Wang et al. in 2021 further leveraged the Single-probe fabrication to create a microprobe with a larger tip size, suitable for ambient liquid extraction MSI but not single-cell analysis 114 . This study aimed to address the limited imaging coverage of low-abundance or low-polarity lipids, such as glycerolipids and sphingolipids, in complex tissues. To do so, they applied a porous graphitic carbon (PGC) material to selectively imprint brain tissue sections, enriching neutral lipids while removing polar phospholipids. Subsequent scanning of the PGC-imprinted tissue with the ambient liquid extraction MSI system revealed that hydrophobic interactions dominate in protic solvents on the PGC surface, while polar interactions dominate in aprotic solvents. A recent study performed by this group presents a novel MSI approach that enhances spatial lipidomics analysis using a graphene oxide/titanium dioxide (GO/TiO2) nanocomposite as a mixed-mode adsorptive material . By combining the chelation affinity of TiO2 with the hydrophobic interaction of GO, the material facilitates selective enrichment of poorly ionizable glycolipids and glycerides while reducing ion suppression and peak interference from high-abundance polar lipids. Optimized solvent systems enabled on-plate separation of lipid classes and efficient two-step ambient liquid extraction MSI. This method significantly improved lipid coverage, detecting a greater variety of glycolipids, glycerides, and phospholipids compared to traditional MSI techniques. Application to rat cerebellum tissue demonstrated higher imaging quality and comprehensive lipid profiling, advancing the depth and scope of spatial lipidomics studies. Their future work will focus on scaling the nanocomposite coating for single-cell MSI.