BMSS: High Throughput HDMSE Blood Product Lipidomic Screening Using a DESI Inlet

Importance of the Topic

High-throughput lipidomic profiling is crucial for large cohort biomedical studies to reduce instrument time, minimize batch effects, and preserve sample integrity.

Objectives and Study Overview

This study evaluates the feasibility of using desorption electrospray ionization high-definition MSE (DESI-HDMSE) as a rapid direct screening approach for lipid profiling in human serum.
The method was applied to 500 serum samples from the HUSERMET population study to assess throughput, data quality, and potential biomarker discovery.

Methodology

Serum samples (n=500) were protein-precipitated with isopropanol (1:4 v/v). Two microliters of supernatant were spotted onto Teflon-coated glass slides.
A single line scan per spot was performed with DESI-HDMSE, covering both positive and negative ionization modes.
Acquisition time per slide of 44 samples was 8 minutes, enabling analysis of all samples in under 3 hours per polarity.
Data processing platforms included MassLynx, DriftScope HD Imaging, Progenesis QI, and UNIFI for multivariate analysis and database searching.

Instrumentation Used

DESI XS inlet mounted on a SYNAPT G2-XS QToF mass spectrometer.
Key parameters:

• Capillary voltage: 0.6 kV
• Gas flow: 5 bar
• Spray solvent: 98% MeOH, 2% water at 2 μL/min
• Heated transfer line: 300 °C
• Positive mode step size: 50 μm, HDMSE 8 scans/s
• Negative mode step size: 100 μm, HDMSE 2 scans/s

Main Results and Discussion

Excellent signal intensity was observed across samples (mid e5 in positive mode, mid e4 in negative mode).
No significant drying patterns (“coffee ring”) were detected despite air-drying of spots.
Spectral differences among samples allowed visual detection of lipid profile variations and potential contaminants.
Data imported into Progenesis QI showed clear sample quality assessment and PCA clustering; no significant biomarkers were found in this healthy cohort.

Benefits and Practical Applications

Rapid screening (<15 seconds per sample) reduces total analysis time and file size, lowers risk of batch-related degradation, and flags problematic samples prior to LC–MS.
The simple sample preparation matches LC–MS protocols, enabling storage and follow-up analyses on selected subsets.

Future Trends and Potential Applications

Integration of DESI-HDMSE with automated sample handling for clinical lipidomics.
Extension to other biofluids or tissue sections for rapid phenotyping.
Combination with advanced ion mobility separation and machine learning for biomarker discovery in patient cohorts.

Conclusion

DESI-HDMSE provides a viable high-throughput prescreening tool for serum lipidomics, offering fast analysis, reliable data quality, and effective triage for downstream LC–MS investigations.