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Miniaturized metabolomics methods for enabling the study of biomass-restricted samples
This thesis investigated miniaturized mass spectrometry (MS)-based analytical methods to address challenges in analyzing biomass-restricted biological samples. Conventional MS techniques often require large sample volumes, limiting their applicability in non-invasive sampling studies. To overcome this, the research focused on establishing micro-flow liquid chromatography-mass spectrometry (micro-flow LC-MS) and sheathless capillary electrophoresis-mass spectrometry (CE-MS) methods, tailoring workflows for the analysis of biomass-restricted samples.
Micro-flow LC-MS was applied to analyze endocannabinoids and oxylipins, utilizing various ionization sources to enhance sensitivity and robustness. The use of low flow rates in these workflows significantly improved ionization efficiency, enabling the analysis of human cerebrospinal fluid and plasma using minimal sample volumes. For polar and charged metabolites such as creatinine, a sheathless CE-MS method was developed,...
Show moreThis thesis investigated miniaturized mass spectrometry (MS)-based analytical methods to address challenges in analyzing biomass-restricted biological samples. Conventional MS techniques often require large sample volumes, limiting their applicability in non-invasive sampling studies. To overcome this, the research focused on establishing micro-flow liquid chromatography-mass spectrometry (micro-flow LC-MS) and sheathless capillary electrophoresis-mass spectrometry (CE-MS) methods, tailoring workflows for the analysis of biomass-restricted samples.
Micro-flow LC-MS was applied to analyze endocannabinoids and oxylipins, utilizing various ionization sources to enhance sensitivity and robustness. The use of low flow rates in these workflows significantly improved ionization efficiency, enabling the analysis of human cerebrospinal fluid and plasma using minimal sample volumes. For polar and charged metabolites such as creatinine, a sheathless CE-MS method was developed, demonstrating high sensitivity and suitability for neonatal healthcare with only 5 µL of plasma.
Throughout the thesis, these miniaturized methods were validated through clinical applications, revealing significant improvements in detection sensitivity, method robustness, and biological insight. The final chapter emphasized the transformative potential of integrating miniaturized analytical techniques with efficient sample handling and microsampling devices, enabling advanced metabolomics and clinical research using biomass-restricted specimens.
- All authors
- He, B.
- Supervisor
- Hankemeier, T.; Ramautar, R.
- Co-supervisor
- Harms, A.C.
- Committee
- Irth, H.; Lange, E.C.M. de; Stelt, M. van der; Dominguez-Vega, E.; Chen, D.Y.; Vreeken, R.J.
- Qualification
- Doctor (dr.)
- Awarding Institution
- Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
- Date
- 2025-05-01
- ISBN (print)
- 9789493289772