Characterization of extended channel bioreactors for continuous-flow protein production
- 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)
In this paper, protein based therapeutics are an important class of drugs, used to treat a variety of medical conditions including cancer and autoimmune diseases. Requiring continuous cold storage, and having a limited shelf life, the ability to produce such therapeutics at the point-of-care would open up new opportunities in distributing medicines and treating patients in more remote locations. Here, the authors describe the first steps in the development of a microfluidic platform that can be used for point-of-care protein synthesis. While biologic medicines, including therapeutic proteins, are commonly produced using recombinant deoxyribonucleic acid (DNA) technology in large batch cell cultures, the system developed here utilizes cell-free protein synthesis (CFPS) technology. CFPS is a scalable technology that uses cell extracts containing the biological machinery required for transcription and translation and combines those extracts with DNA, encoding a specific gene, and the additional metabolites required to produce proteins in vitro. While CFPS reactions are typically performed in batch or fed-batch reactions, a well-engineered reaction scheme may improve both the rate of protein production and the economic efficiency of protein synthesis reactions, as well as enable a more streamlined method for subsequent purification of the protein product—all necessary requirements for point-of-care protein synthesis. In this work, the authors describe a new bioreactor design capable of continuous production of protein using cell-free protein synthesis. The bioreactors were designed with three inlets to separate reactive components prior to on-chip mixing, which lead into a long, narrow, serpentine channel. These multiscale, serpentine channel bioreactors were designed to take advantage of microscale diffusion distances across narrow channels in reactors containing enough volume to produce a therapeutic dose of protein, and open the possibility of performing these reactions continuously and in line with downstream purification modules. Here, the authors demonstrate the capability to produce protein over time with continuous-flow reactions and examine basic design features and operation specifications fundamental to continuous microfluidic protein synthesis.
- Research Organization:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- AC05-00OR22725; ERKCZ01
- OSTI ID:
- 1238735
- Alternate ID(s):
- OSTI ID: 1421221
- Journal Information:
- Journal of Vacuum Science and Technology B, Vol. 33, Issue 6; ISSN 2166-2746
- Publisher:
- American Vacuum Society/AIPCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
Integration of cell-free protein synthesis and purification in one microfluidic chip for on-demand production of recombinant protein
|
journal | September 2018 |
New generation of bioreactors that advance extracellular matrix modelling and tissue engineering
|
journal | October 2018 |
Toward Microfluidic Reactors for Cell-Free Protein Synthesis at the Point-of-Care
|
journal | December 2015 |
On-chip manufacturing of synthetic proteins for point-of-care therapeutics
|
journal | March 2019 |
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