Clinical workflow solutions

Importance of the topic

Clinical assays rely on highly sensitive, selective and robust analytical workflows to detect low-abundance biomarkers, hormones, drugs of abuse and metabolites in complex biological matrices. Optimized combinations of sample preparation, chromatography columns and mass spectrometry platforms shorten analysis time, improve data quality and increase laboratory throughput, which is critical for timely decision making in clinical research, toxicology, endocrinology and forensic applications.

Study objectives and overview

This brochure presents integrated solutions from Thermo Fisher Scientific for five representative clinical workflows: metabolomics profiling, vitamin D screening, estrone/estradiol quantitation, drugs of abuse testing and alcohol biomarker monitoring. For each workflow it details the goals, sample preparation strategies, chromatographic separation, mass spectrometry detection and required consumables to achieve high sensitivity, reproducibility and rapid turnaround.

Methodology and instrumentation

Sample preparation techniques:

• Protein precipitation using HyperSep plates
• SPE cleanup with SOLA and SOLAµ cartridges and plates
• Vacuum or positive-pressure manifolds for high throughput processing

Chromatography and detection:

• Vanquish UHPLC systems coupled to Orbitrap IQ-X Tribrid or TSQ Altis/Quantiva triple quadrupole mass spectrometers
• Columns: Acclaim PA2 for polar analytes, Accucore Biphenyl for aromatic and isobaric separation, Hypersil GOLD PFP and aQ C18 for mixed polarity, and targeted LC platforms for rapid drug screening
• Direct-connect guard holders, UHPLC filter cartridges and SureSTART vials/caps for system protection and sample integrity

Main results and discussion

Metabolomics: Acclaim PA2 column achieved baseline separation of polar catecholamines with retention of highly aqueous species in under 30 minutes.
Vitamin D: SOLAµ HRP plate combined with Hypersil GOLD PFP column resolved 25(OH)D3 and its 3-epimer with 25 μL elution volumes, eliminating evaporation steps and enhancing throughput.
Estrone/estradiol: Accucore Biphenyl column and TSQ Altis platform delivered sensitive detection of low-level estrogens in serum with high specificity and reproducibility.
Drugs of abuse: Accucore Biphenyl UHPLC method separated 23 analytes, including isobaric opioids, in under four minutes while maintaining chromatographic robustness.
Alcohol biomarkers: Hypersil GOLD aQ column quantified ethyl sulfate and ethyl glucuronide in urine with stable isotope standards on a TSQ Quantiva, extending detection window beyond parent ethanol.

Benefits and practical applications

The integrated workflows reduce sample handling steps, lower solvent and consumable use, and minimize method development time. High-efficiency columns and optimized SPE formats improve sensitivity for trace analytes and support high-throughput clinical and forensic screening. The use of standardized vials, plates and guard systems ensures reproducibility and system longevity across multiple assays.

Future trends and potential applications

Emerging clinical demands will drive further miniaturization of sample prep, expansion of high-resolution and ion mobility-enabled MS techniques, and integration of automated end-to-end platforms. Advanced data processing with machine learning will enhance biomarker discovery and quantitative accuracy, while multiplexed assays will enable comprehensive metabolic and proteomic profiling in routine diagnostics.

Conclusion

The Thermo Fisher Scientific clinical workflow portfolio demonstrates how strategic selection of sample preparation tools, chromatography columns and mass spectrometry systems can deliver rapid, sensitive and robust analyses across a spectrum of clinical assays. These end-to-end solutions support laboratories in meeting stringent quality requirements and addressing evolving research and diagnostic challenges.

References

• Application note: Rapid analysis of 25-Hydroxyvitamin D3, epi-25-Hydroxyvitamin D3, and 25-Hydroxyvitamin D2 in plasma using high-resolution mass spectrometry
• Technical note: Achieving high sensitivity and robustness in estrone and estradiol analysis in human serum by TSQ Altis mass spectrometer
• Technical note: Fast separation of 23 drugs of abuse including isobaric opioids from human urine by UHPLC-MS/MS
• Technical note: Measuring alcohol biomarkers ethyl sulfate and ethyl glucuronide in urine – a splitting headache