A New Outlook on Soft Ionization for GC–MS

Mar 01, 2014

Despite the advantages of soft ionization ion-source technologies for improving confidence in the identification of a range of challenging analytes, soft ionization remains a niche technique for gas chromatography–mass spectrometry (GC–MS). This article discusses the reasons for this limitation as well as new developments that make lower-energy electron ionization possible without the disadvantages that have historically been associated with it. The specific benefits of this technique are discussed by reference to several examples across the GC–MS field.

The term "soft ionization" encapsulates a range of techniques that ultimately result in analyte molecules that become ionized without imparting excess energy to them. The result is a limited degree of analyte fragmentation, meaning that the molecular ion passes intact through the mass spectrometer and to the detector. This ability to provide information about the unfragmented molecule makes soft ionization of great value to analysts.

For macromolecules, the ready fragmentation of the molecular ion means that soft ionization is the only suitable technique and, in this field, matrix-assisted laser desorption–ionization (MALDI) is a popular method for ionizing DNA, proteins, peptides, sugars, polymers, and dendrimers.

However, for smaller analytes amenable to gas chromatography (GC), high-energy electron ionization (EI), typically at 70 eV, is by far the most popular technique. Large libraries of spectra such as those curated by the National Institute of Standards and Technology (NIST) and Wiley are available for matching and identification, and have long been used by analysts across a wide range of gas chromatography–mass spectrometry (GC–MS) applications. In this field, methods for soft ionization have historically been viewed as more specialized, and more often used in cases where EI at 70 eV does not provide adequate results.

There are multiple reasons for this. The major factor is that EI, which although by its nature is applicable to almost every vaporized substance, cannot be used successfully at lower energies. This is because of inefficient channeling of electrons from the filament ("e-gun") into the ion chamber, giving an extremely low signal and an unacceptable loss of sensitivity.

Therefore, to achieve soft ionization, analysts have turned to other techniques, of which chemical ionization (CI) is the most common. CI also results in a drop in sensitivity, but to a far lesser extent than EI. Unfortunately, however, CI requires a different ion-source configuration, with additional source pressurization and the use of reagent gases. If a single instrument is being used, this can be a time-consuming transition and a considerable drain on laboratory resources if required on a regular basis.

The challenge, therefore, remained of developing a convenient soft ionization technique that retained the performance and wide applicability of standard 70-eV electron ionization. Hence, we were excited by the development of an e-gun design that removes the link between the energy of the electrons and the ionization efficiency, by introducing an additional electrostatic element between the e-gun and the ion chamber. This allows the ionization energy of the electrons to be varied on a sliding scale from conventional 70 eV to lower energies, without loss of sensitivity.