Ultrasensitive Trace Sample Proteomics for Pancreatic Ductal Adenocarcinoma Diagnosis Empowered by Dual-Affinity Spherical Ln-MOFs.

Low-abundance exosomal proteins from trace plasma volumes remain challenging to profile by mass spectrometry. Here, we report a lanthanide metal-organic framework (Ln-MOF) functionalized with boronic acid and carboxylate dual ligands, which captures exosomal proteins via synergistic phosphate coordination, boronate-diol complexation, and cation-π interactions. Compared with traditional ultracentrifugation, which identifies 1003 proteins from 200 µL of plasma, the Ln-MOF method identifies 1523 proteins from only 50 µL of plasma. Notably, the method enriches glycoproteins and phosphoproteins by 2.1-fold and 1.8-fold, respectively. Applying this platform to pancreatic ductal adenocarcinoma (PDAC) patients and healthy controls, we delineate tumor tissue hypermetabolism vs. systemic immune suppression.