26 MS Ionization Sources*

The role of the ionization source in a mass spectrometer is to convert the molecules in a sample into ions. Hard ionization methods, such as electron impact (EI) and secondary ion MS (SIMS), tend to ionize sample molecules with significant fragmentation. In contrast, soft ionization methods produce mostly molecular ions with much less fragmentation. Examples include chemical ionization (CI and APCI), electrospray ionization (ESI), matrix-assisted laser desorption ionization (MALDI), and other methods not discussed here.

Hard Ionization Methods

EI converts gas-phase molecules into positive ions by knocking out one of their electrons with a beam of accelerated electrons. This electron beam is from a heated tungsten filament with a strong potential applied. The EI process is very inefficient and produces a lot of fragmentation, with few (if any) surviving molecular ions. It must be possible to vapourize a sample to use EI.

SIMS is used for MS analysis of surfaces. An ion beam is directed to a surface and the energy of an ion impacting a surface is converted into sputtered gas-phase material, including ions. Fragmentation is extensive.

Soft Ionization Methods

CI coverts sample molecules into positive ions through gas-phase reactions. A small-molecule reagent gas (e.g. methane, ammonia, isobutane) is vapourized in large excess relative to sample ions and is ionized by EI. Through multiple reactions, ionized reagent gases transfer protons to sample molecules to yield positively-charged molecular ions, with only limited fragmentation. Other reagent gases can abstract protons to yield negatively-charged molecular ions.

A variation of CI is atmospheric pressure chemical ionization (APCI). Liquid sample is converted into an aerosol, heated to evaporate the solvent, and the solvent vapour is converted into a plasma (i.e. ionized gas) via a corona discharge needle with high potential applied. The plasma then ionizes a sample molecule by proton transfer (to yield a cation) or proton abstraction (to yield an anion).

ESI is somewhat similar to APCI but has a different ionization mechanism. A liquid sample is nebulized through a metal needle held at very high potential (kV), producing charged aerosol droplets. Heat and a flow of inert gas drive evaporation of solvent, resulting in greater and greater charge density per droplet. A series of Coulombic fission events produces smaller and smaller charged droplets until only gas-phase analyte ions remain. These ions may be pre-formed in solution (because of ionizable functional groups) or acquire a charge from solvent ions at the surface of the droplets (e.g. proton transfer). ESI can produce both positively and negatively charged ions, including multiple charged ions. Fragmentation is limited.

Another soft ionization method is photoionization (PI) using UV light, which can also be done at atmospheric pressure (APPI) using a heated nebulizer.

MALDI is done by incorporating analyte into a matrix made up of an acidic organic molecule that absorbs UV light (e.g. nicotinic acid, dihydroxybenzoic acid). The energy of a high-power pulsed UV laser is absorbed by the matrix, resulting in desorption of a hot (gaseous) plume of some of the matrix. The analyte is ionized by proton transfer from the matrix and some is carried along in the plume. Fragmentation is minimal.  The inventions of MALDI and ESI were recognized with the Nobel Prize in Chemistry in 2002.

Choosing an Ionization Source

The best choice of ionization source depends, in large part, on the nature of the sample. For example, some analytes ionize well by some mechanisms and poorly by others, and may or may not be volatile, soluble, or thermostable. Preference for molecular ions versus fragments may also be a consideration.

Connections

• ESI produces a charged aerosol, where much of the charge arises from redox reactions (Ch. 16) at the liquid/needle interface (e.g. involving solvent or needle material).
• PI uses energy from photon absorption (Ch. 6) to ionize a molecule. Any excess energy of the photon beyond the ionization energy of the molecule is converted into the kinetic energy of the electron.
• MALDI uses energy from photon absorption (Ch. 6) to produce a gaseous plume, which is similar to the LIBS technique (Ch. 11), but uses much less laser power to avoid atomization and minimize molecular fragmentation.

Post-Reading Questions

1. Define “hard” and “soft” ionization.
2. Sort the MS ionization sources discussed in this chapter into hard and soft categories.
3. In what way is APCI different than CI?
4. Given their mechanisms, which ionization methods are likely not used in LC-MS or GC-MS systems?

Topic Learning Objectives

The chapter is a primer for the following learning objectives, which will be covered in lecture and/or with additional assigned reading:

• Understand the advantages and disadvantages of hard and soft ionization.
• Understand the operating principles of ionization sources.
• Draw simple diagrams for ionization sources.
• Recommend an ionization method for a particular type of sample (or chromatography).