Painting and heating: A nonconventional, scalable route to sensitive biomolecular analysis with plasmon‐enhanced spectroscopy

Abstract We present a solution‐processed method of silver nanostructured layer formation over a cellulose membrane to develop a low‐cost, paper‐based surface‐enhanced Raman spectroscopy (SERS) molecular detection platform. Our synthesis method enables the formation of distinct spatial regions with controllable wettabilities for optimum analyte flow through the paper analytical device. The ink‐based coating technique ensures uniform absorption for strong and reproducible plasmonic enhancement for SERS measurements. Furthermore, the silver coating‐induced hydrophobicity leads to self‐regulation of analyte distribution over the detection area leading to uniform enhancement with reduced fluorescence interference. Through systematic measurements, we determine the optimal concentration of the silver ink precursor for plasmonic activity, which influences the electric field enhancement for the Raman spectra as well as the substrate hydrophobicity. Our findings of plasmonic activity are validated through finite‐difference time‐domain simulations that also illustrate the underexplored advantage of a cellulose membrane base in achieving hotspots in the vicinity of the plasmonic nanostructures. Using this substrate, we report label‐free SERS detection of nanomolar concentrations of P‐selectin, a key clinical marker of heparin‐induced thrombocytopaenia. The facile fabrication process combined with the control over analyte flow patterns offer significant advantages for development of paper‐based SERS analytical devices, especially for use in resource‐limited settings.