The matrix suppression effect in matrix-assisted laser desorption/ionization: application to negative ions and further characteristics

Knochenmuss, Richard; Karbach, Volker; Wiesli, Ursula; Breuker, Kathrin; Zenobi, Renato

doi:10.1002/(sici)1097-0231(19980515)12:9<529::aid-rcm188>3.0.co;2-e

Cited by 91 publications

(100 citation statements)

References 18 publications

(28 reference statements)

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“…In addition, quenching of matrix ions at the expense of analyte protonation (also called the "matrix suppression effect" [15,57]) could be detected by means of angular and time resolved intensity distributions of matrix and analyte ions [6,7]. However, despite numerous investigations and indications regarding the analyte protonation, the final elucidation of the actual mechanism is still missing.…”

Section: The Gas Phase Protonation Modelmentioning

confidence: 99%

Compelling Evidence for Lucky Survivor and Gas Phase Protonation: The Unified MALDI Analyte Protonation Mechanism

Jaskolla

Karas

2011

J. Am. Soc. Mass Spectrom.

163

166

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This work experimentally verifies and proves the two long since postulated matrix-assisted laser desorption/ionization (MALDI) analyte protonation pathways known as the Lucky Survivor and the gas phase protonation model. Experimental differentiation between the predicted mechanisms becomes possible by the use of deuterated matrix esters as MALDI matrices, which are stable under typical sample preparation conditions and generate deuteronated reagent ions, including the deuterated and deuteronated free matrix acid, only upon laser irradiation in the MALDI process. While the generation of deuteronated analyte ions proves the gas phase protonation model, the detection of protonated analytes by application of deuterated matrix compounds without acidic hydrogens proves the survival of analytes precharged from solution in accordance with the predictions from the Lucky Survivor model. The observed ratio of the two analyte ionization processes depends on the applied experimental parameters as well as the nature of analyte and matrix. Increasing laser fluences and lower matrix proton affinities favor gas phase protonation, whereas more quantitative analyte protonation in solution and intramolecular ion stabilization leads to more Lucky Survivors. The presented results allow for a deeper understanding of the fundamental processes causing analyte ionization in MALDI and may alleviate future efforts for increasing the analyte ion yield.

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Section: The Gas Phase Protonation Modelmentioning

confidence: 99%

Compelling Evidence for Lucky Survivor and Gas Phase Protonation: The Unified MALDI Analyte Protonation Mechanism

Jaskolla

Karas

2011

J. Am. Soc. Mass Spectrom.

163

166

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“…Another phenomenon hindering the use of MALDI for quantitative measurements is the suppression effect, which has also been discussed in a number of publications (19,29,30,32,33,44). Suppression can especially distort the data when complex biological samples are analyzed that contain thousands of components in a wide concentration range.…”

mentioning

confidence: 99%

“…For example, preparations with ␣-cyano-4-hydroxycinnamic acid (CHCA) 1 deliver relatively homogenous samples (27) (which is why CHCA was used as the matrix in our experiments and in most other quantitative studies). On the other hand, dramatically nonlinear relationships of relative signal intensities and concentrations have been described despite the preparation of homogenous samples (32,33). The most common attempt to overcome the problem of poor reproducibility is the use of internal standards (5, 6, 8, 10, 11, 19 -22, 34).…”

