Document Type



Doctor of Philosophy (PhD)


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First Advisor's Name

Francisco Fernandez-Lima

First Advisor's Committee Title

Committee chair

Second Advisor's Name

Jeremy W. Chambers

Second Advisor's Committee Title

Committee member

Third Advisor's Name

Piero Gardinali

Third Advisor's Committee Title

Committee member

Fourth Advisor's Name

Anthony DeCaprio

Fourth Advisor's Committee Title

Committee member

Fifth Advisor's Name

Bruce McCord

Fifth Advisor's Committee Title

Committee member


Mass spectrometry, ion mobility, biological samples

Date of Defense



There is a need for fast, accurate and cost-effective protocols capable of assessing biomolecules at the molecular level (e.g., proteins, lipids and metabolites) from biological specimens. Mass spectrometry (MS) based techniques have become the analytical gold standard for identification and characterization of biomarkers in biological samples. The high throughput and short analysis time scales enables to follow biological processes while providing detailed chemical and spatial characterization. One of the current challenges in biological MS, is the high molecular complexity, chemical diversity and dynamic range. In this dissertation, the use of multi-modal mass spectrometry workflows -mass spectrometry imaging and ion mobility spectrometry - enables the untargeted and targeted analysis of biomolecules. The performance of mass spectrometry imaging techniques such as TOF-SIMS and MALDI-FTICR MS was evaluated for the spatial characterization of lipids, a chemotherapeutic drug agent, and neuropeptides. The orthogonality between ambient sampling liquid extraction surface analysis (LESA), ion mobility spectrometry and mass spectrometry (LESA-IMS-MS) was evaluated for the detection of small molecules from complex biological samples, such as common biological organs (e.g., liver, brain, and skin) and three-dimensional multicellular spheroid (MCS) models of cancer cell lines. This dissertation showcases the development of new workflows that integrate ambient sampling with complementary gas-phase post-ionization separation techniques to study complex biological samples.



Previously Published In

Haler, J.; Sisley, E.; Cintron-Diaz, Y.; Meitei, S.; Cooper, H.; Fernandez-Lima, F., Workflow for fast lipid screening using LESA-FT-ICR-MS. Anal Methods, 2019, 11, 2385. DOI: 10.1039/c8ay02739k

Cintron-Diaz, Y.; Acanda de la Rocha, A.; Castellanos, A.; Chambers, J.; and Fernandez-Lima, F., Mapping chemotherapeutic drug distribution in cancer cell spheroids using 2D-TOF-SIMS and LESA-TIMS-MS. Analyst, 2020, DOI: 10.1039/C9AN02245G

K. Jeanne Dit Fouque, M. Wellmann, D. Leyva Bombuse, M. Santos-Fernandez, Y. L. Cintron-Diaz, M. E. Gomez-Hernandez, D. Kaplan, V. G. Voinov and F. Fernandez-Lima, Effective Discrimination of Gas-Phase Peptide Conformers using TIMS-ECD-ToF MS/MS. Analytical Methods (accepted for publication on 10-18-2021)



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