Dual-Functionalized Glass Micropipette Sensor for Simultaneous High Sensitivity Detection of Cancer Biomarkers

Early cancer detection is crucial for improving patient survival rates. However, current single-biomarker detection methods often face challenges, such as insufficient sensitivity, poor accuracy, and false positives. To address these issues, we report a dual-functionalized glass micropipet sensor (DFMS) capable of simultaneously detecting two cancer biomarkers, nucleic acids and proteins. The inner surface of the sensor is functionalized with amino-modified silicon nanowires (SiNWs) to capture disease-related miRNAs, enabling ionic-current-based detection, while the outer surface is decorated with gold nanoparticles to anchor specific protein aptamers for Raman-based detection. This dual-functionalization significantly enhances the sensitivity and selectivity by combining ionic current amplification with plasmonic Raman signal enhancement. The sensor achieves detection limits of 1 aM for miRNAs and 0.001 ng/mL for proteins, with minimal mutual interference between the two detection modes, ensuring accurate and independent detection. Validation with prostate cancer biomarkers miRNA-1246 and PSA, as well as gastric cancer biomarkers miRNA-106a and CD44, demonstrates its outstanding sensitivity, selectivity, stability, and broad applicability, providing a novel approach for early cancer detection with significant clinical implications.