Nano-PALDI

Hayasaka et al. [157] reported the determination of the fatty acid distribution in mouse retina by using AgNPs in nano-PALDI-IMS. The sections were sliced to a thickness of 10 pm and sprayed with AgNPs or DHB matrix solution at 50 mg/mL in 70 % methanol/0.1%TFA. The mouse retinal sections were analyzed at a high spatial resolution with a scan pitch of 10 pm. The MS images showed the distribution of palmitic acid, linoleic acid, oleic acid, stearic acid, eicosapentaenoic acid (EPA), arachidonic acid, and docosahexaenoic acid (DHA). 

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. 

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). 

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