Plasmon-Enhanced Light Harvesting for Improving Near-Infrared Fluorescence Detection in Blood Matrices

Abstract When organic dyes are used for fluorescence detection in blood, their signal intensity is often significantly reduced due to absorption, scattering, and quenching caused by biomolecules in the sample matrix. Our previous study has shown that shifting the detection wavelength from the visible spectrum to the near-infrared (NIR) region can alleviate these issues.1 This report further demonstrates that incorporating a plasmonic nanostructure with fluorophores can counteract NIR fluorescence attenuation in blood. Specifically, upon transitioning the sample matrix from a buffer solution to blood or plasma, the plasmonic fluorescence probes (Au nanostar@SiO2@CF750@SiO2 core@tri-shell) retain strong fluorescence signals, whereas their plasmon-free counterparts suffer significant fluorescence quenching. This difference arises because organic fluorophores alone have limited light absorption and are vulnerable to light scattering by biomolecules, while plasmonic metals act as nanoscale light antennas, which harvest light that would otherwise be scattered or transmitted out of the assay as waste, allowing for the absorbed light energy to transfer to the organic fluorophores via excitation enhancement (localized electromagnetic field enhancement) and emission enhancement mechanisms (Purcell effect). As a result, the plasmonic probe minimizes fluorescence loss in complex biological media. Taking this advantage, the plasmonic fluorescence probe and a plasma separation unit were integrated into a paper-based lateral flow strip (PLFS). As a result, the integrated PLFS can directly detect ubiquitin C-terminal hydrolase L1 (UCH-L1) from a small volume of a whole-blood sample, achieving a limit of detection of 20.0 pg/mL. This provides an effective tool for point-of-care testing of whole blood.