Recent progress in surface-enhanced Raman spectroscopy for biological and biomedical applications: from cells to clinics.

The application of surface-enhanced Raman spectroscopy (SERS) in biological and biomedical detection schemes is feasible due to its excellent molecular specificity and high sensitivity as well as the capability of SERS to be performed in complex biological compositions. SERS-based investigation of cells, which are the basic structure and functional unit of organisms, represents the starting point of this review. It is demonstrated that SERS provides a deep understanding of living cells as well as their microenvironment which is needed to assess the development of diseases. The clinical relevance of SERS is proved by its application for the detection of cancer cells and tumour margins under in vivo conditions and examples for theranostic approaches are discussed. This review article provides a comprehensive overview of the recent progress within the last 3 years.

Surface-enhanced Raman spectroscopy and microfluidic platforms: challenges, solutions and potential applications.

The exhaustive body of literature published in the last four years on the development and application of systems based on surface-enhanced Raman spectroscopy (SERS) combined with microfluidic devices demonstrates that this research field is a current hot topic. This synergy, also referred to as lab-on-a-chip SERS (LoC-SERS) or nano/micro-optofluidics SERS, has opened the door for new opportunities where both techniques can profit. On the one hand, SERS measurements are considerably improved because the processes previously performed on a large scale in the laboratory and prone to human error can now be carried out in nanoliter volumes in an automatic and reproducible manner; on the other hand, microfluidic platforms need detection methods able to sense in small volumes and therefore, SERS is ideal for this task. The present review not only aims to provide the reader an overview of the recent developments and advancements in this field, but it also addresses the key aspects of fundamental SERS theory that influence the interpretation of SERS spectra, as well as the challenges brought about by the experimental conditions and chemometric data analysis.

Droplet based microfluidics: spectroscopic characterization of levofloxacin and its SERS detection.

Levofloxacin (Levo), a second generation fluoroquinolone, has both clinical and environmental relevance. Therefore, the implementation of fast, robust and cost effective techniques for its monitoring is required. Here, its spectroscopic characterization and its detection in aqueous environment were carried out using surface enhanced Raman spectroscopy combined with droplet based microfluidics. The Levo molecule interacts with the silver nanoparticles via the carboxylate group and it adopts an upright or slightly tilted orientation. Furthermore, it is shown that the presence of Cl(-) ions has a strong influence on the enhancement efficiency of the Raman signal of the target molecule. Thus, for the determination of the limit of detection (LOD) the measurements were carried out in the absence of any electrolytes. The estimated LOD is ∼0.8 µM and the linear dynamic window ranges between 1-15 µM. These results were achieved after the normalization of the SERS signal to the Raman mode at 230 cm(-1). This band was attributed to the ν(Ag-O) stretching and it accounts for the Levo molecules in the first layer on the Ag nanoparticles.

The effect of silver thickness on the enhancement of polymer based SERS substrates.

We investigated silver-covered polymer based nanogratings as substrates for surface-enhanced Raman spectroscopy (SERS), in particular with respect to the thickness of the plasmonically active silver film. In order to obtain accurate geometrical input data for the simulation process, we inspected cross sections of the gratings prepared by breaking at cryogenic temperature. We noticed a strong dependence of the simulation results on geometrical variations of the structures. Measurements revealed that an increasing silver film thickness on top of the nanogratings leads to a blue shift of the plasmonic resonance, as predicted by numerical simulations, as well as to an increased field enhancement for an excitation at 488 nm. We found a clear deviation of the experimental data compared to the simulated results for very thin silver films due to an island-like growth at a silver thickness below 20 nm. In order to investigate the SERS activity. we carried out measurements with crystal violet as a model analyte at an excitation wavelength of 488 nm. The SERS enhancement increases up to a silver thickness of about 30 nm, whereas it remains nearly constant for thicker silver films.