195:- This has the same sample preparation as MALDI does as this simulates the chemical ionization properties of MALDI. ME-SIMS does not sample nearly as much material. However, if the analyte being tested has a low mass value then it can produce a similar looking spectra to that of a MALDI spectra. ME-SIMS has been so effective that it has been able to detect low mass chemicals at sub cellular levels that was not possible prior to the development of the ME-SIMS technique. The second technique being used is called sample metallization (Meta-SIMS) - This is the process of gold or silver addition to the sample. This forms a layer of gold or silver around the sample and it is normally no more than 1-3 nm thick. Using this technique has resulted in an increase of sensitivity for larger mass samples. The addition of the metallic layer also allows for the conversion of insulating samples to conducting samples, thus charge compensation within SIMS experiments is no longer required.
450:
the distribution of different molecules can be generated. In contrast, MRI with MSI combines the continuous 3D representation of MRI image with detailed structural representation using molecular information from MSI. Even though, MSI itself can generate 3D images, the picture is just part of the reality due to the depth limitation in the analysis, while MRI provides, for example, detailed organ shape with additional anatomical information. This coupled technique can be beneficial for cancer precise diagnosis and neurosurgery.
277:
of the abundance of the selected ions in the surface of the sample in relation with the spatial distribution are generated. This technique is applicable to solid, liquid, frozen and gaseous samples. Moreover, DESI allows analyzing a wide range of organic and biological compounds, as animal and plant tissues and cell culture samples, without complex sample preparation
Although, this technique has the poorest resolution among other, it can create high-quality image from a large area scan, as a whole body section scanning. Fn
47:
across the sample. This results in pictures of the spatially resolved distribution of a compound pixel by pixel. Each data set contains a veritable gallery of pictures because any peak in each spectrum can be spatially mapped. Despite the fact that MSI has been generally considered a qualitative method, the signal generated by this technique is proportional to the relative abundance of the analyte. Therefore, quantification is possible, when its challenges are overcome. Although widely used traditional methodologies like
188:; the primary ion beam is emitted across the sample while secondary mass spectra are recorded. SIMS proves to be advantageous in providing the highest image resolution but only over small area of samples. More, this technique is widely regarded as one of the most sensitive forms of mass spectrometry as it can detect elements in concentrations as small as 10-10 atoms per cubic centimeter.
503:
diseases by tracking proteins, lipids, and cell metabolism. For example, identifying biomarkers by MSI can show detailed cancer diagnosis. In addition, low cost imaging for pharmaceuticals studies can be acquired, such as images of molecular signatures that would be indicative of treatment response for a specific drug or the effectiveness of a particular drug delivery method.
207:
88:(MALDI) could be applied to visualize large biomolecules (as proteins and lipids) in cells and tissue to reveal the function of these molecules and how function is changed by diseases like cancer, which led to the widespread use of MSI. Nowadays, different ionization techniques have been used, including SIMS, MALDI and
700:"Imaging Trace Metals in Biological Systems" pp 81–134 in "Metals, Microbes and Minerals: The Biogeochemical Side of Life" (2021) pp xiv + 341. Authors Yu, Jyao; Harankhedkar, Shefali; Nabatilan, Arielle; Fahrni, Christopher; Walter de Gruyter, Berlin. Editors Kroneck, Peter M.H. and Sosa Torres, Martha.
