Programmable Nanodevice and Amplifier Module‐Based DNA Cascaded Logic Circuits for Breast Tumor Cell Subtype Discrimination

Sensitive analysis of multiple disease-related biomarkers with DNA logic circuits can facilitate accurate discrimination of cell subtypes, which is essential for early disease diagnosis. Nevertheless, the reported DNA logic circuits usually suffer from poor efficiency, single signal output, and low sensitivity. Herein, a series of versatile DNA logic circuits (i.e., AND, OR-AND, INHIBIT-AND, fan-in circuit, and moderate-scale circuit) are developed based on the integration of an amplifier module with a DNA nanodevice for sensitive detection of multiple cellular RNAs and accurate discrimination of diverse tumor cell subtypes. The proposed nanodevice can proceed in a programmable, autonomous, modular, and cascade manner, facilitating the construction of logic circuits with the capabilities of sensing, monitoring, recording, signal-processing, and actuation. The introduction of an amplifier module into the proposed DNA logic circuits significantly enhances the sensitivity, and they can be applied for simultaneous monitoring of multiple RNAs with an attomolar sensitivity. Importantly, the proposed logic circuits can accurately distinguish different breast cell subtypes with high accuracy and good specificity, providing a new potential platform for clinical diagnosis.