Editing Ion source (section)

==Spray ionization==
[[File:Apci.png|thumb|300px|Atmospheric-pressure chemical ionization source]]
Spray ionization methods involve the formation of aerosol particles from a liquid [[Solution (chemistry)|solution]] and the formation of bare ions after solvent evaporation.<ref name="Dass2007">{{cite book|author=Chhabil Dass|title=Fundamentals of Contemporary Mass Spectrometry|url=https://books.google.com/books?id=CYx9wzBzlIsC|date=11 May 2007|publisher=John Wiley & Sons|isbn=978-0-470-11848-1|pages=45–57}}</ref>

Solvent-assisted ionization (SAI) is a method in which charged droplets are produced by introducing a solution containing analyte into a heated inlet tube of an atmospheric pressure ionization mass spectrometer.  Just as in Electrospray Ionization (ESI), desolvation of the charged droplets produces multiply charged analyte ions. Volatile and nonvolatile compounds are analyzed by SAI, and high voltage is not  required to achieve sensitivity comparable to ESI.<ref name="Pagnotti2011">{{cite journal |vauthors=Pagnotti VS, Chubatyi ND, McEwen CN |journal=Anal. Chem. |title=Solvent Assisted Inlet Ionization: an Ultrasensitive New Liquid Introduction Ionization Method for Mass Spectrometry |volume=83 |issue=11 |pages=3981–3985 |date=2011 |doi=10.1021/ac200556z |pmid=21528896}}</ref> Application of a voltage to the solution entering the hot inlet through a zero dead volume fitting connected to fused silica tubing produces ESI-like mass spectra, but with higher sensitivity.<ref name="Pagnotti2012">{{cite journal |vauthors=Pagnotti VS, Chakrabarty S, Harron AF, McEwen CN |title=Increasing the Sensitivity of Liquid Introduction Mass Spectrometry by Combining Electrospray Ionization and Solvent Assisted Inlet Ionization |journal=Anal. Chem. |volume=84 |issue=15 |pages=6828–6832 |date=2012 |doi=10.1021/ac3014115 |pmid=22742705}}</ref> The inlet tube to the mass spectrometer becomes the ion source.

===Matrix-Assisted Ionization===
Matrix-Assisted Ionization (MAI) is similar to MALDI in sample preparation, but a laser is not required to convert analyte molecules included in a matrix compound into gas-phase ions.  In MAI, analyte ions have charge states similar to electrospray ionization but obtained from a solid matrix rather than a solvent.  No voltage or laser is required, but a laser can be used to obtain spatial resolution for imaging.  Matrix-analyte samples are ionized in the vacuum of a mass spectrometer and can be inserted into the vacuum through an atmospheric pressure inlet. Less volatile matrices such as 2,5-dihydroxybenzoic acid require a hot inlet tube to produce analyte ions by MAI, but more volatile matrices such as 3-nitrobenzonitrile require no heat, voltage, or laser.  Simply introducing the matrix-analyte sample to the inlet aperture of an atmospheric pressure ionization mass spectrometer produces abundant ions. Compounds at least as large as bovine serum albumin [66 kDa] can be ionized with this method.<ref name="Trimpin2013">{{cite journal |vauthors=Trimpin S, Wang B, Lietz CB, Marshall DD, Richards AL, Inutan ED |title=New Ionization Processes and Applications for Use in Mass Spectrometry |journal=Rev. Biochem. Mol. Biol. |year=2013 |volume=48 |issue=5 |pages=409–429|doi=10.3109/10409238.2013.806887 |pmid=23883414 }}</ref> In this method, the inlet to the mass spectrometer can be considered the ion source.

===Atmospheric-pressure chemical ionization===
{{Main|Atmospheric-pressure chemical ionization}}
Atmospheric-pressure chemical ionization uses a solvent spray at atmospheric pressure.<ref name="pmid17405144">{{cite journal |vauthors=Prakash C, Shaffer CL, Nedderman A |title=Analytical strategies for identifying drug metabolites |journal=Mass Spectrometry Reviews |volume=26 |issue=3 |pages=340–69 |date=2007 |pmid=17405144 |doi=10.1002/mas.20128|bibcode = 2007MSRv...26..340P }}</ref> A spray of solvent is heated to relatively high temperatures (above 400 degrees Celsius), sprayed with high flow rates of nitrogen and the entire aerosol cloud is subjected to a [[corona discharge]] that creates ions with the evaporated solvent acting as the chemical ionization reagent gas. APCI is not as "soft" (low fragmentation) an ionization technique as ESI.<ref name="pmid16723751">{{cite journal |vauthors=Zaikin VG, Halket JM |title=Derivatization in mass spectrometry--8. Soft ionization mass spectrometry of small molecules |journal=European Journal of Mass Spectrometry |volume=12 |issue=2 |pages=79–115 |date=2006 |pmid=16723751 |doi=10.1255/ejms.798|s2cid=34838846 }}</ref> Note that atmospheric pressure ionization (API) should not be used as a synonym for APCI.<ref>{{Cite book|date=2009|doi=10.1351/goldbook.A00492|chapter=Atmospheric pressure ionization in mass spectrometry|title = IUPAC Compendium of Chemical Terminology|isbn = 978-0-9678550-9-7}}</ref>

