Abstract

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 NMR-based metabolomics on the small organism Caenorhabditis elegans, point he way towards possible solutions created using techniques specific to micro-electromechanical systems (MEMS) fabrication, and highlight currently insurmountable challenges.

Highlights

  • Metabolomics is the study of the molecules of life, as expressed by the reagents and products of biochemical reactions taking place within the cells of a living organism

  • Nuclear magnetic resonance (NMR) signals of small samples can be detected in numerous ways, including variously arranged microcoil resonators, stripline resonators, superconducting quantum interference devices (SQUIDs), magnetic resonance force microscopy probes, and nitrogen vacancy centres in diamond

  • In order to assess future solution strategies, the current limit of detection that is preventing the in vivo metabolomic monitoring of C. elegans requires qualification

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Summary

Introduction

Metabolomics is the study of the molecules of life, as expressed by the reagents and products of biochemical reactions taking place within the cells of a living organism. An organism metabolome is a time-dependent fingerprint of the state of a cell, and full knowledge of the metabolome would, in principle, reveal many cellular-level upstream mechanisms that form part of the omic chain (genomics, transcriptomics, proteomics, and so on), and link them with downstream behavioural responses. Nuclear magnetic resonance (NMR) is a noninvasive alternative to mass spectroscopy for extracting detailed information about the metabolic composition of a target sample. The worms can be maintained at −80 °C and revived

NMR Signal Strength in the Context of Metabolomics
Types of NMR Experiments
Signal-to-noise Ratio of Microdetectors
Signal Detection
Signal Enhancement
Signal Localisation Using Strong Gradients
Mixture Analysis
Findings
Conclusions
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