Matrix-assisted laser desorption/ionization

MALDI TOF mass spectrometer

Matrix-assisted laser desorption/ionization (MALDI) is a soft ionization technique used in mass spectrometry, allowing the analysis of biomolecules (biopolymers such as DNA, proteins, peptides and sugars) and large organic molecules (such as polymers, dendrimers and other macromolecules), 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 produces far fewer multiply charged ions.

MALDI methodology is a three-step process. First, the sample is mixed with a suitable matrix material and applied to a metal plate. Second, a pulsed laser irradiates the sample, triggering ablation and desorption of the sample and matrix material. Finally, the analyte molecules are ionized by being protonated or deprotonated in the hot plume of ablated gases, and can then be accelerated into whichever mass spectrometer is used to analyse them.[1]

History

The term matrix-assisted laser desorption ionization (MALDI) was coined in 1985 by Franz Hillenkamp, Michael Karas and their colleagues.[2] These researchers found that the amino acid alanine could be ionized more easily if it was mixed with the amino acid tryptophan and irradiated with a pulsed 266 nm laser. The tryptophan was absorbing the laser energy and helping to ionize the non-absorbing alanine. Peptides up to the 2843 Da peptide melittin could be ionized when mixed with this kind of “matrix”.[3] The breakthrough for large molecule laser desorption ionization came in 1987 when Koichi Tanaka of Shimadzu Corporation and his co-workers used what they called the “ultra fine metal plus liquid matrix method” that combined 30 nm cobalt particles in glycerol with a 337 nm nitrogen laser for ionization.[4] Using this laser and matrix combination, Tanaka was able to ionize biomolecules as large as the 34,472 Da protein carboxypeptidase-A. Tanaka received one-quarter of the 2002 Nobel Prize in Chemistry for demonstrating that, with the proper combination of laser wavelength and matrix, a protein can be ionized.[5] Karas and Hillenkamp were subsequently able to ionize the 67 kDa protein albumin using a nicotinic acid matrix and a 266 nm laser.[6] Further improvements were realized through the use of a 355 nm laser and the cinnamic acid derivatives ferulic acid, caffeic acid and sinapinic acid as the matrix.[7] The availability of small and relatively inexpensive nitrogen lasers operating at 337 nm wavelength and the first commercial instruments introduced in the early 1990s brought MALDI to an increasing number of researchers.[8] Today, mostly organic matrices are used for MALDI mass spectrometry.

Matrix and sample preparation

UV MALDI Matrix List
Compound Other Names Solvent Wavelength (nm) Applications
2,5-dihydroxy benzoic acid[9] DHB, Gentisic acid acetonitrile, water, methanol, acetone, chloroform 337, 355, 266 peptides, nucleotides, oligonucleotides, oligosaccharides
3,5-dimethoxy-4-hydroxycinnamic acid[7][10] sinapic acid; sinapinic acid; SA acetonitrile, water, acetone, chloroform 337, 355, 266 peptides, proteins, lipids
4-hydroxy-3-methoxycinnamic acid[7][10] ferulic acid acetonitrile, water, propanol 337, 355, 266 proteins
α-Cyano-4-hydroxycinnamic acid[11] CHCA acetonitrile, water, ethanol, acetone 337, 355 peptides, lipids, nucleotides
Picolinic acid[12] PA Ethanol 266 oligonucleotides
3-hydroxy picolinic acid[13] HPA Ethanol 337, 355 oligonucleotides

The matrix consists of crystallized molecules, of which the three most commonly used are 3,5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid), α-cyano-4-hydroxycinnamic acid (CHCA, alpha-cyano or alpha-matrix) and 2,5-dihydroxybenzoic acid (DHB).[14] A solution of one of these molecules is made, often in a mixture of highly purified water and an organic solvent such as acetonitrile (ACN) or ethanol. A counter ion source such as Trifluoroacetic acid (TFA) is usually added to generate the [M+H] ions. A good example of a matrix-solution would be 20 mg/mL sinapinic acid in ACN:water:TFA (50:50:0.1).

Notation for cinnamic acid substitutions.

The identification of suitable matrix compounds is determined to some extent by trial and error, but they are based on some specific molecular design considerations:

The matrix solution is mixed with the analyte (e.g. protein-sample). A mixture of water and organic solvent allows both hydrophobic and water-soluble (hydrophilic) molecules to dissolve into the solution. This solution is spotted onto a MALDI plate (usually a metal plate designed for this purpose). The solvents vaporize, leaving only the recrystallized matrix, but now with analyte molecules embedded into MALDI crystals. The matrix and the analyte are said to be co-crystallized. Co-crystallization is a key issue in selecting a proper matrix to obtain a good quality mass spectrum of the analyte of interest.

