Plasmonic and electrostatic interactions enable uniformly-enhanced liquid bacterial surface-enhanced Raman scattering (SERS).

Surface-enhanced Raman spectroscopy (SERS) is a promising cellular identification and drug susceptibility testing platform, provided it can be performed in a controlled liquid environment that maintains cell viability. We investigate bacterial liquid-SERS, studying plasmonic and electrostatic interactions between gold nanorods and bacteria that enable uniformly-enhanced SERS. We synthesize five nanorod sizes with longitudinal plasmon resonances ranging from 670-860 nm and characterize SERS signatures of Gram-negative Escherichia coli and Serratia marcescens, and Gram-positive Staphylococcus aureus and Staphylococcus epidermidis bacteria in water. Varying the concentration of bacteria and nanorods, we achieve large-area SERS enhancement that is independent of nanorod resonance and bacteria type; however, bacteria with higher surface charge density exhibit significantly higher SERS signal. Using cryo-electron microscopy and zeta potential measurements, we show that higher signal results from attraction between positively-charged nanorods and negatively-charged bacteria. Our robust liquid-SERS measurements provide a foundation for bacterial identification and drug testing in biological fluids.