Organoids, Organ-on-a-Chip, and the Case for Online LC–MS

Organoid and organ-on-a-chip models have become a growing part of how researchers study human biology without relying solely on animal models or standard cell lines. For an audience built around separation science, they also raise a very practical question: how do you actually analyze something this small and this complex? LCGC International spoke with Steven Ray Wilson of the University of Oslo about both halves of that story—what these models are, and why analyzing them is so demanding.^1,2

Wilson describes organoids as miniature, lab-grown organ structures built from a patient's own cells or from a group of patients, capable of reproducing select functions of the organs they model. Researchers use them to test drugs and toxicity in a system that behaves more like real human tissue than conventional cell culture. Placed on microfluidic devices—platforms that move fluid through the tissue to mimic circulation or organ-to-organ interaction—those same organoids become what researchers call an organ-on-a-chip system, opening the door to high-throughput analyses for personalized medicine that are directly relevant to human biology rather than extrapolated from animal data.

That same scale is also the challenge. Organoid samples can be millimeter-sized for a single organoid, which immediately raises sensitivity issues for whatever method is measuring them, while the samples themselves sit in a complex mixture rather than a clean, isolated matrix. Wilson pointed to the cell culture media surrounding the organoids as an example, describing it as functioning like the blood of these miniature organ systems. His group's response has been to minimize manual sample prep steps and move toward online, automated workflows ahead of liquid chromatography–mass spectrometry (LC–MS) analysis, which protects data quality on samples that can't be easily replaced, and, as a side benefit, cuts plastic consumption: one of the group's current platforms uses only one-twentieth of the plastic of a conventional approach.

Wilson answered the following questions:

• Why are organoids and organ-on-a-chip models important, and what exactly does organ-on-a-chip mean?
• What are the main analytical challenges these models present compared with conventional biological samples?
• Why is online sample preparation coupled to LC–MS particularly suited to these small and complex samples?

References

1. Wilson, S. R. H. Liquid Chromatography, Organoids, and Organ-on-a-Chip: An Update. Presented at ISC 2026, in Prague, Czech Republic. https://www.czech-in.org/cmPortalv15/Searchable/isc26/config/normal#!sessionschedule (accessed 2026-09-18).
2. Wilson, S. R. H.; Røberg-Larsen, H.; Matheson, A. Self-Cleaning LC–MS in Organoid/Organ-on-Chip Systems for Small Molecule Analysis. The Column 2024, 20 (8), 2–4.