View source for Physics:Matrix-assisted laser desorption electrospray ionization

'''Matrix-assisted laser desorption electrospray ionization''' ('''MALDESI''') was first introduced in 2006 as a novel [[Physics:Ambient ionization|ambient ionization technique]] which combines the benefits of [[Physics:Electrospray ionization|electrospray ionization (ESI)]] and matrix-assisted laser desorption/ionization (MALDI).<ref name=":0">{{Cite journal|last1=Sampson|first1=Jason S.|last2=Hawkridge|first2=Adam M.|last3=Muddiman|first3=David C.|date=December 2006|title=Generation and detection of multiply-charged peptides and proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) fourier transform ion cyclotron resonance mass spectrometry|journal=Journal of the American Society for Mass Spectrometry|volume=17|issue=12|pages=1712–1716|doi=10.1016/j.jasms.2006.08.003|pmid=16952462|s2cid=1727083|issn=1044-0305|doi-access=free}}</ref> An [[Physics:Infrared|infrared (IR)]] or [[Physics:Ultraviolet|ultraviolet (UV)]] [[Physics:Laser|laser]] can be utilized in MALDESI to [[Physics:Excited state|resonantly excite]] an endogenous or exogenous matrix. The term '[[Physics:Matrix (mass spectrometry)|matrix]]' refers to any molecule that is present in large excess and absorbs the energy of the laser, thus facilitating [[Physics:Desorption|desorption]] of analyte molecules. The original MALDESI design was implemented using common organic matrices, similar to those used in MALDI, along with a UV laser. The current MALDESI source employs endogenous water or a thin layer of exogenously deposited ice as the energy-absorbing matrix where O-H symmetric and asymmetric stretching bonds are resonantly excited by a mid-IR laser.<ref name=":1">{{Cite journal|last1=Robichaud|first1=Guillaume|last2=Barry|first2=Jeremy A.|last3=Muddiman|first3=David C.|date=2014-01-03|title=IR-MALDESI Mass Spectrometry Imaging of Biological Tissue Sections Using Ice as a Matrix|url= |journal=Journal of the American Society for Mass Spectrometry|volume=25|issue=3|pages=319–328|doi=10.1007/s13361-013-0787-6|pmid=24385399|pmc=3950934|bibcode=2014JASMS..25..319R|issn=1044-0305}}</ref> [[File:IR-MALDESI Imaging Schematic.png|300 px|thumb|The schematic of IR-MALDESI imaging source]]
The IR-MALDESI source can be used for [[Physics:Mass spectrometry imaging|mass spectrometry imaging (MSI)]], a technique using MS data analyzed from a sample area to detect hundreds to thousands of [[Physics:Biomolecule|biomolecule]]s and visualize their spatial distributions. The IR-MALDESI MSI source was designed and implemented in 2013,<ref name=":2">{{Cite journal|last1=Robichaud|first1=Guillaume|last2=Barry|first2=Jeremy A.|last3=Garrard|first3=Kenneth P.|last4=Muddiman|first4=David C.|date=2012-12-04|title=Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Imaging Source Coupled to a FT-ICR Mass Spectrometer|url= |journal=Journal of the American Society for Mass Spectrometry|volume=24|issue=1|pages=92–100|doi=10.1007/s13361-012-0505-9|pmid=23208743|pmc=3689149|issn=1044-0305}}</ref> and is coupled to a high resolving power hybrid [[Physics:Quadrupole mass analyzer|Quadrupole]]-[[Physics:Orbitrap|Orbitrap]] mass spectrometer. The computer controlled motorized stage and a charge-coupled device (CCD) camera are placed in a nitrogen purged enclosure where ambient ions and relative humidity can be regulated. A water-cooled Peltier thermoelectric plate is used to control the sample stage temperature (−10&nbsp;°C to 80&nbsp;°C). The source has single- or multi-shot capabilities with adjustable laser fluence, repetition rate, and delay between the laser trigger and MS ion accumulation.