502:
A remarkable ability of MSI is to find out the localization of biomolecules in tissues, even though there are no previous information about them. This feature has made MSI a unique tool for clinical research and pharmacological research. It provides information about biomolecular changes related with
276:
Desorption electrospray
Ionization is a less destructive technique, which couples simplicity and rapid analysis of the sample. The sample is sprayed with an electrically charged solvent mist at an angle that causes the ionization and desorption of various molecular species. Then, two-dimensional maps
194:
Developments within SIMS: Some chemical modifications have been made within SIMS to increase the efficiency of the process. There are currently two separate techniques being used to help increase the overall efficiency by increasing the sensitivity of SIMS measurements: matrix-enhanced SIMS (ME-SIMS)
449:
with MRI can be highlighted. Fluorescence staining can give information of the appearance of some proteins present in any process inside a tissue, while MSI may give information about the molecular changes presented in that process. Combining both techniques, multimodal picture or even 3D images of
444:
Combining various MSI techniques can be beneficial, since each particular technique has its own advantage. For example, when information regards both proteins and lipids are necessary in the same tissue section, performing DESI to analyze the lipid, followed by MALDI to obtain information about the
109:
This technique is performed using a focused ionization beam to analyze a specific region of the sample by generating a mass spectrum. The mass spectrum is stored along with the spatial coordination where the measurement took place. Then, a new region is selected and analyzed by moving the sample or
46:
by their molecular masses. After collecting a mass spectrum at one spot, the sample is moved to reach another region, and so on, until the entire sample is scanned. By choosing a peak in the resulting spectra that corresponds to the compound of interest, the MS data is used to map its distribution
518:
The main advantage of MSI for studying the molecules location and distribution within the tissue is that this analysis can provide either greater selectivity, more information or more accuracy than others. Moreover, this tool requires less investment of time and resources for similar results. The
122:
detector is used to measure the spatial origin of the ions generated at the sample surface by the ion optics of the instruments. The resolution of the spatial information will depend on the magnification of the microscope, the quality of the ions optics and the sensitivity of the detector. A new
479:
There are many free software packages available for visualization and mining of imaging mass spectrometry data. Converters from Thermo Fisher format, Analyze format, GRD format and Bruker format to imzML format were developed by the
Computis project. Some software modules are also available for
131:
The ionization techniques available for MSI are suited to different applications. Some of the criteria for choosing the ionization method are the sample preparation requirement and the parameters of the measurement, as resolution, mass range and sensitivity. Based on that, the most common used
110:
the ionization beam. These steps are repeated until the entire sample has been scanned. By coupling all individual mass spectra, a distribution map of intensities as a function of x and y locations can be plotted. As a result, reconstructed molecular images of the sample are obtained.
1612:
A. Römpp; T. Schramm; A. Hester; I. Klinkert; J.P. Both; R.M.A. Heeren; M. Stoeckli; B. Spengler (2011). "Chapter imzML: Imaging Mass
Spectrometry Markup Language: A Common Data Format for Mass Spectrometry Imaging in Data Mining in Proteomics: From Standards to Applications".
233:
is recorded. Although MALDI has the benefit of being able to record the spatial distribution of larger molecules, it comes at the cost of lower resolution than the SIMS technique. The limit for the lateral resolution for most of the modern instruments using MALDI is 20
224:
can be used as a mass spectrometry imaging technique for relatively large molecules. It has recently been shown that the most effective type of matrix to use is an ionic matrix for MALDI imaging of tissue. In this version of the technique the sample, typically a thin
55:
achieve the same goal as MSI, they are limited in their abilities to analyze multiple samples at once, and can prove to be lacking if researchers do not have prior knowledge of the samples being studied. Most common ionization technologies in the field of MSI are
1766:
Gamboa-Becerra, Roberto; Ramírez-Chávez, Enrique; Molina-Torres, Jorge; Winkler, Robert (2015-07-01). "MSI.R scripts reveal volatile and semi-volatile features in low-temperature plasma mass spectrometry imaging (LTP-MSI) of chilli (Capsicum annuum)".
210:
Mouse kidney: (a) MALDI spectra from the tissue. (b) H&E stained tissue. N-glycans at m/z = 1996.7 (c) is located in the cortex and medulla while m/z = 2158.7 (d) is in the cortex, (e) An overlay image of these two masses, (f) untreated control
179:
and collecting and analyzing ejected secondary ions. There are many different sources for a primary ion beam. However, the primary ion beam must contain ions that are at the higher end of the energy scale. Some common sources are: Cs,
100:
The MSI is based on the spatial distribution of the sample. Therefore, the operation principle depends on the technique that is used to obtain the spatial information. The two techniques used in MSI are: microprobe and microscope.
483:
For processing .imzML files with the free statistical and graphics language R, a collection of R scripts is available, which permits parallel-processing of large files on a local computer, a remote cluster or on the Amazon cloud.
445:
peptide, and finalize applying a stain (haematoxylin and eosin) for medical diagnosis of the structural characteristic of the tissue. On the other side of MSI with other imaging techniques, fluorescence staining with MSI and
1556:
Schramm, Thorsten; Hester, Zoë; Klinkert, Ivo; Both, Jean-Pierre; Heeren, Ron M. A.; Brunelle, Alain; Laprévote, Olivier; Desbenoit, Nicolas; Robbe, Marie-France; Stoeckli, Markus; Spengler, Bernhard (2012-08-30).
1283:
Angelo, Michael; Bendall, Sean C; Finck, Rachel; Hale, Matthew B; Hitzman, Chuck; Borowsky, Alexander D; Levenson, Richard M; Lowe, John B; Liu, Scot D; Zhao, Shuchun; Natkunam, Yasodha; Nolan, Garry P (2014).
2051:
Inglese, Paolo; Strittmatter, Nicole; Doria, Luisa; Mroz, Anna; Speller, Abigail; Poynter, Liam; Dannhorn, Andreas; Kudo, Hiromi; Mirnezami, Reza; Goldin, Robert D.; Nicholson, Jeremy K. (2018-01-09).
