Flexible cotton swab modified with ZIF-67/Ag nanostructures for ultrasensitive SERS-based detection of anti-PLA2R antibody in membranous nephropathy

Surface-enhanced Raman scattering (SERS) has emerged as a powerful analytical technique for the sensitive point-of-care detection of anti-phospholipase A2 receptor antibodies (anti-PLA2R-Abs), a primary biomarker for membranous nephropathy (MN). However, conventional SERS substrates lack the integrated sample enrichment capability and flexible format required for efficient and convenient clinical analysis. To address this limitation, we hypothesized that an immersion-type flexible SERS medium based on conventional cotton swab could be developed for ultra-sensitive on-site detection of anti-PLA2R-Abs. Through a precisely controlled in-situ synthesis and a following ion sputtering, we engineered a ZIF-67/Ag nanocomposite on the nanofiber structure of a cotton swab, which combined molecular enrichment capability with dual signal enhancement mechanisms. The fibrous architecture of the cotton swab enabled highly efficient anchoring of biomarker-containing liquid samples, offering a significant advantage over silicon wafers. A substrate was yielded to exhibit not only outstanding SERS activity with an enhancement factor (EF) of 3.51 × 10 8 but also excellent uniformity and reproducibility. Using this structure, a quantitative assay of anti-PLA2R-Abs was facilitated across five orders of magnitude (1 × 10 −4 to 1 × 10 −9  mg/mL), achieving a limit of detection (LOD) as low as 0.185 ng/mL. Moreover, its diagnostic efficacy was further validated in clinical samples. This work presents a clinically viable point-of-care diagnostic platform that simplifies sample processing while significantly enhancing detection sensitivity for nephrology applications, thereby contributing to the advancement of point-of-care diagnostics.