Over the past ten years, transformative developments in the laser technology,<ref name=":3">{{Cite journal|last1=Ekelöf|first1=Måns|last2=Manni|first2=Jeffrey|last3=Nazari|first3=Milad|last4=Bokhart|first4=Mark|last5=Muddiman|first5=David C.|date=2018-02-17|title=Characterization of a novel miniaturized burst-mode infrared laser system for IR-MALDESI mass spectrometry imaging|url= |journal=Analytical and Bioanalytical Chemistry|volume=410|issue=9|pages=2395–2402|doi=10.1007/s00216-018-0918-9|pmid=29455285|pmc=5851870|issn=1618-2642}}</ref> data acquisition, motor-control software (RastirX<ref name=":4">{{Cite journal|last1=Garrard|first1=Kenneth P.|last2=Ekelöf|first2=Måns|last3=Khodjaniyazova|first3=Sitora|last4=Bagley|first4=M. Caleb|last5=Muddiman|first5=David C.|date=2020-12-02|title=A Versatile Platform for Mass Spectrometry Imaging of Arbitrary Spatial Patterns|url=https://doi.org/10.1021/jasms.0c00128|journal=Journal of the American Society for Mass Spectrometry|volume=31|issue=12|pages=2547–2552|doi=10.1021/jasms.0c00128|pmid=32539373|pmc=8761386|s2cid=219700969|issn=1044-0305}}</ref>), and imaging processing software (MSiReader<ref name=":5">{{Cite journal|last1=Robichaud|first1=Guillaume|last2=Garrard|first2=Kenneth P.|last3=Barry|first3=Jeremy A.|last4=Muddiman|first4=David C.|date=2013-03-28|title=MSiReader: An Open-Source Interface to View and Analyze High Resolving Power MS Imaging Files on Matlab Platform|url= |journal=Journal of the American Society for Mass Spectrometry|volume=24|issue=5|pages=718–721|doi=10.1007/s13361-013-0607-z|pmid=23536269|pmc=3693088|bibcode=2013JASMS..24..718R|issn=1044-0305}}</ref><ref name=":6">{{Cite journal|last1=Bokhart|first1=Mark T.|last2=Nazari|first2=Milad|last3=Garrard|first3=Kenneth P.|last4=Muddiman|first4=David C.|date=2017-09-20|title=MSiReader v1.0: Evolving Open-Source Mass Spectrometry Imaging Software for Targeted and Untargeted Analyses|url= |journal=Journal of the American Society for Mass Spectrometry|volume=29|issue=1|pages=8–16|doi=10.1007/s13361-017-1809-6|pmid=28932998|pmc=5786496|issn=1044-0305}}</ref>) have promoted IR-MALDESI as a powerful tool for the direct analysis and MSI of diverse biological, forensic, and pharmaceutical samples.

==Principles of operation==

In a typical MALDESI MS experiment, a thin layer of ice is deposited on the sample as the energy-absorbing medium. A [[Physics:Infrared|mid-IR laser]]<ref name=":3" /> that excites the O-H stretching mode of water is used to [[Physics:Desorption|desorb]] the neutral materials from the biological samples. The plume of desorbed compounds interacts with an orthogonal electrospray plume where they partition into charged electrospray droplets and are ionized via a process similar to ESI. The ions are subsequently introduced into a mass spectrometer.<ref name=":1" /> The ESI-like ionization mechanism has been experimentally demonstrated and studied in depth,<ref name=":7">{{Cite journal|last1=Dixon|first1=R. Brent|last2=Muddiman|first2=David C.|date=2010|title=Study of the ionization mechanism in hybrid laser based desorption techniques|url=http://dx.doi.org/10.1039/b926422a|journal=The Analyst|volume=135|issue=5|pages=880–2|doi=10.1039/b926422a|pmid=20419234|bibcode=2010Ana...135..880D|issn=0003-2654}}</ref><ref name=":8">{{Cite journal|last1=Rosen|first1=Elias P.|last2=Bokhart|first2=Mark T.|last3=Ghashghaei|first3=H. Troy|last4=Muddiman|first4=David C.|date=2015-04-04|title=Influence of Desorption Conditions on Analyte Sensitivity and Internal Energy in Discrete Tissue or Whole Body Imaging by IR-MALDESI|url= |journal=Journal of the American Society for Mass Spectrometry|volume=26|issue=6|pages=899–910|doi=10.1007/s13361-015-1114-1|pmid=25840812|pmc=4425634|bibcode=2015JASMS..26..899R|issn=1044-0305}}</ref><ref name=":9">{{Cite journal|last1=Tu|first1=Anqi|last2=Muddiman|first2=David C.|date=2019-09-09|title=Internal Energy Deposition in Infrared Matrix-Assisted Laser Desorption Electrospray Ionization With and Without the Use of Ice as a Matrix|url= |journal=Journal of the American Society for Mass Spectrometry|volume=30|issue=11|pages=2380–2391|doi=10.1007/s13361-019-02323-2|pmid=31502226|pmc=6937789|bibcode=2019JASMS..30.2380T|issn=1044-0305}}</ref> showing equivalent softness as ESI and enabling the detection of intact protein complexes.

