Practical quantitative biomedical applications of MALDI-TOF mass spectrometry

Bucknall, Martin P.; Fung, Kim Y. C.; Duncan, Mark W.

doi:10.1016/s1044-0305(02)00426-9

Cited by 159 publications

(138 citation statements)

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“…In 2002, we reported a more comprehensive and practical study in which automated MALDI-TOF MS was used to quantify a range of components in biological extracts and fluids [31]. Growth hormone was measured in rat pituitary tissue; insulin in human pancreatic tissue; homovanillic acid in human urine; and LVV-hemorphin-7, epinephrine and norepinephrine in human adrenal and pheochromocytoma tissues.…”

Section: Low Molecular Mass Analytesmentioning

confidence: 99%

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Duncan¹,

Röder²,

Hunsucker³

2008

Briefings in Functional Genomics and Proteomics

195

162

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This review summarizes the essential characteristics of matrix-assisted laser desorption/ionization (MALDI) timeof-flight mass spectrometry (TOF MS), especially as they relate to its applications in quantitative analysis. Approaches to quantification by MALDI-TOF MS are presented and published applications are critically reviewed.Keywords: quantification; quantitative analysis; MALDI; mass spectrometry; biomarkers OVERVIEWSince its inception in 1987 [1], matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF MS) has been applied for the analysis of a wide range of biomolecules. Initial applications were almost exclusively for the qualitative analysis of biopolymers because MALDI-TOF MS provided a fast and accurate approach to molecular mass and purity information: Is my material the right mass and is it free from contaminants? Because of the speed of analysis, ease of use, relative low equipment cost, ease of data interpretation and limited potential for cross-contamination between samples/users, MALDI-TOF MS systems were considered walk-up instruments where investigators run their own samples and determine, within minutes, whether they were on the right track with their work.There were, however, two specific areas of application where MALDI-TOF MS was initially viewed as impractical: i.e. the analysis of low mass analytes and quantitative applications. Low mass analysis is complicated by the vast molar excess of the matrix that can swamp any analyte-specific signal in the low m/z region of the spectrum. Quantitative analysis was viewed as implausible because crystallization does not yield a uniform distribution of the analyte and matrix across the target surface and this gives rise to regions where the analyte signal is especially intense relative to other locations on the target surface. MALDI MS was therefore viewed as inherently irreproducible because, for a given amount of analyte loaded onto the target, the measured ion intensity varies.Subsequently, it has been shown that both these perceived limitations can be overcome and quantification can be routine, both for low and high mass analytes. Now, an extensive list of published applications includes quantification of amino acids, lipids, natural products, drugs, polymers, herbicides, metabolites, toxins, oligonucleotides, carbohydrates, peptides and proteins. (Selected applications from these areas are discussed at the end of this review.) Here, we focus on the quantitative applications of MALDI and illustrate applications relating to both low and high-molecular mass analytes. We also discuss the strategies for applying MALDI to relative and absolute quantification. While MALDI is most commonly combined with TOF analysers, other analyser options are possible and applications employing these are also presented. Our aim is not to provide an exhaustive catalogue of published applications, but to discuss the general principles and to illustrate the

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Section: Low Molecular Mass Analytesmentioning

confidence: 99%

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Duncan¹,

Röder²,

Hunsucker³

2008

Briefings in Functional Genomics and Proteomics

195

162

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“…Lately MALDI-TOF MS has become a popular method for quantitative analysis of biomolecules (oligonucleotides, proteins, glycoproteins, etc.) originating from various sample types (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(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).…”

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confidence: 99%

“…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). Using an isotopically labeled analogue of the analyte as the internal standard seems to be the best solution (6,8). A variety of stable isotope labeling methods have recently been developed for relative quantitation, including isotope-coded affinity tags (ICAT), isobaric tags for relative and absolute quantitation (iTRAQ), stable isotope labeling with amino acids in cell culture (SILAC) (35)(36)(37)(38)(39), 18 O (40 -42), and absolute quantitation of abundance (AQUA) (43).…”

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confidence: 99%

“…Suppression can especially distort the data when complex biological samples are analyzed that contain thousands of components in a wide concentration range. Other disadvantages of MALDI are the differential ionization efficiencies of different compounds of even similar chemical nature and the limited dynamic range due to saturation of the mass spectrometer detector (7,8,21,22). Fluctuation of laser power also contributes to the variable signal intensities of analytes.…”

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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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“…In addition to the differential display of peptides and proteins, attempts for the absolute quantification of proteins in biological samples by MS analysis have been made (Bucknall, Fung, & Duncan, 2002;Chelius & Bondarenko, 2002;Wu et al, 2002). Such ''targeted proteomics'' studies usually focus on one or a few proteins, for which authentic standards are available.…”

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confidence: 99%

Mass spectrometry in aging research

Schöneich

2004

Mass Spectrometry Reviews

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This review covers the application of mass spectrometric techniques to aging research. Modern proteomic strategies will be discussed as well as the targeted analysis of specific proteins for the correlation of post-translational modifications with protein function. Selected examples will show both the power and also current limitations of the respective techniques. Experimental results and strategies are discussed in view of current theories of the aging process. # 2004 Wiley Periodicals, Inc., Mass Spec Rev 24: [701][702][703][704][705][706][707][708][709][710][711][712][713][714][715][716][717][718] 2005

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Practical quantitative biomedical applications of MALDI-TOF mass spectrometry

Cited by 159 publications

References 50 publications

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Quantitative matrix-assisted laser desorption/ionization mass spectrometry

Investigating the Quantitative Nature of MALDI-TOF MS

Mass spectrometry in aging research

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