Laser ablation electrospray ionization

Last updated
Schematic representation of laser ablation electrospray ionization (LAESI) Schematic Representation of Laser Ablation Electrospray Ionization (LAESI) .png
Schematic representation of laser ablation electrospray ionization (LAESI)

Laser ablation electrospray ionization (LAESI) is an ambient ionization method for mass spectrometry that combines laser ablation from a mid-infrared (mid-IR) laser with a secondary electrospray ionization (ESI) process. The mid-IR laser is used to generate gas phase particles which are then ionized through interactions with charged droplets from the ESI source. LAESI was developed in Professor Akos Vertes lab by Peter Nemes in 2007 and it was marketed commercially by Protea Biosciences, Inc until 2017. Fiber-LAESI for single-cell analysis approach was developed by Bindesh Shrestha in Professor Vertes lab in 2009. LAESI is a novel ionization source for mass spectrometry (MS) that has been used to perform MS imaging of plants, [1] [2] [3] tissues, [4] [5] [6] [7] cell pellets, [8] and even single cells. [9] [10] [11] [12] In addition, LAESI has been used to analyze historic documents [13] and untreated biofluids such as urine and blood. [1] The technique of LAESI is performed at atmospheric pressure and therefore overcomes many of the obstacles of traditional MS techniques, including extensive and invasive sample preparation steps and the use of high vacuum. Because molecules and aerosols are ionized by interacting with an electrospray plume, LAESI's ionization mechanism is similar to SESI and EESI techniques.

Contents

LAESI can be used to perform MS analysis of many different classes of compounds ranging from small molecules, such as pharmaceuticals, saccharides, [1] [2] [3] [9] [10] lipids, [5] [7] and metabolites [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] to larger biomolecules like peptides [1] and proteins. [1] LAESI has also been shown to have a quantitative dynamic range of 4 decades and a limit of detection (LOD) of 8 fmol with verapamil, a small pharmaceutical molecule. [1] The technique has a lateral resolution of <200 μm for imaging applications [7] [14] and has been used for 3D imaging of plant tissues. [3] Additionally, in cell-by-cell LAESI imaging experiments single cells can be used as the pixels of the molecular image. [12] This LAESI application uses etched optical fibers to produce laser spot sizes of <50 µm to deliver the laser energy and has also been utilized in single cell analysis experiments. [9] [10] [11] [12]

Principle of operation

LAESI produces ions for MS analysis under normal atmospheric conditions for samples containing water. [15] The entire process can be divided into two steps.

Generation of analyte species

When a mid-IR laser beam is applied to a target which contains a hydroxide group, the target will absorb energy from this laser beam leading to evaporation of moisture from the targeted area. [16] A small-scale explosion occurs in the target and a small portion of the sample is ablated into the gas phase by a short (5 ns), mid-IR (2,940 nm) laser pulse. [17] [18] The plume expands until it collapses into the sample due to the pressure exerted by the atmosphere. At this point a jet of material is ejected from the sample surface. [17] [19] As mid-IR has low energy most of the ejected particles from sample remain neutral. [16] [20]

Reacting analyte species with charged solvent species

An electrospray ionization (ESI) source is located above the sample for post-ablation ionization. [21] The jet of ablated material is intersected and ionized by a spray plume from the ESI source located above the sample. The ionized molecules are then swept into the mass spectrometer for analysis. Because an ESI source is used for ionization, the LAESI mass spectra are similar to traditional ESI spectra, which can exhibit multiply charged analyte peaks, and extend the effective mass range of detection to biomolecules >100,000 Da in size. [19] [20]

Applications

LAESI can be used to perform MS imaging experiments of diverse tissue samples, not only in three dimensions but also with respect to time. Similarly, LAESI can also be used for process monitoring applications because each individual analysis requires less than 2 seconds to perform. Because of the speed of a LAESI analysis, the technique is amenable to rapid, sensitive, and direct analysis of aqueous samples in 96- and 384-well microplates. These analyses can also be performed on liquid samples, such as biofluids, containing peptides, proteins, metabolites, and other biomarkers for clinical, diagnostic, and discovery workflows. [22] LAESI technology allows high throughput analysis of these sample types and the use of internal standards and calibration curves permit the absolute quantitation of targeted biomolecules. [23] [22] [20]

