Surface markers on supermeres outperform extracellular vesicles in colorectal cancer diagnosis.

Extracellular nanocarriers, such as extracellular vesicles (EVs), lipoproteins, supermeres, and exomeres are diverse lipid-protein-nucleic acid assemblies. Among them, supermeres hold significant diagnostic potential but are challenging to characterize due to limited surface biomarker information and labor-intensive isolation methods. This study introduces an isolation-free Ion Exchange Membrane Sensing method for the detection of supermeres within 30 min using 50 µL of sample, with a sensitivity of 10⁶-10⁷ supermeres/mL. Validation through ultracentrifugation (UC) and surface plasmon resonance (SPR) confirms the detection accuracy and specificity. Supermeres carry key proteins such as HSPA13, ENO2, and DDR1 analogous to tetraspanin in EV. Supermeres outperform small EVs (sEVs) and exomeres across multiple shared and unique surface proteins critical to colorectal cancer diagnosis, highlighting their superior clinical utility and potential as next-generation biomarkers in precision medicine.