Towards microfluidic reactors for cell-free protein synthesis at the point-of-care
Abstract
Cell-free protein synthesis (CFPS) is a powerful technology that allows for optimization of protein production without maintenance of a living system. Integrated within micro- and nano-fluidic architectures, CFPS can be optimized for point-of care use. Here, we describe the development of a microfluidic bioreactor designed to facilitate the production of a single-dose of a therapeutic protein, in a small footprint device at the point-of-care. This new design builds on the use of a long, serpentine channel bioreactor and is enhanced by integrating a nanofabricated membrane to allow exchange of materials between parallel reactor and feeder channels. This engineered membrane facilitates the exchange of metabolites, energy, and inhibitory species, prolonging the CFPS reaction and increasing protein yield. Membrane permeability can be altered by plasma-enhanced chemical vapor deposition and atomic layer deposition to tune the exchange rate of small molecules. This allows for extended reaction times and improved yields. Further, the reaction product and higher molecular weight components of the transcription/translation machinery in the reactor channel can be retained. As a result, we show that the microscale bioreactor design produces higher protein yields than conventional tube-based batch formats, and that product yields can be dramatically improved by facilitating small molecule exchange withinmore »
- Authors:
-
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
- Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- Work for Others (WFO)
- OSTI Identifier:
- 1238743
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Small
- Additional Journal Information:
- Journal Volume: 12; Journal Issue: 6; Journal ID: ISSN 1613-6810
- Publisher:
- Wiley
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Timm, Andrea C., Shankles, Peter G., Foster, Carmen M., Doktycz, Mitchel John, and Retterer, Scott T. Towards microfluidic reactors for cell-free protein synthesis at the point-of-care. United States: N. p., 2015.
Web. doi:10.1002/smll.201502764.
Timm, Andrea C., Shankles, Peter G., Foster, Carmen M., Doktycz, Mitchel John, & Retterer, Scott T. Towards microfluidic reactors for cell-free protein synthesis at the point-of-care. United States. https://doi.org/10.1002/smll.201502764
Timm, Andrea C., Shankles, Peter G., Foster, Carmen M., Doktycz, Mitchel John, and Retterer, Scott T. Tue .
"Towards microfluidic reactors for cell-free protein synthesis at the point-of-care". United States. https://doi.org/10.1002/smll.201502764. https://www.osti.gov/servlets/purl/1238743.
@article{osti_1238743,
title = {Towards microfluidic reactors for cell-free protein synthesis at the point-of-care},
author = {Timm, Andrea C. and Shankles, Peter G. and Foster, Carmen M. and Doktycz, Mitchel John and Retterer, Scott T.},
abstractNote = {Cell-free protein synthesis (CFPS) is a powerful technology that allows for optimization of protein production without maintenance of a living system. Integrated within micro- and nano-fluidic architectures, CFPS can be optimized for point-of care use. Here, we describe the development of a microfluidic bioreactor designed to facilitate the production of a single-dose of a therapeutic protein, in a small footprint device at the point-of-care. This new design builds on the use of a long, serpentine channel bioreactor and is enhanced by integrating a nanofabricated membrane to allow exchange of materials between parallel reactor and feeder channels. This engineered membrane facilitates the exchange of metabolites, energy, and inhibitory species, prolonging the CFPS reaction and increasing protein yield. Membrane permeability can be altered by plasma-enhanced chemical vapor deposition and atomic layer deposition to tune the exchange rate of small molecules. This allows for extended reaction times and improved yields. Further, the reaction product and higher molecular weight components of the transcription/translation machinery in the reactor channel can be retained. As a result, we show that the microscale bioreactor design produces higher protein yields than conventional tube-based batch formats, and that product yields can be dramatically improved by facilitating small molecule exchange within the dual-channel bioreactor.},
doi = {10.1002/smll.201502764},
journal = {Small},
number = 6,
volume = 12,
place = {United States},
year = {Tue Dec 22 00:00:00 EST 2015},
month = {Tue Dec 22 00:00:00 EST 2015}
}
Web of Science
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