Library · Signals, sensing & imaging
What Mass Spectrometry Imaging got wrong, from 17 theses
Summary written by a model from the records below: Mass spectrometry imaging workflows frequently encounter physical and chemical obstacles during tissue preparation, matrix application, and on-tissue ionization. Downstream computational pipelines also struggle with low spatial signal intensities, spectral divergence across analytical platforms, and incomplete molecular annotations. These records come from graduate theses, 2021 to 2026, each labeled with its degree where the repository states it, and each links to its thesis. They were extracted by language models reading the full text, so treat each as a lead to read, not a verdict.
Plus 8 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
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Sample preparation and matrix deposition methods degrade tissue sections and disrupt spectral quality
Tissue preparation approaches like non-aromatic solvent deparaffinization, matrix sublimation under high vacuum, and cryoprotectant additives caused tissue degradation, premature matrix loss, or electrospray ablation. Matrix application workflows also suffered from low throughput, dye migration from histological stains, and chemical selectivity that introduced adducts and poor reproducibility.
Tried and failed
applying MALDI matrices for laser desorption mass spectrometry applied to ambient laser desorption mass spectrometry. Outcome: worse than baseline. Reason: caused severe chemical selectivity, abundant matrix adduct formation, and poor reproducibility
Towards single cell analysis using ambient mass spectrometry techniques · Imperial · PhD
Tried and failed
matrix sublimation for MALDI mass spectrometry imaging applied to tissue sections under high vacuum. Outcome: unstable. Reason: sample chamber heating under high vacuum caused premature matrix loss off slides via reverse sublimation
Addressing pharmacological challenges to the treatment of pediatric brain tumors using modern technology · Harvard · PhD
Tried and failed
cryoprotectant additives in tissue embedding matrix applied to desorption electrospray ionization mass spectrometry. Outcome: worse than baseline. Reason: caused lower signal intensity, altered adduct profiles, and tissue ablation under electrospray
Biochemical histology analysis of tissue samples by Desorption Electrospray Ionization (DESI) mass spectrometry imaging · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected MALDI-based mass spectrometry imaging (MSI) as a primary screening method for large candidate probiotic libraries due to multi-hour sample prep per slide, matrix optimization challenges, and low throughput.
Metabolomic Analysis of Chemical Interactions between Burkholderia thailandensis and Host to Inform Alternative Treatments · Georgia Tech · PhD
Considered and rejected
Considered and rejected: Rejected using neutral red cell staining for AP-MALDI-MS imaging because matrix spraying dispersed the dye across the insert membrane and obscured metabolic signals.
Investigating anti-tumour effects and associated metabolomic impacts of repurposed therapeutics for glioblastoma · Nottingham · PhD
Tried and failed
non-aromatic solvent deparaffinization applied to FFPE tissue mass spectrometry imaging. Outcome: worse than baseline. Reason: caused tissue section degradation and yielded inferior spectral information compared to xylene
Biochemical histology analysis of tissue samples by Desorption Electrospray Ionization (DESI) mass spectrometry imaging · Imperial · PhD
Cross-instrument spectral differences and platform shifts impair tissue classification models
Classifiers trained on mass spectrometry tissue profiles failed to generalize across instruments or sampling modalities because of spectral feature shifts and inter-instrument variance. Restricting feature sets to shared platform variables or encountering dominant background blood signals further degraded diagnostic predictive accuracy.
Tried and failed
cross-modality supervised learning without domain adaptation applied to mass spectrometry tissue classification. Outcome: did not generalise. Reason: distribution shift and spectral feature differences between differing sampling and ionization techniques
Advanced development of mass spectrometry technologies for intraoperative molecular diagnostics · UT Austin · PhD
Tried and failed
positive mode ambient ionization mass spectrometry applied to fine needle aspiration tissue classification. Outcome: worse than baseline. Reason: dominant blood triacylglycerol signals and variable alkali metal adduct splitting obscured diagnostic markers
Adapting ambient ionization mass spectrometry methods for disease characterization and tissue classification · UT Austin · PhD
Tried and failed
restricting feature selection to shared platform variables applied to mass spectrometry tissue classification models. Outcome: worse than baseline. Reason: filtering for features present across both instruments discarded predictive information, lowering classification accuracy
Advancements in ambient ionization and MALDI mass spectrometry imaging methods and their application in disease diagnosis and characterization · UT Austin · PhD
Tried and failed
mass spectrometry feature classification for sensory prediction applied to meat quality and palatability classification. Outcome: did not generalise. Reason: models failed cross-instrument validation on an off-site mass spectrometer due to inter-instrument spectral variance
Evaluating the Ability of Rapid Evaporative Ionization Mass Spectrometry to Predict the Palatability of Long Aged Beef Cuts · Texas Tech · Master's
In-source analyte fragmentation and poor desorption ionization limit detection of labile and intact molecules
Desorption electrospray and matrix-assisted laser desorption ionization led to in-source loss of fragile functional groups like phosphate and sulfate moieties. Direct on-tissue tandem analysis and intact protein imaging also failed due to unstable precursor ion abundance and inherently low ionization efficiency for large biomolecules.
