Liver organoids, mass spectrometry, and separation science

Abstract

Organoids are predicted to change the future of medicine by acting as an in vitro 3D representation of human organ functionality. Organoids are grown from patient derived stem cells or adult tissue, which promise to enable new and faster drug discovery, disease modeling and personalized medicine under more realistic conditions. Organoids are still at the developmental stage and fundamental questions concerning the functionality of the developed organoids remain to be answered. Compared to other biosampling techniques, mass spectrometry (MS) has rarely been used in organoid analyses. This thesis leverages MS and separation science to analyze the biological properties of liver organoids, spanning from protein identification to small molecule drug metabolite detection. With the aim of developing selective, high throughput analyses and online biosampling integration, both conventional and cutting edge electromembrane extraction (EME) sample preparation approaches were explored.

Using bioanalytical tools including MS and separation science, we could establish that the liver organoids displayed liver organ functionality. The bioanalytical strategies we developed for liver organoid analyses contribute to greater insight into organoid response and functionality and could be important tools in future organoid development. Furthermore, online organoid integration using electromembrane extraction developed here could be used as a starting point towards developing future organ-on-a-chip systems integrated with mass spectrometry, which would be valuable in drug development, disease modeling, and personalized medicine.