Programming cell-free biosensors with DNA strand displacement circuits

Cell-free biosensors are powerful platforms for monitoring human and environmental health. Here, we expand their capabilities by interfacing them with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions betw...

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Bibliographic Details
Published in:Nature chemical biology Vol. 18; no. 4; pp. 385 - 393
Main Authors: Jung, Jaeyoung K, Archuleta, Chloé M, Alam, Khalid K, Lucks, Julius B
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.04.2022
Subjects:
Analog circuits
Analog to digital converters
Biosensing Techniques
Biosensors
Circuit design
Circuits
Computation
Data processing
Deoxyribonucleic acid
Displacement
DNA
DNA - metabolism
Environmental health
Humans
Information processing
Logic circuits
Nanotechnology
Nucleic acids
Reaction kinetics
Recombination, Genetic
RNA
ISSN:1552-4450, 1552-4469, 1552-4469
Online Access:Get full text
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Summary:Cell-free biosensors are powerful platforms for monitoring human and environmental health. Here, we expand their capabilities by interfacing them with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions between nucleic acid strands. We develop design rules for interfacing a small molecule sensing platform called ROSALIND with toehold-mediated strand displacement to construct hybrid RNA-DNA circuits that allow fine-tuning of reaction kinetics. We use these design rules to build 12 different circuits that implement a range of logic functions (NOT, OR, AND, IMPLY, NOR, NIMPLY, NAND). Finally, we demonstrate a circuit that acts like an analog-to-digital converter to create a series of binary outputs that encode the concentration range of the molecule being detected. We believe this work establishes a pathway to create 'smart' diagnostics that use molecular computations to enhance the speed and utility of biosensors.
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ISSN:1552-4450
1552-4469
1552-4469
DOI:10.1038/s41589-021-00962-9