Nanodome coins for intracellular surface-enhanced Raman spectroscopy

Surface-enhanced Raman spectroscopy offers a tremendous potential for intracellular sensing, because it combines fingerprint specificity with sensitive signals. However, the colloidal gold nanoparticles used for this purpose lead to strong spatiotemporal variations in intracellular SERS experiments. This unpredictable behaviour, which complicates reproducible measurements, strongly contrasts to the advances made in the last decades on the fabrication of controllable and robust plasmonic substrates with high enhancement factors. Here, we propose an alternative approach to intracellular SERS by developing planar, nanostructured microcoins which enable to use top-down fabricated substrates for intracellular applications. We develop a nanosphere-lithography based technique for the fabrication of gold-nanotriangle and -nanodome structured silicon-nitride micron-sized chips (micro-coins). These microcoins can be lifted off form their substrate and are subsequently incorporated into fibroblast- and HeLa cells. In a model experiment, the SERS sensors are used for the label-free detection of extraneous molecules in live cells. The use of reproducible SERS substrates for intracellular sensing is expected to be an important step towards reproducible and quantitative live-cell, label-free measurements.