Bioreactor brings on-demand portability to biopharmaceutical drug production
By manipulating yeast into producing specific proteins, a new portable device developed at MIT can produce a range of biopharmaceutical drugs on demand. The system would grant remote or on-the-move medical professionals access to vaccines and other therapies that are normally produced in large fermentation plants.
At the core of the system is a particular strain of yeast known as Pichia pastoris, which has been modified to react to different chemical triggers to produce one of two therapeutic proteins. When exposed to estrogen β-estradiol, the yeast expressed recombinant human growth hormone (rHGH), while exposure to methanol triggered production of the protein interferon.
"Imagine you were on Mars or in a remote desert, without access to a full formulary, you could program the yeast to produce drugs on demand locally," says Tim Lu, the senior author of the paper. "We altered the yeast so it could be more easily genetically modified, and could include more than one therapeutic in its repertoire."
Inside the device, the yeast cells are kept in a tiny microbioreactor fitted out with a microfluidic chip that monitors cell density, oxygen levels, temperature and pH balance to maintain the best environment for the cells to grow. When it comes time to brew a treatment, the doctors simply add a liquid containing the required chemical trigger into the device.
The mixture sits in a chamber with a silicone rubber membrane along one side, which is gas permeable to allow oxygen to get in and carbon dioxide to get out. Pressurized gas on the other side of the membrane massages the liquid to thoroughly mix it with the yeast cells.
"This makes sure that the 1 ml (of liquid) is homogenous, and that is important because diffusion at these small scales, where there is no turbulence, takes a surprisingly long time," says Rajeev Ram, another senior author of the paper.
When it's done, the device will have produced one dose of a treatment. If a different protein is desired, the liquid can simply be flushed out through a filter, leaving the yeast cells behind to work on the next batch. Doing this effectively was a stumbling block for previous attempts at these kinds of microbioreactors.
"You want to keep the cells because they are your factory," says Ram. "But you also want to rapidly change their chemical environment, in order to change the trigger for protein production."
Ultimately, the portability of the device could make it a handy partner to produce critical vaccines at the point of care where this was previously impossible, including on the battlefield, inside ambulances, in remote areas and in developing countries.
The team is now examining the potential for the system to be used in combinatorial treatments that involve multiple therapeutics, such as antibodies, being used together.
The research was published in the journal Nature Communications.