Droplets, electrospray

Deflection and disintegration of liquid droplets falling past a wire held at +6 000 V. [From D. B. Hager and N. J. Dovlchi, Behavior of Microscopic Liquid Droplets Near a Strong Electrostatic Field Droplet Electrospray"Anal. Chem. 1994,66, IS93. 

See also D. B. Hager, N. J. Dovlchi, J. Klassen, and P. Kebarie, Droplet Electrospray Mass Spectrometry," Anal. Chem. 1994, 66,3944 ]... 

Fused Droplet Electrospray Ionization and Extractive Electrospray Ionization... 

Sun, S., Kennedy, R.T. (2014) Droplet Electrospray Ionization Mass Spectrometry for High Throughput Screening for Enzyme Inhibitors. Anal. Chem. 86 9309-9314. 

Chang, D.Y., Lee, C.C., Shiea, J. (2002) Detecting large biomolecules from high-salt solutions by fused-droplet electrospray ionization mass spectrometry. Analytical Chemistry, 74, 2465-2469. 

Electrospray laser desorption ionization (ELDI) is a technique developed for characterizing solid, liqnid, and gas samples without or with minimal sample pretreatment [33]. An ELDI sonrce consists of a sample plate, a laser beam, and an electrospray nnit. Unlike MALDI, no application of organic matrix on the sample is needed before laser desorption. In ELDI, a pnlsed UV or IR laser beam is nsed to vaporize and desorb analytes on solid snrfaces the desorbed analytes are snbseqnently ionized in an ESI plnme positioned several millimeters above the laser spot. The ionization mechanisms of ELDI are similar to those of fused droplet-electrospray ionization (ED-ESI) [34], where charged solvent (e.g., methanol and water) species snch as H+,... 

Instead of a separate sample sprayer, an ultrasonic nebulizer may also deliver a sample-containing aerosol, which is transported and admixed to the electrospray mist by action of a mild stream of nitrogen. As the droplets of both origins are fused inside a small housing enclosing the spray, this approach has been termed jused-droplet electrospray ionization, and thus, led to the the somewhat confusing acronym FD-ESI [39,40]. 

Shieh, I.F. Lee, C.Y. Shiea, J. Eliminating the Interferences from TRIS Buffo and SDS in Protein Analysis by Fused-Droplet Electrospray Ionization Mass Spectrometry. J. Proteome Res. 2005, 4, 606-612. 

Grimm and Beauchamp have shown that the gas-phase ions ultimately resulting from FIDI can be detected with a mass spectrometer and that the method might have some analytical potential. These experiments bear some resemblance to earher work by Hager et al., who also produced neutral droplets with a vibrating orifice and then exposed them to a nonhomogeneous electric field near a rod electrode and detected the ions with a mass spectrometer. These authors named the method droplet electrospray. As could be expected, due to the small number of droplets, the sensitivity of the droplet method was much lower than that obtained with ESIMS. 

A solution of an analyte in a solvent can be sprayed (nebulized) from an electrically charged narrow tube to give small electrically charged droplets that desorb solvent molecules to leave ions of the analyte. This atmospheric-pressure ionization is known in various forms, the one most relevant to this section being called electrospray. For additional detail, see Chapters 8, 9, and 11. 

Aerosols can be produced as a spray of droplets by various means. A good example of a nebulizer is the common household hair spray, which produces fine droplets of a solution of hair lacquer by using a gas to blow the lacquer solution through a fine nozzle so that it emerges as a spray of small droplets. In use, the droplets strike the hair and settle, and the solvent evaporates to leave behind the nonvolatile lacquer. For mass spectrometry, a spray of a solution of analyte can be produced similarly or by a wide variety of other methods, many of which are discussed here. Chapters 8 ( Electrospray Ionization ) and 11 ( Thermospray and Plasmaspray Interfaces ) also contain details of droplet evaporation and formation of ions that are relevant to the discussion in this chapter. Aerosols are also produced by laser ablation for more information on this topic, see Chapters 17 and 18. 

The term nebulizer is used generally as a description for any spraying device, such as the hair spray mentioned above. It is normally applied to any means of forming an aerosol spray in which a volume of liquid is broken into a mist of vapor and small droplets and possibly even solid matter. There is a variety of nebulizer designs for transporting a solution of analyte in droplet form to a plasma torch in ICP/MS and to the inlet/ionization sources used in electrospray and mass spectrometry (ES/MS) and atmospheric-pressure chemical ionization and mass spectrometry (APCI/MS). 

For a discussion of droplet and ion formation in electrospray mass spectrometry, please see Chapter 8. 

Nebulizers are used to introduce analyte solutions as an aerosol spray into a mass spectrometer. For use with plasma torches, it is necessary to produce a fine spray and to remove as much solvent as possible before the aerosol reaches the flame of the torch. Various designs of nebulizer are available, but most work on the principle of interacting gas and liquid streams or the use of ultrasonic devices to cause droplet formation. For nebulization applications in thermospray, APCI, and electrospray, see Chapters 8 and 11. 

Electrospray uses an electric field to produce a spray of fine droplets. 

Eventually, not only neutral solvent molecules but also ions start to desorb from the surface of each droplet, Ions, residual droplets, and vapor formed by electrospray are extracted through a small hole into two evaporation chambers (evacuated) via a nozzle and a skimmer, passing from there into the analyzer of the mass spectrometer, where a mass spectrum of the original sample is obtained. 

A sample to be examined by electrospray is passed as a solution in a solvent (made up separately or issuing from a liquid chromatographic column) through a capillary tube held at high electrical potential, so the solution emerges as a spray or mist of small droplets (i.e., it is nebulized). As the droplets evaporate, residual sample ions are extracted into a mass spectrometer for analysis. 

Another big advance in the appHcation of ms in biotechnology was the development of atmospheric pressure ionization (API) techniques. There are three variants of API sources, a heated nebulizer plus a corona discharge for ionization (APCl) (51), electrospray (ESI) (52), and ion spray (53). In the APCl interface, the Ic eluent is converted into droplets by pneumatic nebulization, and then a sheath gas sweeps the droplets through a heated tube that vaporizes the solvent and analyte. The corona discharge ionizes solvent molecules, which protonate the analyte. Ions transfer into the mass spectrometer through a transfer line which is cryopumped, to keep a reasonable source pressure. 

Electrospray ionization mass spectrometry (ESI-MS) is an analytical method for mass determination of ionized molecules. It is a commonly used method for soft ionization of peptides and proteins in quadmpole, ion-trap, or time-of-flight mass spectrometers. The ionization is performed by application of a high voltage to a stream of liquid emitted from a capillaty. The highly charged droplets are shrunk and the resulting peptide or protein ions are sampled and separated by the mass spectrometer. 

The flow rate of liquid in the HPLC-electrospray system is paramount in determining performance both from chromatographic and mass spectrometric perspectives. The flow rate affects both the size and size distribution of the droplets formed during the electrospray process (not all droplets are the same size) and, consequently, the number of charges on each droplet. This, as we will see later, has an effect on the appearance of the mass spectrum which is generated. It should also be noted that the smaller the diameter of the spraying capillary, then... 

These solutions are not always practicable and HPLC flow rates of up to 2 mlmin may be accommodated directly by the use of electrospray in conjunction with pneumatically assisted nebulization (the combination is also known as lonspray ) and/or a heated source inlet. The former is accomplished experimentally by using a probe that provides a flow of gas concentrically to the mobile phase stream, as shown in Figure 4.8, which aids the formation of droplets from the bulk liquid, and will allow a flow rate of around 200 p. min to be used. 

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