“Organ-in-a-Column” Coupled On-line with Liquid Chromatography-Mass Spectrometry

Organoids, i.e.,
laboratory-grown organ models developed from stem
cells, are emerging tools for studying organ physiology, disease modeling,
and drug development. On-line analysis of organoids with mass spectrometry
would provide analytical versatility and automation. To achieve these
features with robust hardware, we have loaded liquid chromatography
column housings with induced pluripotent stem cell (iPSC) derived
liver organoids and coupled the “organ-in-a-column”
units on-line with liquid chromatography-mass spectrometry (LC-MS).
Liver organoids were coloaded with glass beads to achieve an even
distribution of organoids throughout the column while preventing clogging.
The liver organoids were interrogated “on column” with
heroin, followed by on-line monitoring of the drug’s phase
1 metabolism. Enzymatic metabolism of heroin produced in the “organ-in-a-column”
units was detected and monitored using a triple quadrupole MS instrument,
serving as a proof-of-concept for on-line coupling of liver organoids
and mass spectrometry. Taken together, the technology allows direct
integration of liver organoids with LC-MS, allowing selective and
automated tracking of drug metabolism over time.