Matrix‐free mass spectrometry imaging of mouse brain tissue sections on silicon nanopost arrays

Abstract

Mass spectrometry imaging (MSI) is capable of detection and identification of diverse classes of compounds in brain tissue sections, whereas simultaneously mapping their spatial distributions.Given the vast array of chemical components present in neurological systems, as well as the innate diversity within molecular classes, MSI platforms capable of detecting a wide array of species are useful for achieving a more comprehensive understanding of their biological roles and significance. Currently, matrix-assisted laser desorption ionization (MALDI) is the method of choice for the molecular imaging of brain samples by mass spectrometry. However, nanostructured laser desorption ionization platforms, such as silicon nanopost arrays (NAPA), are emerging as alternative MSI techniques that can provide complementary insight into molecular distributions in the central nervous system. In this work, the molecular coverage of mouse brain lipids afforded by NAPA-MSI is compared to that of MALDI-MSI using two common MALDI matrices. In positive ion mode, MALDI spectra were dominated by phosphatidylcholines and phosphatidic acids. NAPA favored the ionization of phosphatidylethanolamines and glycosylated ceramides, which were poorly detected in MALDI-MSI. In negative ion mode, MALDI favored sulfatides and free fatty acids, whereas NAPA spectra were dominated by signal from phosphatidylethanolamines. The complementarity in lipid coverages between the NAPA-and MALDI-MSI platforms presents the possibility of selective lipid analysis and imaging dependent upon which platform is used. Nanofabrication of the NAPA platform offers better uniformity compared to MALDI, and the wider dynamic range offered by NAPA promises improved quantitation in imaging.

Mass Spectrometry Imaging of Lipids in Human Skin Disease Model Hidradenitis Suppurativa by Laser Desorption Ionization from Silicon Nanopost Arrays

“…It has been shown to provide ultra-trace sensitivity and the detection of a wide range of compounds and compound classes 37–40 . Previous MSI experiments examining mouse brain tissue sections on NAPA revealed enhanced ionization efficiency for certain lipid classes, such as HexCers and PEs, when compared to MALDI 41 . This enhanced sensitivity for difficult-to-detect species in tissues offers the possibility of using NAPA-MS to complement MALDI-MS for studying the roles of neutral lipids and other lipid classes in biological processes and disease.…”

Mass spectrometry imaging of triglycerides in biological tissues by laser desorption ionization from silicon nanopost arrays

“…The complete tissue extraction protocol and UPLC‐MS/MS conditions have been previously described . Briefly, lipid extracts from intact mouse lung and human skin tissue samples were prepared and analyzed by data‐dependent UPLC‐MS/MS to help aid in the lipid assignments from MSI experiments.…”

“…Silicon nanoposts arrays (NAPAs) are a highly uniform matrix‐free LDI platform shown to provide ultra‐trace sensitivity and broad molecular coverage . Furthermore, MSI of biological tissues on NAPA indicated that detection of certain lipid classes, e.g., hexosylceramides (HexCers) and phosphatidylethanolamines (PEs), was enhanced compared to MALDI . Here, we present NAPA as a matrix‐free LDI‐MSI platform offering enhanced ionization efficiency of neutral lipids, such as TGs, and demonstrate imaging applications for mouse lung and human skin tissue sections.…”

Mass spectrometry imaging based on laser desorption ionization from inorganic and nanophotonic platforms

“…Glycerophospholipids, sphingolipids, and fatty acids were annotated and spatially profiled throughout the tissue sections (see Figure 3C). More recently, advantages of NAPA in MSI were demonstrated in comparative studies to MALDI imaging of various lipid classes in tissue sections from mouse brain, lung, normal human skin, and hidradenitis suppurativa‐affected human skin 61 . Compared to MALDI, NAPA provided significantly enhanced ionization for PEs, phosphatidylethanolamine‐plasmalogens, hexosylceramides, and TGs in these complex biological samples 61 …”

“…Some of them, including desorption ionization on silicon (DIOS), 47 nanostructured indium tin oxide slides for surface‐assisted LDI, 48 nanowire‐assisted LDI, 49 silica plate imprinting LDI, 50 and LDI from laser‐engineered graphene paper and polydopamine‐coated AR surfaces, 44,51 have been utilized in a limited number of imaging applications. A few inorganic materials and substrates for LDI, in particular, AuNP and AgNP, 33,34,36,52‐55 nanostructure‐initiator mass spectrometry (NIMS), 30,56‐59 and nanophotonic ionization from silicon nanopost arrays (NAPAs), 60,61 have been more broadly explored for MSI.…”