DPiMS-MS (PESI) combined with vacuum differential mobility spectrometry for rapid forensic analysis

Importance of the Topic

Ambient ionisation mass spectrometry enables rapid, walk-up analysis with minimal sample preparation, offering significant advantages in forensic testing of biological fluids. However, the lack of chromatographic separation increases chemical noise and risk of isobaric interference. Incorporating vacuum differential mobility spectrometry (vDMS) provides an orthogonal separation step, greatly improving specificity and confidence in analyte identification.

Objectives and Study Overview

This work aims to integrate a low-pressure vDMS device onto a Shimadzu DPiMS-8060 (PESI) triple quadrupole mass spectrometer and evaluate its performance for rapid forensic analysis of small molecules and steroids in artificial saliva. Acetaminophen, metformin and cortisol serve as model compounds to demonstrate interference removal and enhanced selectivity.

Methodology and Instrumentation

Instrumentation Used:

• PESI source coupled to a Shimadzu DPiMS-8060 triple quadrupole MS.
• Prototype vDMS module installed between the desolvation line and quadrupole array, operated at ~33 mbar with electric fields expressed in Townsend (Td).
• Data acquired and processed using LabSolutions v5.97 and custom PESI MS software.

Method Details:

• Analytes prepared in various solvents and artificial saliva to assess solvent impact on vDMS separation.
• Dispersion (EdN) and correction (EcN) fields were scanned to identify conditions that resolve isobaric interferences.
• Comparative full-scan MS analyses performed with vDMS off and on, followed by targeted transmission of cortisol ions under optimized settings.

Main Results and Discussion

• Acetaminophen: an interference from methanol/formate was separated at moderate field strengths.
• Metformin: only a single species was detected, indicating interference-free transmission.
• Cortisol: blank saliva showed a false positive peak at m/z 363 without vDMS. At high field settings (≥150 Td), interfering species were baseline resolved while cortisol and its H+, Na+ and K+ adducts were retained.
• Targeted mode: fixed EcN/EdN allowed selective ion transmission, effectively eliminating background peaks and improving signal clarity.
• Solvent effects: vDMS with PESI exhibited minimal influence from solvent vapors, unlike LC-vDMS-MS workflows, due to low solvent throughput.

Benefits and Practical Applications

• Enhanced selectivity and reduced chemical noise lowers false positives and may improve limits of quantification.
• Maintains sub-minute acquisition speed of PESI with added mobility separation.
• Applicable to diverse complex matrices, including urine and plasma, for forensic, clinical, and environmental screening.

Future Trends and Potential Applications

• Expand vDMS-enabled ambient MS to a broader range of analytes and real-world samples.
• Integrate with high-throughput targeted workflows in forensic and clinical laboratories.
• Optimize waveform designs, pressure regimes and device architectures to enhance separation power and sensitivity.

Conclusion

The addition of vacuum differential mobility spectrometry to DPiMS-MS (PESI) significantly improves the specificity of ambient mass spectrometry assays, enabling rapid, high-throughput screening with reduced interferences. This approach enhances analytical reliability and extends the applicability of ambient ionisation techniques in forensic and clinical settings.

References

• Shvartsburg A. A. et al., Anal. Chem., 90(1), 936–943 (2018).
• Girard M. et al., Anal. Bioanal. Chem., 414, 7243–7252 (2022).