Advanced Nanoparticle-Based Labels for Lateral Flow Immunoassays

Abstract

Lateral flow immunoassays (LFIAs) are among the most common tools used in point-of-care testing. However, conventional gold nanoparticle labels often lack the sensitivity needed to detect low-abundance biomarkers. To overcome this limitation, new nanomaterials have been developed to improve LFIA performance, but comparative evaluation of individual labels is lacking. Therefore, this study provides a systematic comparison of standard gold nanoparticles, gold nanoshells (AuNSs), and photon-upconversion nanoparticles (UCNPs) with different surface chemistries. The best-performing labels, AuNSs and polyacrylic acid-modified Tm-doped UCNPs (PAA-Tm UCNPs), were then used to detect human serum albumin (HSA) in urine and prostate-specific antigen (PSA) in serum. These analytes serve as biomarkers for kidney damage and prostate cancer, respectively. AuNSs showed high sensitivity in buffer tests; however, their performance in serum was affected by aggregation, resulting in highly variable recoveries of 30–216% for PSA-spiked serum. Conversely, PAA-Tm UCNPs exhibited high colloidal stability and maintained strong analytical performance in biological samples. The optimized UCNP-based LFIA achieved limits of detection of 63 pg mL−1 for HSA in urine and 34 pg mL−1 for PSA in serum. Additionally, the UCNP platform enabled PSA quantitation with high trueness, yielding recoveries of 82–119% in spiked serum. These findings emphasize the importance of label selection and surface-engineering strategy in developing more reliable clinical diagnostic tests.