Over the past decade, misuse of amphetamine-type stimulants has grown significantly worldwide. The high prevalence and associated morbidity and mortality of ATS abuse is now a major public health issue, with a sharp increase in overdose deaths related to ATS.[1] According to the Substance Abuse and Mental Health Services Administration, the number of people over the age of 12 misusing ATS increased from 1.7 million in 2016 to 5.1 million wordwide in 2020. Therefore, there is a growing need to the control ATS abuse.[2] The identification and classification of ATS involve a crucial step in the process of fighting against the crime of drug production, trafficking, and abuse, with ATS detection in biological specimens playing a significant role in drug screening, including of addiction, drugged driving, and monitoring of regional drug abuse.[3, 4]
Currently, oral fluid is widely accepted as an alternative specimen to urine and blood for testing of illicit drugs because it allows measurement of drug concentration levels and is easy to collect by non-medical personnel.[5, 6] Crime laboratories rely on a variety of methods to detect suspected ATS in oral fluid, including Au immunochromatographic assays, chromatography (thin-layer chromatography, liquid chromatography, and high-performance liquid chromatography), and chromatography-mass spectrometry.[7] Nevertheless, despite advances in the field, these chromatography techniques require significant time investment, human resources, and expertise as well as harmful organic solvents. Furthermore, immunological testing methods have a considerable probability of yielding false positive or false negative results.[8] Other challenges include the required sensitivity for screening to avoid true positive and false positive responses, large sample amounts needed for analysis, and the inherent attributes of various molecules. Therefore, an oral fluid-based, portable, completely automated, miniaturized, and one-touch device for illicit drug abuse screening is required.
Surface-enhanced Raman spectroscopy (SERS) is a highly surface-sensitive and selective technique that enhances Raman scattering by molecules adsorbed on rough metal surfaces or by nanostructures such as plasmonic-magnetic silica nanotubes, Au, and/or Ag nanoparticles (NPs).[9, 10] The enhanced Raman signal arises from the electromagnetic interaction of light with the metals, known as localized surface plasmon resonance.[11] The surface plasmon resonance effect is determined by the shape, size, and dielectric constants of both the metallic NPs and the surrounding material.[12] As the shape or size of NPs changes, the surface geometry changes, leading to a shift in surface electric field density. To enhance the Raman signal, the sample molecules must be adsorbed on or very close to the surface of the metal NPs. At a maximum distance between the sample and metal surface of ~ 10 nm, the SERS signal can achieve more than 8 orders of magnitude greater scattering than Raman signal. Consequently, SERS is among the most sensitive analytical techniques for the detection of low concentrations (nanogram level) of a wide range of compounds in different matrices.[13]
The identification and classification of illicit ATS in oral fluid is an issue of primary importance for forensic laboratories and practical work. To the best of our knowledge, few studies have been reported on the detection of ATS in oral fluid with SERS. Previous methods based on Au-doped and Ag-doped sol-gel substrates need a complex system of capillaries and sample pretreatment, and their reproducibility is poor. Herein, we explore a new procedure for the identification and classification of ATS in oral fluid samples with SERS specificity by employing an Si substrate coated with Ag NPs doped with trace amounts of Au nanobipyramids. The distance between ATS molecules and the metal surface was achieved through electrostatic interactions between organic cations. The results herein will provide rapid, confirmatory, and non-destructive analyses to detect ultra-traces of ATS in oral fluid and achieve a very low limit of detection (LOD) while using a relatively simple analytical approach. This approach will have practical application in the field of forensic science.