TY - JOUR
T1 - "Organ-in-a-column" coupled on-line with liquid chromatography-mass spectrometry
AU - Kogler, Stan
AU - Aizenshtadt, Aleksandra
AU - Harrison, Sean
AU - Skottvoll, Froydis Sved
AU - Berg, Henriette Engen
AU - Abadpour, Shadab
AU - Scholz, Hanne
AU - Sullivan, Gareth
AU - Thiede, Bernd
AU - Lundanes, Elsa
AU - Bogen, Inger Lise
AU - Krauss, Stefan
AU - Roberg-Larsen, Hanne
AU - Wilson, Steven Ray
N1 - Funding: This work was supported by the Research Council of Norway through its Centre of Excellence scheme, project number 262613, and project number 295910 (National Network of Advanced Proteomics Infrastructure). Support was also provided by UiO:Life Science and the Olav Thon Foundation.
PY - 2022/12/20
Y1 - 2022/12/20
N2 - 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.
AB - 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.
U2 - 10.1021/acs.analchem.2c04530
DO - 10.1021/acs.analchem.2c04530
M3 - Article
C2 - 36484723
SN - 0003-2700
VL - 94
SP - 17677
EP - 17684
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 50
ER -