The formation of ice matrix starts with purging the enclosure to below 12% relative humidity with the dry nitrogen gas source prior to cooling the Peltier stage down to −10&nbsp;°C. Afterwards, the cooled sample is exposed to ambient relative humidity, causing the rapid formation of an ice layer on the sample. The ice thickness is maintained throughout the entire experiment by keeping the relative humidity of the enclosure at 10%±2% via the nitrogen purged enclosure.<ref name=":1" /> Previously, ice was used as a matrix in IR-MALDI experiments;<ref>{{Cite journal|last1=Nelson|first1=R.|last2=Rainbow|first2=M.|last3=Lohr|first3=D.|last4=Williams|first4=P|date=1989-12-22|title=Volatilization of high molecular weight DNA by pulsed laser ablation of frozen aqueous solutions|url=http://dx.doi.org/10.1126/science.2595370|journal=Science|volume=246|issue=4937|pages=1585–1587|doi=10.1126/science.2595370|pmid=2595370|bibcode=1989Sci...246.1585N|issn=0036-8075}}</ref> however, the ion yields for such experiments have been very low. The electrospray post-ionization employed in IR-MALDESI helps alleviate issues associated with low ionization yield. An exogenously deposited ice matrix has been shown to improve the ion abundance by a factor of approximately 15.<ref name=":10">{{Cite journal|last1=Barry|first1=Jeremy A.|last2=Robichaud|first2=Guillaume|last3=Bokhart|first3=Mark T.|last4=Thompson|first4=Corbin|last5=Sykes|first5=Craig|last6=Kashuba|first6=Angela D. M.|last7=Muddiman|first7=David C.|date=2014-04-18|title=Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay|url= |journal=Journal of the American Society for Mass Spectrometry|volume=25|issue=12|pages=2038–2047|doi=10.1007/s13361-014-0884-1|pmid=24744212|pmc=4201889|bibcode=2014JASMS..25.2038B|issn=1044-0305}}</ref>

MALDESI is a complex interactive system, making it challenging to generate the optimum geometry in just one single experiment. The experimental settings involved in the communication between the sampling stage, mass spectrometer and laser desorption, such as stage height, ESI-Spot distance and laser repetition rate, have undergone progressive optimization by several design of experiments (DOE).<ref name=":11">{{Cite journal|last1=Barry|first1=Jeremy A.|last2=Muddiman|first2=David C.|date=2011-11-08|title=Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments|url= |journal=Rapid Communications in Mass Spectrometry|volume=25|issue=23|pages=3527–3536|doi=10.1002/rcm.5262|pmid=22095501|pmc=3781580|bibcode=2011RCMS...25.3527B|issn=0951-4198}}</ref><ref name=":8" /><ref name=":1" /> In addition to the source geometry optimization, the electrospray solvent composition has an effect on the MALDESI signals (i.e. influencing molecular coverage and ion abundance). In a study to improve the detection of tissue-specific lipids, the electrospray parameters have been tailored for positive and negative ionization polarities. Under the optimal parameters, lipid abundances increased by 3-fold with 15% greater coverage in positive polarity, while in negative mode lipid abundance achieved 1.5-fold increase with 10% more coverage.<ref name=":12">{{Cite journal|last1=Bagley|first1=M. Caleb|last2=Ekelöf|first2=Måns|last3=Muddiman|first3=David C.|date=2020-02-05|title=Determination of Optimal Electrospray Parameters for Lipidomics in Infrared-Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging|url=https://doi.org/10.1021/jasms.9b00063|journal=Journal of the American Society for Mass Spectrometry|volume=31|issue=2|pages=319–325|doi=10.1021/jasms.9b00063|pmid=32031399|s2cid=211045862|issn=1044-0305}}</ref>

While the first generation of MALDESI system was coupled to [[Fourier transform]] (FT) ion cyclotron resonance mass spectrometer,<ref name=":2" /> the current source is interfaced with a Thermo Exploris 240 or a Q Exactive Plus mass spectrometer equipped with an [[Physics:Orbitrap|Orbitrap mass analyzer]]. These mass analyzers offer equally accurate mass measurements but generally shorten the data acquisition duration. MALDESI source can also be coupled to drift tube [[Ion-mobility spectrometry–mass spectrometry|ion mobility spectrometer]]-mass spectrometer (IMS-MS) for high-throughput screening.<ref>{{Cite journal|last1=Ekelöf|first1=Måns|last2=Dodds|first2=James|last3=Khodjaniyazova|first3=Sitora|last4=Garrard|first4=Kenneth P.|last5=Baker|first5=Erin S.|last6=Muddiman|first6=David C.|date=2020-03-04|title=Coupling IR-MALDESI with Drift Tube Ion Mobility-Mass Spectrometry for High-Throughput Screening and Imaging Applications|url= |journal=Journal of the American Society for Mass Spectrometry|volume=31|issue=3|pages=642–650|doi=10.1021/jasms.9b00081|issn=1044-0305|pmc=7263366|pmid=31971795}}</ref> These integrations provide more reliable raw data for MSI as well as direct analysis of various biological specimens because long analysis time could cause physiological changes to the samples under interrogation.

