Developing IR-780 as a Novel Matrix for Enhanced MALDI MS Imaging of Endogenous High-Molecular-Weight Lipids in Brain Tissues

Abstract

The matrix plays a prominent role in expanding the ability of matrix assisted laser desorption/ionization mass spectrometry (MALDI MS). However, on account of the unclarity of necessary properties of the matrix in MALDI MS, development of a new matrix is still in the exploratory stage and lacks systematic theoretical guidance. Meanwhile, most of the existing matrices are unable to simultaneously detect various high-molecular-weight (high-MW) lipids including (poly-)­phosphoinositides, cardiolipins, and gangliosides. In this study, we have successfully screened and optimized the application of commercially available IR-780 as a novel matrix for simultaneously profiling and imaging high-MW lipids in brain tissues by MALDI MS for the first time. The properties of IR-780 related to the matrix of MALDI MS, mainly including the optical properties (UV absorption, fluorescence emission, and photothermal efficiency), proton affinity, collision cross-sections (CCSs), salt-tolerance ability, and homogeneity, were comprehensively characterized, which demonstrated that high photothermal ability and large CCSs might guarantee the superior performance of IR-780 as matrix for the analysis of high-MW lipids in biological samples. This work provided some references for the development of a novel matrix, and especially, the concept of CCS was first introduced as a parameter for the development of a matrix. In addition, the simultaneous identification and imaging of endogenous high-MW lipids in rat brain tissues subjected to traumatic brain injury were successfully performed.

Effect of MALDI matrices on lipid analyses of biological tissues using MALDI‐2 postionization mass spectrometry

“…[20][21][22][23] Nevertheless, these methods are targeted and only provide improvements for molecules with specific chemical functionality. Nontagging approaches to increase sensitivity include the development of novel matrices, [24][25][26] the incorporation of chemical additives to matrices, the removal of interfering species from tissue sections by organic solvent and aqueous washes, 27,28 and the use of laser wavelengths that better match the absorption bands of the matrices. 29 As an example, adding 2-hydroxy-5-methoxybenzoic acid to 2 0 ,5 0dihydroxybenzoic acid (DHB) allowed for a threefold increase in signalto-noise (S/N) for oligosaccharides compared with DHB alone.…”

Effect of MALDI Matrices on Lipid Analyses of Biological Tissues Using MALDI-2 Post-Ionization Mass Spectrometry

“…Non-tagging approaches to increase sensitivity include the development of novel matrices, [24][25][26] the incorporation of chemical additives to matrices, removal of interfering species from tissue sections by organic solvset and aqueous washes 27,28 , and use of laser wavelengths that better match the absorption bands of the matrices. 29 As an example, adding 2-hydroxy-5-methoxybenzoic acid to 2,5dihydroxybenzoic acid (DHB) allowed for a 3-fold increase in signal-to-noise (S/N) for oligosaccharides compared to DHB alone.…”

Recent developments of novel matrices and on-tissue chemical derivatization reagents for MALDI-MSI

“…Small organic molecules are the most widespread matrices used in MALDI-MSI. Since recent reviews [11,20] have already described some novel organic matrices applied for MALDI-MSI including 1,5-diaminonapthalene [24], 4phenyl-a-cyanocinnamic acid amide [25], alkylated 2,5-DHB [26], 1,8-di(piperidinyl)-naphthalene [27], and 4,5-(bis(dimethylamino)naphthalen-1-yl)furan-2,5-dione (4maleicanhydrido proton sponge, MAPS) [28], this work selected only the latest efforts about novel organic matrices for MALDI-MSI from 2017. This section contains the rationally designed and synthesized as well as commercially available small organic molecules whose properties as bona fide MALDI matrices for the detection and imaging of analytes in tissue sections have recently been discovered or characterized ( Fig.…”

“…IR-780 is a commercially available near-infrared fluorescent dye. Li and coworkers [28] successfully screened and optimized the application of IR-780 as a matrix for visualization of various high-molecule lipids, including (poly-)phosphoinositides, cardiolipins, and gangliosides in acute traumatic brain injury tissues in negative ion mode. IR-780 was proved to possess various good properties including strong UV absorption, high proton affinity, good salt tolerance ability, homogeneous co-crystallization, and high vacuum stability.…”