Advantages and limitations

Advantages

This technique needs very little or no sample preparation and it has high sensitivity. [22] [15] This ionization technique does not need any external matrix. Therefore, the spatial resolution is not compromised by the presence of matrix crystal resulting in high spatial resolution. [20] This ionization technique can be carried out in natural and uneven biological surface. [23] Finally, as laser ablation and electronspray ionization work independently, they can be independently manipulated to achieve greater resolution. [20]

Limitations

LAESI is a relatively new technique for those samples which contain water and are relatively stable. However, it has limitations for those samples which have a lower water content. For example, this technique does not ionize dry skin, nails, tooth and bone well; this is due to low water content in these samples. [16] [22] Also, it needs a relatively large sampling area, compared to some other common ionization techniques. [20]

See also

Related Research Articles

<span class="mw-page-title-main">Ion source</span> Device that creates charged atoms and molecules (ions)

An ion source is a device that creates atomic and molecular ions. Ion sources are used to form ions for mass spectrometers, optical emission spectrometers, particle accelerators, ion implanters and ion engines.

<span class="mw-page-title-main">Electrospray ionization</span> Technique used in mass spectroscopy

Electrospray ionization (ESI) is a technique used in mass spectrometry to produce ions using an electrospray in which a high voltage is applied to a liquid to create an aerosol. It is especially useful in producing ions from macromolecules because it overcomes the propensity of these molecules to fragment when ionized. ESI is different from other ionization processes since it may produce multiple-charged ions, effectively extending the mass range of the analyser to accommodate the kDa-MDa orders of magnitude observed in proteins and their associated polypeptide fragments.

<span class="mw-page-title-main">Lipidomics</span>

Lipidomics is the large-scale study of pathways and networks of cellular lipids in biological systems The word "lipidome" is used to describe the complete lipid profile within a cell, tissue, organism, or ecosystem and is a subset of the "metabolome" which also includes other major classes of biological molecules. Lipidomics is a relatively recent research field that has been driven by rapid advances in technologies such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, dual polarisation interferometry and computational methods, coupled with the recognition of the role of lipids in many metabolic diseases such as obesity, atherosclerosis, stroke, hypertension and diabetes. This rapidly expanding field complements the huge progress made in genomics and proteomics, all of which constitute the family of systems biology.

<span class="mw-page-title-main">Matrix-assisted laser desorption/ionization</span> Ionization technique

In mass spectrometry, matrix-assisted laser desorption/ionization (MALDI) is an ionization technique that uses a laser energy-absorbing matrix to create ions from large molecules with minimal fragmentation. It has been applied to the analysis of biomolecules and various organic molecules, which tend to be fragile and fragment when ionized by more conventional ionization methods. It is similar in character to electrospray ionization (ESI) in that both techniques are relatively soft ways of obtaining ions of large molecules in the gas phase, though MALDI typically produces far fewer multi-charged ions.

<span class="mw-page-title-main">Atmospheric-pressure chemical ionization</span> Ionization method

Atmospheric pressure chemical ionization (APCI) is an ionization method used in mass spectrometry which utilizes gas-phase ion-molecule reactions at atmospheric pressure (105 Pa), commonly coupled with high-performance liquid chromatography (HPLC). APCI is a soft ionization method similar to chemical ionization where primary ions are produced on a solvent spray. The main usage of APCI is for polar and relatively less polar thermally stable compounds with molecular weight less than 1500 Da. The application of APCI with HPLC has gained a large popularity in trace analysis detection such as steroids, pesticides and also in pharmacology for drug metabolites.

<span class="mw-page-title-main">Desorption electrospray ionization</span>

Desorption electrospray ionization (DESI) is an ambient ionization technique that can be coupled to mass spectrometry (MS) for chemical analysis of samples at atmospheric conditions. Coupled ionization sources-MS systems are popular in chemical analysis because the individual capabilities of various sources combined with different MS systems allow for chemical determinations of samples. DESI employs a fast-moving charged solvent stream, at an angle relative to the sample surface, to extract analytes from the surfaces and propel the secondary ions toward the mass analyzer. This tandem technique can be used to analyze forensics analyses, pharmaceuticals, plant tissues, fruits, intact biological tissues, enzyme-substrate complexes, metabolites and polymers. Therefore, DESI-MS may be applied in a wide variety of sectors including food and drug administration, pharmaceuticals, environmental monitoring, and biotechnology.