== MSiReader ==
MSiReader is a [[Software:MATLAB|Matlab]] application, providing visualization and analyses of high-resolution accurate mass data collected via MALDESI. MSiReader was developed at North Carolina State University and was first released in 2013.<ref name=":5" /> It has now become one of the most important free, open-source software options for MSI data,<ref name=":6" /> and is compatible with most common MSI data formats (e.g., [[Biology:Mass spectrometry data format|mzXML, imzML, img, ASCII]]). There are many essential functions available in MSiReader, namely heat map generation with high mass measurement accuracy,<ref name=":6" /> peak normalization,<ref>{{Cite journal|last1=Tu|first1=Anqi|last2=Muddiman|first2=David C.|date=2019-06-25|title=Systematic evaluation of repeatability of IR-MALDESI-MS and normalization strategies for correcting the analytical variation and improving image quality|url= |journal=Analytical and Bioanalytical Chemistry|volume=411|issue=22|pages=5729–5743|doi=10.1007/s00216-019-01953-5|pmid=31240357|pmc=6706294|issn=1618-2642}}</ref> absolute and relative quantification,<ref name=":6" /><ref name=":13">{{Cite journal|last1=Rosen|first1=Elias P.|last2=Thompson|first2=Corbin G.|last3=Bokhart|first3=Mark T.|last4=Prince|first4=Heather M. A.|last5=Sykes|first5=Craig|last6=Muddiman|first6=David C.|last7=Kashuba|first7=Angela D. M.|date=2016-01-19|title=Analysis of Antiretrovirals in Single Hair Strands for Evaluation of Drug Adherence with Infrared-Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging|url= |journal=Analytical Chemistry|volume=88|issue=2|pages=1336–1344|doi=10.1021/acs.analchem.5b03794|issn=0003-2700|pmc=5301654|pmid=26688545}}</ref> and polarity switching.<ref>{{Cite journal|last1=Nazari|first1=Milad|last2=Muddiman|first2=David C.|date=2016-01-04|title=Polarity switching mass spectrometry imaging of healthy and cancerous hen ovarian tissue sections by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)|url= |journal=Analyst|language=en|volume=141|issue=2|pages=595–605|doi=10.1039/C5AN01513H|issn=1364-5528|pmc=4701606|pmid=26402586|bibcode=2016Ana...141..595N}}</ref> Advanced features like [[Principal component analysis|principal component analysis]] (MSiPCA), MSiCorrelation,<ref>{{Cite journal|last1=Ekelöf|first1=Måns|last2=Garrard|first2=Kenneth P.|last3=Judd|first3=Rika|last4=Rosen|first4=Elias P.|last5=Xie|first5=De-Yu|last6=Kashuba|first6=Angela D. M.|last7=Muddiman|first7=David C.|date=2018-12-01|title=Evaluation of Digital Image Recognition Methods for Mass Spectrometry Imaging Data Analysis|url= |journal=Journal of the American Society for Mass Spectrometry|volume=29|issue=12|pages=2467–2470|doi=10.1007/s13361-018-2073-0|issn=1044-0305|pmc=6250575|pmid=30324263|bibcode=2018JASMS..29.2467E}}</ref> and 3D visualization<ref name=":14">{{Cite journal|last1=Bai|first1=Hongxia|last2=Khodjaniyazova|first2=Sitora|last3=Garrard|first3=Kenneth P.|last4=Muddiman|first4=David C.|date=2020-02-05|title=Three-Dimensional Imaging with Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry|url=https://doi.org/10.1021/jasms.9b00066|journal=Journal of the American Society for Mass Spectrometry|volume=31|issue=2|pages=292–297|doi=10.1021/jasms.9b00066|pmid=32031410|issn=1044-0305|pmc=8284694}}</ref><ref name=":15">{{Cite journal|last1=Bai|first1=Hongxia|last2=Linder|first2=Keith E.|last3=Muddiman|first3=David C.|date=2021-01-02|title=Three-dimensional (3D) imaging of lipids in skin tissues with infrared matrix-assisted laser desorption electrospray ionization (MALDESI) mass spectrometry|journal=Analytical and Bioanalytical Chemistry|volume=413|issue=10|pages=2793–2801|language=en|doi=10.1007/s00216-020-03105-6|pmid=33388847|pmc=8285079|s2cid=230110155|issn=1618-2650|doi-access=free}}</ref> have also been added to MSiReader. To date, MSiReader is used by over 1250 researchers and cited in more than 325 publications since 2013. It is released under the BSD 3 open-source license and can be downloaded freely from the public MSiReader website [https://msireader.wordpress.ncsu.edu/ www.msireader.com]. A standalone version that does not require a Matlab license is also available.

