Mass spectrometry continues to expand far beyond traditional pharmaceutical analysis and environmental testing. Increasingly, LC-MS workflows are being applied to regenerative medicine, cellular therapeutics, metabolomics, and even the development of next-generation portable mass spectrometry systems.
In a recent episode of Concentrating on Chromatography, Organomation General Manager David Oliva spoke with Joseph Corstvet, PhD candidate in the Fernandez Lab at Georgia Tech, about two rapidly emerging areas in analytical chemistry:
- LC-MS metabolomics for monitoring mesenchymal stromal cell (MSC) health and senescence
- Development of triboelectric nanogenerator (TENG) ionization systems for more accessible and portable mass spectrometry
The discussion highlighted how chromatography and sample preparation continue to play foundational roles in both cutting-edge biomedical research and the future of analytical instrumentation.
Watch full conversation:
Mesenchymal stromal cells (MSCs) are receiving enormous attention in regenerative medicine because of their immunomodulatory and tissue repair capabilities. Researchers are exploring MSC-based therapies for inflammatory diseases, tissue injuries, and immune disorders.
According to Corstvet, MSCs are particularly attractive because they function as living therapies rather than traditional small molecule drugs.
“These are living cells,” Corstvet explained during the interview. “They have a lot higher potential for treatment than a typical small molecule or biologic would.”
One major challenge, however, is cellular senescence during culture expansion. Before MSCs can be administered therapeutically, they must often be expanded in bioreactors or culture systems to reach sufficient cell numbers. During this process, cells gradually age and lose potency.
Unlike traditional pharmaceutical dosing, where a specific mass of active ingredient is administered, cellular therapies are far more complex. A culture may contain the correct number of cells, but if many of those cells are senescent, therapeutic efficacy can decline significantly.
This creates a major analytical challenge for researchers and biomanufacturers: how do you accurately monitor cell health during culture?
One of the most interesting sections of the interview focused on why metabolomics may be uniquely suited for monitoring cellular senescence.
In metabolomics, researchers often describe metabolism as “closest to the phenotype” of a cell. While genomic information tends to remain relatively stable, metabolism changes dynamically in response to environmental conditions, stress, nutrient availability, and cellular aging.
As Corstvet explained, even something as simple as drinking coffee immediately alters metabolism.
This dynamic responsiveness makes metabolomics especially useful for distinguishing healthy MSCs from senescent MSCs, which may appear genomically similar despite substantial functional differences.
Traditional senescence assays such as beta-galactosidase staining remain widely used, but they have limitations. Enzyme activity can sometimes occur in healthy cells as well, creating ambiguity in interpretation.
Corstvet and his collaborators instead use untargeted LC-MS metabolomics workflows to identify biomarker panels capable of predicting cellular age and senescence.
The long-term vision is highly compelling for biomanufacturing:
A small aliquot could be periodically sampled from a bioreactor, analyzed via LC-MS, and evaluated against a regression model capable of predicting culture health and cellular aging in near real time.
For laboratories involved in cell therapy development, this represents a potentially transformative quality control strategy.
While the interview heavily emphasized mass spectrometry, chromatography remained central to the workflow.
Corstvet specifically discussed the importance of liquid chromatography for lipidomics applications. Without chromatographic separation, highly ionizable compounds can dominate ionization efficiency and suppress detection of lower-abundance metabolites.
In their MSC senescence research, the group utilized reverse-phase LC coupled to high-resolution mass spectrometry to separate lipid classes prior to ionization.
One particularly important detail involved the choice of a C30 reverse-phase column rather than a traditional C18 column.
According to Corstvet, the C30 stationary phase provided significantly improved retention and separation for highly nonpolar lipids, especially triglycerides. This enhanced chromatographic performance improved both lipid annotation confidence and overall metabolome coverage.
The study itself analyzed approximately 4,000 detected features, eventually narrowing these to roughly 200 annotated lipids through tandem MS and database matching workflows.
