Nanoparticle-assisted laser desorption/ionization (nano- PALDI)-based imaging mass spectrometry (IMS) and its application to brain sciences

Imaging mass spectrometry (IMS; also referred to as mass spectrometry imaging [MSI]) is an emerging mass-spectrometrybased imaging technique that enables visualization of the distribution of various biomolecules in biological tissue sections. This technique, which can be used for a variety of tissues having vast structures, was initially developed as a tool for protein imaging. However, because of the general versatility of IMS and the lack of established imaging technology for small organic molecules, the number of studies reporting IMS of small molecules has recently increased. In fact, IMS is an effective technique for the visualization of endogenous small metabolites, especially lipids, facilitated by the unique advantages of massspectrometry- based molecular detection. For IMS, the choice of a proper analyte ionization technique is critical. Matrix-assisted laser desorption/ionization (MALDI) has been regarded as the most effective analyte ionization method and has been applied to the analyses of brain disorders, such as Alzheimer’s and Parkinson’s diseases. Despite the promising capability of MALDIbased IMS for imaging of small metabolites, this technique suffers from several critical drawbacks, especially with regard to spatial resolution. One of the critical limitations of the spatial resolution of MALDI-IMS is the size of the organic matrix crystal and analyte migration during the matrix-crystallization process. To overcome these problems, we report herein a nanoparticle (NP)-assisted laser desorption/ionization (nano-PALDI)-based IMS technique, in which NPs are used as the ionization-enhancing reagent and the organic matrix crystallization process is eliminated. Another important advantage of the use of NPs for IMS comes from the recently increasing availability of various NPs with different coremetals, surface modifications, and particle diameters, which has expanded the range of molecular species that can be analyzed by means of this technique, to include species that cannot be ionized by MALDI-IMS. Hence, we believe that this new approach will lead to a better understanding of physiological processes as well as the diagnosis and pathophysiology of complex biological process, especially in the brain. This chapter summarizes the recent technological developments in the field of IMS and also describes the utilization of nano-PALDI in IMS as an attractive alternative to traditional MALDI-IMS.