MALDI Process Research Articles

An investigation of the ionicity of selected ionic liquid matrices used for matrix-assisted laser desorption/ionization

Ionic liquid matrices (ILMs) have been applied for MALDI-MS analysis for more than 20 years. Despite this, there is still insufficient knowledge regarding their properties. In this work, we tested the ionicity of selected ILMs and discussed their impact on the MALDI process. The targets were the following mixtures: CHCA/TEA, FER/TEA, HABA/α-MBA, 2,5-DHB/α-MBA (CHCA - α-cyano-4-hydroxycinnamic acid, FER – ferulic acid, HABA − 2-(4-hydroxyphenylazo)benzoic acid, 2,5-DHB − 2,5-dihydroxybenzoic acid, TEA – triethylamine, α-MBA - α-methylbenzylamine). These are ILMs which in our previous study showed liquidity at room temperature. We decided to apply several empirical and theoretical techniques due to the complexity of the problem. Thermogravimetric analysis (TGA) with IR was used to test the process at a higher temperature (simulation of a laser shot). 1H NMR was used for the determination in pure ILMs of intermolecular interactions, which have a high impact on ionicity. Conductivity and rheological measurements were performed to determine the Walden plot, from which the excess of ionicity can be concluded. DFT calculations were used to support the statements of dissociation processes in the gas phase and solution. The auto-ionization of matrices in MALDI was also tested. The interpretation of the Walden plot shows that HABA/α-MBA is a very good ionic liquid, which can be derived from a proposed “pedal motion”-like mechanism. The ionicity of other matrices was reduced because of intermolecular interactions (proved by TGA-IR and 1H NMR). The MALDI-MS analysis shows that the obtained mass spectra, namely the base peaks, depend on amine gas proton affinity. Furthermore, the DFT calculation results and the TGA-IR analysis support the mechanism of retro-proton transfer after the laser shot in the gas phase. Finally, it was concluded that the four tested ILMs are differentiated in ionicity, but its extent has no impact on the auto-ionization of the matrix.

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2017-2018.

This review is the tenth update of the original article published in 1999 on the application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2018. Also included are papers that describe methods appropriate to glycan and glycoprotein analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, new methods, matrices, derivatization, MALDI imaging, fragmentation and the use of arrays. The second part of the review is devoted to applications to various structural types such as oligo- and poly-saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Most of the applications are presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and highlights the impact that MALDI imaging is having across a range of diciplines. MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress.

Lithium Hydroxide Hydrolysis Combined with MALDI TOF Mass Spectrometry for Rapid Sphingolipid Detection.

Sphingolipids have diverse structural and bioactive functions that play important roles in many key biological processes. Factors such as low relative abundance, varied structures, and a dynamic concentration range provide a difficult analytical challenge for sphingolipid detection. To further improve mass-spectrometry-based sphingolipid analysis, lithium adduct consolidation was implemented to decrease spectral complexity and combine signal intensities, leading to increased specificity and sensitivity. We report the use of lithium hydroxide as a base in a routine hydrolysis procedure in order to effectively remove common ionization suppressants (such as glycolipids and glycerophospholipids) and introduce a source of lithium into the sample. In conjunction, an optimized MALDI matrix system, featuring 2',4',6'-trihydroxyacetophenone (THAP) is used to facilitate lithium adduct consolidation during the MALDI process. The result is a robust and high-throughput sphingolipid detection scheme, particularly of low-abundance ceramides. Application of our developed workflow includes the detection of differentially expressed liver sphingolipid profiles from a high-fat-induced obesity mouse model. We also demonstrate the method's effectiveness in detecting various sphingolipids in brain and plasma matrices. These results were corroborated with data from UHPLC HR MS/MS and MALDI FT-ICR, verifying the efficacy of the method application. Overall, we demonstrate a high-throughput workflow for sphingolipid analysis in various biological matrices by the use of MALDI TOF and lithium adduct consolidation.

