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Electronic microprocessor systems are based on semiconductor logic gates, which employ electronic input and output signals and power supplies [1]. A critical feature, which contributes to the undoubted success of electronic circuits, is input–output signal homogeneity: the same electron voltage value emerging as an output of one gate can be admitted as an input of another gate. Such connections of logic gates can achieve selected functions of varying complexity. This very large‐scale integration is a crucial component of modern silicon processors [2,3]. The development of more powerful microprocessors depends on continued progress in miniaturizing their components. However, if current trends continue, conventional silicon chips will soon reach their physical limits [4]. Several research groups have created molecular ensembles that perform logic operations [2,3,5–9]. Even though small‐scale integration of logic elements has been achieved, there is still a lack of examples of universal large‐scale integration. Therefore, the challenges of component integration must be further addressed to advance the molecular computation field, as well as for its practical implementations [2,3].

DNA has been considered as an excellent candidate both for in vitro computation [10] and as a convenient building block for molecular switches and other devices [11–13]. Pioneered by Stojanovic [14], a great number of nucleic acid‐based logic gates of various designs have been proposed in the last 17 years [15–26]. Despite significant progress in the design of individual molecular logic gates, there is still a great challenge in solving the following technical problems: achieving high scale integration of molecular logic units, precise localization of the molecular gates in nano‐environment for efficient inter‐gate communication, and achieving reusability of DNA hardware [27–30]. Moreover, connecting the gates to an appropriate interface for convenient communication with human users is needed [31,32].

This chapter describes approaches for connecting DNA logic gates in circuits with the emphasis on (i) deoxyribozyme (Dz) logic gates, (ii) strand displacement (seesaw) logic gates, and (iii) DNA logic gates connected via four‐way junctions (4WJs). Most common problems on the way toward creating long chains of communicating DNA logic gates are discussed.