Logic Sensing of MicroRNA in Living Cells Using DNA-Programmed Nanoparticle Network with High Signal Gain

Molecular circuits capable of implementing Boolean logic in cellular environments have emerged as an important tool for in situ sensing, elucidating, and modulating cell functions. The performance of existing molecular computation devices in living cells is limited because of the low level of biomolecular inputs and moderate signal gain. Herein, we devised a new class of DNA-programmed nanoparticle network with integrated molecular computation and signal amplification functions for logic sensing of dual microRNA (miRNA) molecules in living cells. The nanoparticle network, which is composed of DNA-bridged gold nanoparticles and quantum dots (QDs), could simultaneously interface with two miRNA molecules, amplify the molecular inputs, perform a calculation through AND logic gate, and generate QD photoluminescence (PL) as an output signal. Significant improvement in imaging sensitivity is achieved by integrating the signal amplifier into the molecular computation device. It allows discrimination of specific cancer cell types via intelligent sensing of miRNA patterns in living cells.