Single-cell imaging and metabolic heterogeneity

Spatial resolution determines how finely an image can be resolved. MSI DPI ranges from 20 to 200 μm (at the tissue level), whilst MSI LDPI reaches 2–3 μm and, when optimised for hippocampal tissue, can reach 4 μm—a scale approaching that of a single cell, making ‘single-cell-scale imaging’ possible. Cells are the fundamental units of life; many pathological and physiological changes first occur at the cellular level, and tissue homogenisation analysis tends to ‘average out’ these differences.

Metabolic heterogeneity refers to the non-uniform composition and abundance of metabolites across different cells or regions within the same tissue. For example, in melanoma tissue, the distribution of metabolites differs between the stratum corneum, the granular layer, the tumour region and normal tissue, revealing metabolic differences within the tumour microenvironment; in the mouse hippocampus, the spatial distribution of various metabolic molecules across different subregions can be distinguished, correlating with their physiological functions (such as the functional roles of cholesterol in the hippocampus). High-resolution imaging preserves spatial information, enabling researchers to see ‘what is present where, and where it is abundant or scarce’, rather than merely an averaged total.

Two imaging sources from New Source utilise non-polar discrimination and highly sensitive photochemical ionisation to visualise lipids, neurotransmitters, vitamins, amino acids, sugars and other substances at the subcellular scale. The list of detectable substances on the official website includes: histamine, adenosine, choline, adenine, vitamin D₃, cholesterol, glutamate, threonine, guanine, ceramides, and various lipids (fatty acids, PE, PA, MAG, DG, HexCer, GalCer, etc.). Metabolic imaging at the single-cell scale provides a crucial tool for cutting-edge research in life sciences, environmental toxicology and plant metabolism, where ‘localisation, identification and quantification’ are required.

In practical applications, this capability has been utilised to analyse metabolic heterogeneity in the melanoma microenvironment, to image metabolites in specific regions of the mouse hippocampus (in conjunction with brain science), and to study the molecular distribution in unconventional samples such as fossils, lacquerware and the retina. Its significance lies not merely in ‘capturing finer-resolution images’, but in enabling metabolic information to be correlated with morphology at the single-cell level for the first time—when combined with H&E histological staining or immunohistochemistry, molecular images and histological maps can be cross-validated within the same field of view. MSI DPI and MSI LDPI are compatible with Agilent, AB SCIEX and Thermo mass spectrometers.