== RastirX ==
The Rastir software, also built on a Matlab platform, was developed to enable users to visually define a rectangular [[Region of interest|region-of-interest]] (ROI) surrounding a tissue section for MALDESI experiments. Motion control commands and laser and instrument synchronization parameters are automatically generated by Rastir to move the sample stage under the laser beam to acquire the MS data voxel-by-voxel. The latest software version, denoted RastirX, allows users to draw arbitrary ROI on a live video image of a sample with the computer mouse. The ROI can be further modified scan-by-scan, which leads to a significantly shorter acquisition time and less contamination from off-tissue compounds than using a rectangular ROI. This arbitrary ROI tool has been applied in several projects.<ref name=":4" /><ref name=":16">{{Cite journal|last1=Khodjaniyazova|first1=Sitora|last2=Hanne|first2=Nicholas J.|last3=Cole|first3=Jacqueline H.|last4=Muddiman|first4=David C.|date=2019-11-28|title=Mass spectrometry imaging (MSI) of fresh bones using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)|url= |journal=Analytical Methods|language=en|volume=11|issue=46|pages=5929–5938|doi=10.1039/C9AY01886G|pmid=33815571|issn=1759-9679|pmc=8018523}}</ref>

==Applications==

Since its debut in 2006, MALDESI has experienced great advancements in laser technology (from UV lasers to various mid-IR wavelength lasers),<ref name=":0" /><ref name=":3" /><ref name=":17">{{Cite journal|last1=Sampson|first1=Jason S.|last2=Murray|first2=Kermit K.|last3=Muddiman|first3=David C.|date=2009-04-01|title=Intact and top-down characterization of biomolecules and direct analysis using infrared matrix-assisted laser desorption electrospray ionization coupled to FT-ICR mass spectrometry|url= |journal=Journal of the American Society for Mass Spectrometry|volume=20|issue=4|pages=667–673|doi=10.1016/j.jasms.2008.12.003|issn=1044-0305|pmc=3717316|pmid=19185512}}</ref> ESI settings<ref name=":8" /><ref name=":11" /><ref name=":12" /> and associated software.<ref name=":4" /><ref name=":5" /><ref name=":6" /><ref name=":7" /><ref name=":8" /> All the progress has made IR-MALDESI a competitive imaging and direct analysis tool to investigate a wide variety of biological samples. By associating ''[[Physics:Mass-to-charge ratio|m/z]]'' with positions where they are acquired, unique ion maps of analytes can be generated, which provides valuable information for spatial distributions of [[Chemistry:Lipid|lipid]]s, [[Chemistry:Peptide|peptide]]s, [[Biology:Metabolomics|metabolomics]], and other small biomolecules from mammalian samples<ref name=":0" /><ref name=":10" /><ref name=":15" /><ref name=":17" /><ref name=":12"/><ref name=":18">{{Cite journal|last1=Bokhart|first1=Mark T.|last2=Rosen|first2=Elias|last3=Thompson|first3=Corbin|last4=Sykes|first4=Craig|last5=Kashuba|first5=Angela D. M.|last6=Muddiman|first6=David C.|date=2015-03-01|title=Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization|url= |journal=Analytical and Bioanalytical Chemistry|language=en|volume=407|issue=8|pages=2073–2084|doi=10.1007/s00216-014-8220-y|issn=1618-2650|pmc=4495968|pmid=25318460}}</ref> to plant tissues.<ref name=":19">{{Cite journal|last1=Bagley|first1=M. Caleb|last2=Pace|first2=Crystal L.|last3=Ekelöf|first3=Måns|last4=Muddiman|first4=David C.|date=2020|title=Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging analysis of endogenous metabolites in cherry tomatoes|url= |journal=The Analyst|volume=145|issue=16|pages=5516–5523|doi=10.1039/d0an00818d|pmid=32602477|pmc=7423647|bibcode=2020Ana...145.5516B|issn=0003-2654}}</ref><ref>{{Cite journal|last1=Kalmar|first1=Jaclyn Gowen|last2=Oh|first2=Yeonyee|last3=Dean|first3=Ralph A.|last4=Muddiman|first4=David C.|date=2019-11-23|title=Investigating host-pathogen meta-metabolic interactions of Magnaporthe oryzae infected barley using infrared matrix-assisted laser desorption electrospray ionization mass spectrometry|url=http://dx.doi.org/10.1007/s00216-019-02216-z|journal=Analytical and Bioanalytical Chemistry|volume=412|issue=1|pages=139–147|doi=10.1007/s00216-019-02216-z|pmid=31760448|s2cid=208261491|issn=1618-2642}}</ref><ref name=":20">{{Cite journal|last1=Bagley|first1=M. Caleb|last2=Stepanova|first2=Anna N.|last3=Ekelöf|first3=Måns|last4=Alonso|first4=Jose M.|last5=Muddiman|first5=David C.|date=2020|title=Development of a relative quantification method for infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging of Arabidopsis seedlings|journal=Rapid Communications in Mass Spectrometry|language=en|volume=34|issue=6|pages=e8616|doi=10.1002/rcm.8616|pmid=31658400|issn=1097-0231|doi-access=free}}</ref>