This type of work highlights the critical role chromatography still plays in modern metabolomics. Even with today’s ultra-high-resolution mass analyzers, chromatographic separation remains essential for:
- Reducing ion suppression
- Improving quantitative reproducibility
- Increasing metabolite coverage
- Enhancing confidence in lipid identification
- Improving retention time reproducibility
For LC-MS laboratories, especially those handling complex biological matrices, sample preparation and chromatographic optimization remain just as important as the mass spectrometer itself.
The conversation also touched on an issue familiar to many analytical chemists: reproducibility.
Untargeted metabolomics workflows often involve thousands of detected features across large sample cohorts. Small changes in chromatography conditions, gradients, column chemistry, or even replacement columns can significantly alter retention behavior.
Corstvet emphasized that retention time reproducibility is crucial for accurate annotation and interpretation.
If compounds elute at significantly different times between runs, researchers may lose confidence that the same metabolite is being measured consistently.
The Georgia Tech workflow reportedly achieved retention time variation within approximately five to ten seconds, which is excellent for untargeted LC-MS lipidomics.
This level of reproducibility becomes especially important when translating biomarker discovery workflows into future QC assays for regulated environments.
The second major focus of the interview explored triboelectric nanogenerators (TENGs) and their potential applications in mass spectrometry ionization.
Traditional electrospray ionization (ESI) typically relies on dedicated DC power supplies to generate charged droplets for ion formation. TENG systems instead generate charge using triboelectricity — essentially static electricity produced by contact between materials.
Corstvet described the mechanism using a familiar analogy:
“It’s like wool socks on carpet or a balloon in your hair.”
The current TENG systems developed in the Fernandez Lab reportedly can be assembled for approximately $250 in materials and generated pulse voltages approaching 9 kilovolts.
Importantly, these systems create extremely brief high-voltage pulses rather than continuous DC output. This pulsed operation can reduce emitter damage while still generating effective ionization.
For researchers interested in portable or lower-cost MS systems, this could become highly significant.
One of the most forward-looking portions of the discussion involved accessibility and portability in analytical instrumentation.
Mass spectrometers remain expensive, with even lower-end systems often costing tens or hundreds of thousands of dollars. Instrumentation costs, software licensing, and maintenance remain major barriers for smaller laboratories.
Corstvet believes ionization innovation could help lower some of these barriers.
TENG systems require relatively low power consumption — reportedly around 20–25 watts in their current configuration — making them attractive for battery-powered or mobile systems.
Portable MS could create entirely new analytical opportunities, including:
- Environmental field testing
- On-site water analysis
- Mobile air quality monitoring
- Clinical bedside analysis
- Rapid industrial screening
Although portable systems currently lack the analytical performance of high-end Orbitrap or time-of-flight platforms, significant momentum exists within the field toward miniaturization and field deployment.
Interestingly, Corstvet noted that ion mobility and portable systems appear to be among the fastest-growing areas in mass spectrometry today.
For Organomation customers, one particularly relevant insight involved the role of sample preparation within modern LC-MS workflows.
Despite the sophistication of today’s instrumentation, many workflows still depend heavily on reliable extraction, evaporation, concentration, and solvent handling techniques.
Corstvet described using IPA-based extraction workflows for whole-cell lipid extraction prior to LC-MS analysis. He also noted that sample preparation itself accounted for a relatively small percentage of total workflow time compared to instrument operation and data processing.
Still, reproducible extraction and concentration remain foundational for generating reliable metabolomics data.
As metabolomics, lipidomics, and cell therapy QC workflows continue expanding, demand for efficient solvent evaporation and concentration technologies will likely continue growing alongside them.
The interview ultimately painted a fascinating picture of where analytical chemistry may be heading next.
On one side, researchers continue pushing the limits of high-resolution LC-MS metabolomics for applications like regenerative medicine and disease monitoring.
On the other, scientists are simultaneously rethinking the infrastructure of mass spectrometry itself — exploring how ionization technologies, portability, and lower-cost instrumentation could make MS more accessible outside traditional laboratories.
For analytical chemists, chromatography professionals, and sample preparation specialists, both trends are worth watching closely.
As LC-MS workflows become increasingly integrated into clinical research, biomanufacturing, and field-deployable analysis, robust chromatography and reproducible sample preparation will remain critical enabling technologies.