In 2024, Lu et al. developed a novel method to address challenges in lipidomics, specifically for glycosphingolipids (GSLs), which are difficult to ionize and analyze 117 . This method introduces a photoinduced enrichment and deglycosylation approach, implemented in an ambient liquid extraction MS system, to improve GSL detection coverage and structural elucidation in single-cell analysis. Using TiO₂ in ammonia-based protic solvents, GSL standards were selectively adsorbed. Under UV irradiation, GSLs underwent deglycosylation (losing one hexosyl group) with a high conversion efficiency (>70%), then desorbed from TiO₂. Coating the TiO₂ onto a capillary probe enabled selective GSL enrichment while separating them from high-abundance phospholipids, reducing ion suppression. UV exposure triggered rapid photodesorption without solvent changes, achieving six-fold GSL enrichment. This enhanced GSL detection nine-fold compared to traditional methods, allowing for detailed fatty acyl and sphingosine chain elucidation through increased MS/MS fragmentation. The method was applied to analyze nerve cells with improved identifications of lipids, including GSLs and hexosylceramides, after neuron injury. This innovative TiO₂-coated probe provided low limit of detection (3.7 ng/mL), high linearity (r > 0.99), and repeatability (RSD < 20%). In brain tissue analysis, this technique identified 38 more lipids than using conventional methods. Overall, this approach significantly advances single cell lipidomics by enhancing GSL detection and structural analysis, providing valuable insights for biomedical and photooxidation research.