Au nanoparticle-based sensor for apomorphine detection in plasma

Artificially roughened gold surfaces with controlled nanostructure produced by pulsed laser deposition have been investigated as sensors for apomorphine detection aiming at clinical application. The use of such gold surfaces has been optimized using aqueous solutions of apomorphine in the concentration range between 3.3 × 10−4 M and 3.3 × 10−7 M. The experimental parameters have been investigated and the dynamic concentration range of the sensor has been assessed by the selection of two apomorphine surface enhanced Raman scattering (SERS) peaks. The sensor behavior used to detect apomorphine in unfiltered human blood plasma is presented and discussed

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

Synthesis by pulsed laser ablation of 2D nanostructures for advanced biomedical sensing

Au nanoparticle arrays with controlled nanostructure were produced by pulsed laser ablation on glass. Such substrates were optimized for biomedical sensing by means of SERS keeping fixed all process parameters but the laser pulse (LP) number that is a key deposition parameter. It allows to fine-tune the Au surface nanostructure with a considerable improvement in the SERS response towards the detection of apomorphine in blood serum (3.3 × 10-6 M), when LP number is increased from 1 × 104 to 2 × 104. This result is the starting point to correlate the intensity of selected SERS signals of apomorphine to its concentration in the blood of patients with Parkinson's disease

Un metodo spettroscopico per la quantificazione di farmaci in fluidi biologici

Viene discussa una tecnica spettroscopica innovativa per determinare la concentrazione di farmaci in fluidi biologici. Introduciamo il contesto dei farmaci caratterizzati da un ristretto indice terapeutico in relazione all'epilessia e al morbo di Parkinson. Ricapitoliamo quindi gli elementi essenziali della spettroscopia Raman e dell’intensificazione del segnale per effetto dell’interazione di un analita con una superficie metallica corrugata alla scala nanometrica. L'ottimizzazione dell'intensifi- cazione dello spettro di un dato analita dipende dalla scelta del metallo e dai dettagli nanostrutturali della sua superficie. Consideriamo in dettaglio la sintesi di superfici di metalli nobili condotta mediante ablazione laser pulsata in gas inerte ad alta pres- sione. Mostriamo quindi il comportamento spettroscopico di queste superfici per determinare la concentrazione di farmaci in diversi fluidi, incluso il sangue umano. Consideriamo in particolare la carbamazepina (un farmaco antiepilettico ampiamente adottato nei Paesi in via di sviluppo) e l’apomorfina (un farmaco usato per il tratta- mento di pazienti affetti dal morbo di Parkinson)

Laser-Synthesized SERS Substrates as Sensors toward Therapeutic Drug Monitoring

The synthesis by pulsed laser ablation and the characterization of both the surface nanostructure and the optical properties of noble metal nanoparticle-based substrates used in Surface Enhanced Raman Spectroscopy are discussed with reference to application in the detection of anti-epileptic drugs. Results on two representative drugs, namely Carbamazepine and Perampanel, are critically addressed

Laser tailored nanoparticle arrays to detect molecules at dilute concentration

By nanosecond pulsed laser ablation in an ambient gas gold nanoparticles (NPs) were produced that self-assemble on a substrate resulting in increasingly elaborated architectures of growing thickness, from isolated NP arrays up to percolated films. NPs nucleate and grow in the plasma plume propagating through the gas. Process parameters including laser wavelength, laser energy density, target to substrate distance, nature and pressure of the gas affect plasma expansion, thus asymptotic NP size and kinetic energy. NP size, energy and mobility at landing determine film growth and morphology that affect the physico-chemical properties of the film. Keeping fixed the other process parameters, we discuss the sensitive dependence of film surface nanostructure on Ar pressure and on laser pulse number. The initial plume velocity and average ablated mass per pulse allow predicting the asymptotic NP size. The control of growth parameters favors fine-tuning of NP aggregation, relevant to plasmonics to get optimized substrates for surface enhanced Raman spectroscopy (SERS). Their behavior is discussed for testing conditions of interest for clinical application. Both in aqueous and in biological solutions we obtained good sensitivity and reproducibility of the SERS signals for the anti-Parkinson drug apomorphine, and for the anti-epilepsy drug carbamazepine