Mass spectrometry imaging (MSI) is a technique used in mass spectrometry to visualize the spatial distribution of molecules, as biomarkers, metabolites, peptides or proteins 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 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 radiochemistry and immunohistochemistry 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 DESI imaging, MALDI imaging, secondary ion mass spectrometry imaging and Nanoscale SIMS (NanoSIMS).

Sample preparation for mass spectrometry is used for the optimization of a sample for analysis in a mass spectrometer (MS). Each ionization method has certain factors that must be considered for that method to be successful, such as volume, concentration, sample phase, and composition of the analyte solution. Quite possibly the most important consideration in sample preparation is knowing what phase the sample must be in for analysis to be successful. In some cases the analyte itself must be purified before entering the ion source. In other situations, the matrix, or everything in the solution surrounding the analyte, is the most important factor to consider and adjust. Often, sample preparation itself for mass spectrometry can be avoided by coupling mass spectrometry to a chromatography method, or some other form of separation before entering the mass spectrometer. In some cases, the analyte itself must be adjusted so that analysis is possible, such as in protein mass spectrometry, where usually the protein of interest is cleaved into peptides before analysis, either by in-gel digestion or by proteolysis in solution.

<span class="mw-page-title-main">Laser spray ionization</span>

Laser spray ionization refers to one of several methods for creating ions using a laser interacting with a spray of neutral particles or ablating material to create a plume of charged particles. The ions thus formed can be separated by m/z with mass spectrometry. Laser spray is one of several ion sources that can be coupled with liquid chromatography-mass spectrometry for the detection of larger molecules.

<span class="mw-page-title-main">Matrix-assisted laser desorption electrospray ionization</span>

Matrix-assisted laser desorption electrospray ionization (MALDESI) was first introduced in 2006 as a novel ambient ionization technique which combines the benefits of electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). An infrared (IR) or ultraviolet (UV) laser can be utilized in MALDESI to resonantly excite an endogenous or exogenous matrix. The term 'matrix' refers to any molecule that is present in large excess and absorbs the energy of the laser, thus facilitating 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.

<span class="mw-page-title-main">Desorption atmospheric pressure photoionization</span>

Desorption atmospheric pressure photoionization (DAPPI) is an ambient ionization technique for mass spectrometry that uses hot solvent vapor for desorption in conjunction with photoionization. Ambient Ionization techniques allow for direct analysis of samples without pretreatment. The direct analysis technique, such as DAPPI, eliminates the extraction steps seen in most nontraditional samples. DAPPI can be used to analyze bulkier samples, such as, tablets, powders, resins, plants, and tissues. The first step of this technique utilizes a jet of hot solvent vapor. The hot jet thermally desorbs the sample from a surface. The vaporized sample is then ionized by the vacuum ultraviolet light and consequently sampled into a mass spectrometer. DAPPI can detect a range of both polar and non-polar compounds, but is most sensitive when analyzing neutral or non-polar compounds. This technique also offers a selective and soft ionization for highly conjugated compounds.

<span class="mw-page-title-main">Capillary electrophoresis–mass spectrometry</span>

Capillary electrophoresis–mass spectrometry (CE–MS) is an analytical chemistry technique formed by the combination of the liquid separation process of capillary electrophoresis with mass spectrometry. CE–MS combines advantages of both CE and MS to provide high separation efficiency and molecular mass information in a single analysis. It has high resolving power and sensitivity, requires minimal volume and can analyze at high speed. Ions are typically formed by electrospray ionization, but they can also be formed by matrix-assisted laser desorption/ionization or other ionization techniques. It has applications in basic research in proteomics and quantitative analysis of biomolecules as well as in clinical medicine. Since its introduction in 1987, new developments and applications have made CE-MS a powerful separation and identification technique. Use of CE–MS has increased for protein and peptides analysis and other biomolecules. However, the development of online CE–MS is not without challenges. Understanding of CE, the interface setup, ionization technique and mass detection system is important to tackle problems while coupling capillary electrophoresis to mass spectrometry.

<span class="mw-page-title-main">Ambient ionization</span>

Ambient ionization is a form of ionization in which ions are formed in an ion source outside the mass spectrometer without sample preparation or separation. Ions can be formed by extraction into charged electrospray droplets, thermally desorbed and ionized by chemical ionization, or laser desorbed or ablated and post-ionized before they enter the mass spectrometer.

