Synthesis and cell-free cloning of DNA libraries using programmable microfluidics

Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using pro...

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Main Authors: Ben Yehezkel, Tuval, Rival, Arnaud, Raz, Ofir, Cohen, Rafael, Marx, Zipora, Cámara, Miguel, Dubern, Jean-Frédéric, Koch, Birgit, Heeb, Stephan, Krasnogor, Natalio, Delattre, Cyril, Shapiro, Ehud
Format: Article
Published: Oxford University Press 2016
Online Access:https://eprints.nottingham.ac.uk/34900/
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author Ben Yehezkel, Tuval
Rival, Arnaud
Raz, Ofir
Cohen, Rafael
Marx, Zipora
Cámara, Miguel
Dubern, Jean-Frédéric
Koch, Birgit
Heeb, Stephan
Krasnogor, Natalio
Delattre, Cyril
Shapiro, Ehud
author_facet Ben Yehezkel, Tuval
Rival, Arnaud
Raz, Ofir
Cohen, Rafael
Marx, Zipora
Cámara, Miguel
Dubern, Jean-Frédéric
Koch, Birgit
Heeb, Stephan
Krasnogor, Natalio
Delattre, Cyril
Shapiro, Ehud
author_sort Ben Yehezkel, Tuval
building Nottingham Research Data Repository
collection Online Access
description Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using programmable digital microfluidics. Specifically, we developed Programmable Order Polymerization (POP), Microfluidic Combinatorial Assembly of DNA (M-CAD) and Microfluidic In-vitro Cloning (MIC) and applied them to de novo synthesis, combinatorial assembly and cellfree cloning of genes, respectively. Proof-of-concept for these methods was demonstrated by programming an autonomous microfluidic system to construct and clone libraries of yeast ribosome binding sites and bacterial Azurine, which were then retrieved in individual droplets and validated. The ability to rapidly and robustly generate designer DNA molecules in an autonomous manner should have wide application in biological research and development.
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institution University of Nottingham Malaysia Campus
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publishDate 2016
publisher Oxford University Press
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spelling nottingham-349002020-05-04T17:34:46Z https://eprints.nottingham.ac.uk/34900/ Synthesis and cell-free cloning of DNA libraries using programmable microfluidics Ben Yehezkel, Tuval Rival, Arnaud Raz, Ofir Cohen, Rafael Marx, Zipora Cámara, Miguel Dubern, Jean-Frédéric Koch, Birgit Heeb, Stephan Krasnogor, Natalio Delattre, Cyril Shapiro, Ehud Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using programmable digital microfluidics. Specifically, we developed Programmable Order Polymerization (POP), Microfluidic Combinatorial Assembly of DNA (M-CAD) and Microfluidic In-vitro Cloning (MIC) and applied them to de novo synthesis, combinatorial assembly and cellfree cloning of genes, respectively. Proof-of-concept for these methods was demonstrated by programming an autonomous microfluidic system to construct and clone libraries of yeast ribosome binding sites and bacterial Azurine, which were then retrieved in individual droplets and validated. The ability to rapidly and robustly generate designer DNA molecules in an autonomous manner should have wide application in biological research and development. Oxford University Press 2016-02-29 Article PeerReviewed Ben Yehezkel, Tuval, Rival, Arnaud, Raz, Ofir, Cohen, Rafael, Marx, Zipora, Cámara, Miguel, Dubern, Jean-Frédéric, Koch, Birgit, Heeb, Stephan, Krasnogor, Natalio, Delattre, Cyril and Shapiro, Ehud (2016) Synthesis and cell-free cloning of DNA libraries using programmable microfluidics. Nucleic Acids Research, 44 (4). e35/1-e35/12. ISSN 1362-4962 http://nar.oxfordjournals.org/content/44/4/e35 doi:10.1093/nar/gkv1087 doi:10.1093/nar/gkv1087
spellingShingle Ben Yehezkel, Tuval
Rival, Arnaud
Raz, Ofir
Cohen, Rafael
Marx, Zipora
Cámara, Miguel
Dubern, Jean-Frédéric
Koch, Birgit
Heeb, Stephan
Krasnogor, Natalio
Delattre, Cyril
Shapiro, Ehud
Synthesis and cell-free cloning of DNA libraries using programmable microfluidics
title Synthesis and cell-free cloning of DNA libraries using programmable microfluidics
title_full Synthesis and cell-free cloning of DNA libraries using programmable microfluidics
title_fullStr Synthesis and cell-free cloning of DNA libraries using programmable microfluidics
title_full_unstemmed Synthesis and cell-free cloning of DNA libraries using programmable microfluidics
title_short Synthesis and cell-free cloning of DNA libraries using programmable microfluidics
title_sort synthesis and cell-free cloning of dna libraries using programmable microfluidics
url https://eprints.nottingham.ac.uk/34900/
https://eprints.nottingham.ac.uk/34900/
https://eprints.nottingham.ac.uk/34900/