Sanggon Kim1 Yangzhi Zhu1 Leonard Apontti1 Ruoxue Yan1

1, University of California, Riverside, Riverside, California, United States

Dynamic quantitative analysis of biological molecules is indispensable to understand complex cellular processes and gain insights into disease mechanisms resulting from abnormalities of the organelles. Nanowire optical endoscopes, which utilize a nanowire waveguide to shuttle light into a target subcellular region without perturbing the outer cell membranes, hold great potentials to meet such ironclad requirements. The nanometer-sized internal light source from the waveguide to locally probe chemical environments can significantly suppress the background fluorescence, minimize photodamages and directly access subcellular regions with pL~fL sensing volumes. Combined with high-sensitivity molecular-specific SERS (Surface Enhanced Raman Spectroscopy) markers, the NW endoscope may lead to label-free, single-molecule, multiplexed sensing of target bio-species with high spatial and temporal resolution and provide a unique means of probing cellular dynamics. In this work, we report a proton-sensing SERS live-cell endoscope for the first time. By coupling excitation laser from a tapered optical fiber to a plasmonic nanowire with high crystallinity and atomically smooth surface, the laser can be delivered into the cell with a high efficiency leading to lower fluorescent background and photodamages imposed upon the cell by reducing the illumination area. In addition, the guidance of light as propagating surface plasmon polariton is diffraction-free and therefore, the reduction of the insertion volume of the probe can be fulfilled. Using an interfacial photothermal assembly method, we were able to assemble silver nanocubes, which are functionalized with a pH sensitive Raman marker to act as proton-specific, field- enhancing nano-cavity antennas, were integrated on the very tip of the nanowire waveguide. This highly integrated SERS endoscope can report intracellular pH accurately without damaging the cell membranes or perturbing normal cellular functions.