Naphthalene and naphthalene-like compounds can also be used as a matrix to ionize a sample

The matrix can be used to tune the instrument to ionize the sample in different ways. As mentioned above, acid-base like reactions are often utilized to ionize the sample, however, molecules with conjugated pi systems, such as naphthalene like compounds, can also serve as an electron acceptor and thus a matrix for MALDI/TOF.[17] This is particularly useful in studying molecules that also possess conjugated pi systems.[18] The most widely used application for these matrices is studying porphyrin like compounds such as chlorophyll. These matrices have been shown to have better ionization patterns that do not result in odd fragmentation patterns or complete loss of side chains.[19] It has also been suggested that conjugated porphryin like molecules can serve as a matrix and cleave themselves eliminating the need for a separate matrix compound.[20]

Technology and instrumentation

There are several variations of the MALDI technology and comparable instruments are today produced for very different purposes. From more academic and analytical, to more industrial and high throughput. The MS field has expanded into requiring ultrahigh resolution mass spectrometry such as the FT-ICR instruments[21][22] as well as more high-throughput instruments.[23] As many MALDI MS instruments can be bought with an interchangeable ionization source (Electrospray ionization, MALDI, Atmospheric pressure ionization, etc.) the technologies often overlap and many times any soft ionization method could potentially be used. For more variations of soft ionization methods go to Soft laser desorption or Ion source.

Laser

MALDI techniques typically employ the use of UV lasers such as nitrogen lasers (337 nm) and frequency-tripled and quadrupled Nd:YAG lasers (355 nm and 266 nm respectively). Although not as common, infrared lasers are used due to their softer mode of ionization. IR-MALDI also has the advantage of greater material removal (useful for biological samples), less low-mass interferences, and compatibility with other matrix-free laser desorption mass spectrometry methods.[24]

Ionization mechanism

The laser is fired at the matrix crystals in the dried-droplet spot. The matrix absorbs the laser energy and it is thought that primarily the matrix is desorbed and ionized (by addition of a proton) by this event. The hot plume produced during ablation contains many species: neutral and ionized matrix molecules, protonated and deprotonated matrix molecules, matrix clusters and nanodroplets. Ablated species may participate in the ionization of analyte, though the mechanism of MALDI is still debated. The matrix is then thought to transfer protons to the analyte molecules (e.g., protein molecules), thus charging the analyte.[25] An ion observed after this process will consist of the initial neutral molecule [M] with ions added or removed. This is called a quasimolecular ion, for example [M+H]+ in the case of an added proton, [M+Na]+ in the case of an added sodium ion, or [M-H]− in the case of a removed proton. MALDI is capable of creating singly charged ions or multiply charged ions ([M+nH]n+) depending on the nature of the matrix, the laser intensity, and/or the voltage used. Note that these are all even-electron species. Ion signals of radical cations (photoionized molecules) can be observed, e.g., in the case of matrix molecules and other organic molecules.

A recent method termed matrix-assisted ionization [MAI] uses matrix preparation identical to MALDI but does not require laser ablation to produce analyte ions of volatile or nonvolatile compounds. Simply exposing the matrix [e.g. 3-nitrobenzonitrile] with analyte to the vacuum of the mass spectrometer creates ions with nearly identical charge states to electrospray ionization.[26] It is suggested that there are likely mechanistic commonality between this process and MALDI.[27]

Time of Flight

Sample target for a MALDI mass spectrometer

The type of a mass spectrometer most widely used with MALDI is the TOF (time-of-flight mass spectrometer), mainly due to its large mass range. The TOF measurement procedure is also ideally suited to the MALDI ionization process since the pulsed laser takes individual 'shots' rather than working in continuous operation. MALDI-TOF instrument or reflectron is equipped with an "ion mirror" that reflects ions using an electric field, thereby doubling the ion flight path and increasing the resolution. Today, commercial reflectron TOF instruments reach a resolving power m/Δm of well above 20,000 FWHM (full-width half-maximum, Δm defined as the peak width at 50% of peak height).

