Advances in spectroscopic studies have enabled an enriched understanding of small biological molecules. Recently, these molecules have been studied in the gas phase, free from the interaction of other molecules. The focus of this study is to apply and optimize laser desorption jet-cooling spectroscopy in order to study the intrinsic properties of biological molecules. However, a challenge with this technique has been shot-to-shot variability in the instrument. In attempts to obtain a more stable signal in the instrument various laser desorption substrates were explored. Additionally, fine-tuning gas-phase spectroscopy has the potential to lead to a broad study of biological molecules along with their controlled interactions with various solvents. This innovative technique may provide a deeper insight towards their biological activity as well as the involvement of small biological molecules in early prebiotic scenarios.