1959:
Addie, Ruben D.; Balluff, Benjamin; Bovée, Judith V. M. G.; Morreau, Hans; McDonnell, Liam A. (2015-07-07). "Current State and Future
Challenges of Mass Spectrometry Imaging for Clinical Research".
1916:
Swales, John G.; Hamm, Gregory; Clench, Malcolm R.; Goodwin, Richard J.A. (March 2019). "Mass spectrometry imaging and its application in pharmaceutical research and development: A concise review".
979:
Addie, Ruben D.; Balluff, Benjamin; Bovée, Judith V. M. G.; Morreau, Hans; McDonnell, Liam A. (2015). "Current State and Future
Challenges of Mass Spectrometry Imaging for Clinical Research".
1513:
Nilsson, Anna; Goodwin, Richard J. A.; Shariatgorji, Mohammadreza; Vallianatou, Theodosia; Webborn, Peter J. H.; Andrén, Per E. (2015-02-03). "Mass
Spectrometry Imaging in Drug Development".
1628:
Klinkert, I.; Chughtai, K.; Ellis, S. R.; Heeren, R. M. A. (2014). "Methods for Full
Resolution Data Exploration and Visualization for Large 2D and 3D Mass Spectrometry Imaging Datasets".
480:
viewing mass spectrometry images in imzML format: Biomap (Novartis, free), Datacube
Explorer (AMOLF, free), EasyMSI (CEA), Mirion (JLU), MSiReader (NCSU, free) and SpectralAnalysis.
471:
format. Several imaging MS software tools support it. The advantage of this format is the flexibility to exchange data between different instruments and data analysis software.
1440:
Chaurand P, Norris JL, Cornett DS, Mobley JA, Caprioli RM (2006). "New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry".
123:
region still needs to be scanned, but the number of positions drastically reduces. The limitation of this mode is the finite depth of vision present with all microscopes.
1197:
Bodzon-Kulakowska, Anna; Suder, Piotr (2016-01-01). "Imaging mass spectrometry: Instrumentation, applications, and combination with other visualization techniques".
428:
386:
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by way of comparison, 1 cc of Carbon (diamond) contains about 1.8 x 10 atoms. 10 to 10 corresponds to 6 parts per trillion (ppt) to 60 parts per billion (ppb).
153:
221:
133:
85:
519:
table below shows a comparison of advantages and disadvantages of some available techniques, including MSI, correlated with drug distribution analysis.
565:
Ex vivo; requires antibodies, which vary in sensitivity and specificity; difficulties assigning; detection threshold; lack of standard scoring system
490:
SPUTNIK is an R package containing various filters to remove peaks characterized by an uncorrelated spatial distribution with the sample location or
145:
1373:
Powers, Thomas W.; Neely, Benjamin A.; Shao, Yuan; Tang, Huiyuan; Troyer, Dean A.; Mehta, Anand S.; Haab, Brian B.; Drake, Richard R. (2014).
1118:(2013). "Chapter 2. Technologies for Detecting Metals in Single Cells. Section 2.1, Secondary Ion Mass Specctrometry". In Banci, Lucia (ed.).
1155:
1135:
92:, as well as other technologies. Still, MALDI is the current dominant technology with regard to clinical and biological applications of MSI.
1375:"MALDI Imaging Mass Spectrometry Profiling of N-Glycans in Formalin-Fixed Paraffin Embedded Clinical Tissue Blocks and Tissue Microarrays"
191:
Multiplexed ion beam imaging (MIBI) is a SIMS method that uses metal isotope labeled antibodies to label compounds in biological samples.
2053:"Network analysis of mass spectrometry imaging data from colorectal cancer identifies key metabolites common to metastatic development"
141:
89:
57:
688:
the sensitivity varies by element (or molecule) as well as by nature of the surface being analyzed and conditions of the analysis.
1810:
Bemis, Kyle D.; Harry, April; Eberlin, Livia S.; Ferreira, Christina; van de Ven, Stephanie M.; Mallick, Parag; Stolowitz, Mark;
1341:
Delcorte A, Befahy S, Poleunis C, Troosters M, Bertrand P. "Improvements of metal adhesion to silicon films: a ToF-SIMS study".
198:
Subcellular (50 nm) resolution is enabled by NanoSIMS allowing for absolute quantitative analysis at the organelle level.
164:
137:
77:
65:
1248:
Chabala J, Soni K, Li J, Gavlirov K, Levi-Setti R (1995). "High resolution chemical imaging with scanning ion probe SIMS".