MALDI has been coupled with IMS-TOF MS to identify phosphorylated and non-phosphorylated peptides.[28][29]

MALDI-FT-ICR MS has been demonstrated to be a useful technique where high resolution MALDI-MS measurements are desired.[30]

Atmospheric pressure matrix-assisted laser desorption/ionization

Atmospheric pressure (AP) matrix-assisted laser desorption/ionization (MALDI) is an ionization technique (ion source) that in contrast to vacuum MALDI operates at normal atmospheric environment.[31] The main difference between vacuum MALDI and AP-MALDI is the pressure in which the ions are created. In vacuum MALDI, ions are typically produced at 10 mTorr or less while in AP-MALDI ions are formed in atmospheric pressure. In the past the main disadvantage of AP MALDI technique compared to the conventional vacuum MALDI has been its limited sensitivity; however, ions can be transferred into the mass spectrometer with high efficiency and attomole detection limits have been reported.[32] AP-MALDI is used in mass spectrometry (MS) in a variety of applications ranging from proteomics to drug discovery. Popular topics that are addressed by AP-MALDI mass spectrometry include: proteomics; mass analysis of DNA, RNA, PNA, lipids, oligosaccharides, phosphopeptides, bacteria, small molecules and synthetic polymers, similar applications as available also for vacuum MALDI instruments. The AP-MALDI ion source is easily coupled to an ion trap mass spectrometer[33] or any other MS system equipped with ESI (electrospray ionization) or nanoESI source.

Applications

Biochemistry

In proteomics, MALDI is used for the rapid identification of proteins isolated by using gel electrophoresis: SDS-PAGE, size exclusion chromatography, affinity chromatography, strong/weak ion exchange, isotope coded protein labelling (ICPL),and two-dimensional gel electrophoresis. Peptide mass fingerprinting is the most popular analytical application of MALDI-TOF mass spectrometers. MALDI TOF/TOF mass spectrometers are used to reveal amino acid sequence of peptides using post-source decay or high energy collision-induced dissociation (further use see mass spectrometry).

Loss of sialic acid has been identified in papers when DHB has been used as a matrix for MALDI MS analysis of glycosylated peptides. Using sinapinic acid, 4-HCCA and DHB as matrices, S. Martin studied loss of sialic acid in glycosylated peptides by metastable decay in MALDI/TOF in linear mode and reflector mode.[34] A group at Shimadzu Corporation derivatized the sialic acid by an amidation reaction as a way to improve detection sensitivity[35] and also demonstrated that ionic liquid matrix reduces a loss of sialic acid during MALDI/TOF MS analysis of sialylated oligosaccharides.[36] THAP,[37] DHAP,[38] and a mixture of 2-aza-2-thiothymine and phenylhydrazine[39] have been identified as matrices that could be used to minimize loss of sialic acid during MALDI MS analysis of glycosylated peptides.

It has been reported that a reduction in loss of some post-translational modifications can be accomplished if IR MALDI is used instead of UV MALDI[40]

In molecular biology, a mixture of 5-methoxysalicylic acid and spermine can be used as a matrix for oligonucleotides analysis in MALDI mass spectrometry,[41] for instance after oligonucleotide synthesis.

Organic chemistry

Some synthetic macromolecules, such as catenanes and rotaxanes, dendrimers and hyperbranched polymers, and other assemblies, have molecular weights extending into the thousands or tens of thousands, where most ionization techniques have difficulty producing molecular ions. MALDI is a simple and fast analytical method that can allow chemists to rapidly analyze the results of such syntheses and verify their results.

Polymer chemistry

In polymer chemistry MALDI can be used to determine the molar mass distribution.[42] Polymers with polydispersity greater than 1.2 are difficult to characterize with MALDI due to the signal intensity discrimination against higher mass oligomers.[43][44][45]

A good matrix for polymers is dithranol[46] or AgTFA.[47] The sample must first be mixed with dithranol and the AgTFA added afterwards; otherwise the sample would precipitate out of solution.

Microbiology

MALDI/TOF spectra are used for the identification of micro-organisms such as bacteria or fungi. A portion of a colony of the microbe in question placed onto the sample target and overlaid with matrix. The mass spectra generated are analyzed by dedicated software and compared with stored profiles. Species diagnosis by this procedure is much faster, more accurate and cheaper than other procedures based on immunological or biochemical tests. MALDI/TOF may become the standard method for species identification in medical microbiological laboratories over the next few years.[48]

Its applications in microbiology have found uses in the research field since the 1980s but have only reached the wider scientific community in recent years. The development of more compact instruments justified its application on the field on the basis of ease of use, robustness and rapidity of results. In routine use in hospitals' laboratories around the world for the rapid confirmation and microbiological identification of suspected septicaemia and other infection cases it is now (as of December 2015) finding its way into the commercial microbiology testing market.

