Quality Control of Mass‐Encoded Nanodevices by Compartmented DNA Origami Frames for Precision Information Coding and Logic Mapping

Abstract Encoded nanostructures afford an ideal platform carrying multi‐channel signal components for multiplexed assay and information security. However, with the demand on exclusivity and reproducibility of coding signals, precise control on the structure and composition of nanomaterials featuring fully distinguishable signals remains challenging. By using the multiplexing capability of mass spectrometry (MS) and spatial addressability of DNA origami nanostructures, we herein propose a quality control methodology for constructing mass‐encoded nanodevices (namely MNTs‐TDOFs) in the scaffold of compartmented tetrahedral DNA origami frames (TDOFs), in which the arrangement and stoichiometry of four types of mass nanotags (MNTs) can be finely regulated and customized to generate characteristic MS patterns. The programmability of combinatorial MNTs and orthogonality of individual compartments allows further evolution of MNTs‐TDOFs to static tagging agents and dynamic nanoprobes for labeling and sensing of multiple targets. More importantly, structure control at single TDOF level ensures the constancy of prescribed MS outputs, by which a high‐capacity coding system was established for secure information encryption and decryption. In addition to the multiplexed outputs in parallel, the nanodevices could also map logic circuits with interconnected complexity and logic events of c‐Met recognition and dimerization on cell surface for signaling regulation by MS interrogation.