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Updated: Jun 3, 2026

Sample Preparation for Probe Electrospray Ionization Mass Spectrometry
Published on: February 19, 2020
High pressure (>1 atm) electrospray ionization mass spectrometry
Lee Chuin Chen1, Mridul Kanti Mandal, Kenzo Hiraoka
1Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-3-11 Takeda, Kofu, Yamanashi 400-8511, Japan. leechuin.yamanashi@gmail.com
High pressure electrospray ionization (ESI) enhances sample desolvation and prevents gaseous breakdown. This method achieves stable ionization for challenging samples like pure water and reduces fragmentation of labile compounds.
Area of Science:
- Analytical Chemistry
- Mass Spectrometry
- Physical Chemistry
Background:
- Electrospray ionization (ESI) is a crucial technique in mass spectrometry.
- Optimizing ESI performance, especially for challenging samples, remains an active area of research.
- Controlling ion source parameters is key to improving ionization efficiency and analyte stability.
Purpose of the Study:
- To investigate the effects of high pressure on electrospray ionization (ESI) in mass spectrometry.
- To determine if elevated pressure in the ion source chamber improves ionization stability and analyte protection.
- To explore the feasibility of using high pressure ESI for samples with high surface tension, such as pure water.
Main Methods:
- Custom ion source chamber pressurized with compressed air to above atmospheric pressure.
- Coupling the high-pressure ion source to a commercial time-of-flight mass spectrometer.
- Utilizing a nozzle-skimmer interface for ion transmission.
- Investigating onset voltages for electrospray and corona discharge under varying pressures.
Main Results:
- Electrospray onset voltage remained independent of operating pressure.
- Corona discharge onset voltage increased with pressure, following Paschen's law.
- Stable electrospray ionization was achieved for high surface tension solutions (e.g., pure water) in both positive and negative ion modes.
- Optimizing operating pressure reduced fragmentation of labile compounds.
Conclusions:
- Pressurizing the ESI ion source with air offers benefits beyond increased desolvation gas, including avoidance of gaseous breakdown.
- High pressure ESI enables stable ionization of challenging samples and protects labile compounds from fragmentation.
- This technique provides a viable method for enhancing ESI-MS performance.
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