Its main advantage over other microbiological identification methods is its ability to reliably identify, at low cost and rapidly, a wide variety of micro-organisms directly from the selective medium used to isolate/detect them. The absence of the need to purify the suspect (or "presumptive") colony[49] allowing for much faster turn-around times.

Medicine

MALDI/TOF spectra are often utilized in tandem with other analysis and spectroscopy techniques in the diagnosis of diseases. MALDI/TOF is a diagnostic tool with much potential because it allows for the rapid identification of proteins and changes to proteins without the cost or computing power of sequencing nor the skill or time needed to solve a crystal structure in X-ray crystallography.

One of example of this is necrotizing enterocolitis (NEC), which is a devastating disease that affects the bowels of premature infants. The symptoms of NEC are very similar to those of sepsis, and many infants die awaiting diagnosis and treatment. MALDI/TOF was used to quickly analyze fecal samples and find differences between the mutant and the functional protein responsible for NEC. There is hope that a similar technique could be used as a quick, diagnostic tool that would not require sequencing.[50]

Another example of the diagnostic power of MALDI/TOF is in the area of cancer. Pancreatic cancer remains one of the most deadly and difficult to diagnose cancers.[51] Impaired cellular signaling due to mutations in membrane proteins has been long suspected to contribute to pancreatic cancer.[52] MALDI/TOF has been used to identify a membrane protein associated with pancreatic cancer and at one point may even serve as an early detection technique.[53]

MALDI/TOF can also potentially be used to dictate treatment as well as diagnosis. MALDI/TOF serves as a method for determining the drug resistance of bacteria, especially to β-lactamases (Penicillin family). The MALDI/TOF detects the presence of carbapenemases, which indicates drug resistance to standard antibiotics. It is predicted that this could serve as a method for identifying a bacterium as drug resistant in as little as three hours. This technique could help physicians decide whether to prescribe more aggressive antibiotics initially.[54]

Reproducibility and improving performance

Reproducibility is a known weakness of MALDI where the same analysis protocol can potentially yield different results, especially over time. Two key aspects are sample preparation and calibration. It is important for both sensitivity, reproducibility, and quantification of mass analysis. As MALDI is an invaluable technique for providing characterization data (e.g. the overall molecular weight, the mass of repeating units/amino acid sequences, and the identity of end groups) of high-mass synthetic or biological macromolecules; the technique requires regular calibration of the mass scale to assure mass accuracy. Traditionally, calibration systems have fallen into two categories: polydisperse systems (synthetic polymers [55] [56] or ion clusters [57] [58] [59] [60] [61] ) or monodisperse biomolecules (typically peptides or proteins). Of these, peptides and proteins had become the preferred calibrant because they were monodisperse and widely available. While these biomacromolecules fulfill the calibration requirements, their poor stability at ambient conditions and the high cost of their purification has complicated their regular use.

With the announcement by Bruker on the FDA approval of the use of MALDI Biotyper CA [62] [63] for the indentation of Gram negative bacterial colonies cultured from human specimens in clinical microbiology diagnostics the need of more robust and user-friendly calibrants is of outmost importance. A versatile synthetic analog, marketed under the brand name SpheriCal, is one available high-throughput MALDI calibrant. [64] Prepared as sets of discrete, monodisperse dendrimers, these calibrants have an extended shelf-life and good compatibility with a wide range of solvents and matrices, when compared to protein analogs. Their stability enables the calibrations samples to be premixed (matrix, cation, calibrant) and are available as 20 discrete calibration masses up to 30,000 Da. Standard peptide and protein calibration kits, on the other hand, only contain a few masses above 10 000 Da. Most notably Trypsinogen and Albumin-Bovine. The latter is usually seen as both [M+H] and [M+2H]2+ where Albumin-Bovine is not recommended for calibration purposes as it has been seen shifting to higher masses due to unspecific adduct formations.

In analysis of biological systems, Inorganic salts, which are also part of protein extracts, interfere with the ionization process. The salts can be removed by solid phase extraction or by washing the dried-droplet MALDI spots with cold water. Both methods can also remove other substances from the sample. The matrix-protein mixture is not homogenous because the polarity difference leads to a separation of the two substances during co-crystallization. The spot diameter of the target is much larger than that of the laser, which makes it necessary to make many laser shots at different places of the target, to get the statistical average of the substance concentration within the target spot. The matrix chemical composition, the addition of trifluoroacetic acid, formic acid, fructose, delay time between the end of laser pulse and start of ion acceleration in the ion source (in vacuum MALDI sources), laser wavelength, UV energy (as well as its density and homogeneity)in a focused light spot produced by pulsed laser, and the impact angle of the laser on the target are among critical parameters for the quality and reproducibility of the MALDI-TOF MS method.

