A Versatile Microfluidic Device for Automating Synthetic Biology

Shih, Steve C.  C.; Goyal, Garima; Kim, Peter W.; Koutsoubelis, Nicolas; Keasling, Jay D.; Adams, Paul D.; Hillson, Nathan J.; Singh, Anup K.

doi:10.1021/acssynbio.5b00062

A Versatile Microfluidic Device for Automating Synthetic Biology

Journal Article · Mon Jun 15 00:00:00 EDT 2015 · ACS Synthetic Biology

DOI:https://doi.org/10.1021/acssynbio.5b00062· OSTI ID:1378593

Shih, Steve C. C. ^[1]; Goyal, Garima ^[2]; Kim, Peter W. ^[1]; Koutsoubelis, Nicolas ^[3]; Keasling, Jay D. ^[4]; Adams, Paul D. ^[5]; Hillson, Nathan J. ^[2]; Singh, Anup K. ^[1]

Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States). Technology Division; Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States). Technology Division; Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States). Fuels Synthesis Division; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Bioscience Division
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States). Fuels Synthesis Division; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Bioscience Division
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States). Fuels Synthesis Division; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Bioscience Division; Univ. of California, Berkeley, CA (United States). Dept. of Chemical & Biomolecular Engineering, Dept. of Bioengineering
Joint BioEnergy Inst. (JBEI), Emeryville, CA (United States). Technology Division; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Bioscience Division

New microbes are being engineered that contain the genetic circuitry, metabolic pathways, and other cellular functions required for a wide range of applications such as producing biofuels, biobased chemicals, and pharmaceuticals. Although currently available tools are useful in improving the synthetic biology process, further improvements in physical automation would help to lower the barrier of entry into this field. We present an innovative microfluidic platform for assembling DNA fragments with 10× lower volumes (compared to that of current microfluidic platforms) and with integrated region-specific temperature control and on-chip transformation. Integration of these steps minimizes the loss of reagents and products compared to that with conventional methods, which require multiple pipetting steps. For assembling DNA fragments, we implemented three commonly used DNA assembly protocols on our microfluidic device: Golden Gate assembly, Gibson assembly, and yeast assembly (i.e., TAR cloning, DNA Assembler). Here, we demonstrate the utility of these methods by assembling two combinatorial libraries of 16 plasmids each. Each DNA plasmid is transformed into Escherichia coli or Saccharomyces cerevisiae using on-chip electroporation and further sequenced to verify the assembly. Lastly, we anticipate that this platform will enable new research that can integrate this automated microfluidic platform to generate large combinatorial libraries of plasmids and will help to expedite the overall synthetic biology process.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1378593

Journal Information:: ACS Synthetic Biology, Journal Name: ACS Synthetic Biology Journal Issue: 10 Vol. 4; ISSN 2161-5063

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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A Versatile Microfluidic Device for Automating Synthetic Biology

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