491:
2109:
446:
1665:"MSiReader: An Open-Source Interface to View and Analyze High Resolving Power MS Imaging Files on Matlab Platform"
119:
1475:
Patel, Ekta (1 January 2015). "MALDI-MS imaging for the study of tissue pharmacodynamics and toxicodynamics".
506:
Ion colocalization has been studied as a way to infer local interactions between biomolecules. Similarly to
1725:
2076:
2004:"MALDI Imaging mass spectrometry: current frontiers and perspectives in pathology research and practice"
1559:"imzML--a common data format for the flexible exchange and processing of mass spectrometry imaging data"
1346:
811:
Rohner T, Staab D, Stoeckli M (2005). "MALDI mass spectrometric imaging of biological tissue sections".
80:(SIMS) to study semiconductor surfaces by Castaing and Slodzian. However, it was the pioneering work of
510:, correlation has been used to quantify the similarity between ion images and generate network models.
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1637:
1386:
1257:
1206:
1028:
870:
52:
701:
185:
1869:"SPUTNIK: An R package for filtering of spatially related peaks in mass spectrometry imaging data"
487:
Another free statistical package for processing imzML and
Analyze 7.5 data in R exists, Cardinal.
2064:
1941:
1792:
1594:
1080:
Amstalden Van Hove E, Smith D, Heeren R (2010). "A concise review of mass spectrometry imaging".
921:"Future technology insight: mass spectrometry imaging as a tool in drug research and development"
836:
1867:
Inglese, Paolo; Correia, Gonçalo; Takats, Zoltan; Nicholson, Jeremy K.; Glen, Robert C. (2018).
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Cobice, D F; Goodwin, R J A; Andren, P E; Nilsson, A; Mackay, C L; Andrew, R (2015-07-01).
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1820:: an R package for statistical analysis of mass spectrometry-based imaging experiments"
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Comparison of advantages and disadvantages of techniques assessing drug distribution
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Mass spectrometry technique that can visualize the spatial distribution of molecules
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Ex vivo; requires radio-labelled drug; does not distinguish drug from metabolites.
1972:
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1093:
992:
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McDonnell, Liam A.; Heeren, Ron M.A. (2007-07-01). "Imaging mass spectrometry".
2020:
2003:
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Monroe E, Annangudi S, Hatcher N, Gutstein H, Rubakhin S, Sweedler J (2008).
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In vivo possible; good resolution; can be coupled to CT X-ray, gamma camera
168:
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31:
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774:"Subcellular quantitative imaging of metabolites at the organelle level"
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1122:. Metal Ions in Life Sciences. Vol. 12. Springer. pp. 15–40.
43:
39:
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Race, A. M.; Palmer, A. D.; Dexter, A.; Steven, R. T.; Styles, I. B.;
1526:
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was proposed to exchange data in a standardized XML file based on the
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Robichaud, G.; Garrard, K. P.; Barry, J. A.; Muddiman, D. C. (2013).
254:
m. MALDI experiments commonly use either an Nd:YAG (355 nm) or N
1301:
593:
Expensive; short-lived isotopes; need cyclotron to produce isotopes
2060:
440:
Combination of various MSI techniques and other imaging techniques
205:
144:
which are described below. Still, other minor techniques used are
184:, O, Ar and Ga. SIMS imaging is performed in a manner similar to
579:
Not quantitative; poor resolution; autofluorescent interference
468:
861:
McDonnell LA, Heeren RM (2007). "Imaging mass spectrometry".
1250:
International Journal of Mass Spectrometry and Ion Processes
658:
Semi-quantitative; ion-suppression effects; complex analysis
459:
Standard data format for mass spectrometry imaging datasets
613:
Not quantitative; poor selectivity; high background noise
630:
Not quantitative; poor reproducibility; high background
562:
Short processing time; easy interpretation; inexpensive
154:
nanospray desorption electrospray ionization (nano-DESI)
30:
to visualize the spatial distribution of molecules, as
651:
Multiplex; label-free imaging; good spatial resolution
1669:
Journal of the American Society for Mass Spectrometry
1286:"Multiplexed ion beam imaging of human breast tumors"
416:
374:
332:
287:
Comparison of typical parameters among MSI techniques
240:
1615:
Methods in Molecular Biology, Humana Press, New York
548:
Very high spatial resolution; reliable quantitation
84:
and colleagues in the late 1990s, demonstrating how
422:
380:
338:
246:
150:aser-ablation-inductively coupled plasma (LA-ICP)
76:More than 50 years ago, MSI was introduced using
856:
854:
852:
850:
722:"SIMS and MADLI MS Imaging of the spinal cord"
268:in tissue have been studied by MALDI imaging.