Additionally, the thickness of the MALDI plate can affect the TOF measurements.[65] The smaller plates (less thick) will have longer TOF measurements. This can potentially shift peaks in the spectra and make it difficult to compare to other published results.

See also

References

  1. ↑ Karas, Michael; Krüger, Ralf (2003). "Ion Formation in MALDI: The Cluster Ionization Mechanism". Chemical Reviews. 103 (2): 427–440. doi:10.1021/cr010376a. ISSN 0009-2665.
  2. ↑ Karas, M.; Bachmann, D.; Hillenkamp, F. (1985). "Influence of the Wavelength in High-Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules". Analytical Chemistry. 57 (14): 2935–9. doi:10.1021/ac00291a042.
  3. ↑ Karas, M.; Bachmann, D.; Bahr, U.; Hillenkamp, F. (1987). "Matrix-Assisted Ultraviolet Laser Desorption of Non-Volatile Compounds". International Journal of Mass Spectrometry and Ion Processes. 78: 53–68. Bibcode:1987IJMSI..78...53K. doi:10.1016/0168-1176(87)87041-6.
  4. ↑ Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T.; Matsuo, T. (1988). "Protein and Polymer Analyses up to m/z 100 000 by Laser Ionization Time-of flight Mass Spectrometry". Rapid Communications in Mass Spectrometry. 2 (20): 151–3. doi:10.1002/rcm.1290020802.
  5. ↑ Markides, K.; Gräslund, A. (9 October 2002). "Advanced information on the Nobel Prize in Chemistry 2002" (PDF). The Royal Swedish Academy of Sciences. pp. 1–13. Retrieved 2013-08-28.
  6. ↑ Karas, M.; Hillenkamp, F. (1988). "Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons". Analytical Chemistry. 60 (20): 2299–301. doi:10.1021/ac00171a028. PMID 3239801.
  7. 1 2 3 Beavis, R. C.; Chait, B. T.; Standing, K. G. (1989). "Matrix-assisted laser-desorption mass spectrometry using 355 nm radiation". Rapid Communications in Mass Spectrometry. 3 (12): 436–9. doi:10.1002/rcm.1290031208. PMID 2520224.
  8. ↑ Karas, M.; Bahr, U. (1990). "Laser Desorption Ionization Mass Spectrometry of Large Biomolecules". Trends in Analytical Chemistry. 9 (10): 321–5. doi:10.1016/0165-9936(90)85065-F.
  9. ↑ Strupat, K.; Karas, M.; Hillenkamp, F. (1991). "2,5-Dihidroxybenzoic acid: A new matrix for laser desorption—ionization mass spectrometry". International Journal of Mass Spectrometry and Ion Processes. 72 (111): 89–102. Bibcode:1991IJMSI.111...89S. doi:10.1016/0168-1176(91)85050-V.
  10. 1 2 Beavis, R. C.; Chait, B. T.; Fales, H. M. (1989). "Cinnamic acid derivatives as matrices for ultraviolet laser desorption mass spectrometry of proteins". Rapid Communications in Mass Spectrometry. 3 (12): 432–5. doi:10.1002/rcm.1290031207. PMID 2520223.
  11. ↑ Beavis, R. C.; Chaudhary, T.; Chait, B. T. (1992). "α-Cyano-4-hydroxycinnamic acid as a matrix for matrix-assisted laser desorption mass spectrometry". Organic Mass Spectrometry. 27 (2): 156–8. doi:10.1002/oms.1210270217.
  12. ↑ Tang, K.; Taranenko, N. I.; Allman, S. L.; Cháng, L. Y.; Chen, C. H.; Lubman, D. M. (1994). "Detection of 500-nucleotide DNA by laser desorption mass spectrometry". Rapid Communications in Mass Spectrometry. 8 (9): 727–30. doi:10.1002/rcm.1290080913. PMID 7949335.
  13. ↑ Wu, K. J.; Steding, A.; Becker, C. H. (1993). "Matrix-assisted laser desorption time-of-flight mass spectrometry of oligonucleotides using 3-hydroxypicolinic acid as an ultraviolet-sensitive matrix". Rapid Communications in Mass Spectrometry. 7 (2): 142–6. doi:10.1002/rcm.1290070206. PMID 8457722.
  14. ↑ Korfmacher, Walter A. (2009). Using Mass Spectrometry for Drug Metabolism Studies. CRC Press. p. 342. ISBN 9781420092219.