=== Biological ===

==== Proteins and peptides ====
The ESI-like process enabled MALDESI to detect multiply charged peptides and proteins, which could not be realized by MALDI because MALDI generates primarily singly- and doubly-charged ions.<ref name=":0" />

==== Lipids and metabolomics ====
IR-MALDESI has been successfully applied for visualizing lipid distributions on the whole-body level, namely neonatal mouse<ref name=":18" /> and zebrafish.<ref>{{Cite journal|last1=Stutts|first1=Whitney L.|last2=Knuth|first2=Megan M.|last3=Ekelöf|first3=Måns|last4=Mahapatra|first4=Debabrata|last5=Kullman|first5=Seth W.|last6=Muddiman|first6=David C.|date=2020-04-01|title=Methods for Cryosectioning and Mass Spectrometry Imaging of Whole-Body Zebrafish|url=https://doi.org/10.1021/jasms.9b00097|journal=Journal of the American Society for Mass Spectrometry|volume=31|issue=4|pages=768–772|doi=10.1021/jasms.9b00097|pmid=32129621|pmc=9375048 |s2cid=212407131|issn=1044-0305}}</ref> By employing oversampling method<ref>{{Cite journal|last1=Jurchen|first1=John C.|last2=Rubakhin|first2=Stanislav S.|last3=Sweedler|first3=Jonathan V.|date=October 2005|title=MALDI-MS imaging of features smaller than the size of the laser beam|journal=Journal of the American Society for Mass Spectrometry|volume=16|issue=10|pages=1654–1659|doi=10.1016/j.jasms.2005.06.006|pmid=16095912|s2cid=23884944|issn=1044-0305|doi-access=free}}</ref> where the stage moving distance is smaller than the laser beam diameter, IR-MALDESI MSI at the cellular level was achieved at a spot-to-spot distance of ~10 micrometer.<ref>{{Cite journal|last1=Nazari|first1=Milad|last2=Muddiman|first2=David C.|date=2015-03-01|title=Cellular-level mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) by oversampling|url= |journal=Analytical and Bioanalytical Chemistry|language=en|volume=407|issue=8|pages=2265–2271|doi=10.1007/s00216-014-8376-5|issn=1618-2650|pmc=4359048|pmid=25486925}}</ref> Moreover, the lipidomic detectability of IR-MALDESI at the single-cell level has been demonstrated with isolated [[Biology:HeLa|HeLa cell]].<ref>{{Cite journal|last1=Xi|first1=Ying|last2=Tu|first2=Anqi|last3=Muddiman|first3=David C.|date=2020-11-01|title=Lipidomic profiling of single mammalian cells by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)|url= |journal=Analytical and Bioanalytical Chemistry|language=en|volume=412|issue=29|pages=8211–8222|doi=10.1007/s00216-020-02961-6|issn=1618-2650|pmc=7606626|pmid=32989513}}</ref>

In addition to soft tissues (e.g., hen ovaries<ref>{{Cite journal|last1=Lakeh|first1=Mahsa Akbari|last2=Tu|first2=Anqi|last3=Muddiman|first3=David C.|last4=Abdollahi|first4=Hamid|date=2019|title=Discriminating normal regions within cancerous hen ovarian tissue using multivariate hyperspectral image analysis|url=https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/rcm.8362|journal=Rapid Communications in Mass Spectrometry|language=en|volume=33|issue=4|pages=381–391|doi=10.1002/rcm.8362|pmid=30468547|bibcode=2019RCMS...33..381A|s2cid=53715626|issn=1097-0231}}</ref> and rat liver tissues<ref name=":9" />), IR-MALDESI is capable to detect metabolites from unmodified healthy and stroke-affected mouse bones embedded in plaster of Paris, resulting in putatively annotated 826 and 669 tissue-specific species.<ref name=":16" />

