Ultrasensitive\nRapid Antigen Test by Geometric Lateral\nFlow Assays and Highly Doped Upconversion Nanoparticles

The paper-based lateral flow assay (LFA) testing strips\nare currently\nthe most widely used for point-of-care testing (POCT), valued for\ntheir rapid result turnaround times in a few minutes. However, their\nsensitivity has been limited. Upconversion nanoparticles (UCNPs),\nespecially highly doped ones, have emerged as promising luminescent\nreporters to enhance the LFA sensitivity. These UCNPs exhibit a nonlinear\nenhancement in luminescence with excitation power density, necessitating\nhigher power densities for higher brightness. In this study, we utilized\na geometric paper strip design to minimize the immune reaction area\nand maximize the excitation power density, enabling ultrasensitive\ndetection of the SARS-CoV-2 nucleoprotein antigen. This design also\nslowed the antigen flow on the paper strip, extending the reaction\ntime between antigen and antibody, thereby enhancing the efficiency\nof the immune reaction. Through this design, our approach achieved\nover a 100-fold enhancement in the limit of detection (LOD) compared\nwith the widely used LFAs, based on gold colloidal nanoparticles and\neuropium nanoparticles. This innovation expands the scope of LFA applications\nthat require a low LOD.