229:section, is moved in two dimensions while the
146:laser ablation electrospray ionization (LAESI)
2002:Aichler, Michaela; Walch, Axel (April 2015).
281:Comparative between the ionization techniques
167:(SIMS) is used to analyze solid surfaces and
8:
610:Label-free; sub-cellular spatial resolution
1726:"SpectralAnalysis: software for the masses"
222:Matrix-assisted laser desorption ionization
86:matrix-assisted laser desorption/ionization
64:, secondary ion mass spectrometry imaging (
1918:International Journal of Mass Spectrometry
1630:International Journal of Mass Spectrometry
2019:
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1416:
1398:
1317:
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952:
890:
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90:desorption electrospray ionization (DESI)
521:
323:Elemental ions, small molecules, lipids
284:
712:
672:
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1769:Analytical and Bioanalytical Chemistry
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514:Advantages, challenges and limitations
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7:
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813:Mechanisms of Ageing and Development
767:
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627:Label-free imaging; high resolution
508:colocalization in microscopy imaging
258:(337 nm) laser for ionization.
584:Positron emission tomography (PET)
175:the surface with a focused primary
1617:. Vol. 696. pp. 205–224.
576:In vivo possible; reasonable cost
407:Small molecules, lipids, peptides
14:
545:Where and how much radioactivity
68:) and Nanoscale SIMS (NanoSIMS).
772:Siuzdak, Gary (September 2023).
447:magnetic resonance imaging (MRI)
925:British Journal of Pharmacology
165:Secondary ion mass spectrometry
78:secondary ion mass spectrometry
1:
1885:10.1093/bioinformatics/bty622
1836:10.1093/bioinformatics/btv146
702:DOI 10.1515/9783110589771-004
1973:10.1021/acs.analchem.5b00416
1745:10.1021/acs.analchem.6b01643
1400:10.1371/journal.pone.0106255
1270:10.1016/0168-1176(94)04119-R
1094:10.1016/j.chroma.2010.01.033
993:10.1021/acs.analchem.5b00416
1575:10.1016/j.jprot.2012.07.026
1128:10.1007/978-94-007-5561-1_2
1082:Journal of Chromatography A
2126:
2021:10.1038/labinvest.2014.156
1930:10.1016/j.ijms.2018.02.007
1650:10.1016/j.ijms.2013.12.012
790:10.1038/s42255-023-00882-z
365:Lipids, peptide, proteins
214:
1781:10.1007/s00216-015-8744-9
1689:10.1007/s13361-013-0607-z
1199:Mass Spectrometry Reviews
1021:Mass Spectrometry Reviews
863:Mass Spectrometry Reviews
825:10.1016/j.mad.2004.09.032
587:Where, what and activity
160:SIMS and NanoSIMS imaging
26:) is a technique used in
20:Mass spectrometry imaging
2008:Laboratory Investigation
1120:Metallomics and the Cell
118:In this technique, a 2D
620:force microscopy (AFM)
618:Electrochemical atomic
2084:Cite journal requires
1354:Cite journal requires
738:10.1002/pmic.200800127
424:
382:
340:
248:
212:
132:ionization method are
1563:Journal of Proteomics
1116:Penner-Hahn, James E.
598:Coherent anti-Stokes
556:Immunohistochemistry
425:
383:
341:
249:
209:
127:Ion source dependence
1961:Analytical Chemistry
1733:Analytical Chemistry
1515:Analytical Chemistry
981:Analytical Chemistry
423:{\displaystyle \mu }
414:
381:{\displaystyle \mu }
372:
339:{\displaystyle \mu }
330:
247:{\displaystyle \mu }
238:
53:immunohistochemistry
1681:2013JASMS..24..718R
1642:2014IJMSp.362...40K
1391:2014PLoSO...9j6255P
1262:1995IJMSI.143..191C
1211:2016MSRv...35..147B
1033:2007MSRv...26..606M
875:2007MSRv...26..606M
524:
304:Spatial Resolution
298:Type of Ionization
289:
186:electron microscopy
96:Operation principle
1489:10.4155/bio.14.280
603:microscopy (CARS)
531:Question answered
522:
492:spatial randomness
420:
378:
336:
295:Ionization Source
285:
244:
213:
120:position-sensitive
2110:Mass spectrometry
1967:(13): 6426–6433.
1830:(14): 2418–2420.
1775:(19): 5673–5684.
1739:(19): 9451–9458.
1569:(16): 5106–5110.
1527:10.1021/ac504734s
1454:10.1021/pr060346u
1219:10.1002/mas.21468
1156:978-94-007-5561-1
1137:978-94-007-5560-4
1088:(25): 3946–3954.