===Thermospray ionization===
{{Main|Thermospray ionization}}
Thermospray ionization is a form of atmospheric pressure ionization in [[mass spectrometry]]. It transfers ions from the liquid phase to the gas phase for analysis. It is particularly useful in [[liquid chromatography-mass spectrometry]].<ref>{{cite journal | last1 = Blakley | first1 = C. R. | last2 = Carmody | first2 = J. J. | last3 = Vestal | first3 = M. L. | date = 1980| title = Liquid Chromatograph-Mass Spectrometer for Analysis of Nonvolatile Samples | journal = Analytical Chemistry | volume = 1980 | issue = 52| pages = 1636–1641|doi=10.1021/ac50061a025 }}</ref>

[[File:NanoESIFT.jpg|thumb|300px|Electrospray ion source]]

===Electrospray ionization===
{{Main|Electrospray ionization}}
In electrospray ionization, a liquid is pushed through a very small, charged and usually metal, [[capillary]].<ref>{{cite journal | doi = 10.1002/mas.1280090103 |author1=Fenn, J. B. |author2=Mann, M. |author3=Meng, C. K. |author4=Wong, S. F. |author5=Whitehouse, C. M. | title = Electrospray Ionization-Principles and Practice | journal = [[Mass Spectrometry Reviews]] | date = 1990 | volume = 9 | issue = 1 | pages = 37–70|bibcode = 1990MSRv....9...37F }}</ref> This liquid contains the substance to be studied, the [[analyte]], dissolved in a large amount of [[solvent]], which is usually much more [[Volatility (chemistry)|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 its anion or cation form. Because like charges repel, the liquid pushes itself out of the capillary and forms an aerosol, a mist of small droplets about 10 [[micro-|μm]] across. The aerosol is at least partially produced by a process involving the formation of a [[Taylor cone]] and a jet from the tip of this cone. An uncharged carrier gas such as [[nitrogen]] is sometimes used to help [[nebulizer|nebulize]] the liquid and to help evaporate the neutral solvent in the droplets. As the solvent evaporates, the analyte molecules are forced closer together, repel each other and break up the droplets. This process is called Coulombic fission because it is driven by repulsive [[Coulombic force]]s between charged molecules. The process repeats until the analyte is free of solvent and is a bare ion. The ions observed are created by the addition of a [[proton]] (a hydrogen ion) and denoted {{chem2|[M + H]+}}, or of another [[cation]] such as sodium ion, {{chem2|[M + Na]+}}, or the removal of a proton, {{chem2|[M \s H]-}}. Multiply charged ions such as {{chem2|[M + 2H]^{2+} }} are often observed. For [[macromolecules]], there can be many charge states, occurring with different frequencies; the charge can be as great as {{chem2|[M + 25H]^{25+} }}, for example.{{Citation needed|date=October 2024}}

====Probe electrospray ionization====
{{Main|Probe electrospray ionization}}
Probe electrospray ionization (PESI) is a modified version of electrospray, where the capillary for sample solution transferring is replaced by a sharp-tipped solid needle with periodic motion.<ref>{{cite journal |author1=Hiraoka K. |author2=Nishidate K. |author3=Mori K. |author4=Asakawa D. |author5=Suzuki S. | title = Development of probe electrospray using a solid needle | journal = [[Rapid Communications in Mass Spectrometry]] | date = 2007| volume = 21 | pages = 3139–3144 | doi = 10.1002/rcm.3201 | pmid = 17708527 | issue = 18| bibcode = 2007RCMS...21.3139H }}</ref>

===Contactless atmospheric pressure ionization===

Contactless atmospheric pressure ionization is a technique used for analysis of liquid and solid samples by mass spectrometry.<ref name="HsiehChang2011">{{cite journal|last1=Hsieh|first1=Cheng-Huan|last2=Chang|first2=Chia-Hsien|last3=Urban|first3=Pawel L.|last4=Chen|first4=Yu-Chie|title=Capillary Action-Supported Contactless Atmospheric Pressure Ionization for the Combined Sampling and Mass Spectrometric Analysis of Biomolecules|journal=Analytical Chemistry|volume=83|issue=8|date=2011|pages=2866–2869|issn=0003-2700|doi=10.1021/ac200479s|pmid=21446703}}</ref> Contactless API can be operated without an additional electric power supply (supplying voltage to the source emitter), gas supply, or [[syringe pump]]. Thus, the technique provides a facile means for analyzing chemical compounds by mass spectrometry at atmospheric pressure.

