Surface-enhanced Raman spectroscopy (SERS) is a rapidly emerging technology that offers a fast, extremely sensitive, and quantitative approach to trace chemical detection. Such a technique incorporated into a portable device is attractive to law enforcement and emergency room personnel for rapid accurate on-site screening of illicit and abused drugs. Toward this, we are developing an analyzer in a hand-held unit, based on SERS that is integrated with a capillary sensor embedded with activated gold nanoparticles in a porous glass matrix. In this preliminary study, we have used this gold sol-gel capillary to measure aqueous solutions of 14 high-priority drugs to define sensitivity (lowest measured concentration [LMC] and estimated limit of detection [LOD]), determine concentration dependence and quantification capabilities by constructing calibration curves, examine effects of pH at 3, 7, and 11 on SERS measurements, and perform multicomponent analysis of fentanyl laced drug mixtures and spectral identification on our portable and handheld units. Of particular significance, fentanyl was detected with an LMC of 1 ng/ml and estimated LOD at 0.11 ng/ml, while other representative drugs such as cocaine and phenylcyclidine produced LMCs and LODs at 5.0 and 0.77 ng/ml, and 10.0 and 0.62 ng/ml, respectively. These sub-nanogram per milliliter detection limits are comparable or lower than previously reported and confirm that this gold sol-gel has the potential to meet the sensitivity requirements for saliva analysis. Most importantly, these sensors can be manufactured easily and cheaply and when integrated with our portable Raman units produce highquality spectra and accurate identification within 1.2 s.drug detection, drugs of abuse, illicit drugs, SERS, surface-enhanced Raman | INTRODUCTIONThe unabated use of illicit and abused drugs, including stimulants such as cocaine, methamphetamine, MDMA, and opioids such as heroin, methadone, and fentanyl, and to a lesser extent hallucinogens such as PCP, continue to represent a major health problem on a global scale. The World Health Organization (WHO) in 2021

We used surface-enhanced Raman spectroscopy (SERS) for the rapid and sensitive detection and quantification of caffeine in solution. Such a technique incorporated into a portable device is finding wide applications in trace chemical analysis in various fields, including law enforcement, medicine, environmental monitoring, and food quality control. To realize such applications, we are currently developing portable and handheld trace chemical analyzers based on SERS, which are integrated with a sensor embedded with activated gold nanoparticles in a porous glass matrix. In this study, we used this gold SERS-active substrate to measure aqueous solutions of the drug caffeine as a test chemical to benchmark sensor performance by defining sensitivity (lowest measured concentration (LMC) and estimated limit of detection (LOD)), determining concentration dependence and quantification capabilities by constructing calibration curves; by evaluating the effects of pH values of 3, 7, and 11; and by examining the reproducibility of the SERS measurements. The results demonstrate that the SERS sensor is sensitive, with caffeine detected at an LMC of 50 parts per billion (ppb) with an LOD of 0.63 ppb. The results further show that the sensor is very stable and can be used to make reproducible measurements, even under extremely acidic to basic pH conditions. Vibrational assignments of all observed SERS peaks are made and reported for the first time for caffeine on a gold substrate.