Tried and failed
DESI mass spectrometry imaging applied to nucleotide di- and triphosphates detection. Outcome: no signal. Reason: in-source phosphate loss during ionization and acquisition
Using LC-MS and mass spectrometry imaging techniques to identify metabolic adaptations of breast cancer metastases to the lung · Imperial · PhD
Tried and failed
direct on-tissue tandem mass spectrometry applied to spatial tissue sections. Outcome: no signal. Reason: unstable signal and low spatial abundance of precursor ions on tissue
Mass spectrometry imaging using desorption electrospray ionisation with histological imaging to characterise the chemical composition of burned skin · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected MALDI mass spectrometry imaging for glycosaminoglycan analysis because fragile sulfate substituents dissociate without stabilization.
Development of mass spectrometry-based multi-omic methods for the study of the brain extracellular matrix · Boston University · PhD
Considered and rejected
Considered and rejected: Decided against utilizing intact protein imaging alone for endometriosis tissue profiling due to poor molecular coverage from low ionization efficiency of large intact proteins, replacing it with sequential N-glycan and on-tissue tryptic peptide imaging.
Advancements in ambient ionization and MALDI mass spectrometry imaging methods and their application in disease diagnosis and characterization · UT Austin · PhD
Tissue matrices and introduced standards trigger severe on-tissue ion suppression
Ambient desorption ionization methods applied directly to tissue sections suffered from low ionization sensitivity and strong matrix interference. Depositing or spiking internal standards directly into biological tissue matrices caused mutual ion suppression that obscured target analytes and endogenous metabolites.
Tried and failed
spiking internal standards into biological matrix applied to mass spectrometry imaging quality control. Reason: added isotope-labeled compound caused ion suppression of endogenous metabolites and lipids
Evaluation and development of reference materials to support mass spectrometry imaging of endogenous metabolites in tissue · Imperial · PhD
Tried and failed
on-tissue internal standard deposition for mass spectrometry imaging applied to metabolite detection in tissue sections. Outcome: no signal. Reason: matrix-assisted ionization suffered severe on-tissue ion suppression of the spotted metabolite standard
Evaluation and development of reference materials to support mass spectrometry imaging of endogenous metabolites in tissue · Imperial · PhD
Tried and failed
flow focusing ambient desorption ionization mass spectrometry applied to drug detection in biological tissue. Outcome: no signal. Reason: severe ion suppression and low ionization sensitivity in tissue matrices
Instrumental development of DESI imaging MS and its applications · Imperial · PhD
Low signal intensity and sparse metabolite annotation undermine spatial and statistical modeling
Spatial segmentation algorithms failed when low signal intensities from labeled features prevented distinct cluster boundary resolution. Incomplete metabolite annotation and limited sample cohorts also prevented pathway enrichment significance and degraded cross-validation accuracy.
Tried and failed
semi-supervised clustering spatial segmentation applied to mass spectrometry imaging data. Outcome: data insufficient. Reason: low signal intensities from isotope labeling prevented detailed feature resolution across segments
Advanced analyses for mass spectrometry: From atomic to molecular · Iowa State · PhD
Tried and failed
mass spectrometry imaging classification with patient-level cross-validation applied to tissue spatial lipidomics profiles. Outcome: did not generalise. Reason: small sample size led to poor clustering and reduced predictive accuracy under cross-validation
A next-generation -omics analysis of the radiotherapy response in rectal cancer · Imperial · PhD
Tried and failed
metabolite pathway enrichment analysis applied to mass spectrometry imaging data. Outcome: no signal. Reason: low annotation coverage of small polar metabolites precluded statistical pathway significance
Machine Learning Enabled Stem Cell Lipidomics · Georgia Tech · PhD
Left open by the authors
Problems the authors named and did not get to.
Left open
Develop and validate a mass spectrometry acquisition workflow combining SureQuant trigger peptides with isobaric multiplex labeling for sample multiplexing. Blocker: Requires wet lab sample preparation, isobaric mass tags (TMTpro), and a high-resolution mass spectrometer (Orbitrap Exploris 480).
