MALDI detection limits

In order to meaningfully compare MALDI detection limits to the other techniques, specifically defined analytical conditions must be established. The case of peptide mapping is a good starting point because this class of chemical species ionizes well using both MALDI and ESI. Moreover, a relatively large body of work using both NanoLC/ESI and NanoLC/MALDI has been reported from which some initial conclusions may be drawn. As... 

Table 9.8 shows the results of MALDI-ToFMS experiments of the selected additives in PP, HDPE, PA6 and PMMA. The observed detection limits are in the technical range of interest. Identification of the additives... 

Note Modem FT-ICR mass spectrometers offer ultrahigh resolving power (R= 10 -10 ) [193,194] and highest mass accuracy (Am = 10" -10 u, cf. examples in Chaps. 3.3.2 and 3.4.1), attomol detection limits (with nanoESI or MALDI sources), high mass range and MS capabilities. [195]... 

Of course, the sensitivity of an instrumental setup is of key importance to low detection limits nevertheless, the detection limit is a clearly different quantity. The detection limit may either be stated as a relative measure in trace analysis, e.g., 1 ppb of dioxin in waste oil samples (equivalent to 1 pg kg" of sample), or as an absolute measure, e.g., 10 femtomol of substance P with a certain MALDI instrument. 

The spot size of MALDI preparations and thus the amount of sample necessary to yield a useful layer can be further reduced by so-called anchor targets (Bruker Daltonik). Anchor targets exhibit small hydrophilic spots on a hydrophobic surface. As a result, the evaporating drop of matrix-analyte solution is anchored to such a point where it shrinks until the onset of crystallization exactly within this hydrophilic area. [110] The resulting preparation covers an about lOOfold smaller surface than obtained from a freely spreading drop. In addition to improved detection limits, this technique simplifies automated spot finding due to their precisely defined location on the target. 

Note In MALDI-MS, the combination of the actual analyte and the procedure of sample preparation represent the true limiting factors for sample consumption and detection limit. 

Bogan MJ, Agnes GR. 2004. WaU-less sample preparation of micron-sized sample spots for femtomole detection limits of proteins from liquid based UV-MALDI matrices. J Am Soc Mass Spectrom 15 486. 

In 1974, Comarisov and Marshall60 developed Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). This technique allows mass spectrometric measurements at ultrahigh mass resolution (R = 100000-1000000), which is higher than that of any other type of mass spectrometer and has the highest mass accuracy at attomole detection limits. FTICR-MS is applied today together with soft ionization techniques, such as nano ESI (electrospray ionization) or MALDI (matrix assisted laser/desorption ionization) sources. 

Fourier transform ICR mass spectrometers together with any type of ion source, such as nanoESI, MALDI (or also an inductively coupled plasma ion source) permit mass spectrometric measurements to be performed at ultrahigh mass resolution (R = m/hm = 105—106) with a very low detection limit and the highest possible mass accuracy (Am = 10 3—10 4 Da). In addition, a high mass range is possible and FTICR-MS can be applied for MS/MS experiments.48 A comparison of different separation systems used in inorganic mass spectrometry is presented in Table 3.1. 

MALDI-TOF-MS facilitates the analysis of carotenoids and other natural products with detection limits that are lower than most other techniques. For example, subpicomole quantities can be detected (Wingerath et al., 1999). The enhanced sensitivity is the result of the efficiency of the pulsed ionization and detection system in which a complete mass spectrum is recorded with each laser flash. Like FAB and LSIMS, molecular ions are the most abundant sample ions, although some protonated molecules and [M-H]+ ions may be formed as well. Abundant molecular ions of carotenoid esters have been observed using MALDI-TOF-MS (Kaufmann et al., 1996 Wingerath et al., 1996),... 

FAB and PD have been replaced by electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) in the analytical mass spectrometry laboratory, because both of these newer techniques have a wider mass range of analysis and have lower detection limits. ESI and MALDI have become invaluable ionization techniques for nonvolatile components. This is particularly true for a wide range of biological molecules including proteins, peptides, nucleic acids, etc. Samples can be analyzed by ESI using either direct injection or introduction through liquid chromatography. 

MALDI is considered the most sensitive of these techniques, with detection limits in the femtomoles/microliter range being relatively behind these other two, and this probably explains the general lack of continued interest in them in recent years. Of course statements concerning the relative sensitivities of the four ionization techniques have to take into account the chemical differences between compound classes, which plays a major part in the ionization of a given compound by a given ionization technique. 

The detection limit of ESI and MALDI depends on several factors, such as the nature of the sample and its preparation and purity, the instrument used and the skill of the operator. For peptides and proteins, the detection limit is in practice somewhere between femtomoles and picomoles, even if attomole limits have been reported [25-27],... 

As mentioned above, MSI for tissue section analysis is based on MALDI-TOF technology. This latter allows very sensitive detection of a wide variety of compounds, with masses up to 10 kDa. For biomolecules of larger molecular weights, MSI is no longer very sensitive due to detection limitations, but also due to the MALDI process... 

Concentration detection limits in CE-MS with the ESI interface are similar to those with UV detection. Sample sensitivity can be improved by using ion-trapping or time-of-flight (TOE) mass spectrometers. MS analysis can also be performed off-line, after appropriate sample collection, using plasma desorption-mass spectrometry (PD-MS) or matrix-assisted laser desorption-mass spectrometry (MALDI-MS). 

It has been shown by Egner et al. (64,65) that it is possible to analyze compounds directly from prepared polystyrene beads. This approach has been useful to verify and improve the synthetic method for the generation of combinatorial libraries. Assuming that there are approximately 106 beads in 1 gram of polystyrene resin, and the substitution factor for the solid phase chemistry is 0.4 mmol/g or more, there is about 400 pmol of compound attached to each single bead. MALDI-TOF analysis has detection limits in the femtomole region, which makes it compatible with single-bead analysis (76). 

Wei, H. Nolkrantz, K. Powell, D.H. Woods, J.H. Ko, M.-C. Kennedy, R.T. Electrospray Sample Deposition for Matrix-Assisted Laser Desorption/lonization (MALDI) and Atmospheric Pressure MALDI Mass Spectrometry With Attomole Detection Limits, Rapid Commun. Mass Spectrom. 18, 1193-1200 (2004). 

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