Artificially roughened gold nanoparticle arrays with tailored SERS properties for the detection of drugs in biological fluids

The fast and cheap quantitative detection of a specific analyte in such a biochemically challenging medium as the blood is an active research area and several experimental methodologies are currently envisaged to this complex task. The established clinical practice is generally based upon physical- chemical analytical methods. While High-Performance Liquid Chromatography (HPLC) certainly plays a relevant role, recently the use of spectroscopic methods based on light scattering and plasmonics (e.g. , Surface Enhanced Raman Spectroscopy–SERS) emerged as a promising and complementary approach. SERS can provide information at the molecular structure level with minimal sample preparation (compared to standard HPLC) and consistently lower times and costs. Here we introduce our results on the use of artificially corrugated, nanostructured gold substrates to quantitatively detect apomorphine (APO), a drug against Parkinson’s and Alzheimer’s diseases, and carbamazepine (CBZ), an antiepileptic drug. By using nanostructured gold substrates in a label-free dip and dry procedure we were able to detect the SERS signal of APO at 20 μg/ml (6.6×10-5M) in human plasma. The quick quantification of drug concentration in biological fluids is expected to significantly help in the clinical practice. Indeed, it would increase the capability to check for the compliance of the treatment that is mandatory information to assure a good quality of life in patients. Compared to APO, CBZ turns out to produce weaker SERS signals. This highlights the need for a careful tailoring of surface morphology of the substrate used to detect the drug. We used pulsed laser ablation (PLA) to synthesize thin gold films on glass. The technique is particularly versatile to explore ample ranges of surface morphologies by tuning deposition parameters. By nanosecond PLA in an ambient gas nanoparticles (NPs) nucleate and grow in the propagating laser-generated plasma plume. Such NPs mutually self-assemble on a substrate producing elaborated architectures of increasing thickness, with controllable morphology. Besides laser wavelength, target to substrate distance, gas nature and pressure, at fixed laser energy density the energy per pulse and the spot size strongly affect the amount of ablated matter and thus plume energetics. At landing on the substrate NP size, energy and mobility affect film growth, morphology and physico-chemical properties. Gold targets were ablated in Ar atmosphere (100 Pa), changing the pulse number (5000-20000), keeping constant target to substrate distance, incidence angle, laser wavelength and energy density. Using various substrates films made of NP arrays were deposited whose morphology ranged from individual NPs uniformly covering the glass surface, to island structures, as observed by SEM and TEM. Controlling growth parameters favours fine-tuning of NP aggregation, critical to maximize the SERS response.