1041:10.1002/mas.20124
987:(13): 6426–6433.
937:10.1111/bph.13135
931:(13): 3266–3283.
883:10.1002/mas.20124
778:Nature Metabolism
732:(18): 3746–3754.
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600:Raman scattering
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28:mass spectrometry
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956:
916:
905:
904:
894:
858:
845:
844:
808:
802:
801:
784:(9): 1446–1448.
769:
760:
759:
749:
717:
689:
686:
680:
677:
542:Autoradiography
525:
429:
427:
426:
421:
387:
385:
384:
379:
345:
343:
342:
337:
290:
262:Pharmacodynamics
253:
251:
250:
245:
82:Richard Caprioli
2125:
2124:
2120:
2119:
2118:
2116:
2115:
2114:
2100:
2099:
2098:
2097:
2083:
2073:
2050:
2049:
2045:
2001:
2000:
1996:
1958:
1957:
1953:
1915:
1914:
1910:
1866:
1865:
1861:
1809:
1808:
1804:
1765:
1764:
1760:
1728:
1719:
1718:
1714:
1662:
1661:
1657:
1627:
1626:
1622:
1611:
1610:
1606:
1555:
1554:
1550:
1512:
1511:
1504:
1474:
1473:
1469:
1442:J. Proteome Res
1439:
1438:
1434:
1372:
1371:
1367:
1353:
1343:
1340:
1339:
1335:
1302:10.1038/nm.3488
1290:Nature Medicine
1282:
1281:
1277:
1247:
1246:
1242:
1196:
1195:
1176:
1138:
1114:
1113:
1109:
1079:
1078:
1074:
1018:
1017:
1008:
978:
977:
970:
918:
917:
908:
860:
859:
848:
810:
809:
805:
771:
770:
763:
719:
718:
714:
709:
698:
696:Further reading
693:
692:
687:
683:
678:
674:
669:
624:Where and what
607:Where and what
516:
500:
477:
461:
456:
454:Data processing
442:
412:
411:
370:
369:
328:
327:
283:
274:
257:
236:
235:
219:
204:
183:
162:
129:
116:
107:
98:
74:
17:
12:
11:
5:
2123:
2121:
2113:
2112:
2102:
2101:
2096:
2095:
2086:|journal=
2061:10.1101/230052
2043:
2014:(4): 422–431.
1994:
1951:
1908:
1879:(1): 178–180.
1873:Bioinformatics
1859:
1824:Bioinformatics
1814:(2015-03-15).
1802:
1758:
1712:
1675:(5): 718–721.
1655:
1620:
1604:
1548:
1502:
1467:
1432:
1385:(9): e106255.
1365:
1356:|journal=
1333:
1296:(4): 436–442.
1275:
1240:
1205:(1): 147–169.
1174:
1136:
1107:
1072:
1027:(4): 606–643.
1006:
968:
906:
846:
819:(1): 177–185.
803:
761:
711:
710:
708:
705:
697:
694:
691:
690:
681:
671:
670:
668:
665:
662:
661:
654:
647:
644:Where and what
640:
632:
631:
628:
625:
622:
615:
614:
611:
608:
605:
595:
594:
591:
588:
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581:
580:
577:
574:
571:
567:
566:
563:
560:
557:
553:
552:
549:
546:
543:
539:
538:
537:Disadvantages
535:
532:
529:
515:
512:
499:
496:
476:
473:
460:
457:
455:
452:
441:
438:
435:
434:
431:
419:
408:
405:
402:
401:Solvent Spray
399:
393:
392:
389:
377:
366:
363:
360:
359:UV laser beam
357:
351:
350:
347:
335:
324:
321:
318:
315:
309:
308:
305:
302:
299:
296:
293:
282:
279:
273:
270:
266:toxicodynamics
255:
243:
215:Main article:
203:
200:
181:
161:
158:
128:
125:
115:
112:
106:
103:
97:
94:
73:
70:
49:radiochemistry
15:
13:
10:
9:
6:
4:
3:
2:
2122:
2111:
2108:
2107:
2105:
2091:
2078:
2070:
2066:
2062:
2058:
2054:
2047:
2044:
2039:
2035:
2031:
2027:
2022:
2017:
2013:
2009:
2005:
1998:
1995:
1990:
1986:
1982:
1978:
1974:
1970:
1966:
1962:
1955:
1952:
1947:
1943:
1939:
1935:
1931:
1927:
1923:
1919:
1912:
1909:
1904:
1900:
1895:
1890:
1886:
1882:
1878:
1874:
1870:
1863:
1860:
1855:
1851:
1846:
1841:
1837:
1833:
1829:
1825:
1821:
1819:
1813:
1806:
1803:
1798:
1794:
1790:
1786:
1782:
1778:
1774:
1770:
1762:
1759:
1754:
1750:
1746:
1742:
1738:
1734:
1727:
1723:
1716:
1713:
1708:
1704:
1699:
1694:
1690:
1686:
1682:
1678:
1674:
1670:
1666:
1659:
1656:
1651:
1647:
1643:
1639:
1635:
1631:
1624:
1621:
1616:
1608:
1605:
1600:
1596:
1592:
1588:
1584:
1580:
1576:
1572:
1568:
1564:
1560:
1552:
1549:
1544:
1540:
1536:
1532:
1528:
1524:
1520:
1516:
1509:
1507:
1503:
1498:
1494:
1490:
1486:
1483:(1): 91–101.
