Clinical Application of SPME: Analysis of VOCs in Exhaled Breath as Cancer Biomarkers

Importance of the Topic

The analysis of volatile organic compounds (VOCs) in exhaled breath offers a non-invasive approach for disease diagnosis, monitoring metabolic processes, and supporting clinical research. This method leverages characteristic odor profiles to detect biomarkers associated with pathologies such as lung cancer, diabetes, and renal or liver diseases.

Objectives and Study Overview

This study aimed to apply solid phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC-MS) for the identification of VOC biomarkers in the breath of lung cancer patients compared to healthy volunteers. A total of twelve patients with lung cancer and ten healthy individuals were sampled under controlled conditions.

Methodology and Instrumentation

Breath samples were collected into 1 L Tedlar® bags maintained at 25 °C. A Carboxen®/polydimethylsiloxane (CAR/PDMS, 75 µm) SPME fiber was exposed to the sample for 15 minutes, followed by direct desorption in the GC-MS inlet. External calibration was performed using standard mixtures of VOCs.

Instrumentation Used

• SPME fiber: Carboxen®/PDMS, 75 µm film thickness
• Fiber holder: Manual SPME holder
• GC column: Supel-Q™ PLOT (25 m × 0.25 mm I.D., 3 µm film)
• Injection: Splitless for 1 min, then split at 35:1
• Oven program: 40 °C (2 min) → 140 °C at 10 °C/min → 270 °C at 5 °C/min (3 min)
• Carrier gas: Helium at 40 cm/s
• MS detector: Full scan (m/z 15–220), EI source at 220 °C

Main Results and Discussion

Validation showed strong linearity (r² ≥ 0.991), low limits of detection (0.3–3.3 ppb), and precision with RSDs below 9.4%. Statistical analysis identified methyl vinyl ketone, 1-propanol, 2-propanol, and o-xylene as significantly elevated in lung cancer patients compared to controls.

Contributions and Practical Applications

The SPME-GC-MS protocol is simple, solvent-free, fully automatable, and compatible with standard laboratory equipment. It provides a sensitive and reproducible strategy for breath biomarker discovery, with potential applications in clinical research, toxicology, and quality control.

Future Trends and Opportunities

• Validation in larger, multicenter cohorts to establish clinical utility
• Integration with metabolomic profiling and machine learning for enhanced biomarker panels
• Development of portable SPME-GC-MS systems for point-of-care testing
• Expansion to other disease biomarkers and environmental exposure studies

Conclusion

SPME-GC-MS analysis of exhaled VOCs demonstrates strong potential as a non-invasive tool for lung cancer biomarker detection. The method’s sensitivity, reproducibility, and ease of adoption make it an attractive option for clinical research, pending further validation in larger patient cohorts.

Reference

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