IR-MALDESI is an invaluable tool to study metabolism of plant and vegetable samples, as these samples are naturally rich in water. An extensive metabolomic analysis of cherry tomatoes by IR-MALDESI was recently reported.<ref name=":19" /> In the analysis of [[Biology:Arabidopsis|''Arabidopsis'' seedlings]], the amounts of [[Biology:Auxin|auxin-related]] compounds, was relatively quantified using stable-isotope-labelled (SIL) [[Chemistry:Indole-3-acetic acid|indole-3-acetic acid]] (IAA). Moreover, in this study, agarose was used as an appropriate substrate for first time used in IR-MALDESI.<ref name=":20" />

==== Neurotransmitters ====
IR-MALDESI has shown the ability to measure selected [[Biology:Neurotransmitter|neurotransmitter]]s in rat brains exposed to flame retardant [[Chemistry:Tetrabromobisphenol A|tetrabromobisphenol A]] without any chemical derivatization.<ref>{{Cite journal|last1=Bagley|first1=M. Caleb|last2=Ekelöf|first2=Måns|last3=Rock|first3=Kylie|last4=Patisaul|first4=Heather|last5=Muddiman|first5=David C.|date=2018-12-01|title=IR-MALDESI mass spectrometry imaging of underivatized neurotransmitters in brain tissue of rats exposed to tetrabromobisphenol A|url= |journal=Analytical and Bioanalytical Chemistry|language=en|volume=410|issue=30|pages=7979–7986|doi=10.1007/s00216-018-1420-0|issn=1618-2650|pmc=6235718|pmid=30317443}}</ref> The follow-up work that focused on neurotransmitters and their pathway-related metabolites in rat placenta sections reported 49 putatively identified neurotransmitters and metabolites.<ref>{{Cite journal|last1=Pace|first1=Crystal L.|last2=Horman|first2=Brian|last3=Patisaul|first3=Heather|last4=Muddiman|first4=David C.|date=2020-06-01|title=Analysis of neurotransmitters in rat placenta exposed to flame retardants using IR-MALDESI mass spectrometry imaging|url= |journal=Analytical and Bioanalytical Chemistry|language=en|volume=412|issue=15|pages=3745–3752|doi=10.1007/s00216-020-02626-4|issn=1618-2650|pmc=7228838|pmid=32300844}}</ref>

==== Glycans ====
[[Chemistry:Glycan|Glycan]]s are structurally complex molecules that pose many analytical challenges. The direct analysis of ''N''-linked glycans from bovine fetuin by IR-MALDESI in both positive and negative ionization modes was presented, which indicates that IR-MALDESI can be an alternative technique for ''N''-linked glycans profiling.<ref>{{Cite journal|last1=Pace|first1=Crystal L.|last2=Muddiman|first2=David C.|date=2020-08-05|title=Direct Analysis of Native N-Linked Glycans by IR-MALDESI|url=https://doi.org/10.1021/jasms.0c00176|journal=Journal of the American Society for Mass Spectrometry|volume=31|issue=8|pages=1759–1762|doi=10.1021/jasms.0c00176|pmid=32603137|pmc=8285077|issn=1044-0305}}</ref>

==== Three dimensional MSI ====
Although most traditional 3D MSI build on reconstruction of 2D images of analytes from serial sections, the serial-section-based 3D imaging is time-consuming and can lose significant biological information. IR-MALDESI is an ablation-based technique, which is able to measure and generate 3D heat maps of biomolecules from pharmaceutical tablets<ref name=":14" /> and nude mouse skin<ref name=":15" /> by sequentially imaging a sample with consecutive ablation events.

=== Pharmaceutical ===
In a proof-of-concept study, [[Biology:HIV|HIV]] antiretroviral drugs in incubated cervical tissues were imaged and quantified using IR-MALDESI, and the results were evaluated by a validated LC-MS/MS method.<ref name=":10" /> So far, the pharmaceutical application of IR-MALDESI has extended from tissue sections<ref name=":10" /><ref name=":18" /><ref>{{Cite journal|last1=Thompson|first1=Corbin G.|last2=Bokhart|first2=Mark T.|last3=Sykes|first3=Craig|last4=Adamson|first4=Lourdes|last5=Fedoriw|first5=Yuri|last6=Luciw|first6=Paul A.|last7=Muddiman|first7=David C.|last8=Kashuba|first8=Angela D. M.|last9=Rosen|first9=Elias P.|date=2015-05-01|title=Mass Spectrometry Imaging Reveals Heterogeneous Efavirenz Distribution within Putative HIV Reservoirs|url= |journal=Antimicrobial Agents and Chemotherapy|language=en|volume=59|issue=5|pages=2944–2948|doi=10.1128/AAC.04952-14|issn=0066-4804|pmc=4394831|pmid=25733502}}</ref> to single hair strands.<ref name=":13" />

