Revolutionizing Lipid Mapping: Microfluidics and Mass Spectrometry in C. elegans

Understanding the spatial distribution of fat molecules within living organisms is vital for deciphering mechanisms underlying aging, disease, and metabolism. The small, transparent nematode Caenorhabditis elegans serves as a valuable model for studying fat storage owing to its genetic similarities to humans and well-mapped anatomy. However, high-resolution visualization of lipids has historically been challenging due to its tiny size.

A groundbreaking study by researchers at Okayama University, Japan, led by Professor Masazumi Fujiwara and Ph.D. student Sara Mandic, in collaboration with Professor Ron M. A. Heeren from Maastricht University, has introduced an innovative microfluidics-based methodology that enables detailed 3D lipid imaging in C. elegans. Their approach, published in Scientific Reports on July 8, 2025, combines matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with traditional lipid staining techniques.

The process involves immobilizing young adult worms on a custom-designed microfluidic chip embedded in a gelatin–carboxymethyl cellulose matrix. The worms are then sectioned with a cryotome, with each slice analyzed through MALDI-MSI to detect specific lipid molecules. Concurrently, Oil Red O staining is applied to visualize neutral fats, confirming the lipid mapping results. This method preserves the internal structures of the organism, allowing for precise spatial localization of lipids.

According to Mandic, this is the first technique that provides such high-resolution, location-specific lipid maps within C. elegans, revealing how lipids are distributed across different tissues like the pharynx, intestine, and reproductive system. For example, a lipid associated with cholesterol metabolism was predominantly found in the pharynx and front intestine, suggesting roles in nutrient absorption.

The team extended their analysis by reconstructing three-dimensional images from stacked tissue slices, offering a comprehensive view of lipid organization throughout the entire organism. This 3D mapping revealed consistent lipid patterns across individual worms, demonstrating the method's accuracy and reproducibility.

This advanced technique enables researchers to study lipid dynamics in specific tissues, contributing significantly to biomedical research. Its applications extend to exploring effects of genetic mutations, environmental stressors, pharmaceuticals, and aging, all of which are relevant to human health. The team plans to implement this workflow in various mutant strains of C. elegans and integrate it with lipid quantification tools.

In conclusion, this pioneering methodology equips scientists with a powerful tool to visualize and analyze lipid metabolism with unprecedented precision, paving the way for deeper insights into metabolic disorders, aging processes, and disease mechanisms in humans.