Electrospray ionization

Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized. The invention of electrospray ionization was rewarded with the attribution of the Nobel Prize in Chemistry to John Fenn in 2002.

How it works

In electrospray ionization a liquid is pushed through a very small charged, usually metal, capillary. This liquid contains the substance which is to be studied, the analyte, dissolved in a large amount of solvent, which is usually much more volatile than the analyte. Volatile acids, bases or buffers are often added to this solution as well. The analyte exists as an ion in solution either in a protonated form or as an anion. As like charges repel, the liquid pushes itself out of the capillary and forms a mist or an aerosol of small droplets about 10 $\mu$ m across. This jet of aerosol droplets is at least partially produced by a process involving the formation of a Taylor cone and a jet from the tip of this cone. A neutral carrier gas, such as nitrogen gas, is sometimes used to help nebulize the liquid and to help evaporate the neutral solvent in the small droplets. As the small droplets evaporate, suspended in the air, the charged analyte molecules are forced closer together. The proximity of the molecules becomes unstable as the similarly charged molecules come closer together and the droplets once again explode. This is referred to as Coulombic fission because it is the repulsive Coulombic forces between charged analyte molecules that drive it. This process repeats itself until the analyte is free of solvent and is a lone ion. There remains debate as to the exact mechanisms of electrospray processes particularly in the later part of the process as the lone ion is formed. The lone ion then continues along to the mass analyzer of a mass spectrometer.

In electrospray processes the ions observed are quasimolecular ions that are ionized by the addition of a proton (hydrogen ion) to give (M=analyte molecule, H=hydrogen ion), or other cation such as sodium ion ^*" target="_blank" >for example. In electrospray multiply charged ions such as macromolecules there will often be a distribution of many charge states and the charge on the ions can be great such as [M+25H" target="_blank" >^*. Note that these are all even-electron species. Electrons themselves (alone) have neither been added or removed as with some other ionizations. The formation of ions in electrospray is somewhat homologous to acid-base reactions. Redox reactions do occur and a circuit with measurable current flow exists but atomic and molecular ions are the primary carriers of charge in the solution and gas phases.

Issues of debate

There are two major competing theories about the final production of lone ions, the charged residue model (CRM) and the ion evaporation model (IEM).

The Charged Residue Model suggests that at the fission event, the droplet breaks in half either into two identical droplets (even fissioning) or into two disproportionate droplets (uneven fissioning). The charge makeup of these daughter droplets would be comparable with respect to their relative size.

The Ion Evaporation(Desorption) Model which suggests that the force of columbic repulsion is great enough to push or desorb ions directly out of the droplet. Characteristally, the fission event correspond to an almost negligible loss in droplet mass, but a significant drop in charge.

It has been suggested that both models probably occur for different analytes/solvents and in the limit of both models they have a tendency to converge. That is to say that the distinction between a droplet containing an analyte molecule and an analyte molecule surrounded by a layer of solvent eventually disappears and columbic fission looks a lot like ion evaporation. The real question is scale and timing and the techniques to definitively determine this are not available.

The use of the word "ionization" in "electrospray ionization" is criticized by some due to that many of the ions observed are thought to be preformed in solution before the electrospray process or created by simple changes in concentrations as the aerosolized droplets shrink. It is argued that electrospray is simply an interface for transferring ions from the solution phase to the gas phase.

Variants

There exist many variations on the basic electrospray technique. Two important ones are microspray (µ-spray) and nanospray. The primary difference is in the reduced flow rate of the analyte containing liquid; however many other differences, such as the reduced internal diameter of the tubing or lack of nebulization gas, exist because of the difference in flow rate. These variants are important because they generally offer better sensitivity over traditional electrospray. The µ and nano designations refer to the flow rate of the analyte containing liquid; µLiters/minute and nanoLiters/minute respectively.

Applications

Liquid chromatography-mass spectrometry

see also the main article on liquid chromatography-mass spectrometry

Electrospray ionization is the primary ion source used in liquid chromatography-mass spectrometry. This is due to being a liquid-gas interface that is capable of coupling liquid chomatography with mass spectrometry.

Noncovalent gas phase interactions

Electrospray ionization is also ideal in studying noncovalent gas phase interactions. The electrospray process is capable of transferring liquid-phase noncovalent complexes into the gas phase without disrupting the noncovalent interaction. This means that a cluster of two molecules can be studied in the gas phase by other mass spectrometry techniques. An interesting example of this is studying the interactions between enzymes and drugs which are inhibitors of the enzyme. Because inhibitors generally work by noncovalently binding to its target enzyme with reasonable affinity the noncovalent complex can be studied in this way. Competition studies have been done in this way to screen for potential new drug candidates.

Collodial thrusters

Electrospray techniques are employed in the control of satellites by allowing precise and effective thrusts. Here the method's property of fine-controllable particle ejection is put to use.

Deposition of particles for nanostructures

In nanotechnology the electrospray method may be employed to deposit single particles on surfaces. This is accomplished by spraying colloids and making sure that in average there is not more than one particle per droplet. Consequent drying of the surrounding solvent results in an aerosol stream of single particles of the desired type. Here the ionizing property of the process is not crucial for the application but may be put to use in electrostatic precipitation of the particles.