1482:
1478:
1471:
1468:
1463:
1459:
1455:
1451:
1447:
1443:
1436:
1433:
1428:
1424:
1419:
1414:
1410:
1406:
1401:
1396:
1392:
1388:
1384:
1380:
1376:
1369:
1366:
1361:
1348:
1337:
1334:
1329:
1325:
1320:
1315:
1311:
1307:
1303:
1299:
1295:
1291:
1287:
1279:
1276:
1271:
1267:
1263:
1259:
1255:
1251:
1244:
1241:
1236:
1232:
1228:
1224:
1220:
1216:
1212:
1208:
1204:
1200:
1193:
1191:
1189:
1187:
1185:
1183:
1181:
1179:
1175:
1172:
1168:
1164:
1160:
1157:
1153:
1147:
1143:
1139:
1133:
1129:
1125:
1121:
1117:
1111:
1108:
1103:
1099:
1095:
1091:
1087:
1083:
1076:
1073:
1068:
1064:
1060:
1056:
1051:
1046:
1042:
1038:
1034:
1030:
1026:
1022:
1015:
1013:
1011:
1007:
1002:
998:
994:
990:
986:
982:
975:
973:
969:
964:
960:
955:
950:
946:
942:
938:
934:
930:
926:
922:
915:
913:
911:
907:
902:
898:
893:
888:
884:
880:
876:
872:
869:(4): 606–43.
868:
864:
857:
855:
853:
851:
847:
842:
838:
834:
830:
826:
822:
818:
814:
807:
804:
799:
795:
791:
787:
783:
779:
775:
768:
766:
762:
757:
753:
748:
743:
739:
735:
731:
727:
723:
716:
713:
706:
704:
703:
695:
685:
682:
676:
673:
666:
660:
659:
655:
653:
652:
648:
646:
645:
641:
639:
638:
634:
633:
629:
626:
623:
621:
617:
616:
612:
609:
606:
604:
601:
597:
596:
592:
589:
586:
583:
582:
578:
575:
572:
570:Fluorescence
569:
568:
564:
561:
558:
555:
554:
550:
547:
544:
541:
540:
536:
533:
530:
527:
526:
520:
513:
511:
509:
504:
497:
495:
493:
488:
485:
481:
474:
472:
470:
466:
458:
453:
451:
448:
439:
432:
417:
409:
406:
403:
400:
398:
395:
394:
391:0-100 000 Da
390:
375:
367:
364:
361:
358:
356:
353:
352:
348:
333:
325:
322:
319:
316:
314:
311:
310:
306:
303:
300:
297:
294:
292:
291:
288:
280:
278:
271:
269:
267:
263:
259:
241:
232:
231:mass spectrum
228:
223:
218:
217:MALDI imaging
208:
202:MALDI imaging
201:
199:
196:
192:
189:
187:
178:
174:
170:
166:
159:
157:
155:
151:
147:
143:
139:
135:
126:
124:
121:
113:
111:
104:
102:
95:
93:
91:
87:
83:
79:
71:
69:
67:
63:
62:MALDI imaging
59:
54:
50:
45:
41:
37:
33:
29:
25:
21:
2077:cite journal
2046:
2011:
2007:
1997:
1964:
1960:
1954:
1921:
1917:
1911:
1876:
1872:
1862:
1827:
1823:
1817:
1805:
1772:
1768:
1761:
1736:
1732:
1715:
1672:
1668:
1658:
1633:
1629:
1623:
1614:
1607:
1566:
1562:
1551:
1518:
1514:
1480:
1476:
1470:
1445:
1441:
1435:
1382:
1378:
1368:
1347:cite journal
1336:
1293:
1289:
1278:
1253:
1249:
1243:
1202:
1198:
1119:
1110:
1085:
1081:
1075:
1024:
1020:
984:
980:
928:
924:
866:
862:
816:
812:
806:
781:
777:
729:
725:
715:
699:
684:
675:
657:
656:
650:
649:
643:
642:
636:
635:
619:
602:
599:
528:Methodology
517:
505:
501:
498:Applications
489:
486:
482:
478:
462:
443:
396:
354:
312:
286:
275:
272:DESI imaging
260:
220:
197:
193:
190:
163:
130:
117:
108:
99:
75:
66:SIMS imaging
58:DESI imaging
23:
19:
18:
1812:Vitek, Olga
1477:Bioanalysis
1256:: 191–212.
