Materials-Driven Fluorescent Sensor Array of Dye-Derived Carbon Dots for Sensitive Detection of Multiple Proteins and...

Accurate protein recognition is crucial for early disease diagnosis and biomarker screening. Progesterone receptor membrane component-1 (PGRMC1) is a promising cancer biomarker, yet its sensitive and selective detection in complex biological samples remains challenging. Here, a molecularly programmable multichannel fluorescence sensor array was constructed by employing three chemically distinct carbon dots (CDs), synthesized from Congo red coupled with ascorbic acid, citric acid, and glutathione, as parallel sensing units to generate multiple fluorescence response channels. This precursor-engineering strategy enabled the precise modulation of surface functional groups, redox properties, and protein-interaction behaviors, offering a novel route to tailor CDs for specific sensing targets. The resulting CDs functioned as complementary fluorescent sensing units, collectively forming a cross-reactive array capable of 100% accurate discrimination of 11 proteins in both buffer and whole blood samples. For the clinically relevant biomarker PGRMC1, the array displayed a broad linear response (0.010-1.000 ng/mL) and an ultralow limit of detection of 0.013 ng/mL (95% confidence interval from 0.004 to 0.021 ng/mL). More importantly, the analysis of 64 blinded clinical blood samples achieved robust differentiation between breast cancer patients and healthy individuals, demonstrating its translational potential for early cancer diagnosis. Fluorescence lifetime analysis combined with density functional theory calculations elucidated the underlying mechanism of interaction between the CDs and proteins, highlighting the contribution of precursor-dependent surface states. This study introduces a new design paradigm for CD-based fluorescent arrays and showcases their strong promise for complex biological analysis, precision biomarker detection, and clinical diagnostics.