Charge Distribution between Different Classes of Glycerophospolipids in MALDI-MS Imaging.

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is widely used to visualize and analyze the distribution of membrane lipids in an increasingly large number of applications. In this context, different lipoforms of glycerophospholipids (GPLs) are among the prime targets of interest. For this group of analytes, however, ion suppression effects have been described to strongly favor the detection of certain GPL classes over others, thereby hampering the analysis of suppressed species and greatly restraining quantitative analysis. These effects are generally attributed to the distribution of available charge carriers during the MALDI process. Here, we present a systematic investigation of charge distribution between different classes of GPL under MALDI-MSI conditions. For this, we constructed arrays of artificial tissues with different formulated lipid composition that contained predefined amounts of only two specific GPL classes and analyzed them with MALDI-MSI in positive- and negative-ion modes. Next to a characterization of expected ion suppression effects, analysis of these binary systems revealed yet undescribed signal intensity enhancement for the combinations of certain GPL classes. Furthermore, the comprehensive data allowed us to compile a hierarchy of charge affinities for the investigated GPL classes in both polarities. Additional experiments revealed that laser post-ionization (MALDI-2) has great potential to overwrite changes in signal intensity caused by charge distribution among different GPL classes observed in standard MALDI-MSI.

Multiple strong field ionization of metallocenes: Applicability of ADK rates to the production of multiply charged transition metal (Cr, Fe, Ni, Ru, Os) cations

The reactions of a neutral molecule with a singly charged ion in the gas phase have been studied extensively in connection with catalytic reactions, interstellar and planetary atmospheric chemistry, and the MALDI process. In contrast, the reactions of a neutral molecule with a multiply charged ion have rarely been reported, in part because it is difficult to produce such ions in abundance. In this study, we report the production of multiply charged transition metal cations from metallocenes in intense femtosecond laser fields. The most highly charged metals observed at 3 × 1015 W cm−2 are Cr6+, Fe6+, Ni6+, Ru7+, and Os8+. The production of carbon-containing cations originating in cyclopentadienyl ligands is small relative to that of metal cations because the ligands are dominantly liberated as neutral fragments. Metal cations having higher charges are formed by the sequential (stepwise) tunnel ionization of the singly (doubly) charged metal cations that are liberated from the excited metallocene cation (dication). The experimentally measured and theoretically calculated saturation intensities of cation generation are compared. The quasiclassical tunneling theory under a single active electron approximation has been known to underestimate the saturation intensity of singly charged metal cations. However, we investigate that this theory overestimates the saturation intensity of multiply charged metal cations referred to as an enhanced ionization. Moreover, the degree of overestimation becomes significant as the charge number of the metal cation increases. The characteristic deviation of the theoretical predictions from the experimental results is a key issue for the future clarification of the multiple-tunneling ionization processes. We suggest that the polarizabilities depending on the charge number, and presumably the excitation of cations, might be important in the multiple ionization of transition metals. In addition, the production of multiply charged metal cations in abundance, and the reduced production of carbon and hydrocarbon fragment cations achieved by femtosecond laser ionization, will be valuable as sources of multiply charged metal cations for future ion–molecule reaction studies.

Competition between metal cationization and protonation/reduction in MALDI process: An example of riboflavin

In order to better understand effects of metal cationization on protonation and reduction in MALDI process, mass spectra of riboflavin complexes with different alkali metal ions generated by a series of laser shots at a fixed target spot were consecutively recorded with the matrix of 2,5-dihydroxybenzoic acid (DHB). Progressive changes in the spectra, including the decrease of reduction extent for the metalized molecule ions and the increase of relative intensities of metalized species compared to protonated species, were observed with the increase of laser shots. Covariance mapping analysis was also performed for the data. Results show that different metalized ions are positively correlated each other; while metalized ions and protonated species are negatively correlated. These results not only reflect competition between metalization and protonation/reduction in laser plume, but also show that the winner of it might be changed during the process of sample consumption by laser irradiation.

