There are many types of ionization methods are used in mass spectrometry methods. The classic methods that most chemists are familiar with are electron impact (EI) and Fast Atom Bombardment (FAB). These techniques are not used much with modern mass spectrometry except EI for environmental work using GC-MS. More modern techniques of atmospheric pressure chemical Ionization (APCI) , electrospray ionization (ESI), matrix assisted laser desorption ionization (MALDI) and other derivative methods have taken their place in the mass spectrometry laboratory. The reason for APCI over EI is that APCI forms a protonated molecule and is completely compatible with Liquid Chromatography (LC), while EI is more likely to fragment the ion leading to a possible more ambiguous identification of the molecule weight and is incompatible with LC. ESI along with Matrix assisted laser desorption ionization (MALDI) has basically eliminated the use of FAB, because it produces the protonated molecules, which made FAB so popular, but is much more sensitive. In addition, MALDI along with ESI allowed for ionization and measurement of large molecular weight that could not be done before, even by FAB.  ESI has an advantage in its easy compatibility with LC.  While MALDI has advantages for imaging mass spectrometry.

Electron Impact ionization (EI) - EI is done by volatilizing a sample directly in the source that is contained in a vacuum system directly attached to the analyzer. The gas phase molecules are bombarded by a beam of electrons formed by heating a filament bias at a negative voltage compared to the source. The bias voltage is most commonly at -70 volts. The electron beam ejects an ion from the gas phase molecule producing a radical ion.  This technique is considered a hard ionization technique, because it causes the ion to fragment.   EI is also the method that is most commonly used for GC-MS.

Fast Atom Bombardment (FAB) - FAB is a technique that was popular in the 80's to early 90's because it was the first technique that allowed ionization of non-volatile compounds that could be done simply. It was done by bombarding a sample in a vacuum with a beam of atoms, typically Ar or Xe, accelerated to Kilovolt energies. The sample was typically mixed in a matrix. The two most common matrixes were glycerol and 3 Nitro-benzoic acid. The matrix allowed the sample to refresh itself. The ions formed by FAB were adducts to the molecule, where the adducts could be protons, sodium ions, potassium ions or ammonium ions. A variation of FAB was replacement of the atom beam with a beam of ions, typically cesium ions, which was called secondary ion mass spectrometry (SIMS). SIMS spectra were typically identical to FAB spectra and the terms became interchangeable.

Electrospray ionization (ESI) - ESI is the ionization technique that has become the most popular ionization technique. The electrospray is created by putting a high voltage on a flow of liquid at atmospheric pressure, sometimes this is assisted by a concurrent flow of gas. The created spray is directed to an opening in the vacuum system of the mass spectrometer, where the droplets are de-solvated by a combination of heat, vacuum and acceleration into gas by voltages. Eventually the ions are ejected from the droplets and accelerated into the mass analyzer by voltages. For larger molecules, the ions may contain multiple charges, allowing the detection of very large molecules on analyzers that have limited mass to charge (m/Z)) ratio ranges. Because of the natural use of a flowing liquid, it is easily adapted to liquid chromatography (LC).

There are many other techniques that are variations of electrospray, for example, nanospray is a derivative of ESI that basically is a low flow version and is highly sensitive because ESI sensitivity is dependent on concentration not the amount of sample used. Static nanospray or picospray is a similar derivative, but flow is created by only the electrostatic spray or a small gas pressure, this allows a few micro liters to last over one hour. In addition, static nanospray has the advantage of less carryover, because the needle is disposed of after each sample. Another similar ionization technique is to spray a surface with the ESI spray and have the spray extract ions from the surface into the mass spectrometer. This technique is called desorption electrospray ionization (DESI) and produces spectra similar to electrospray, but is analyzing the sample on a surface.

Atmospheric Pressure Chemical Ionization (APCI)- APCI is a method that is typically done using a similar source as ESI, but instead of putting a voltage on the spray itself, the voltage is placed on a needle that creates a corona discharge at atmospheric pressures. This discharge creates ions, in theory mostly H3O+ or water clusters. The  sample is injected into the discharge by a spray created by a flow of liquid combined with a heated gas that volatilizes the sample. The ions are formed by proton transfer from the H3O+ or the water clusters to the sample.  These ions are then extracted into the same opening vacuum that is used for electrospray. Another variation of this technique is atmospheric pressure photo ionization (APPI), where the initial ionization is performed by photo ionization, usually of a dopant that absorbs the light and is added to the sample flow.

A variation of the APCI technique used in our laboratory is atmospheric solids analysis probe (ASAP), which basically uses the APCI source. The sample is not injected into the flow of liquid, but placed on a probe placed directly into the corona discharged. In this technique the liquid flow may be turned off, but heated gas is needed to volatilize the sample.  A flow of liquid can be used to change the chemistry in the discharge to reduce the fragmentation.  The advantage of this technique over the traditional method is ease of use and less carryover of sample.

Matrix Assisted Laser Desorption Ionization (MALDI)-MALDI is a method of ionization in which the sample is bombarded with a laser. The sample is typically mixed with a matrix that absorbs the laser radiation and transfer a proton to the sample. Some small mass samples can be ionized without matrix, but this is typically called laser desorption. The laser is always pulsed, and typically in a vacuum. In addition, MALDI mostly forms singularly charged ions. This means MALDI is mostly performed on specially built time-of-flight instruments. One major application of MALDI besides simple analysis is imaging mass spectrometry.