Library · Biology & lab methods
What Gas & Liquid Chromatography (GC-MS/HPLC) got wrong, from 17 theses
Summary written by a model from the records below: The evaluated chromatographic records demonstrate recurring operational challenges that range from column fouling and severe detection limits to slow analysis speeds. Researchers frequently encountered sample matrix interferences, ionization suppression, and inadequate retention that forced the abandonment or redesign of chromatographic workflows. These records come from graduate theses, 2021 to 2025, 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 10 problems the authors left open, listed at the end.
Failure modes, by theses reporting them
Select a mode to jump to its records.
Chromatography methods suffered from slow throughput and could not track fast reaction kinetics
Standard chromatography and spectrometry techniques were abandoned or rejected because long run times and sample destruction significantly reduced overall experimental throughput. These methods also required ex situ sampling and were unable to monitor transient chemical reaction kinetics in real time.
Considered and rejected
Considered and rejected: Rejected gas chromatography–mass spectrometry (GC/MS) as the primary analytical method due to sample destruction, higher cost, and longer run time per sample.
Dacian Use of Roman Imports and the Preservation of Identity: A FTIR Spectroscopic Survey of Ceramic Residues from Four Sites in Braşov County, Transylvania, Romania · University at Buffalo · PhD
Tried and failed
radioactivity- or conductivity-based chromatography and TLC applied to high-throughput lipid quantitative relative profiling. Outcome: too slow. Reason: unsuited for high-throughput quantitative profiling compared to modified ELISA and mass spectrometry methods
A lipidomic approach to elucidating the effects of antifungal compounds on signalling in fungi · Imperial · Doctorate
Considered and rejected
Considered and rejected: Rejected direct gas chromatography (GC), HPLC, and NMR for operando product tracking due to their inability to capture transient reaction kinetics in real time.
ADVANCING ELECTROCATALYSIS WITH ATOMISTIC INSIGHTS AND OPERANDO METHODS · Cornell · PhD
Columns suffered physical degradation, fouling, and aging over repeated use
Chromatography columns experienced clogging, irreversible fouling, and physical damage when exposed to complex matrices containing polymerized sugars, lipophilic compounds, or slime coat constituents. Reused and aged columns also exhibited severe retention time shifts, loss of peak resolution, and baseline drift over time.
Tried and failed
direct thermal desorption gas chromatography-mass spectrometry applied to sugar-rich headspace gas samples. Outcome: unstable. Reason: volatile sugar polymerization upon heating overloaded and damaged the chromatography column
Assessing the microbiome mediated augmented volatile organic compounds response in oesophagogastric cancer · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected setting up a post-hoc calibration curve years later for GC-MS quantification due to column aging, baseline drift, and retention time shift over time.
Non-invasive testing for the diagnosis and assessment of colorectal cancer and adenomatous polyps · Imperial · Doctorate
Considered and rejected
Considered and rejected: Abandoned HPLC for ethanol quantification due to repeated sequence stoppages/column blockage (hypothesised to be caused by cyanobacterial slime coat constituents), switching to a 96-well microtiter enzymatic assay.
Engineered solar-driven recycling systems for sustainable fertilisation · Imperial · PhD
Considered and rejected
Considered and rejected: Rejected direct semi-preparative HPLC on crude methanol extracts because lipophilic and polysaccharide contaminants foul and irreversibly damage RP-HPLC columns.
Microcystins as Lead Structures for Anticancer Agents · Tübingen · PhD
Lost to a baseline
Flash chromatography C18 cartridges suffered from severe retention time shifts and loss of resolution upon reuse compared to fresh columns or Sephadex LH-20.
Microcystins as Lead Structures for Anticancer Agents · Tübingen · PhD
Analytical detection limits and detector sensitivity were insufficient for trace target compounds
Chromatographic setups failed to quantify trace compounds because analyte concentrations fell below analytical detection limits or generated insufficient peak area. Alternative detector configurations and capillary systems lacked the sensitivity required to distinguish trace analyte signals from baseline noise.
Considered and rejected
Considered and rejected: Rejected capillary liquid chromatography (CLC) for the analysis of ionizable and polar PFAS due to poor sensitivity compared to HPLC.
