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Cell-Free Bioreactor Produces Therapeutic Proteins for Point-of-Care Use

By LabMedica International staff writers
Posted on 11 Jan 2016
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Image: Section of a serpentine channel reactor shows the parallel reactor and feeder channels separated by a nanoporous membrane. At left is a single nanopore viewed from the side; at right is a diagram of metabolite exchange across the membrane (Photo courtesy of the Oak Ridge [US] National Laboratory).
Image: Section of a serpentine channel reactor shows the parallel reactor and feeder channels separated by a nanoporous membrane. At left is a single nanopore viewed from the side; at right is a diagram of metabolite exchange across the membrane (Photo courtesy of the Oak Ridge [US] National Laboratory).
A microfluidic bioreactor for cell-free protein synthesis was developed to facilitate the production of a single-dose of a therapeutic protein for point-of-care delivery.

Cell-free protein synthesis (CFPS) is the production of protein using biological machinery without the use of living cells. The in vitro protein synthesis environment is not constrained by a cell wall or the homeostasis conditions necessary to maintain a living cell. Thus CFPS enables direct access and control of the translation environment which is advantageous for a number of applications including optimization of protein production, optimization of protein complexes, the study of protein synthesis, incorporating non-natural amino acids, high-throughput screens, and synthetic biology.

Investigators at the Oak Ridge National Laboratory (TN, USA) described in the December 22, 2015, online edition of the journal Small a small footprint device for point-of-care use that comprised a long, serpentine channel bioreactor that was enhanced by integrating a nanofabricated membrane to allow exchange of materials between parallel "reactor" and "feeder" channels. The engineered membrane facilitated the exchange of metabolites, energy, and inhibitory species and could be altered by plasma-enhanced chemical vapor deposition and atomic layer deposition to fine-tune the exchange rate of small molecules.

These design elements enabled extended reaction times and improved yields. Furthermore, the reaction product and higher molecular weight components of the transcription/translation machinery in the reactor channel could be retained.

"With this approach, we can produce more protein faster, making our technology ideal for point-of-care use," said senior author Dr. Scott Retterer, research scientist in the biological and nanoscale systems group at the Oak Ridge National Laboratory. "The fact it is cell-free reduces the infrastructure needed to produce the protein and opens the possibility of creating proteins when and where you need them, bypassing the challenge of keeping the proteins cold during shipment and storage."

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