Metabolomics and Lipidomics: Translating ‘Molecular Distribution’ into ‘Physiological Narratives’

Metabolomics studies the types, concentrations and changes of all small-molecule metabolites within biological systems. Metabolites are downstream products of gene expression, enzymatic catalysis and environmental influences; they most closely reflect the ‘current’ physiological state of a cell or tissue and are therefore often regarded as a direct readout of the phenotype. Lipidomics is a branch of metabolomics that specialises in the study of the structure, distribution and function of lipid molecules—such as glycerides, phospholipids, sphingolipids and sterols. Lipids form the backbone of cell membranes and are also involved in signal transduction and energy storage; they are particularly crucial in research into the nervous system and tumours.

Traditional metabolomics and lipidomics predominantly involve ‘measuring total quantities after homogenisation’: the tissue is ground, extracted and injected into the analyser, yielding an average result for the entire tissue sample; spatial information is lost the moment homogenisation takes place. Yet many biological questions are precisely spatial in nature—is a particular marker concentrated in the tumour region or the normal region? Is a metabolite distributed along the veins or the margins of a leaf? These ‘where’ questions cannot be answered by homogenised analysis.

Mass spectrometry imaging is precisely the method that advances metabolomics and lipidomics from ‘averaged results’ to ‘spatial distribution results’, and this is the main area of application for Neo Source INSTRUMENT’s two imaging sources. According to data from the official website, compared with commercially available sources, the MSI DPI can detect up to a hundred additional secondary metabolites—including lipids, terpenoids, flavonoids, amino acids and glycosides—in both positive and negative ion modes, with an overall signal enhancement of 1–3 orders of magnitude. This means that a single imaging run can simultaneously localise, identify and semi-quantify a wider variety of molecules.

Specific applications span multiple fields: plant metabolism (spatial distribution of metabolites in sage, ginkgo, tea leaves, tobacco leaves, Atractylodes macrocephala, etc.), animal tissues (neurotransmitters and lipids in mouse brains, lipid biomarkers in melanocytic naevi), pharmacokinetics (distribution of drugs and metabolites across different organs at different time points), and pathological diagnosis. By comparing the spatial distribution map of molecules with H&E-stained histological images, a ‘molecular map’ can be translated into an interpretable physiological or pathological narrative. Both MSI DPI and MSI LDPI can be retrofitted onto mass spectrometers from Agilent, AB SCIEX and Thermo.