High-Speed Sequential DNA Computing Using a Solid-State DNA Origami Register.

DNA computing leverages molecular reactions to achieve diverse information processing functions. Recently developed DNA origami registers, which could be integrated with DNA computing circuits, allow signal transmission between these circuits, enabling DNA circuits to perform complex tasks in a sequential manner, thereby enhancing the programming space and compatibility with various biomolecules of DNA computing. However, these registers support only single-write operations, and the signal transfer involves cumbersome and time-consuming register movements, limiting the speed of sequential computing. Here, we designed a solid-state DNA origami register that compresses output data from a 3D solution to a 2D surface, establishing a rewritable register suitable for solid-state storage. We developed a heterogeneous integration architecture of liquid-state circuits and solid-state registers, reducing the register-mediated signal transfer time between circuits to less than 1 h, thereby achieving fast sequential DNA computing. Furthermore, we designed a trace signal amplifier to read surface-stored signals back into solution. This compact approach not only enhances the speed of sequential DNA computing but also lays the foundation for the visual debugging and automated execution of DNA molecular algorithms.