ORNL cell-free protein synthesis is potential lifesaver

This 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.

OAK RIDGE, Tenn., Dec. 29, 2015 – Lives of soldiers and others injured in remote locations could be saved with a cell-free protein synthesis system developed at the Department of Energy’s Oak Ridge National Laboratory.

The device, a creation of a team led by Andrea Timm and Scott Retterer of the lab’s Biosciences Division, uses microfabricated bioreactors to facilitate the on-demand production of therapeutic proteins for medicines and biopharmaceuticals. Making these miniature factories cell-free, which eliminates the maintenance of a living system, simplifies the process and lowers cost.

“With this approach, we can produce more protein faster, making our technology ideal for point-of-care use,” Retterer said. “The fact it’s 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.”

ORNL’s bioreactor features elegance through a permeable nanoporous membrane and serpentine design fabricated using a combination of electron beam and photolithography and advanced material deposition processes. This design enables prolonged cell-free reactions for efficient production of proteins, making it easily adaptable for use in isolated locations and at disaster sites.

From a functional perspective, the design uses long serpentine channels integrated in a way to allow the exchange of materials between parallel reactor and feeder channels. With this approach, the team can control the exchange of metabolites, energy and species that inhibit production of the desired protein. Through other design features, researchers extend reaction times and improve yields.

“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 with the dual-channel bioreactor,” the authors wrote in their paper, published in the journal Small.

The researchers also note that on-demand biologic synthesis would aid the production of drugs that are costly to mass-produce, including orphan drugs and personalized medicines.

Other authors of the paper, titled “Towards Microfluidic Reactors for Cell-Free Protein Synthesis at the Point-of-Care,” are ORNL’s Peter Shankles, Carmen Foster and Mitchel Doktycz.

Funding for this project was provided by the Defense Advanced Research Projects Agency through a collaboration with researchers from Leidos (https://www.leidos.com) and Northwestern University. This accomplishment represents the culmination of research led by Doktycz and Retterer funded by multiple grants from the National Institutes of Health and DOE over the last decade. A portion of the work was performed at the Center for Nanophase Materials Sciences, a DOE Office of Science User Facility.

UT-Battelle manages ORNL for the DOE's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit http://science.energy.gov/.

ORIGINAL: ORNL

Ron Walli, Communications. wallira@ornl.gov, 865.576.0226

December 29, 2015