Hypersensitive Detection of Neurotransmitters in Biological Media by Optically Enhanced Benchtop NMR Spectroscopy

Abstract

Liquid-state Nuclear Magnetic Resonance (NMR) is an invaluable tool to gain atomic-resolution insights onto molecular structure and dynamics. The impact of NMR spectroscopy, however, is curtailed by high costs and hard-to-maintain high-field magnets. While low-field benchtop NMR spectrometers may address the challenge, severe trade-offs in sensitivity and resolution limit the appeal of this avenue. Here, we introduce a set of novel optically enhanced NMR pulse sequences and procedures (hyperpolarization toolkit) to readily generate 13C and 1H nuclear-spin hyperpolarization in situ on benchtop spectrometers. This approach leads to unprecedented sensitivity gains, enabling atomic-resolution conformation-dependent detection of a broad range of aromatic compounds, including clinically relevant metabolites and biomarkers. Neurotransmitters including epinephrine, serotonin and melatonin are detected at nanomolar/micromolar levels by 1D/2D photochemically-enhanced benchtop NMR in buffer and physiological media including human serum. This advance propels benchtop NMR from a predominantly pedagogical tool to a powerful bioanalytical resource for efficient neurotransmitter identification.