Flocculent Ti3AlC2-Based Two-Dimensional Material Flexible Microneedle Patch for Screening Alzheimer’s Disease Animal Biomarkers and In Situ Revealing Spatial Aggregation of Arachidonic Acid

Efficient diagnosis and pathological elucidation of Alzheimer’s disease (AD) are constrained by the lack of technologies for in situ capture of metabolites in living brain tissues. Metabolic disorders in the parietal lobe highly correlate with AD progression, yet existing methods cannot achieve in situ capture and spatial analysis. A petal-like flocculent Ti3AlC2-based flexible microneedle patch was developed for in situ extraction and mass spectrometry of parietal metabolites in AD rabbits. Sodium hydroxide etching and cetyltrimethylammonium bromide (CTAB) self-assembly constructed a flocculent micro-/nanostructure, enhancing enrichment ~4-fold (2.5-fold after etching + 1.6-fold after CTAB). The stretchable substrate enables conformal attachment to the curved parietal lobe. Application to the exposed cortex demonstrates mechanical flexibility, linear glucose response (R2 = 0.9958) and resistance to salt/protein interference. Serum profiling of 15 AD patients and 15 controls with OPLS-DA shows clear discrimination (top-5 markers combined area under the curve (AUC) = 0.84). Spatial analysis reveals arachidonic acid’s unique pattern of centralized aggregation with peripheral gradient diffusion. This novel in situ device enables brain metabolite detection and reveals abnormal arachidonic acid aggregation, providing evidence for lipid-pathway AD interventions.