Left open
Refine mass spectrometry quantification methods and evaluate lectin microarrays for high-throughput glycome profiling. Blocker: Requires mass spectrometry instruments, wet-lab facilities, and clinical samples
Mass spectrometric investigation into glycomes implicated in human reproductive biology · Imperial · PhD
Left open
Compare the quantification of monoclonal proteins using the Hevylite immunoassay against liquid chromatography-tandem mass spectrometry (LC-MS/MS). Blocker: Requires patient serum samples and wet lab LC-MS/MS equipment.
Evaluation of the Novel Hevylite Immunoassay (HLC) in the Quantification of Monoclonal Proteins in Monoclonal Gammopathies. · Harvard · Master's
Left open
Perform large-scale glycopeptide enrichment using DVA magnetic beads and systematically compare performance against standard enrichment methods using mass spectrometry. Blocker: Requires a wet lab, synthesis of DVA magnetic beads, biological samples, and mass spectrometry instrumentation.
Developing novel mass spectrometry-based approaches to globally investigate protein glycosylation · Georgia Tech · PhD
Left open
Validate DESI-MSI lipid findings using positive ionisation mode UPLC-MS on cellular extracts. Blocker: Requires wet lab facilities, tissue samples/cellular extracts, and mass spectrometry instruments
A next-generation -omics analysis of the radiotherapy response in rectal cancer · Imperial · PhD
Left open
Apply ion accumulation methods such as CASI and SIM-stitching to enhance relative isotopic abundance accuracy in DI-FT-ICR mass spectrometry. Blocker: Requires direct access to a high-field FT-ICR mass spectrometer and sample introduction apparatus.
Applications of High-resolution Mass Spectrometry and Matrix-assisted Laser Desorption/Ionization Mass Spectrometry Imaging-based Non-targeted Metabolomics in Biomarker Discovery · Georgia Tech · PhD
Left open
Perform MS/MS fragmentation to confirm putative DESI-MSI and OrbiSIMS ion annotations and resolve isobaric species in lung metastatic tissue. Blocker: Requires mass spectrometry hardware (MS/MS instrumentation, DESI-MSI, OrbiSIMS) and physical tissue samples.
Using LC-MS and mass spectrometry imaging techniques to identify metabolic adaptations of breast cancer metastases to the lung · Imperial · PhD
Left open
Perform proteomic quantification comparing One Pot PURE and commercial PURE systems to optimize translation factor ratios. Blocker: Requires wet lab access, mass spectrometry instrumentation, and cell-free protein synthesis system samples
Expanding genetic code through the introduction of non-canonical nucleobase and amino acid with novel functionality · UT Austin · PhD
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Melina Kyriazi · Imperial · PhD · 2024
Evaluation and development of reference materials to support mass spectrometry imaging of endogenous metabolites in tissue - Yulia Panina · Imperial · PhD · 2021
Using LC-MS and mass spectrometry imaging techniques to identify metabolic adaptations of breast cancer metastases to the lung - Liam Robert Poynter · Imperial · PhD · 2021
A next-generation -omics analysis of the radiotherapy response in rectal cancer - Anna Karolina Mróz · Imperial · PhD · 2021
Biochemical histology analysis of tissue samples by Desorption Electrospray Ionization (DESI) mass spectrometry imaging - Rui Chen · Nottingham · PhD · 2026
Investigating anti-tumour effects and associated metabolomic impacts of repurposed therapeutics for glioblastoma - Alexandria Van Grouw · Georgia Tech · PhD · 2025
Machine Learning Enabled Stem Cell Lipidomics - Margaret Downs · Boston University · PhD · 2025
Development of mass spectrometry-based multi-omic methods for the study of the brain extracellular matrix - Raven Lei Buckman Johnson · Iowa State · PhD · 2025
Advanced analyses for mass spectrometry: From atomic to molecular - Nicole Aiosa · Georgia Tech · PhD · 2024
Metabolomic Analysis of Chemical Interactions between Burkholderia thailandensis and Host to Inform Alternative Treatments - Linda Ibeto · Imperial · PhD · 2023
Mass spectrometric investigation into glycomes implicated in human reproductive biology - Daniel Simon · Imperial · PhD · 2023
Towards single cell analysis using ambient mass spectrometry techniques - John Chandler Sarchet · Texas Tech · Master's · 2023
Evaluating the Ability of Rapid Evaporative Ionization Mass Spectrometry to Predict the Palatability of Long Aged Beef Cuts
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