NMR microscopy for in vivo metabolomics, digitally twinned by computational systems biology, needs a sensitivity boost

The metabolism of an organism is regulated at the cellular level, yet is strongly influenced by its environment. The precise metabolomic study of living organisms is currently hampered by measurement sensitivity: most metabolomic measurement techniques involve some compromise, in that averaging is performed over a volume significantly larger than a single cell, or require invasion of the organism, or arrest the state of the organism. NMR is an inherently non-invasive chemometric and imaging method, and hence in principle suitable for metabolomic measurements. The digital twin of metabolomics is computational systems biology, so that NMR microscopy is potentially a viable approach with which to join the theoretical and experimental exploration of the metabolomic and behavioural response of organisms. This prospect paper considers the challenge of performing in vivo NMR-based metabolomics on the small organism C. elegans, points the way towards possible solutions created using MEMS techniques, and highlights currently insurmountable challenges.