Tetrahydrocannabinol Sensing in Complex Biofluid with Portable Raman Spectrometer Using Diatomaceous SERS Substrates

Using thin-layer chromatography in tandem with surface-enhanced Raman spectroscopy (TLC-SERS) and tetrahydrocannabinol (THC) sensing in complex biological fluids is successfully conducted with a portable Raman spectrometer. Both THC and THC metabolites are detected from the biofluid of marijuana-users as biomarkers for identifying cannabis exposure. In this article, ultra-sensitive SERS substrates based on diatomaceous earth integrated with gold nanoparticles (Au NPs) were employed to detect trace levels of cannabis biomarkers in saliva. Strong characteristic THC and THC metabolite SERS peaks at 1601 and 1681 cm^-1 were obtained despite the moderate interference of biological molecules native to saliva. Urine samples were also analyzed, but they required TLC separation of THC from the urine sample to eliminate the strong influence of urea and other organic molecules. TLC separation of THC from the urine was performed by porous microfluidic channel devices using diatomaceous earth as the stationary phase. The experimental results showed clear separation between urea and THC, and strong THC SERS characteristic peaks. Principal component analysis (PCA) was used to analyze the SERS spectra collected from various THC samples. The spectra in the principal component space were well clustered for each sample type and share very similar scores in the main principal component (PC1), which can serve as the benchmark for THC sensing from complex SERS spectra. Therefore, we proved that portable Raman spectrometers can enable an on-site sensing capability using diatomaceous SERS substrates to detect THC in real biological solutions. This portable THC sensing technology will play pivotal roles in forensic analysis, medical diagnosis, and public health.