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2013-2014.

This review is the eighth update of the original article published in 1999 on the application of Matrix-assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2014. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation, and arrays. The second part of the review is devoted to applications to various structural types such as oligo- and poly- saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Much of this material is presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. © 2018 Wiley Periodicals, Inc. Mass Spec Rev 37:353-491, 2018.

Structural Characterization of Methylenedianiline Regioisomers by Ion Mobility-Mass Spectrometry, Tandem Mass Spectrometry, and Computational Strategies. 3. MALDI Spectra of 2-Ring Isomers.

Characterization of methylenedianiline (MDA) 2-ring isomers (2,2'-, 2,4'-, and 4,4'-MDA) is reported using matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS), a common technique used for characterizing synthetic polymers. MDA is a precursor to methylene diphenyl diisocyanate (MDI), a hard block component in polyurethane (PUR) synthesis. This work focuses on comparing MALDI results to those of our previous electrospray ionization-mass spectrometry (ESI-MS) studies. In ESI, 2-ring MDA isomers formed single unique [M + H]+ (199 Da) parent ions, whereas in MALDI each isomer shows significant formation of three precursor ions: [M - H]+ = 197 Da, [M•]+ = 198 Da, and [M + H]+ = 199 Da. Structures and schemes are proposed for the MALDI fragment ions associated with each precursor ion. Ion mobility-mass spectrometry (IM-MS), tandem mass spectrometry (MS/MS), and computational methods were all critical in determining the structures for both precursor and fragment ions as well as the fragmentation mechanisms. The present study indicates that the [M - H]+ and [M•]+ ions are formed by the MALDI process, explaining why they were not observed with ESI.

Assuring Consistent Performance of an Insulin-Like Growth Factor 1 MALDImmunoassay by Monitoring Measurement Quality Indicators.

Analytical methods based on mass spectrometry (MS) have been successfully applied in biomarker discovery studies, while the role of MS in translating biomarker candidates to clinical diagnostics is less pronounced. MALDImmunoassays—methods that combine immunoaffinity enrichment with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometric detection—are attractive analytical approaches for large-scale sample analysis by virtue of their ease of operation and high-throughput capabilities. Despite this fact, MALDImmunoassays are not widely used in clinical diagnostics, which is mainly due to the limited availability of internal standards that can adequately correct for variability in sample preparation and the MALDI process itself. Here we present a novel MALDImmunoassay for quantification of insulin-like growth factor 1 (IGF1) in human plasma. Reliable IGF1 quantification in the range of 10–1000 ng/mL was achieved by employing 15N-IGF1 as internal standard, which proved to be an essential feature of the IGF1 MALDImmunoassay. The method was validated according to U.S. Food and Drug Administration (FDA) guidelines, which included demonstrating the effectiveness of IGF1/IGF binding protein (IGF1/IGFBP) complex dissociation using sodium dodecyl sulfate (SDS). Furthermore, the MALDImmunoassay compared well with the IDS-iSYS IGF1 immunoassay with high correlation (R2 = 0.99), although substantially lower levels were reported by the MALDImmunoassay. The method was tested on >1000 samples from a cohort of renal transplant recipients to assess its performance in a clinical setting. On the basis of this study, we identified readouts to monitor the quality of the measurements. Our work shows that MALDI-TOF mass spectrometry is suitable for quantitative biomarker analysis provided that an appropriate internal standard is used and that readouts are monitored to assess the quality of the measurements.

Observing Proton Transfer Reactions Inside the MALDI Plume: Experimental and Theoretical Insight into MALDI Gas-Phase Reactions.

