DNA logic nanomachine for the accurate identification of multiple microRNAs in tumor cells.

The use of dynamic DNA logic circuits for disease diagnosis at the molecular level plays a considerable role in biomedical fields. Nevertheless, how to create programmable nanomachines based on molecular logical gates to accurately identify multiple biomarkers from tumor cells remains a pivotal challenge. Herein, we developed a DNA-based nanomachine for analyzing and imaging multiple microRNAs (miRNAs) in cancerous cells with a logical AND operation. The triangular prism design of DNA nanomachine improved its performance in living cell research with high stability and served as a modularized framework for toehold-mediated strand displacement reactions and catalytic hairpin assembly circuits. The results suggested that the nanomachine could efficiently enter cells with great biocompatibility and rapidly recognize the correct biomolecules with high sensitivity. The well-designed DNA-logic gate nanomachine enabled accurate diagnosis on multiple miRNA patterns in different cell lines and differentiation of aberrant expression in target cells, which provided a novel possibility for intelligent disease diagnosis using smart nanomachines at the molecular level.