=== Forensic ===
Textile fibers are an important form of trace evidence for criminal investigation. One of the characteristics of [[Chemistry:Fiber|fiber]]s that can be used to distinguish the victim from the suspect is color generated by a fiber dye along with its associated impurities.<ref>{{Cite journal|last1=Goodpaster|first1=John V.|last2=Liszewski|first2=Elisa A.|date=2009-08-01|title=Forensic analysis of dyed textile fibers|url=https://doi.org/10.1007/s00216-009-2885-7|journal=Analytical and Bioanalytical Chemistry|language=en|volume=394|issue=8|pages=2009–2018|doi=10.1007/s00216-009-2885-7|pmid=19543886|s2cid=33680156|issn=1618-2650}}</ref> A direct analysis of the dye from the fabric was successfully performed using IR-MALDESI without prior separation by [[Physics:Chromatography|chromatography]].<ref>{{Cite journal|last1=Cochran|first1=Kristin H.|last2=Barry|first2=Jeremy A.|last3=Muddiman|first3=David C.|last4=Hinks|first4=David|date=2013-01-15|title=Direct Analysis of Textile Fabrics and Dyes Using Infrared Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry|url= |journal=Analytical Chemistry|volume=85|issue=2|pages=831–836|doi=10.1021/ac302519n|issn=0003-2700|pmc=3654692|pmid=23237031}}</ref><ref>{{Cite journal|last1=Cochran|first1=Kristin H.|last2=Barry|first2=Jeremy A.|last3=Robichaud|first3=Guillaume|last4=Muddiman|first4=David C.|date=2015-01-01|title=Analysis of trace fibers by IR-MALDESI imaging coupled with high resolving power MS|url= |journal=Analytical and Bioanalytical Chemistry|language=en|volume=407|issue=3|pages=813–820|doi=10.1007/s00216-014-8042-y|issn=1618-2650|pmc=4967535|pmid=25081013}}</ref>

==Related techniques==

There are other hybrid ionization methods which combine resonant or non-resonant laser desorption with post electrospray ionization. One example is electrospray laser desorption ionization (ELDI), which uses an ultraviolet laser to form ions by irradiating the sample directly, then interacting with the electrospray plume without using any matrices.<ref>{{Cite journal|last1=Shiea|first1=Jentaie|last2=Huang|first2=Min-Zon|last3=HSu|first3=Hsiu-Jung|last4=Lee|first4=Chi-Yang|last5=Yuan|first5=Cheng-Hui|last6=Beech|first6=Iwona|last7=Sunner|first7=Jan|date=2005|title=Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids|url=https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/rcm.2243|journal=Rapid Communications in Mass Spectrometry|language=en|volume=19|issue=24|pages=3701–3704|doi=10.1002/rcm.2243|pmid=16299699|bibcode=2005RCMS...19.3701S|issn=1097-0231}}</ref> The infrared version of ELDI has been referred to as [[Physics:Laser ablation electrospray ionization|laser ablation electrospray ionization]] (LAESI). IR-MALDESI differs from these two methods as an exogenous ice matrix is used to enhance the desorption of the sample as well as the geometric parameters of the source. Another technique, [[Physics:Desorption atmospheric pressure photoionization|desorption atmospheric pressure photoionization]] (DAPPI), uses a jet of heated solvent vapor to desorb analytes from the sample surface via a nebulizer microchip. The desorbed molecules are then ionized by photons emitted by a UV lamp and introduced to mass spectrometers.<ref>{{Cite journal|last1=Haapala|first1=Markus|last2=Pól|first2=Jaroslav|last3=Saarela|first3=Ville|last4=Arvola|first4=Ville|last5=Kotiaho|first5=Tapio|last6=Ketola|first6=Raimo A.|last7=Franssila|first7=Sami|last8=Kauppila|first8=Tiina J.|last9=Kostiainen|first9=Risto|date=2007-10-01|title=Desorption Atmospheric Pressure Photoionization|url=https://doi.org/10.1021/ac071152g|journal=Analytical Chemistry|volume=79|issue=20|pages=7867–7872|doi=10.1021/ac071152g|pmid=17803282|issn=0003-2700}}</ref>

==References==
{{Reflist}}

{{Mass spectrometry}}

[[Category:Ion source]]

{{Sourceattribution|Matrix-assisted laser desorption electrospray ionization}}