<span class="mw-page-title-main">Atmospheric-pressure photoionization</span> Soft ionization method

Atmospheric pressure photoionization (APPI) is a soft ionization method used in mass spectrometry (MS) usually coupled to liquid chromatography (LC). Molecules are ionized using a vacuum ultraviolet (VUV) light source operating at atmospheric pressure, either by direct absorption followed by electron ejection or through ionization of a dopant molecule that leads to chemical ionization of target molecules. The sample is usually a solvent spray that is vaporized by nebulization and heat. The benefit of APPI is that it ionizes molecules across a broad range of polarity and is particularly useful for ionization of low polarity molecules for which other popular ionization methods such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are less suitable. It is also less prone to ion suppression and matrix effects compared to ESI and APCI and typically has a wide linear dynamic range. The application of APPI with LC/MS is commonly used for analysis of petroleum compounds, pesticides, steroids, and drug metabolites lacking polar functional groups and is being extensively deployed for ambient ionization particularly for explosives detection in security applications.

<span class="mw-page-title-main">Desorption/ionization on silicon</span> Soft laser desorption method

Desorption/ionization on silicon (DIOS) is a soft laser desorption method used to generate gas-phase ions for mass spectrometry analysis. DIOS is considered the first surface-based surface-assisted laser desorption/ionization (SALDI-MS) approach. Prior approaches were accomplished using nanoparticles in a matrix of glycerol, while DIOS is a matrix-free technique in which a sample is deposited on a nanostructured surface and the sample desorbed directly from the nanostructured surface through the adsorption of laser light energy. DIOS has been used to analyze organic molecules, metabolites, biomolecules and peptides, and, ultimately, to image tissues and cells.

<span class="mw-page-title-main">Matrix-assisted ionization</span>

In mass spectrometry, matrix-assisted ionization is a low fragmentation (soft) ionization technique which involves the transfer of particles of the analyte and matrix sample from atmospheric pressure (AP) to the heated inlet tube connecting the AP region to the vacuum of the mass analyzer.

Peter Nemes is a Hungarian-American chemist, who is active in the fields of bioanalytical chemistry, mass spectrometry, cell/developmental biology, neuroscience, and biochemistry.

<span class="mw-page-title-main">Secondary electrospray ionization</span>

Secondary electro-spray ionization (SESI) is an ambient ionization technique for the analysis of trace concentrations of vapors, where a nano-electrospray produces charging agents that collide with the analyte molecules directly in gas-phase. In the subsequent reaction, the charge is transferred and vapors get ionized, most molecules get protonated and deprotonated. SESI works in combination with mass spectrometry or ion-mobility spectrometry.

Probe electrospray ionization (PESI) is an electrospray-based ambient ionization technique which is coupled with mass spectrometry for sample analysis. Unlike traditional mass spectrometry ion sources which must be maintained in a vacuum, ambient ionization techniques permit sample ionization under ambient conditions, allowing for the high-throughput analysis of samples in their native state, often with minimal or no sample pre-treatment. The PESI ion source simply consists of a needle to which a high voltage is applied following sample pick-up, initiating electrospray directly from the solid needle.