  15. ↑ Fitzgerald, M. C.; Parr, G. R.; Smith, L. M. (1993). "Basic matrixes for the matrix-assisted laser desorption/ionization mass spectrometry of proteins and oligonucleotides". Analytical Chemistry. 65 (22): 3204–11. doi:10.1021/ac00070a007. PMID 8291672.
  16. ↑ Zenobi, R.; Knochenmuss, R. (1998). "Ion formation in MALDI mass spectrometry". Mass Spectrometry Reviews. 17 (5): 337–366. doi:10.1002/(SICI)1098-2787(1998)17:5<337::AID-MAS2>3.0.CO;2-S.
  17. ↑ Nazim Boutaghou, M. and Cole, R. B. (2012), 9,10-Diphenylanthracene as a matrix for MALDI-MS electron transfer secondary reactions. J. Mass Spectrom., 47: 995–1003. doi: 10.1002/jms.3027
  18. ↑ Suzuki, T., Midonoya, H., Shioi, Y.: Analysis of chlorophylls and their derivatives by matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry. Anal. Biochem. 390, 57–62 (2009)
  19. ↑ Wei, J.; Li, H.; Barrow, M. P.; O'Connor, P. B. Structural characterization of chlorophyll-a by high resolution tandem mass spectrometry. J. Am. Soc. Mass Spectrom. 2013, 24, 753-760.
  20. ↑ Srinivasan, N., Haney, C. A., Lindsey, J. S., Zhang, W. and Chait, B. T. (1999), Investigation of MALDI-TOF mass spectrometry of diverse synthetic metalloporphyrins, phthalocyanines and multiporphyrin arrays. J. Porphyrins Phthalocyanines, 3: 283–291. doi: 10.1002/(SICI)1099-1409(199904)3:4<283::AID-JPP132>3.0.CO;2-F
  21. ↑ Talking About a Revolution: FT-ICR Mass Spectrometry Offers High Resolution and Mass Accuracy for Pr | Biocompare Editorial Article
  22. ↑ Ultrahigh resolution mass spectrometry
  23. ↑ , Journal of Microbiological Methods Volume 86, Issue 3, September 2011, Pages 327–336
  24. ↑ "Infrared MALDI". Murray Group at Louisiana State University. Archived from the original on 2011-07-24. Retrieved 2010-01-20.
  25. ↑ Knochenmuss, R (2006). "Ion formation mechanisms in UV-MALDI". Analyst. 131 (9): 966–986. Bibcode:2006Ana...131..966K. doi:10.1039/b605646f. PMID 17047796.
  26. ↑ Trimpin, S, Inutan, ED. "Matrix Assisted Ionization in Vacuum, a Sensitive and Widely Applicable Ionization Method for Mass Spectrometry". J. Am. Soc. Mass Spectrom. 2013. 24: 722–732.
  27. ↑ McEwen, CN, Larsen, BS (2014). "Fifty years of desorption ionization". Int. J. Mass Spectrom. doi.org/10.1016/j.ijms.2014.07.018.
  28. ↑ Ruotolo, B. T.; Gillig, K. J.; Woods, A. S.; Egan, T. F.; Ugarov, M. V.; Schultz, J. A.; Russell, D. H. (2004). "Analysis of Phosphorylated Peptides by Ion Mobility-Mass Spectrometry". Analytical Chemistry. 76 (22): 6727–6733. doi:10.1021/ac0498009.(subscription required)
  29. ↑ Ruotolo, B. T.; Verbeck, G. F.; Thomson, L. M.; Woods, A. S.; Gillig, K. J.; Russell, D. H. (2002). "Distinguishing between Phosphorylated and Nonphosphorylated Peptides with Ion Mobility−Mass Spectrometry". Journal of Proteome Research. 1 (4): 303–306. doi:10.1021/pr025516r.(subscription required)
  30. ↑ Pasa-Tolic, L.; Huang, Y.; Guan, S.; Kim, H. S.; Marshall, A. G. (1995). "Ultrahigh-resolution matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectra of peptides". Journal of Mass Spectrometry. 30 (6): 825–833. doi:10.1002/jms.1190300607.(subscription required)
  31. ↑ Laiko, V. V.; Baldwin, M. A.; Burlingame, A. L. (2000). "Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry". Analytical Chemistry. 72 (4): 652–7. doi:10.1021/ac990998k. PMID 10701247.
  32. ↑ Strupat, K.; Scheibner, O.; Arrey, T.; Bromirski, M. (2011). "Biological Applications of AP MALDI with Thermo Scientific Exactive Orbitrap MS" (PDF). 443-539-1710. Thermo Scientific. Retrieved 17 June 2011.
