Nuclear Magnetic Resonance 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, whereby averaging is performed over a volume significantly larger than a single cell, or require the invasion of the organism, or an arrested state of the organism. Nuclear magnetic resonance (NMR) is an inherently noninvasive chemometric and imaging method, and hence, in principle, suitable for metabolomic measurements. The digital twin of metabolomics is computational systems biology, such that NMR microscopy is potentially a viable approach to joining the theoretical and experimental explorations of the metabolomic and behavioural responses of organisms. In this study, we consider the challenge of performing in vivo NMRbased metabolomics on the small organism Caenorhabditis elegans, point the way towards possible solutions created using techniques specific to micro-electromechanical systems (MEMS) fabrication, and highlight currently insurmountable challenges.