References

  1. 1 2 3 4 5 6 7 Nemes, Peter; Vertes, Akos (2007-09-27). "Laser Ablation Electrospray Ionization for Atmospheric Pressure, in Vivo, and Imaging Mass Spectrometry". Analytical Chemistry. American Chemical Society (ACS). 79 (21): 8098–8106. doi:10.1021/ac071181r. ISSN   0003-2700. PMID   17900146.
  2. 1 2 3 Nemes, Peter; Barton, Alexis A.; Li, Yue; Vertes, Akos (2008-05-13). "Ambient Molecular Imaging and Depth Profiling of Live Tissue by Infrared Laser Ablation Electrospray Ionization Mass Spectrometry". Analytical Chemistry. American Chemical Society (ACS). 80 (12): 4575–4582. doi:10.1021/ac8004082. ISSN   0003-2700. PMID   18473485.
  3. 1 2 3 4 Nemes, Peter; Barton, Alexis A.; Vertes, Akos (2009-07-02). "Three-Dimensional Imaging of Metabolites in Tissues under Ambient Conditions by Laser Ablation Electrospray Ionization Mass Spectrometry". Analytical Chemistry. American Chemical Society (ACS). 81 (16): 6668–6675. doi:10.1021/ac900745e. ISSN   0003-2700.
  4. 1 2 Nemes, Peter; Vertes, Akos (2010-09-03). "Atmospheric-pressure Molecular Imaging of Biological Tissues and Biofilms by LAESI Mass Spectrometry". Journal of Visualized Experiments. MyJove Corporation (43): 1–4. doi:10.3791/2097. ISSN   1940-087X. PMC   3157867 . PMID   20834223.
  5. 1 2 3 Shrestha, Bindesh; Nemes, Peter; Nazarian, Javad; Hathout, Yetrib; Hoffman, Eric P.; Vertes, Akos (2010). "Direct analysis of lipids and small metabolites in mouse brain tissue by AP IR-MALDI and reactive LAESI mass spectrometry". The Analyst. Royal Society of Chemistry (RSC). 135 (4): 751–758. doi:10.1039/b922854c. ISSN   0003-2654. PMID   20349540.
  6. 1 2 Sripadi, Prabhakar; Nazarian, Javad; Hathout, Yetrib; Hoffman, Eric P.; Vertes, Akos (2008-12-14). "In vitro analysis of metabolites from the untreated tissue of Torpedo californica electric organ by mid-infrared laser ablation electrospray ionization mass spectrometry". Metabolomics. Springer Science and Business Media LLC. 5 (2): 263–276. doi:10.1007/s11306-008-0147-x. ISSN   1573-3882. S2CID   8286288.
  7. 1 2 3 4 Nemes, Peter; Woods, Amina S.; Vertes, Akos (2010-01-05). "Simultaneous Imaging of Small Metabolites and Lipids in Rat Brain Tissues at Atmospheric Pressure by Laser Ablation Electrospray Ionization Mass Spectrometry". Analytical Chemistry. American Chemical Society (ACS). 82 (3): 982–988. doi:10.1021/ac902245p. ISSN   0003-2700. PMC   2964874 . PMID   20050678.
  8. 1 2 Sripadi, Prabhakar; Shrestha, Bindesh; Easley, Rebecca L.; Carpio, Lawrence; Kehn-Hall, Kylene; Chevalier, Sebastien; Mahieux, Renaud; Kashanchi, Fatah; Vertes, Akos (2010-09-07). Jacobson, Steven (ed.). "Direct Detection of Diverse Metabolic Changes in Virally Transformed and Tax-Expressing Cells by Mass Spectrometry". PLOS ONE. Public Library of Science (PLoS). 5 (9): e12590. doi: 10.1371/journal.pone.0012590 . ISSN   1932-6203. PMC   2935367 . PMID   20830293.
  9. 1 2 3 4 Shrestha, Bindesh; Vertes, Akos (2010-09-04). "Direct Analysis of Single Cells by Mass Spectrometry at Atmospheric Pressure". Journal of Visualized Experiments. MyJove Corporation (43): 1–4. doi:10.3791/2144. ISSN   1940-087X. PMC   3157873 . PMID   20834224.
  10. 1 2 3 4 Shrestha, Bindesh; Vertes, Akos (2009-09-17). "In Situ Metabolic Profiling of Single Cells by Laser Ablation Electrospray Ionization Mass Spectrometry". Analytical Chemistry. American Chemical Society (ACS). 81 (20): 8265–8271. doi:10.1021/ac901525g. ISSN   0003-2700.
  11. 1 2 Shrestha, Bindesh; Nemes, Peter; Vertes, Akos (2010-06-03). "Ablation and analysis of small cell populations and single cells by consecutive laser pulses". Applied Physics A. Springer Science and Business Media LLC. 101 (1): 121–126. doi:10.1007/s00339-010-5781-2. ISSN   0947-8396. S2CID   98617638.
