Isoporous Membrane Mediated Imprinting Mass Spectrometry Imaging for Spatially-Resolved Metabolomics and Rapid Histopathological Diagnosis

Surface-assisted laser desorption/ionization (SALDI) mass spectrometry imaging (MSI) holds great value in spatial metabolomics and tumor diagnosis. Tissue imprinting on the SALDI target can avoid laser-induced tissue ablation and simplifies the sample preparation. However, the tissue imprinting process always causes lateral diffusion of biomolecules, thereby losing the fidelity of metabolite distribution on tissue. Herein, a membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform and vertical pores onto silicon nanowires (SiNWs) array. Compared with conventional direct imprinting technique, MMI-MSI can not only exclude the adsorption of large biomolecules but also avoid the lateral diffusion of metabolites. The whole time for MMI-based sample preparation can be reduced to 2 min, and the lipid peak number can increase from 46 to 113 in kidney tissue detection. Meanwhile, higher resolution of MSI can be achieved due to the confinement effect of the pore channel in the diffusion of metabolites. Based on MMI-MSI, the tumor margins of liver cancer can be clearly discriminated and their different subtypes can be precisely classified. This work demonstrates MMI-MSI is a rapid, highly sensitive, robust and high-resolution technique for spatially-resolved metabolomics and pathological diagnosis. Membrane-mediated imprinting mass spectrometry imaging (MMI-MSI) strategy is proposed by using isoporous nuclepore track-etched membrane as a mediating imprinting layer to selectively transport metabolites through uniform vertical pores onto silicon nanowires array. MMI-MSI provides new insights into rapid, ultrasensitive, high-resolution, and robust MSI techniques, benefiting large-scale spatially-resolved metabolomics research, especially in clinical histopathological diagnosis. image