Electrochemical label-free biomolecular logic gates regulated by distinct inputs

In current work, with elaborate designs of G-quadruplex containing "Y" junction structures, we demonstrate the construction of several new and label-free electrochemical logic gate operations (OR, AND, NOR, and NAND) by defining two distinct biomolecules, human 8-oxo-7,8-dihydroguanine DNA glycosylase 1 (hOGG1) and microRNA-141 (miRNA-141), as the inputs. The "Y" junction structures are immobilized onto the surface of gold electrode as the signal transduction platform. The presence of the input molecules with different combinations can alter the "Y" junction structures to disrupt the formation of the complete G-quadruplexes via 8-oxoG-site specific cleavage and miRNA-141-triggered displacement of the "Y" junctions. Subsequent association of hemin with the G-quadruplex sequences thus yields significant current variation outputs upon electrochemical reduction of hemin on the electrode, leading to the successful function of different logic operations without the involvement of labeling the DNA sequences with electro-active species. Featured with the advantages of multiple logic operations with distinct inputs and the label-free electrochemical format, such molecular logic gates can potentially provide promising opportunities for the development of simple and robust biological logic gates for various applications.