Rapid Detection of Drugs of Abuse in Saliva Using Surface Enhanced Raman Spectroscopy and Microfluidics

Abstract

We present a microfluidic device that detects trace concentrations of drugs of abuse in saliva within minutes using surface-enhanced Raman spectroscopy (SERS). Its operation is demonstrated using methamphetamine. The detection scheme exploits concentration gradients of chemicals, fostered by the laminar flow in the device, to control the interactions between the analyte, silver nanoparticles (Ag-NPs), and a salt. Also, since all species interact while advecting downstream, the relevant reaction coordinates occur with respect to the position in the channel. The system was designed to allow the analyte first to diffuse into the side stream containing the Ag-NPs, on which it is allowed to adsorb, before salt ions are introduced, causing the Ag-NPs to aggregate, and so creating species with strong SERS signal. The device allows partial separation via diffusion of the analyte from the complex mixture. Also, the reproducible salt-induced NP aggregation decouples the aggregation reaction (necessary for strong SERS) from the analyte concentration or charge. This method enables the creation of a region where detection of the analyte of interest via SERS is optimal, and dramatically extends the classes of molecules and quality of signals that can be measured using SERS, compared to bulk solution methods. The spatial distribution of the SERS signals was used to map the degree of nanoparticle aggregation and species diffusion in the channel, which, together with numerical simulations, was used to describe the kinetics of the colloid aggregation reaction, and to determine the optimal location in the channel for SERS interrogation.

Quantitative detection of codeine in human plasma using surface-enhanced Raman scattering via adaptation of the isotopic labelling principle

“…28 Andreou et al also reported the detection of methamphet-amine in saliva samples using a microfluidic device which controlled the interaction between the drug, Ag nanoparticles, and the aggregation agent. 29 Finally, in a more recent study, we have also demonstrated SERS as a powerful technique for the quantitative detection of the beta-blocker propranolol in human biofluids (serum, plasma, urine) when combined with chemometric approaches. 30 However, the application of SERS for the detection and quantification of drugs in complex biological media can face several challenges, most notably the reproducibility, accuracy and repeatability of the SERS signal which could be due to ran-domly distributed hot spots which occur during sample ana-lysis.…”

Methodologies for assessment of limit of detection and limit of identification using surface-enhanced Raman spectroscopy

“…As the number of analytes increases, it is appropriate to introduce selectivity in the SERS methodology, which commonly is supported by powerful algorithms and chemometric based analyses. A remaining challenge is to introduce sufficient selectivity to resolve signals from an interfering matrix, as for example for drugs in saliva [16][17][18] or antibiotic substances [19] and nicotine [20] in urine. The first step towards this goal is to obtain SERS substrates that are giving rise to reliable, reproducible and satisfying detection limits in the analytical set-up.…”

Magnetically optimized SERS assay for rapid detection of trace drug-related biomarkers in saliva and fingerprints

“…For testing narcotics at home, commercial drug-screening products are available using the Marquis reagent and a similar colorimetric reaction. However, this method requires specialized reactants, large sample volumes and is open to misinterpretation due to subjective color perception (Andreou et al, 2013). These disadvantages prompt the investigation of rapid and on-site assays for monitoring trace level drugs in biological fluids.…”