Environmental Monitoring of Per-and Polyfluoroalkyl Substances Using Microextraction Methodologies · University at Buffalo · PhD
Tried and failed
thermal desorption gas chromatography-mass spectrometry applied to trace polar volatile organic compounds. Outcome: no signal. Reason: insufficient peak area and poor detection sensitivity for highly polar short-chain volatile compounds
Breath analysis for the non-invasive assessment of colorectal cancer · Imperial · Doctorate
Tried and failed
thermal conductivity detection applied to micro gas chromatography analyte detection. Outcome: no signal. Reason: detector sensitivity was insufficient, leaving analytes indistinguishable from baseline noise
Modular GC: A Fully Integrated Micro Gas Chromatography System · Virginia Tech · Master's
Tried and failed
targeted liquid chromatography mass spectrometry screening applied to trace contaminants in drinking water. Outcome: no signal. Reason: analyte concentrations were below the analytical detection limit in point-of-use samples
Occurrence of Per- and Polyfluoroalkyl Substances (PFAS) in Private Water Supplies in Southwest Virginia · Virginia Tech · Master's
Mobile phase additives, solvent handling, and background contamination interfered with mass spectrometry detection
Hyphenated chromatography mass spectrometry workflows failed when required chromatographic buffers suppressed analyte ionization or solvent dilution steps distorted quantitative measurements. Systems were also compromised by background instrument contamination showing up across blank samples and matrix effects requiring derivatization.
Considered and rejected
Considered and rejected: Rejected gas chromatography (GC) due to the requirement of chemical derivatization for thermal stability and higher susceptibility to matrix effects compared to LC-MS/MS.
Evaluación e Impacto de la Presencia de Filtros Ultravioleta Orgánicos por Actividades Antropogénicas en el Medio Marino Costero · University of Las Palmas de Gran Canaria · PhD
Tried and failed
reversed-phase liquid chromatography-mass spectrometry applied to polymer degradation product detection. Outcome: no signal. Reason: the required chromatographic buffer inhibited ionization in mass spectrometry
Engineering the workhorse of biology : the future of protein engineering in three polypeptides · UT Austin · PhD
Tried and failed
solvent dilution before liquid chromatography mass spectrometry applied to trace aqueous analyte quantification. Reason: interfered with analyte concentration quantification in LC-MS
Tire Wear Particle Characterization and PFAS Adsorption · UT Austin
Inadequate retention and excessive thermal ramping compromised peak resolution and purity
Polar chemical standards eluted prematurely near the void volume without establishing adequate retention on chromatographic stationary phases. High thermal ramping rates and heavy matrix interferences further caused detector oversaturation, poor chromatographic peak resolution, and failed sample purification.
Tried and failed
hydrophilic interaction liquid chromatography gradient applied to polar chemical standard mixtures. Reason: analytes eluted prematurely near the void volume within four minutes without adequate chromatographic retention
Evaluation of Chemicals of Emerging Concern and Their Sub-Lethal Biological Effects in Environmental Waters Using Targeted and Non-Targeted Mass-Spectrometry-Based Analyses · University at Buffalo · PhD
Tried and failed
Single-step extraction chromatography purification applied to Low-concentration analyte in complex geological matrices. Reason: Failed to achieve required chemical purity due to severe matrix interference in trace samples
Uncovering Geochemical Evidence for the Moon's High-energy Giant-impact Origin · Harvard · PhD
Tried and failed
fast temperature ramp gas chromatography applied to volatile organic compound profiling. Reason: rapid thermal ramping caused severe detector oversaturation and poor chromatographic peak resolution
Urinary volatile organic compound analysis: a complete methodology for global profiling and application to pancreatic cancer · Imperial · PhD
Left open by the authors
Problems the authors named and did not get to.
Left open
Apply LC-MS to determine organic contaminant degradation pathways and radical-induced pathogen inactivation mechanisms during UV/peroxyacid treatment. Blocker: Requires wet lab facilities, liquid chromatography-mass spectrometry (LC-MS) instrumentation, and chemical/biological samples
Evaluating Peroxyacid and UV/Peroxyacid Disinfection: Pathogen Inactivation, Byproduct Formation, and Co-Removal Of Micropollutants · Georgia Tech · PhD
Left open
Investigate kinetics of Diels-Alder polymer solvolysis and dissolution at low temperatures using gel permeation chromatography to track fragmentation sizes. Blocker: Requires wet lab facilities, polymer synthesis, and GPC equipment
Development Of A High-Performance Reversible Crosslink Epoxy Composite By Using Diels Alder Chemistry · Georgia Tech · 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
Optimize UPLC-MS/MS chromatography for lysophosphatidic acid species using ACQUITY Premier BEH Amide HST columns to reduce peak tailing. Blocker: Requires a wet chemistry laboratory with UPLC-MS/MS equipment, analytical standards, and specialized chromatography columns
A novel quantification method of lysophosphatidic acid and the role of autotaxin/Lysophosphatidic acid axis in acute-on-chronic liver failure · Imperial · PhD
Left open
Develop an extraction and secondary chromatographic method using polar sorbents or anion exchange resins to retain short-chain PFAS analytes. Blocker: Requires an analytical chemistry wet lab, chromatography equipment, and chemical standards.
