Highly sensitive mass spectrometry of non-polar organic compounds with supercritical fluids Coupling supercritical fluid extraction/chromatography (SFE/SFC) with proton transfer reaction (PTR) mass spectrometry (MS) to achieve quick sample preparation, high throughput analysis, and high sensitivity.


May 16, 2022

Background / Context / Abstract:

Supercritical fluid extraction/chromatography (SFE/SFC) is a coupled separation technique that primarily relies on carbon dioxide as an extraction fluid and mobile phase on chromatography. SFE can selectively extract, transport, and deposit materials by controlling the temperature and pressure of the supercritical fluid. The extracted molecules are rapidly separated by SFC, which is higher column efficiency than HPLC.  Analytes in the supercritical fluid are depressurized into a vacuum chamber for PTR process, which efficiently ionize molecules. Due to the need to prevent precipitation of the solute in the depressurization process and the mechanism required to mix the organic solvent necessary for ionization used in conventional atmospheric pressure ionization methods, a complicated interface design and advanced engineering are needed to perform ionization without impairing peak separation.PTR ionization mass spectrometry has been used for a long time to monitor trace-level volatile organic compounds (VOCs) in the gaseous samples. By combining this with SFE/SFC, non-volatile organic compounds with a molecular weight of 1000 or higher can be detected.
SFE/SFC hyphenated to PTR ionization mass spectrometry has the following advantages: (1) the analytes in a supercritical fluid are directly released in a closed vacuum space to ionize the molecules, an ion source can be easily designed; and (2) the carbon dioxide is not ionized, analytes in the sample are effectively ionized without interference.


Detection of caffeine, long-chain fatty acids, fat-soluble vitamins, etc. with ultra-high sensitivity (several amol-fmol)



– Improves sensitivity of lipid/fatty acid detection by several orders of magnitude

– Can be developed at low cost by combining the established technologies (SFE/SFC, PTR, MS)

Potential Applications / Potential Markets:

Mass spectrometry of fatty acids, lipids, and other non-volatile substances in a complex sample matrix.
Since SFC/SFE and PTR have been established as instruments, respectively, and because the ionization mechanism of PTR can be coupled with a mass spectrometer, they can be developed not only as a system but also commercialized as an attachment.

State of Development / Opportunity / Seeking:

・Available for exclusive and non-exclusive licensing
・Exclusive/non-exclusive evaluation for defined period (set up for options)
・Collaborative/supportive research

1. Development partner
2. Licensing 

IP Status:

PCT applied in Japanese


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