Mass spectrometry workflows for improved healthcare

Importance of the topic

Mass spectrometry (MS)–based workflows are revolutionizing precision medicine by enabling earlier and more accurate diagnoses, which guide tailored treatments and improve patient outcomes.
Over 70% of medical decisions rely on clinical laboratory data; integrating MS can accelerate the discovery of disease biomarkers and inform clinical choices from translational research through routine diagnostics.
By bridging the gap between genotype and phenotype through proteomics and metabolomics, MS offers insights that genomics alone cannot provide.

Study objectives and overview

This work reviews emerging trends, challenges, and technological advances in applying MS across three critical phases: discovery research, translational clinical labs, and bedside diagnostics.
The main objectives are to identify pain points in clinical proteomics and metabolomics, highlight strategies for controlling biological and technical variability, and showcase case studies demonstrating MS impact on patient care.
Key areas of focus include:

• Transdisciplinary approaches to disease systems biology
• Real-time quality control and sample standardization
• Automation and high-throughput MS platforms for clinical testing
• Regulatory and reimbursement landscapes for laboratory-developed tests

Methodology and instrumentation

Clinical and discovery labs employ a spectrum of MS techniques tailored to specific analytes and throughput requirements:

• Liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–MS (GC-MS) for small molecules, drugs, steroids, and biomarkers
• High-resolution accurate-mass MS (HRAM) such as the Orbitrap for untargeted proteomics and complex compound identification
• Triple quadrupole instruments for targeted quantification with superior selectivity and low detection limits
• Inductively coupled plasma MS (ICP-MS) for trace element and metal co-factor analysis in clinical samples
• PaperSpray ionization for rapid, minimal-prep analyses of dried bloodspots and biofluids
• TurboFlow online extraction and multichannel uHPLC to improve throughput and reduce manual sample cleanup

Used instrumentation

• Thermo Scientific™ Orbitrap™ mass spectrometers
• Triple quadrupole LC-MS/MS systems
• Thermo Scientific™ TurboFlow™ technology
• Prosolia Velox 360™ PaperSpray™ ion source
• Inductively coupled plasma MS platforms
• Multichannel uHPLC and GC-MS instruments

Main results and discussion

MS workflows have demonstrated enhanced analytical specificity compared with immunoassays, reducing cross-reactivity and lot-to-lot variability.
Case studies reveal that up to 60% of archived tumor specimens may be unsuitable for proteomic analysis without stringent quality control, emphasizing the need for rigorous sample qualification.
Implementing real-time QC at each step—in sample prep, chromatographic separation, and MS acquisition—has proven essential for reducing technical variance and ensuring reproducible results from day one to day one thousand.
Collaborative networks between hospitals, academic centers, and instrument vendors accelerate translational research by providing well-annotated biobanks, robust analytical platforms, and interactive support for method development.
Economic analyses indicate that when considering lifetime operating costs, MS-based tests can deliver lower cost per analyte and higher multiplexing compared to conventional immunoassays, despite higher upfront investment.

Benefits and practical applications

• Personalized prognostics and therapy stratification by measuring proteotypic signatures in diseases lacking clear driver mutations
• Early assessment of therapeutic response and detection of minimal residual disease through sensitive quantification of modified proteins and metabolites
• Discovery of novel drug targets by profiling proteome and metabolome changes in patient cohorts
• High-throughput drug monitoring panels for antiepileptics, immunosuppressants, and abuse screening with improved accuracy
• Trace element analysis in micro-volume samples for pediatric and genetic disorder diagnostics
• Workflow automation that doubles or quadruples sample throughput in high-volume clinical labs

Future trends and applications

Further simplification of MS platforms—toward push-button operation and minimal sample preparation—will drive wider adoption in routine clinical chemistry laboratories.
Integration of point-of-care MS devices and novel ionization methods (e.g., ambient ionization) can bring rapid diagnostics to bedside settings.
Regulatory guidance for laboratory-developed tests will evolve to balance innovation with safety, requiring harmonized standards and reference materials for emerging analytes.
Advances in artificial intelligence and machine learning applied to high-dimensional MS data will enhance biomarker discovery, predictive diagnostics, and personalized therapy planning.
Continuous improvement in HRAM instrumentation will expand untargeted screening capabilities, enabling global proteome and metabolome profiling at clinical pace.

Conclusion

Mass spectrometry has matured from a specialized research tool to a transformative technology across discovery, translational laboratories, and bedside diagnostics.
By combining high selectivity, multiplexing, and real-time QC, MS workflows facilitate precision medicine through biomarker discovery, therapeutic monitoring, and personalized treatment strategies.
Coordinated efforts among clinical researchers, laboratory operators, and instrumentation vendors are pivotal to overcoming challenges in sample quality, regulatory compliance, and automation, ultimately improving patient care one life at a time.

References

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