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

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.