Gold Nanoparticles-Based DNA Logic Gate for miRNA Inputs Analysis Coupling Strand Displacement Reaction and Hybridization Chain Reaction

The molecular level DNA logic gates assisted by nanomaterials hold great promise for disease diagnosis applications. However, designing convenient and sensitive logic gates for molecular diagnostics still remains challenging. In this work, a DNA logic gate platform for miRNA inputs analysis based on the observation of localized surface plasmon resonance variation of gold nanoparticles (AuNPs) is fabricated. As a demonstration, two biomarkers to differentiate indolent and aggressive forms of prostate cancer, miR-200c and miR-605, are selected as examples of logical inputs. In addition, five DNA probes are designed according to strand displacement reaction and hybridization chain reaction which are required for DNA logical operation. Since target miRNA inputs are able to trigger DNA structural transformations, which are further used to precisely regulate salt-induced AuNPs aggregation, miRNA inputs information can be converted to the information of AuNPs states as outputs. This developed system performs amplified detection of low-abundant target miRNAs without the requirement of any enzymes. In addition, single base-pair mismatched miRNAs can be effectively differentiated. High-order logic gates can also be developed with further modifications. Therefore, the DNA AND logic gate is successfully constructed with flexible operations, which has potential in biochemical study and disease diagnosis.