We evaluated the contribution of gas-phase in-plume proton transfer reactions to the formation of protonated and deprotonated molecules in the MALDI process. A split sample holder was used to separately deposit two different samples, which avoids any mixing during sample preparation. The two samples were brought very close to each other and desorbed/ionized by the same laser pulse. By using a combination of deuterated and non-deuterated matrices, it was possible to observe exclusively in-plume proton transfer processes. The hydrogen/deuterium exchange (HDX) kinetics were evaluated by varying the delayed extraction (DE) time, allowing the desorbed ions and neutrals to interact inside the plume for a variable period of time before being extracted and detected. Quantum mechanical calculations showed that the HDX energy barriers are relatively low for such reactions, corroborating the importance of gas-phase proton transfer in the MALDI plume. The experimental results, supported by theoretical simulations, confirm that the plume is a very reactive environment, where HDX reactions could be observed from 0ns up to 400ns after the laser pulse. These results could be used to evaluate the relevance of previously proposed (and partially conflicting) ionization models for MALDI. Graphical Abstract ᅟ.

Generation of gas-phase ions from charged clusters: an important ionization step causing suppression of matrix and analyte ions in matrix-assisted laser desorption/ionization mass spectrometry.

Ionization in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a very complicated process. It has been reported that quaternary ammonium salts show extremely strong matrix and analyte suppression effects which cannot satisfactorily be explained by charge transfer reactions. Further investigation of the reasons causing these effects can be useful to improve our understanding of the MALDI process. The dried-droplet and modified thin-layer methods were used as sample preparation methods. In the dried-droplet method, analytes were co-crystallized with matrix, whereas in the modified thin-layer method analytes were deposited on the surface of matrix crystals. Model compounds, tetrabutylammonium iodide ([N(Bu)4 ]I), cesium iodide (CsI), trihexylamine (THA) and polyethylene glycol 600 (PEG 600), were selected as the test analytes given their ability to generate exclusively pre-formed ions, protonated ions and metal ion adducts respectively in MALDI. The strong matrix suppression effect (MSE) observed using the dried-droplet method might disappear using the modified thin-layer method, which suggests that the incorporation of analytes in matrix crystals contributes to the MSE. By depositing analytes on the matrix surface instead of incorporating in the matrix crystals, the competition for evaporation/ionization from charged matrix/analyte clusters could be weakened resulting in reduced MSE. Further supporting evidence for this inference was found by studying the analyte suppression effect using the same two sample deposition methods. By comparing differences between the mass spectra obtained via the two sample preparation methods, we present evidence suggesting that the generation of gas-phase ions from charged matrix/analyte clusters may induce significant suppression of matrix and analyte ions. The results suggest that the generation of gas-phase ions from charged matrix/analyte clusters is an important ionization step in MALDI-MS. Copyright © 2016 John Wiley & Sons, Ltd.

A Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Method for the Identification of Anthraquinones: the Case of Historical Lakes.

This study deals with the identification of anthraquinoid molecular markers in standard dyes, reference lakes, and paint model systems using a micro-invasive and nondestructive technique such as matrix-assisted laser desorption/ionization time-of-flight-mass spectrometry (MALDI-ToF-MS). Red anthraquinoid lakes, such as madder lake, carmine lake, and Indian lac, have been the most widely used for painting purposes since ancient times. From an analytical point of view, identifying lakes in paint samples is challenging and developing methods that maximize the information achievable minimizing the amount of sample needed is of paramount importance. The employed method was tested on less than 0.5 mg of reference samples and required a minimal sample preparation, entailing a hydrofluoric acid extraction. The method is fast and versatile because of the possibility to re-analyze the same sample (once it has been spotted on the steel plate), testing both positive and negative modes in a few minutes. The MALDI mass spectra collected in the two analysis modes were studied and compared with LDI and simulated mass spectra in order to highlight the peculiar behavior of the anthraquinones in the MALDI process. Both ionization modes were assessed for each species. The effect of the different paint binders on dye identification was also evaluated through the analyses of paint model systems. In the end, the method was successful in detecting madder lake in archeological samples from Greek wall paintings and on an Italian funerary clay vessel, demonstrating its capabilities to identify dyes in small amount of highly degraded samples. Graphical Abstract ᅟ.

