SPATIAL MAPPING OF ION DISTRIBUTIONS IN PNEUMATICALLY ASSISTED ELECTROSPRAYS

Importance of the Topic

The spatial distribution of ions produced by pneumatically assisted electrospray sources directly influences sensitivity, reproducibility and quantitative performance in liquid chromatography–mass spectrometry (LC–MS). Fine control of emitter placement, gas flows and voltages is critical for reliable analysis in proteomics, metabolomics and industrial QC applications. Mapping ion yields in three dimensions provides insight into fundamental ion‐generation mechanisms and guides source optimization for improved robustness.

Study Objectives and Overview

This work aimed to characterize how emitter position relative to the MS inlet and cone affects ion intensity, charge state distributions, adduct formation and in‐source fragmentation under typical high‐flow (650 µL/min) LC–MS conditions. Using automated x–y–z translation, spatial ion‐intensity maps were generated for model peptides angiotensin I and leucine enkephalin across varied cone voltages.

Methodology and Instrumentation

The experimental platform comprised a Waters Acquity UPLC I‐Class delivering angiotensin I or leucine enkephalin solutions at 650 µL/min. A stepper‐motor‐driven emitter mount positioned the spray in a 3D grid. Key parameters included:

• ESI capillary voltage: 800 V
• Desolvation gas flow: 16 L/min at 120 °C
• Nebulizer gas flow: 1.5 L/min
• Cone voltage: 5–79 V
• Gas heater temperature: 600 °C

Data acquisition used MassLynx, while raw files were converted to mzML and processed in R to extract ion intensities ([M+H]+, [M+Na]+ etc.). Imaging involved spline interpolation in x, y and z to visualize spatial variations.

Main Results and Discussion

Spatial maps revealed that:

• Maximum total ion signal occurs when the spray plume is directed onto the sampling cone at an optimal distance along the z-axis.
• Charge state ratios for angiotensin I vary strongly with x-position near the cone, with higher multiply charged ions observed when spraying directly on the cone surface.
• Leucine enkephalin [M+Na]+ adduct abundance showed distinct spatial dependence, whereas the a4/b4 fragment ratio remained largely position‐independent.
• Maintaining an intermediate distance in x reduces sensitivity to emitter position, balancing ion production and desolvation time.

These findings highlight that both electric field geometry and droplet‐surface interactions contribute to ion formation and fragmentation.

Benefits and Practical Applications

Optimizing emitter placement can:

• Enhance method robustness by reducing sensitivity to slight misalignments.
• Improve reproducibility in non‐targeted profiling by stabilizing charge state distributions.
• Increase overall sensitivity without raising source fragmentation.

Such improvements benefit high‐throughput LC–MS in pharmaceutical QC, biomarker discovery and environmental analysis.

Future Trends and Opportunities

Advances may include dynamic emitter repositioning for real‐time sensitivity tuning, integration of imaging feedback to auto‐correct misalignment, and the application of machine‐learning models to predict optimal source configurations. Further exploration of alternative pneumatically assisted spray designs could yield sources with inherently reduced positional dependence.

Conclusion

This study demonstrates that detailed spatial mapping of ion distributions in pneumatically assisted electrospray reveals complex dependencies on emitter position and source parameters. By identifying optimal geometries, users can significantly improve LC–MS sensitivity, reproducibility and method stability.

Reference

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