Evaluating "Forever Chemicals" from Soup to Nuts: Sample Preparation, Targeted Analysis, and Suspect Screening for the Characterization of Per- and Polyfluoroalkyl Substances (PFAS · University at Buffalo · PhD
Left open
Implement on-column Raman spectroscopy through a pressure-resistant sapphire window for step-by-step scan imaging of resin beads under flow conditions. Blocker: Requires specialized physical wet-lab chromatography equipment and a high-pressure sapphire optical cell
Monitoring of biotherapeutic purification by vibrational spectroscopy · Imperial · Doctorate
Left open
Pack functionalized fibrous silica particles into shorter HPLC columns and measure pressure differences and analysis times. Blocker: Requires a wet chemistry laboratory, chemical synthesis equipment, and HPLC instrumentation to pack and test physical columns.
Evaluation of Fibrous Silica Particles for Chromatographic Applications and the Analysis of Human-Derived Biofluids by HPLC and Capillary Electrophoresis · University at Buffalo · PhD
Left open
Use gas chromatography or ion mobility spectrometry to resolve structural isomers and identify RO2 tracer species in VOC oxidation experiments. Blocker: Requires a physical experimental chamber and advanced analytical chemistry instruments (GC, IMS).
Left open
Perform gas chromatography on fermented coffee bean samples to identify predominant volatile compounds and correlate them with sensory attributes. Blocker: Requires physical fermented coffee samples and a gas chromatography lab apparatus
Fermentation of coffee beans with common brewing/winemaking yeast strains for novel flavor properties · Cornell · Master's
Left open
Develop a gas chromatography-mass spectrometry (GC/MS) analytical method to directly identify atmospheric reactive mercury chemical species. Blocker: Requires a physical analytical chemistry laboratory, GC/MS instrumentation, chemical standards, and atmospheric sampling access.
Improvements to the Measurement of Atmospheric Reactive Mercury, and Contributions to the Investigation of Reactive Mercury at Six Sampling Sites · University of Nevada, Reno · Master's
Who has worked on this
Authors of the public theses cited on this page, most-cited first.
- Julia Moschny · Tübingen · PhD · 2021
Microcystins as Lead Structures for Anticancer Agents - Lesly Joanne Franco Deloya · MIT · PhD · 2025
Comprehensive laboratory studies of organic oxidation across a range of photochemical ages and peroxy radical conditions - Aghogho Olomukoro · University at Buffalo · PhD · 2025
Environmental Monitoring of Per-and Polyfluoroalkyl Substances Using Microextraction Methodologies - Hairuo Fu · Harvard · PhD · 2024
Uncovering Geochemical Evidence for the Moon's High-energy Giant-impact Origin - Noora Kano · Imperial · PhD · 2024
A novel quantification method of lysophosphatidic acid and the role of autotaxin/Lysophosphatidic acid axis in acute-on-chronic liver failure - Junyue Wang · Georgia Tech · PhD · 2024
Evaluating Peroxyacid and UV/Peroxyacid Disinfection: Pathogen Inactivation, Byproduct Formation, and Co-Removal Of Micropollutants - Marine Valton · Imperial · PhD · 2023
Engineered solar-driven recycling systems for sustainable fertilisation - James Beattie · Imperial · Doctorate · 2023
Monitoring of biotherapeutic purification by vibrational spectroscopy - Darren Poltorak · University at Buffalo · PhD · 2023
Dacian Use of Roman Imports and the Preservation of Identity: A FTIR Spectroscopic Survey of Ceramic Residues from Four Sites in Braşov County, Transylvania, Romania - Kathleen A. Hohweiler · Virginia Tech · Master's · 2023
Occurrence of Per- and Polyfluoroalkyl Substances (PFAS) in Private Water Supplies in Southwest Virginia - Laura Brunelle · University at Buffalo · PhD · 2023
Evaluation of Chemicals of Emerging Concern and Their Sub-Lethal Biological Effects in Environmental Waters Using Targeted and Non-Targeted Mass-Spectrometry-Based Analyses - Rebecca Dickman · University at Buffalo · PhD · 2023
Evaluating "Forever Chemicals" from Soup to Nuts: Sample Preparation, Targeted Analysis, and Suspect Screening for the Characterization of Per- and Polyfluoroalkyl Substances (PFAS) in Wastewater and
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