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confidence: 99%

Investigating the Quantitative Nature of MALDI-TOF MS

Szaéjli

Feheér

Medzihradszky

2008

Molecular & Cellular Proteomics

138

116

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MALDI-TOF MS has been applied by several groups to relative quantitative measurements. At the same time, the non-quantitative character of this method has been widely reported. We conducted experiments to test the reliability of this technique for quantitation using the statistical method of inverse confidence limit calculation for the first time in this context. The relationship between relative intensities of known amounts of standard peptides and their concentration ratios was investigated. We found that the concentration ratios determined by relative intensity measurements were highly inaccurate and strongly influenced by the molecular milieu of the sample analyzed. Thus, we emphasize the necessity of using the sample itself for calibration. We also performed experiments using an isotope-labeled derivative of the analyte as an internal standard for calibration line generation. As expected, the use of such standard led to a dramatic increase in precision and a less pronounced improvement in accuracy. We recommend performing a similar statistical analysis as a demonstration of reliability for every system where MALDI-TOF MS is used for quantitative measurements. Molecular & Cellular Proteomics 7: 2410 -2418, 2008.MALDI-TOF MS is a widely used analytical technique because of its excellent sensitivity, relatively high speed, and simplicity. As a consequence of producing mostly singly charged ions (1, 2) MALDI is especially suitable for mixture analysis. It is commonly used in proteomic studies (3) frequently without any prefractionation (4) as well as in the analysis of other biomolecules. Lately MALDI-TOF MS has become a popular method for quantitative analysis of biomolecules (oligonucleotides, proteins, glycoproteins, etc.) originating from various sample types (5-22) or even for imaging tissue sections (13)(14)(15)(16)(17)(18)(23)(24)(25)(26). At the same time, several studies discuss the non-quantitative nature of MALDI-TOF MS (7, 8, 13, 19, 22, 26 -30). The main problem of MALDI is its poor reproducibility (sample to sample and shot to shot), which makes most quantitative measurements quite difficult at best (19,27,31). This is especially true for complex samples. The presence of so-called hot spots or sweet spots is the main cause of the poor reproducibility and is therefore a factor strongly increasing measurement times and complicating automated measurements. Furthermore this phenomenon is one of the major factors hampering the use of MALDI MS for spatially resolved imaging (27). The reasons for sweet spot formation are not completely understood. It could be caused by variation in the amount and the crystallization of the matrix, the latter being a function of local analyte concentration. Dependence of signal intensities on the orientation of the matrix-analyte crystals relative to the spectrometer axis is also possible (27). The extent of hot spot formation depends strongly on the matrix used. For example, preparations with ␣-cyano-4-hydroxycinnamic acid (CHCA) 1 deliver relatively homogenous samples (...

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“…Many of the matrices used in TLC-MALDI-MS cause interfering mass peaks at low mass numbers. However, it has been shown that the matrix background can be suppressed by using appropriate analyte-to-matrix molar ratio in MALDI measurements [23,26,[32][33][34][35]. New potential matrices, producing low matrix background, have also been introduced [16,20,21,27,30,31].…”

mentioning

confidence: 99%

Analysis of small molecules by ultra thin-layer chromatography-atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry

Salo

Salomies

Harju

et al. 2005

J. Am. Soc. Mass Spectrom.

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The feasibility of ultra thin-layer chromatography atmospheric pressure matrix-assisted laser desorption ionization mass spectrometry (UTLC-AP-MALDI-MS) has been studied in the analysis of small molecules. Because of a thinner adsorbent layer, the monolithic UTLC plates provide 10 -100 times better sensitivity in MALDI analysis than conventional high performance thin-layer chromatography (HPTLC) plates. The limits of detection down to a low picomole range are demonstrated by UTLC-AP-MALDI-MS. Other advantages of UTLC over HPTLC include faster separations and lower solvent consumption. The performances of AP-MALDI-MS and vacuum MALDI-MS have been compared in the analysis of small drug molecules directly from the UTLC plates. The desorption from the irregular surface of UTLC plates with an external AP-MALDI ion source combined with an ion trap instrument provides clearly less variation in measurements of m/z values when compared with a vacuum MALDI-time-of-flight (TOF) instrument. The performance of the UTLC-AP-MALDI-MS method has been applied successfully to the purity analysis of synthesis products produced by solid-phase parallel synthesis method. (J Am Soc Mass Spectrom 2005, 16, 906 -915)

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The matrix suppression effect in matrix-assisted laser desorption/ionization: application to negative ions and further characteristics

Cited by 91 publications

References 18 publications

Compelling Evidence for Lucky Survivor and Gas Phase Protonation: The Unified MALDI Analyte Protonation Mechanism

Compelling Evidence for Lucky Survivor and Gas Phase Protonation: The Unified MALDI Analyte Protonation Mechanism

Investigating the Quantitative Nature of MALDI-TOF MS

Analysis of small molecules by ultra thin-layer chromatography-atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry

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