1165:electronic-
534:Advantages
307:Mass Range
36:metabolites
2055:: 230052.
1924:: 99–112.
1050:1874/26394
892:1874/26394
726:Proteomics
707:References
433:0-2000 Da
349:0-1000 Da
173:sputtering
169:thin films
114:Microscope
105:Microprobe
32:biomarkers
2030:1530-0307
1981:0003-2700
1946:102892898
1938:1387-3806
1722:Bunch, J.
1636:: 40–47.
1583:1876-7737
1535:0003-2700
1409:1932-6203
1310:1078-8956
1227:1098-2787
1171:1868-0402
1163:1559-0836
1059:1098-2787
945:1476-5381
798:2522-5812
418:μ
376:μ
334:μ
301:Analytes
242:μ
2104:Category
2069:90409488
2038:25621874
1989:25803124
1903:30010780
1854:25777525
1818:Cardinal
1797:22813369
1789:26007697
1753:27558772
1724:(2016).
1707:23536269
1599:25970597
1591:22842151
1543:25526173
1497:25558938
1462:17081040
1427:25184632
1379:PLOS ONE
1328:24584119
1235:25962625
1146:23595669
1102:20223463
1067:17471576
1001:25803124
963:25766375
901:17471576
841:30982189
833:15610777
756:18712768
475:Software
317:Ion gun
177:ion beam
44:proteins
40:peptides
1894:6298046
1845:4495298
1698:3693088
1677:Bibcode
1638:Bibcode
1418:4153616
1387:Bibcode
1319:4110905
1258:Bibcode
1207:Bibcode
1029:Bibcode
954:4500365
871:Bibcode
747:2706659
326:<10
211:tissue.
72:History
2067:
2036:
2028:
1987:
1979:
1944:
1936:
1901:
1891:
1852:
1842:
1795:
1787:
1751:
1705:
1695:
1597:
1589:
1581:
1541:
1533:
1495:
1460:
1425:
1415:
1407:
1326:
1316:
1308:
1233:
1225:
1169:
1161:
1154:
1144:
1134:
1100:
1065:
1057:
999:
961:
951:
943:
899:
839:
831:
796:
754:
744:
573:Where
559:Where
227:tissue
2065:S2CID
1942:S2CID
1793:S2CID
1729:(PDF)
1595:S2CID
837:S2CID
667:Notes
465:imzML
404:Soft
362:Soft
355:MALDI
320:Hard
134:MALDI
2090:help
2034:PMID
2026:ISSN
1985:PMID
1977:ISSN
1934:ISSN
1899:PMID
1850:PMID
1785:PMID
1749:PMID
1703:PMID
1587:PMID
1579:ISSN
1539:PMID
1531:ISSN
1493:PMID
1458:PMID
1423:PMID
1405:ISSN
1360:help
1324:PMID
1306:ISSN
1231:PMID
1223:ISSN
1167:ISSN
1159:ISSN
1152:ISBN
1142:PMID
1132:ISBN
1098:PMID
1086:1217
1063:PMID
1055:ISSN
997:PMID
959:PMID
941:ISSN
897:PMID
829:PMID
794:ISSN
752:PMID
469:mzML
463:The
397:DESI
313:SIMS
264:and
152:and
142:DESI
140:AND
138:SIMS
51:and
2057:doi
2016:doi
1969:doi
1926:doi
1922:437
1889:PMC
1881:doi
1840:PMC
1832:doi
1777:doi
1773:407
1741:doi
1693:PMC
1685:doi
1646:doi
1634:362
1571:doi
1523:doi
1485:doi
1450:doi
1413:PMC
1395:doi
1314:PMC
1298:doi
1266:doi
1254:143
1215:doi
1124:doi
1090:doi
1045:hdl
1037:doi
989:doi
949:PMC
933:doi
929:172
887:hdl
879:doi
821:doi
817:126
786:doi
742:PMC
734:doi
637:MSI
410:50
368:20
171:by
148:, l
60:,
42:or
24:MSI
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2032:.
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2006:.
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1963:.
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Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
