Optimization of laser induced periodic surface structures for surface enhanced Raman spectroscopy of extracellular vesicles

Gold coated laser-induced periodic surface structures (LIPSS) on stainless steel are proposed as effective substrates for surface-enhanced Raman spectroscopy (SERS). The nano-structuring of steel wafers by fem- tosecond laser pulses is achieved and optimised for use in analysing extracellular vesicles (EVs). A variety of parameters are considered - such as writing laser power, polarization, machining speed, and gold layer thick- ness - each with implications for the LIPSS morphology and, in turn, the SERS enhancement. Ultimately, the optimised nanostructure is shown to contribute an in- crease in the SERS enhancement factor of one order of magnitude. As the LIPSS are fabricated via a’one- step’ method, the proposed device reduces both cost and manufacturing time compared to industry standard techniques. The capability of machined structures in detecting extracellular vesicles (EVs) from a choriocar- cinoma cell line (JEG-3), commonly used as a model for placental syncytiotrophoblasts, is demonstrated and applications in the detection of different diseases are discussed. • Laser induced periodic surface structures are induced on stainless steel. • Subsequently, a gold thin-film is deposited for use as a Raman active surface. • Impact of nanoscale morphology on the detection of extracellular vesicles is studied. • The application of such as device to the study of extracellular vesicles is novel.