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2011-2012.

This review is the seventh update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2012. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, and fragmentation are covered in the first part of the review and applications to various structural types constitute the remainder. The main groups of compound are oligo- and poly-saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Much of this material is presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:255-422, 2017.

Effect of polydimethylsiloxane (PDMS) coating on TiO2-based MALDI matrix for dimethyl methylphosphonate (DMMP) analysis

TiO2 nanoparticles were used as MALDI matrix for detecting dimethyl methylphosphate (DMMP) and its efficiency, in terms of DMMP signal intensity in the MALDI-MS analysis, was compared with that of polydimethylsiloxane (PDMS)-coated TiO2 matrix. Intensity of the DMMP signal in the MALDI-MS analysis was significantly increased by using PDMS-coated TiO2 matrix instead of bare ones. It was verified using FT-IR that the enhanced DMMP signal upon PDMS coating on TiO2 matrix is a result of weaker interactions between DMMP molecule and the PDMS-covered surface than that of bare TiO2. A weaker DMMP-matrix interaction can facilitate desorption of DMMP from the matrix surface in the MALDI process, yielding a higher sensitivity to DMMP in the MALDI-MS.

Matrix-assisted laser desorption/ionisation quadrupole ion trap time-of-flight mass spectrometry of novel shape-persistent macrocycles.

Shape-persistent macrocycles (SPMs) represent innovative molecular building blocks for the development of highly organised supramolecular architectures with application in nanotechnology, chemistry, catalysis and optoelectronics. Systematic mass spectrometric characterisation of SPMs and their collision-activated decay is not available to date. Characterisation of alkoxy-decorated SPMs was performed by matrix-assisted laser desorption/ionisation quadrupole ion trap time-of-flight mass spectrometry (MALDI-QIT-TOFMS) and collision-induced dissociation (CID). Laser excitation of SPMs leads to the formation of stable cation radicals which show characteristic fragmentation patterns. All the product ions formed were identified. Photoelectrons generated during the MALDI process and full-ring conjugation were found to be fundamental for the formation of molecular cation radicals and their stabilisation, respectively. Formation of supramolecular aggregates of SPMs by π-π stacking was proven. SPMs are suitable motifs for the preparation of novel fullerene-based donor-acceptor systems. Alkoxy-decorated SPMs represent promising electron-donating building blocks that can be exploited in electronics and optoelectronics for the development of robust and highly efficient laser-activated supramolecular switches.

Improved analysis of ultra-high molecular mass polystyrenes in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using DCTB matrix and caesium salts.

The ionization of polystyrenes in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is typically achieved by the use of silver salts. Since silver salts can cause severe problems, such as cluster formation, fragmentation of polymer chains and end group cleavage, their substitution by alkali salts is highly desirable. The influence of various cations (Ag(+), Cs(+) and Rb(+)) on the MALDI process of polystyrene (PS) mixtures and high mass polystyrenes was examined. The sample preparation was kept as straightforward as possible. Consequently, no recrystallization or other cleaning procedures were applied. The investigation of a polystyrene mixture showed that higher molecular polystyrenes could be more easily ionized using caesium, rather than rubidium or silver salts. In combination with the use of DCTB as matrix a high-mass polymer analysis could be achieved, which was demonstrated by the detection of a 1.1 MDa PS. A fast, simple and robust MALDI sample preparation method for the analysis of ultra-high molecular weight polystyrenes based on the use of DCTB and caesium salts has been presented. The suitability of the presented method has been validated by using different mass spectrometers and detectors.

Fragmentation behavior of poly(methyl methacrylate) during matrix-assisted laser desorption/ionization.