  33. ↑ Laiko, V. V.; Moyer, S. C.; Cotter, R. J. (2000). "Atmospheric pressure MALDI/ion trap mass spectrometry". Analytical Chemistry. 72 (21): 5239–43. doi:10.1021/ac000530d. PMID 11080870.
  34. ↑ Huberty, M. C.; Vath, J. E.; Yu, W.; Martin, S. A. (1993). "Site-specific carbohydrate identification in recombinant proteins using MALD-TOF MS". Analytical Chemistry. 65 (20): 2791–2800. doi:10.1021/ac00068a015.
  35. ↑ Sekiya, S.; Wada, Y.; Tanaka, K. (2005). "Derivatization for Stabilizing Sialic Acids in MALDI-MS". Analytical Chemistry. 77 (15): 4962–4968. doi:10.1021/ac050287o.
  36. ↑ Fukuyama, Y.; Nakaya, S.; Yamazaki, Y.; Tanaka, K. (2008). "Ionic Liquid Matrixes Optimized for MALDI-MS of Sulfated/Sialylated/Neutral Oligosaccharides and Glycopeptides". Analytical Chemistry. 80 (6): 2171–2179. doi:10.1021/ac7021986.
  37. ↑ Papac, D. I.; Wong, A.; Jones, A. J. S. (1996). "Analysis of Acidic Oligosaccharides and Glycopeptides by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry". Analytical Chemistry. 68 (18): 3215–3223. doi:10.1021/ac960324z.
  38. ↑ Harvey, D. J. (1999). "Matrix-assisted laser desorption/ionization mass spectrometry of carbohydrates". Mass Spectrometry Reviews. 18 (6): 349–451. doi:10.1002/(SICI)1098-2787(1999)18:6<349::AID-MAS1>3.0.CO;2-H.
  39. ↑ Lattova, E.; Chen, V. C.; Varma, S.; Bezabeh, T.; Perreault, H. (2007). "Matrix-assisted laser desorption/ionization on-target method for the investigation of oligosaccharides and glycosylation sites in glycopeptides and glycoproteins". Rapid Communications in Mass Spectrometry. 21 (10): 1644–1650. doi:10.1002/rcm.3007.
  40. ↑ Tajiri, M.; Takeuchi, T.; Wada, Y. (2009). "Distinct Features of Matrix-Assisted 6 μm Infrared Laser Desorption/Ionization Mass Spectrometry in Biomolecular Analysis". Analytical Chemistry. 81 (16): 6750–6755. doi:10.1021/ac900695q.
  41. ↑ Distler, A. M.; Allison, J. (2001). "5-Methoxysalicylic acid and spermine: A new matrix for the matrix-assisted laser desorption/ionization mass spectrometry analysis of oligonucleotides". Journal of the American Society for Mass Spectrometry. 12 (4): 456–62. doi:10.1016/S1044-0305(01)00212-4. PMID 11322192.
  42. ↑ Schrepp, W.; Pasch, H. (2003). MALDI-TOF Mass Spectrometry of Synthetic Polymers. Springer-Verlag. ISBN 3-540-44259-6.
  43. ↑ Nielen, M. W. F.; Malucha, S. (1997). "Characterization of polydisperse synthetic polymers by size-exclusion chromatography/matrix-assisted laser desorption/ionization time-of-flight mass spectrometry". Rapid Communications in Mass Spectrometry. 11 (11): 1194. doi:10.1002/(SICI)1097-0231(199707)11:11<1194::AID-RCM935>3.0.CO;2-L.
  44. ↑ Wu, K. J.; Odom, R. W. (1998). "Characterizing synthetic polymers by MALDI MS". Analytical Chemistry. 70 (13): 456A–461A. doi:10.1021/ac981910q. PMID 9666717.
  45. ↑ Schriemer, D. C.; Li, L. (1997). "Mass Discrimination in the Analysis of Polydisperse Polymers by MALDI Time-of-Flight Mass Spectrometry. 2. Instrumental Issues". Analytical Chemistry. 69 (20): 4176. doi:10.1021/ac9707794.
  46. ↑ Schaiberger, Audrey M.; Moss, Jason A. (2008). "Optimized sample preparation for MALDI mass spectrometry analysis of protected synthetic peptides". Journal of the American Society for Mass Spectrometry. 19 (4): 614–619. doi:10.1016/j.jasms.2008.01.010. ISSN 1044-0305.
  47. ↑ Bahr, Ute.; Deppe, Andreas.; Karas, Michael.; Hillenkamp, Franz.; Giessmann, Ulrich. (1992). "Mass spectrometry of synthetic polymers by UV-matrix-assisted laser desorption/ionization". Analytical Chemistry. 64 (22): 2866–2869. doi:10.1021/ac00046a036. ISSN 0003-2700.
