Cascaded logic gate-based electrochemical analysis of multiple miRNAs for cancer recognition

Abstract

Current miRNA detection methods mainly focus on the detection of discrete targets while overlooking the logical relationship among biomoleculars. Integrating electrochemical sensor, DNA framework probes and DNA logic gate technology for analyzing miRNAs with diverse combinations in bodily fluids provide a potential way for recognition of multiple cancers. In this work, a novel cascaded logic gate-based electrochemical (EC) analysis strategy was designed and fabricated for the discrimination of pancreatic cancer (PC), breast cancer (BC) and lung cancer (LC). Cascaded AND logic gates were constructed through the logical relationship among miR-21, miR-155, miR-373, miR-6746 and miR-1343 which abnormally expressed in PC, BC and LC. The output strands of the logic gates were captured by tetrahedral DNA framework probes modified on the electrodes of EC sensor. Three cascaded AND logic gates successfully achieved limits of detection (LOD) of 0.62 nM, 0.37 nM and 0.41 nM, and good linear relationships between current values and the concentration of miRNA combinations within the range from 1 nM to 1 μM (R² > 0.99). It was shown that multiple cascaded logic gate-based EC method could distinguish PC, BC and LC through specific miRNA combinations both in a TM buffer and in a 50 % fetal bovine serum samples. This logic gate-based EC method has the advantages of precision, high speed and logical analysis capability which provides a brand-new tool for system and precision medicine.