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been widely utilized for the structural characterization of various synthetic polymers. However, polymer sample molecules can occasionally decompose even in the MALDI process depending on the measurement conditions. In this work, the fragmentation behavior of radically polymerized poly(methyl methacrylate) (PMMA) during laser irradiation in MALDI was investigated in detail. Two types of PMMA samples with oligomeric molar mass were examined: Sample A was synthesized with an excess content of a chain transfer reagent to form simple molecules with less labile structures. Sample B was polymerized with a greater amount of a peroxide initiator without any chain transfer reagent, which resulted in the formation of various terminal and chain structures including relatively labile ones. The original components and fragment ions for the PMMA samples were precisely assigned using a high-resolution MALDI spiral time-of-flight MS system. Electrospray ionization MS measurements were also performed for comparison. The PMMA chains underwent fragmentation during the MALDI process with high laser intensity even for the relatively stable sample A. The fragmentation reactions proceeded mainly through 1,5-hydrogen rearrangements via a six-membered intermediate structure. Furthermore, PMMA molecules formed via recombination termination in sample B selectively decomposed during the MALDI-MS measurements even with low laser intensity. It was observed that the fragmentation reactions in the PMMA chains in MALDI with high laser power were generally the same as those in the post-source decay or collision-induced dissociation in MALDI-MS/MS measurements. Even with low laser intensity, less stable structures in the PMMA chain, especially head-to-head linkages, were readily decomposed during the MALDI process. Possible fragmentation, therefore, should be considered in the structural characterization of synthetic polymer samples by MALDI-MS.

Single Hair Analysis of Small Molecules Using MALDI-Triple Quadrupole MS Imaging and LC-MS/MS: Investigations on Opportunities and Pitfalls

Single hair analysis normally requires extensive sample preparation microscale protocols including time-consuming steps like segmentation and extraction. Matrix assisted laser desorption and ionization mass spectrometric imaging (MALDI-MSI) was shown to be an alternative tool in single hair analysis, but still, questions remain. Therefore, an investigation of MALDI-MSI in single hair analysis concerning the extraction process, usage of internal standard (IS), and influences on the ionization processes were systematically investigated to enable the reliable application to hair analysis. Furthermore, single dose detection, quantitative correlation to a single hair, and hair strand LC-MS/MS results were performed, and the performance was compared to LC-MS/MS single hair monitoring. The MALDI process was shown to be independent from natural hair color and not influenced by the presence of melanin. Ionization was shown to be reproducible along and in between different hair samples. MALDI image intensities in single hair and hair snippets showed good semiquantitative correlation to zolpidem hair concentrations obtained from validated routine LC-MS/MS methods. MALDI-MSI is superior to LC-MS/MS analysis when a fast, easy, and cheap sample preparation is necessary, whereas LC-MS/MS showed higher sensitivity with the ability of single dose detection for zolpidem. MALDI-MSI and LC-MS/MS segmental single hair analysis showed good correlation, and both are suitable for consumption monitoring of drugs of abuse with a high time resolution.

Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: an update for 2009-2010.

This review is the sixth update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2010. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, arrays and fragmentation are covered in the first part of the review and applications to various structural typed constitutes the remainder. The main groups of compound that are discussed in this section are oligo and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Many of these applications are presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 34: 268–422, 2015.

High-Mass MALDI-MS Using Ion Conversion Dynode Detectors: Influence of the Conversion Voltage on Sensitivity and Spectral Quality

With the development of special ion conversion dynode (ICD) detectors for high-mass matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), the mass-to-charge ratio is no longer a limiting factor. Although these detectors have been successfully used in the past, there is lack of understanding of the basic processes in the detector. We present a systematic study to investigate the performance of such an ICD detector and separate the contributions of the MALDI process from the ones of the ion-to-secondary ion and the secondary ion-to-electron conversions. The performance was evaluated as a function of the voltages applied to the conversion dynodes and the sample amount utilized, and we found that the detector reflects the MALDI process correctly: limitations such as sensitivity or deviations from the expected signal intensity ratios originate from the MALDI process itself and not from the detector.