Ultrasensitive Bi‐Mode Lateral‐Flow Assay via UCNPs‐Based Host‐Guest Assembly of Fluorescent‐Colorimetric Nanoparticles

Abstract Fluorescent‐colorimetric nanoparticles (FCNPs) attract considerable interest as an emerging dual‐signal reporter for on‐site qualitative/quantitative point‐of‐care testing. However, the suboptimal signaling components and self‐assembled structure lacking physical isolation in traditional FCNPs result in low fluorescence brightness, poor stability, and strong internal filtration effect (IFE), which severely limits their wide application in lateral flow assay (LFA). Here, ordered self‐assembly for hydrophobic upconversion nanoparticles (UCNPs) is developed using 3D porous space magnetic dendritic mesoporous silica (MS), stepwise surface silanization, and polydopamine (PDA) flexible scaffold modification to fabricate MS@UCNPs@PDA (MSUD). With rational design, MSUD improves stability and luminescence intensity (131 times higher than quantum dot‐based fluorophores), and also eliminates IFE and fluorescence background interference on LFA strips. The detection limits of MSUD‐labeled LFA for qualitative and quantitative detection of methamphetamine by naked eye‐based colorimetric and smartphone‐based fluorescence strategy are 1.047 × 10 4 pg mL −1 and 47.25 pg mL −1 , ≈10‐ and 2116‐ times lower than that of gold nanoparticles‐LFA, respectively. The practicality of the MSUD‐based LFA is validated in 83 urine/hair forensic samples, with the quantitative determination results in good agreement with the liquid chromatography‐mass spectrometer data. This work presents an innovative strategy for constructing FCNPs, facilitating their progressive development and widespread applications.