Nanophotonic structures can enhance light-mater interaction at nanoscales helping to improve the detection sensitivity of biosensors. In this work, we present a sandwich-type immunosensor by combining a nanophotonic resonant waveguide grating (RWG) structure and upconverting nanoparticles (UCNPs). UCNPs are used to label a target biomarker captured by capture antibody molecules immobilized on the surface of the RWG structure, which is used to enhance the upconversion fluorescence (UCF) of UCNPs through excitation resonance. The immunosensor has an extremely low limit of detection (LOD) in sub-fg/mL level and a detection range of six orders of magnitude and can be used to detect a variety of biomarkers such as cardiac troponin I, tau protein and phosphated-tau protein, etc. The LOD of the immunosensor is greatly reduced due to the increased UCF of UCNPs and the reduction of nonspecific adsorption of detection antibody-conjugated UCNPs on the RWG substrate surface.
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