Integrated Multi-Function Heterogeneous Biochemical Circuit for High-Resolution Electrochemistry based Genetic Analysis.

Dai, Yifan; Xu, Wei; Somoza, Rodrigo A; Welter, Jean F; Caplan, Arnold I; Liu, Chung Chiun

Modular construction of an autonomous and programmable multi-function heterogeneous biochemical circuit that can identify, transform, translate and amplify biological signals into physicochemical signals based on logic design principle can be a powerful capability for the development of diverse biotechnologies. To explore this conceptual validity, we design a CRISPR array mediated primer exchange reaction based biochemical circuit cascades, which probe 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 utility of this unique integrated system.