An Integrated Multi‐Function Heterogeneous Biochemical Circuit for High‐Resolution Electrochemistry‐Based Genetic Analysis

Abstract Modular construction of an autonomous and programmable multi‐functional heterogeneous biochemical circuit that can identify, transform, translate, and amplify biological signals into physicochemical signals based on logic design principles can be a powerful means for the development of a variety of biotechnologies. To explore the conceptual validity, we design a CRISPR‐array‐mediated primer‐exchange‐reaction‐based biochemical circuit cascade, which probes a specific biomolecular input, transform the input into a structurally accessible form for circuit wiring, translate the input information into an arbitrary sequence, and finally amplify the prescribed sequence through autonomous formation of a signaling concatemer. This upstream biochemical circuit is further wired with a downstream electrochemical interface, delivering an integrated bioanalytical platform. We program this platform to directly analyze the genome of SARS‐CoV‐2 in human cell lysate, demonstrating the capability and the utility of this unique integrated system.