===Sonic spray ionization===

Sonic spray ionization is  method for creating ions from a liquid solution, for example, a mixture of methanol and water.<ref name="pmid8779414">{{cite journal |vauthors=Hirabayashi A, Sakairi M, Koizumi H |title=Sonic spray mass spectrometry |journal=Anal. Chem. |volume=67 |issue=17 |pages=2878–82 |date=1995 |pmid=8779414|doi=10.1021/ac00113a023}}</ref> A [[pneumatic]] nebulizer is used to turn the solution into a  [[supersonic]] spray of small droplets. Ions are formed when the solvent evaporates and the statistically unbalanced charge distribution on the droplets leads to a net charge and complete desolvation results in the formation of ions. Sonic spray ionization is used to analyze small organic molecules and drugs and can analyze large  molecules when an electric field is applied to the capillary to help increase the charge density and generate multiple charged ions of proteins.<ref>{{Cite journal|last1=Chen|first1=Tsung-Yi|last2=Lin|first2=Jia-Yi|last3=Chen|first3=Jen-Yi|last4=Chen|first4=Yu-Chie|date=2011-11-22|title=Ultrasonication-assisted spray ionization mass spectrometry for the analysis of biomolecules in solution|journal=Journal of the American Society for Mass Spectrometry|language=en|volume=21|issue=9|pages=1547–1553|doi=10.1016/j.jasms.2010.04.021|pmid=20547459|issn=1044-0305|doi-access=free|bibcode=2010JASMS..21.1547C }}</ref>

Sonic spray ionization has been coupled with [[high performance liquid chromatography]] for the analysis of drugs.<ref name="pmid11908800">{{cite journal |vauthors=Arinobu T, Hattori H, Seno H, Ishii A, Suzuki O |title=Comparison of SSI with APCI as an interface of HPLC-mass spectrometry for analysis of a drug and its metabolites |journal=J. Am. Soc. Mass Spectrom. |volume=13 |issue=3 |pages=204–208 |date=2002 |pmid=11908800 |doi=10.1016/S1044-0305(01)00359-2|doi-access=free |bibcode=2002JASMS..13..204A }}</ref><ref name="pmid12141684">{{cite journal |vauthors=Dams R, Benijts T, Günther W, Lambert W, De Leenheer A |title=Sonic spray ionization technology: performance study and application to a LC/MS analysis on a monolithic silica column for heroin impurity profiling |journal=Anal. Chem. |volume=74 |issue=13 |pages=3206–3212 |date=2002 |pmid=12141684 |doi=10.1021/ac0112824}}</ref> Oligonucleotides have been studied with this method.<ref name="pmid11990592">{{cite journal |vauthors=Huang M, Hirabayashi A, Okumura A, Hirabayashi Y |title=Matrix effect on the analysis of oligonucleotides by using a mass spectrometer with a sonic spray ionization source |journal=Anal Sci |volume=17 |issue=10 |pages=1179–1182 |date=2001 |pmid=11990592 |doi=10.2116/analsci.17.1179|doi-access=free }}</ref><ref name="pmid11999509">{{cite journal |vauthors=Huang M, Hirabayashi A |title=Multi-charged oligonucleotide ion formation in sonic spray ionization |journal=Anal Sci |volume=18 |issue=4 |pages=385–390 |date=2002 |pmid=11999509 |doi=10.2116/analsci.18.385|doi-access=free }}</ref> SSI has been used in a manner similar to desorption electrospray ionization<ref name="pmid16941547">{{cite journal |vauthors=Haddad R, Sparrapan R, Eberlin MN |title=Desorption sonic spray ionization for (high) voltage-free ambient mass spectrometry |journal=Rapid Commun. Mass Spectrom. |volume=20 |issue=19 |pages=2901–2905 |date=2006 |pmid=16941547 |doi=10.1002/rcm.2680|bibcode=2006RCMS...20.2901H }}</ref> for [[ambient ionization]] and has been coupled with [[thin-layer chromatography]] in this manner.<ref name="pmid18331004">{{cite journal |vauthors=Haddad R, Milagre HM, Catharino RR, Eberlin MN |title=Easy Ambient Sonic-Spray Ionization Mass Spectrometry Combined with Thin-Layer Chromatography |journal=Anal. Chem. |volume= 80|issue= 8|pages= 2744–2750|date=2008 |pmid=18331004 |doi=10.1021/ac702216q}}</ref>

===Ultrasonication-assisted spray ionization===

Ultrasonication-assisted spray ionization (UASI) is similar to the above techniques but uses an ultrasonic transducer to achieve atomization of the material and generate ions.<ref>{{cite journal|last=Chen|first=Tsung-Yi|title=Ultrasonication-assisted spray ionization mass spectrometry for the analysis of biomolecules in solution|journal=Journal of the American Society for Mass Spectrometry|author2=Lin, Jia-Yi |author3=Chen, Jen-Yi |author4=Chen, Yu-Chie |pages=1547–1553|doi=10.1016/j.jasms.2010.04.021 |pmid=20547459|volume=21|issue=9|year=2010|doi-access=free|bibcode=2010JASMS..21.1547C }}</ref><ref>{{Cite journal|last=Chen|first=Tsung-Yi|title=Ultrasonication-assisted spray ionization mass spectrometry for on-line monitoring of organic reactions|url=https://zenodo.org/record/999715|journal=Chemical Communications|volume=46|issue=44|pages=8347–9|access-date=4 November 2011|author2=Chao, Chin-Sheng |author3=Mong, Kwok-Kong Tony |author4=Chen, Yu-Chie |doi=10.1039/C0CC02629H|pmid=20957254|date=4 November 2010}}</ref>