  12. 1 2 3 Shrestha, Bindesh; Patt, Joseph M.; Vertes, Akos (2011-03-09). "In Situ Cell-by-Cell Imaging and Analysis of Small Cell Populations by Mass Spectrometry". Analytical Chemistry. American Chemical Society (ACS). 83 (8): 2947–2955. doi:10.1021/ac102958x. ISSN   0003-2700. PMID   21388149.
  13. ↑ Stephens, Catherine H.; Shrestha, Bindesh; Morris, Hannah R.; Bier, Mark E.; Whitmore, Paul M.; Vertes, Akos (2010). "Minimally invasive monitoring of cellulose degradation by desorption electrospray ionization and laser ablation electrospray ionization mass spectrometry". The Analyst. Royal Society of Chemistry (RSC). 135 (9): 2434–2444. doi:10.1039/c0an00155d. ISSN   0003-2654. PMID   20672159.
  14. ↑ Nemes, Peter; Vertes, Akos (2010). "Laser Ablation Electrospray Ionization for Atmospheric Pressure Molecular Imaging Mass Spectrometry". Methods in Molecular Biology. Vol. 656. Totowa, NJ: Humana Press. pp. 159–171. doi:10.1007/978-1-60761-746-4_9. ISBN   978-1-60761-745-7. ISSN   1064-3745.
  15. 1 2 Bartels, Benjamin; Svatoš, Aleš (2015). "Spatially resolved in vivo plant metabolomics by laser ablation-based mass spectrometry imaging (MSI) techniques: LDI-MSI and LAESI". Frontiers in Plant Science. 6: 471. doi: 10.3389/fpls.2015.00471 . ISSN   1664-462X. PMC   4498035 . PMID   26217345.
  16. 1 2 3 Nemes, Peter; Vertes, Akos (2007-11-01). "Laser Ablation Electrospray Ionization for Atmospheric Pressure, in Vivo, and Imaging Mass Spectrometry". Analytical Chemistry. 79 (21): 8098–8106. doi:10.1021/ac071181r. ISSN   0003-2700. PMID   17900146.
  17. 1 2 Chen, Zhaoyang; Vertes, Akos (2008-03-25). "Early plume expansion in atmospheric pressure midinfrared laser ablation of water-rich targets". Physical Review E. American Physical Society (APS). 77 (3): 036316. doi:10.1103/physreve.77.036316. ISSN   1539-3755. PMID   18517520.
  18. ↑ Chen, Zhaoyang; Bogaerts, Annemie; Vertes, Akos (2006-07-24). "Phase explosion in atmospheric pressure infrared laser ablation from water-rich targets". Applied Physics Letters. AIP Publishing. 89 (4): 041503. doi:10.1063/1.2243961. ISSN   0003-6951.
  19. 1 2 Apitz, I.; Vogel, A. (2005). "Material ejection in nanosecond Er:YAG laser ablation of water, liver, and skin". Applied Physics A. Springer Science and Business Media LLC. 81 (2): 329–338. doi:10.1007/s00339-005-3213-5. ISSN   0947-8396. S2CID   97063971.
  20. 1 2 3 4 5 6 Huang, Min-Zong; Cheng, Sy-Chi; Cho, Yi-Tzu; Shiea, Jentaie (2011). "Ambient ionization mass spectrometry: A tutorial". Analytica Chimica Acta. 702 (1): 1–15. doi:10.1016/j.aca.2011.06.017. PMID   21819855.
  21. ↑ Vertes, Akos; Nemes, Peter; Shrestha, Bindesh; Barton, Alexis A.; Chen, Zhaoyang; Li, Yue (2008). "Molecular imaging by Mid-IR laser ablation mass spectrometry". Applied Physics A. Springer Science and Business Media LLC. 93 (4): 885–891. doi:10.1007/s00339-008-4750-5. ISSN   0947-8396. S2CID   97866908.
  22. 1 2 3 4 Kiss, András; Hopfgartner, Gérard (2016). "Laser-based methods for the analysis of low molecular weight compounds in biological matrices". Methods. 104: 142–153. doi:10.1016/j.ymeth.2016.04.017. PMID   27107904.
  23. 1 2 Román, Jessica K.; Walsh, Callee M.; Oh, Junho; Dana, Catherine E.; Hong, Sungmin; Jo, Kyoo D.; Alleyne, Marianne; Miljkovic, Nenad; Cropek, Donald M. (2018-03-01). "Spatially resolved chemical analysis of cicada wings using laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS)". Analytical and Bioanalytical Chemistry. 410 (7): 1911–1921. doi:10.1007/s00216-018-0855-7. ISSN   1618-2642. PMID   29380018. S2CID   3415847.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.