Intramicellar sensor assays: Improving sensing sensitivity of sensor array for thiol biomarkers

Array-based analysis allows for precise disease diagnosis by simultaneously detecting multiple biomarkers. However, most array sensing platforms rely on non-covalent interactions between sensors and analytes, which limits their sensitivity. This study enhances the sensitivity of array analysis for thiol biomarkers by incorporating polyion complex micelles into the sensor array design. Polyion complex micelles are formed through the self-assembly of carbon dots (CDs) and anionic diblock copolymers. The sensing detection process can occur inside the core of the micelle, the confined space and ionic environment within the core reduce the interaction distance between CDs, metal ions, and analytes, thereby significantly improving detection sensitivity while minimizing metal ions consumption. The developed array system can accurately identify multiple thiols across a broad concentration range (0.5-1000 μM) with 100% accuracy. Additionally, support vector machine (SVM) analysis reveals a detection limit of approximately 0.1 μM for individual thiol systems. Compared to non-micellar approaches, this micelle-based array reduces the detection limit for thiol biomarkers by 20-fold and decreases Ag⁺ usage by 40-fold. The system is suitable for both qualitative and quantitative analysis of thiol biomarkers, offering a powerful tool for the accurate diagnosis of thiol-related diseases.