Direct Whole-Blood Multiplexing of Small Molecules via a Micelle-Enhanced Chemiluminescent Paper Sensor with...

The direct detection of small-molecule biomarkers in whole blood remains a significant challenge due to severe interferences from red blood cells (RBCs) and hemoglobin. To address this, we present the first paper-based chemiluminescence analytical device (PCAD) that integrates a core-shell mesoporous silica (CSMS) separation membrane with micellar encapsulation technology. The CSMS membrane acts as a physical barrier to exclude RBCs and simultaneously adsorbs proteins via its mesoporous structure, eliminating background noise without requiring complex pretreatment. Furthermore, we utilize aggregation-induced emission (AIE)-active 1,1,2,3,4,5-hexaphenylsilole (HPS) dyes encapsulated in bis[3,4,6-trichloro-2-(pentyloxycarbonyl)phenyl] oxalate (CPPO)-loaded micelles to overcome the solubility and aggregation limitations of traditional peroxyoxalate systems. Crucially, the micellar environment stabilizes the reactive intermediates, enabling the generation of long-lasting, high-intensity chemiluminescence signals ("glow-type" emission). This feature significantly enhances the signal-to-noise ratio (S/N), ensuring compatibility with low-cost, portable detection systems. As a proof of concept, the PCAD successfully achieves simultaneous determination of three critical metabolic indicators─glucose, uric acid, and xanthine─with low detection limits and excellent reproducibility. The entire process requires only a drop of whole blood without any prior separation steps and delivers results within 45 min using a portable reader. This work establishes a universal, user-friendly platform for on-site diagnosis of metabolic diseases, bridging the gap between laboratory precision and point-of-care convenience.