassay sensitivity.
Main Methods:
- Surface modification of cellulose paper (CP) and nitrocellulose paper (NCP) using an epoxylated zwitterionic copolymer, poly(glycidyl methacrylate-co-sulfobetaine methacrylate) (PGS).
- Characterization of surface modification using Fourier-transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS).
- Assessment of anti-biofouling properties through protein adsorption, red blood cell (RBC), bacteria (Escherichia coli), and tissue cell adhesion tests.
- Evaluation of fluid dynamics using dynamic protein transportation segmentation flow tests.
- Quantification of lateral flow immunoassay sensitivity enhancement.
Main Results:
- Successful surface modification of CP with PGS was confirmed by FT-IR and XPS.
- Zwitterionized cellulose paper (Z-CP) exhibited increased hydrophilicity, reducing vertical climb time by 35 seconds.
- Z-CP demonstrated significant resistance to protein adsorption (average 55% reduction) and reduced adhesion of RBC (89%), E. coli (77%), and tissue cells (84%).
- Modified Z-CP improved protein fluidity efficiency by 6.96 times.
- Z-CP enhanced LFIA detection sensitivity by 2-fold compared to unmodified CP.
- Zwitterionized nitrocellulose paper (Z-NCP) achieved a 10-fold increase in detection sensitivity in nanogold immunoassay lateral flow sensors compared to NCP.
Conclusions:
- Zwitterionization is an effective strategy for creating stable anti-biofouling surfaces on cellulose and nitrocellulose materials.
- The modified papers exhibit superior biocompatibility and reduced non-specific binding, crucial for biosensing applications.
- This surface engineering approach significantly boosts the sensitivity and efficiency of lateral flow immunoassays, paving the way for improved diagnostic tools.