  48. ↑ Seng, P.; Drancourt, M.; Gouriet, F.; La Scola, B.; Fournier, P. E.; Rolain, J. M.; Raoult, D. (2009). "Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry". Clinical Infectious Diseases. 49 (4): 552–3. doi:10.1086/600885. PMID 19583519.
  49. ↑ Capocefalo M., Ridley E. V., Tranfield E. Y. & Thompson K. C. (2015). "Ch. 9 - MALDI-TOF: A rapid microbiological confirmation technique for food and water analysis". In Cook N.; D'Agostino M.; Thompson K. C. Molecular Microbial Diagnostic Methods - Pathways to Implementation for the Food and Water Industries. Elsevier. ISBN 978-0-12-416999-9.
  50. ↑ Sim, K.; Shaw, A. G.; Randell, P.; Cox, M. J.; McClure, Z. E.; Li, M. S.; Haddad, M.; Langford, P. R.; Cookson, W. O.; Moffatt, M. F.; Kroll, J. S. Dysbiosis anticipating necrotizing enterocolitis in very premature infants. Clin. Infect. Dis. 2014.
  51. ↑ Grantzdorffer I, Carl-McGrath S, Ebert MP, Rocken C. Proteomics of pancreatic cancer. Pancreas. 2008;36(4):329–36. doi:10.1097/MPA.0b013e31815cc452.
  52. ↑ Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–90. doi:10.1038/sj.onc.1210421.
  53. ↑ Zhong, N.; Cui, Y.; Zhou, X.; Li, T.; Han, J. Identification of prohibitin 1 as a potential prognostic biomarker in human pancreatic carcinoma using modified aqueous two-phase partition system combined with 2D-MALDI-TOF-TOF-MS/MS. Tumour Biol. 2014.
  54. ↑ Hrabák, Jaroslav (2015). "Detection of Carbapenemases Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) Meropenem Hydrolysis Assay". Methods in molecular biology (Clifton, N.J.) (1064-3745), 1237, p. 91.
  55. ↑ McEwen, C.N., Larsen, B.S.: Accurate mass measurement of proteins using electrospray ionization on a magnetic sector instrument. Rapid Commun. Mass Spectrom.6:173-178 (1992)
  56. ↑ 2. Cody, R.B., Tamura, J., Musselman, B.D.: Electrospray ionization/magnetic sector mass spectrometry: Calibration, resolution, and accurate mass measurements. Anal. Chem. 64,1561–1570 (1992)
  57. ↑ Pleasance, S., Thibault, P., Sim, P.G.; Boyd, R.K.: Caesium iodide clusters as mass calibrants in ionspray mass spectrometry. Rapid Commun. Mass Spectrom. 5, 307–308 (1991)
  58. ↑ Anacleto, J. F., Pleasance,S., Boyd, R. K.: Calibration of ion spray mass spectra using cluster ions. Org. Mass Spectrom. 27, 660–666 (1992)
  59. ↑ Hop, C.E.C.A.: Generation of high molecular weight cluster ions by electrospray ionization: Implications for mass calibration. J. Mass Spectrom. 31, 1314–1316 (1996)
  60. ↑ 6. Moini, M., Jones, B.L., Rogers, R.M., Jiang, L.: Sodium trifluoroacetate as a tune/calibration compound for positive- and negative-ion electrospray ionization mass spectrometry in the mass range of 100-4000 Da, J. Am. Soc. Mass Spectrom. 9, 977-980 (1998)
  61. ↑ 7. Konig, S., Fales, H.M.: Calibration of mass ranges up to m/z 10,000 in electrospray mass spectrometers. J. Am. Soc. Mass Spectrom. 10, 273–276 (1999)
  62. ↑ FDA approval K130831
  63. ↑ Bruker announcement
  64. ↑ Grayson, S. M.; Myers, B. K.; Bengtsson, J.; Malkoch, M. Advantages of Monodisperse and Chemically Robust “SpheriCal” Polyester Dendrimers as a “Universal” MS Calibrant. J. Am. Soc. Mass Spectrom., 25, 303-309 (2014) DOI: 10.1007/s13361-013-0777-8
  65. ↑ Yang, J.; Khatri, D.; Anzel, P.; Daraio, C. Interaction of highly nonlinear solitary waves with thin plates. Int. J. Solids Structures 2012, 49, 1463-1471.

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