Matrix-assisted laser desorption/ionization spatial resolution

The second advantage is the possibility of performing chemical imaging analyses. Even if other techniques, such as matrix-assisted laser desorption/ionization, also allow images to be acquired, ToF-SIMS is, for now, the mass spectrometric technique with the best spatial resolution performance. 

Burrell M, Earnshaw C, Clench M (2007) Imaging matrix assisted laser desorption ionization mass spectrometry a technique to map plant metabolites within tissue at high spatial resolution. J Exp Bot 58(4) 757-763. doi 10.1093/jxb/erll39... 

Snel M, Fuller M (2010) High-spatial resolution matrix-assisted laser desorption ionization imaging analysis of glucosylceramide in spleen sections from a mouse model of gaucher disease. Anal Chem 82(9) 3664-3670. doi 10.1021/ac902939k... 

Since TOF-SIMS has been applied to evaluation of macromolecules such as a protein, it is often compared to matrix-assisted laser desorption/ionization (MALDI) techniques. There are advantages and disadvantages depending on a measurement purpose. For example, TOF-SIMS provides a more detailed distribution of a particular chemical because TOF-SIMS has higher spatial resolution— less than 100 nm—than MALDI, whose... 

IMS experiments may be performed using one of several MS ionization techniques secondary ion mass spectrometry (SIMS), laser desorption/ionization (LDI), desorption electrospray ionization (DESI), and matrix-assisted laser desorption/ionization (MALDI) (2). In general, these techniques offer complementary capabilities (3). SIMS imaging is favored for higher spatial resolution imaging over a low mass range (<1,000 Da), MALDI IMS covers a much wider mass range (up to and over 100,000 Da) but at somewhat lower spatial resolution, and DESI uses ambient pressure for analysis of small molecules but at lower spatial resolution. 

Angel, P.M., Spraggins, J.M., Baldwin, H.S. and Caprioli, R. (2012) Enhanced sensitivity for high spatial resolution lipid analysis by negative ion mode matrix assisted laser desorption ionization imaging mass spectrometry. Anal. Chem. 84, 1557-1564. 

Of these MSI techniques, matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is a soft ionization technique which does not produce fragments, or, at least, produces fewer ions fragments. In addition, its high sensitivity, accuracy, and spatial resolution made it suitable to measure the composition of compounds or biomacromolecules. So it can determine the distribution of peptides, proteins, or other chemicals and so on within thin slices of biological samples. Robinson et al. used MALDI-MS to measure the localization of water-soluble carbohydrates in wheat stems in situ and their method (Figure 10.26) may be useful for researchers of metallomics to carry out the study between metal or non metal and organism. 

However, both soft ionization of analytes and tandem MS are difficult to achieve with typical SIMS technique (8). In contrast, spatial resolution of MALDI-IMS is lower than that of SIMS. The spatial resolution depends on the experimental conditions and the instrument used but is typically 20-100 jim. Limitations of the spatial resolution of MALDI-IMS include the size of the organic matrix crystal and the analyte migration during the matrix application process. To overcome these problems, Taira and colleagues reported a nanoparticle (NP)-assisted laser desorption/ionization (nano-PALDI)-based IMS, in which the matrix crystallization process is eliminated (9). The use of nano-PALDI has enabled researchers to image compounds with spatial resolution at the cellular level (15 (xm almost equal to the size of the diameter of a laser spot). 

Figure 3.11 summarizes such key experimental points. As a first point, we have to choose the appropriate ionization method for the detection of small metabolites, we have alternative choices other than MALDI, such as secondary ion mass spectrometry (SIMS) [15], nanostructure-initiator mass spectrometry (NIMS) [20,21], desorption/ionization on silicon (DIOS) [22], nanoparticle-assisted laser desorptiopn/ ionization (nano-PALDI) [23], and even laser desorption/ionization (LDI) [24,25]. We consider that MALDI is stiU the most versatile method, particularly due to the soft ionization capability of intact analyte. However, other methods each have unique advantages for example, SIMS and nano-PALDI have achieved higher spatial resolution than conventional MALDI-IMS, and above aU, these mentioned alternative methods are all matrix-free methods, and thus can exclude the interruption of the matrix cluster ion. Next, if MALDI is chosen, experimenters should choose a suitable matrix compound, solvent composition, and further matrix application method for their target analyte. All these factors are critical to obtain sufficient sensitivity because they affect efficiency of analyte extraction, condition of cocrystallization, and, above all, analyte-ionization efficiency. In addition, based on the charge state of the analyte molecule, suitable MS polarity (i.e., positive/ negative ion detection mode) should be used in MS measurement. Below, we shall describe the key experimental points for MALDI-IMS applications of representative metabolites. 

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