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dc.contributor.authorKogler, Stian
dc.date.accessioned2020-02-05T23:45:51Z
dc.date.issued2019
dc.identifier.citationKogler, Stian. On-line “Organ-in-a-Column” Liquid Chromatography Electrospray Ionization Mass Spectrometry for Drug Metabolism Studies. Master thesis, University of Oslo, 2019
dc.identifier.urihttp://hdl.handle.net/10852/72829
dc.description.abstractOrganoids and organ-on-a-chip (OoC) are human-induced pluripotent stem cell-derived miniaturized organs that recapitulate organ specific functions. They open up a plethora of opportunities to change the way we test drugs, research diseases, and treat patients. In this context, liquid chromatography (LC) and mass spectrometry (MS) will have to be used, e.g. for monitoring drug metabolism, toxicity screens and organ function. On-line coupling of these technologies would allow for automatized, high-throughput systems. By downsizing the LC-MS part, low abundant analytes can also be determined. In this study, an on-line sampling and analysis system for OoC-technology has been developed. The system features hepatic organoids in a flow-through tube with continuous medium flow (organ-in-a-column, OiC), a two-loop valve system for sampling, reverse phase liquid chromatography (LC) analysis, and electrospray ionization mass spectrometry (ESI-MS). Phase 1 metabolism of heroin to its metabolite morphine was successfully measured on-line with the described system. Live/dead double staining revealed the potential of long-term cultivation of organoids in the system. In parallel, tin oxide coated fused silica nanoelectrospray ionization (nanoESI) emitters suitable for the most narrow bore chromatographic columns have been developed with HF etching and an atomic layer deposition (ALD) approach. The emitters have been tested against commercially available stainless steel (SS) emitters by injections of heroin and showed similar signal-to-noise ratios. These emitters will find a use in a future miniaturized version of the system described herein. In summary, a proof-of-concept system for on-line measurement of heroin metabolites has successfully been developed for a simple OoC-like device. NanoESI emitters for the most narrow columns have also been developed with a conductive ALD-coating of SnO2.eng
dc.language.isoeng
dc.subjectorgan on a chip
dc.subjectatomic layer deposition
dc.subjectnanoLC
dc.subjectorganoids
dc.subjectliquid chromatography
dc.subjectmass spectrometry
dc.subjectorgan-on-a-chip
dc.subjectmetabolism
dc.subjectdrug studies on-line system
dc.subjectonline system
dc.titleOn-line “Organ-in-a-Column” Liquid Chromatography Electrospray Ionization Mass Spectrometry for Drug Metabolism Studieseng
dc.typeMaster thesis
dc.date.updated2020-02-05T23:45:50Z
dc.creator.authorKogler, Stian
dc.date.embargoenddate2022-10-30
dc.rights.termsUtsatt tilgjengeliggjøring: Kun forskere og studenter kan få innsyn i dokumentet. Tilgangskode/Access code B
dc.identifier.urnURN:NBN:no-75955
dc.type.documentMasteroppgave
dc.rights.accessrightsembargoedaccess
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/72829/1/Masteroppgave.pdf


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