A cell-free protein synthesis system created at the US Department of Energy’s Oak Ridge National Laboratory has been likened to a miniature protein factory. The device employs microfabricated bioreactors to facilitate the on-demand production of therapeutic proteins for both medicines and biopharmaceuticals, and could be used to save the lives of soldiers as well as people injured in remote locations.

As described in the journal Small [Timm et al. Small (2015) DOI: 10.1002/smll.201502764], as the devices are cell-free the whole process is simplified, and also less expensive due to obviating the need to maintain a living system. The small footprint device also lessens the necessary infrastructure for producing proteins, and allows for the opportunity to develop then when and where they are required. In turn, this process avoids problems around maintaining the proteins at a low temperature while being transported and stored. As joint team leader Scott Retterer said, “With this approach, we can produce more protein faster, making our technology ideal for point-of-care use.”

"With this approach, we can produce more protein faster, making our technology ideal for point-of-care use”Scott Retterer

The bioreactor has a permeable nanoporous membrane and serpentine design produced from a combination of electron beam and photolithography, and also advanced material deposition processes. The design allows the exchange of materials between parallel reactor and feeder channels, so the researchers could control the exchange of metabolites, energy and species that inhibit production of the desired protein. As part of the approach, the device is also able to extend reaction times and improve yields, allowing for prolonged cell-free reactions for efficient production of proteins, and ensuring it is straightforward to adapt for use in remote locations.

The microscale bioreactor design brings produces higher protein yields than standard tube-based batch formats, with product yields being able to be improved significantly through facilitating small molecule exchange with the dual-channel bioreactor. In addition, the on-demand biologic synthesis was found to facilitate the production of drugs that are expensive to produce on a commercial basis, such as orphan drugs and personalized medicines.

Also, usefully the reaction product and higher molecular weight components of the transcription/translation machinery in the reactor channel are able to be retained. Cell-free protein synthesis is viewed by many as a significant technology for improving protein production without maintenance of a living system. When integrated within micro and nanofluidic architectures, it can be optimized for point-of-care use, and is designed to facilitate the production of a single-dose of a therapeutic protein.