A High-Sensitive Photothermal-Readout Strategy for Commercial Lateral Flow Immunoassays with an Optical Microfiber Mach–Zehnder Interferometer

Conventional lateral flow immunoassays (LFIAs), which rely on visual interpretation for qualitative analysis, are confronted with limitations such as susceptibility to environmental interference, insufficient sensitivity, and a restricted detection range, thereby hindering its capacity to meet the growing demands of modern point-of-care diagnostics. To address this limitation, the photothermal effect, which converts analyte concentration into quantifiable temperature changes, provides LFIA platforms with enhanced sensitivity and stability. Herein, combining an optical microfiber Mach-Zehnder interferometer (mMZI) with conventional gold nanoparticle (Au NP)-based LFIA strips, a more sensitive photothermal platform (mMZI-LFIA) was engineered for quantitative measurement on LFIA. The proposed mMZI, encapsulated by the high thermo-optical coefficient polymer, exhibits excellent thermal sensitivity, enabling it to capture minute temperature variations due to localized heating generated by the Au NPs via the localized surface plasmon resonance effect. As a proof-of-concept, we employed a sandwich format LFIA for the detection of prostate-specific antigen, used as the model system. The results show high sensitivity with a detection limit (LOD) of 0.347 ng mL^-1, which was around 11.5 times more sensitive than traditional colorimetric LFIA based on Au NPs. Meanwhile, the mMZI-LFIA broadened the detection range to 0.5-256 ng mL^-1. Furthermore, to further verify the applicability of the proposed biosensor, quantitative analysis of the competitive Cr³⁺ test strips (0.195-50 ng mL^-1) also achieved LOD (0.235 ng mL^-1) improvement. In this work, the integration of optical microfibers with commercially available LFIA strips has enabled photothermal quantification in conventional LFIA without requiring additional thermal measurement equipment, significantly enhancing detection sensitivity, accuracy, and reliability, thereby offering a promising new pathway toward the development of portable photothermal LFIA systems.