Biopharmaceuticals are typically manufactured on a large scale because they require culturing of uniquely developed cell lines in massive quantities. This limits how quickly drugs can be produced and delivered in specific situations and particularly to remote locations. MIT researchers have now developed a portable microfluidic system that can produce two different proteins from a single strain of a genetically engineered yeast.
The prototype system produces about a dose of a therapeutic protein per 24 hour period, and there should be room to speed that up and perform multiplexing.
The researchers are also looking at using the system to produce multiple types of drugs in one go, now focusing on antibodies as a possible component.
Here are some details of how the system operates according to MIT:
When the researchers exposed the modified yeast to estrogen β-estradiol, the cells expressed recombinant human growth hormone (rHGH). In contrast, when they exposed the cells to methanol, the yeast expressed the protein interferon.
The cells are held within a millimeter-scale table-top microbioreactor, containing a microfluidic chip, which was originally developed by Rajeev Ram, a professor of electrical engineering at MIT, and his team, and then commercialized by Kevin Lee — an MIT graduate and co-author — through a spin-off company.
A liquid containing the desired chemical trigger is first fed into the reactor, to mix with the cells.
Inside the reactor, the cell-and-chemical mixture is surrounded on three sides by polycarbonate; on the fourth side is a flexible and gas-permeable silicone rubber membrane.
By pressurizing the gas above this membrane, the researchers are able to gently massage the liquid droplet to ensure its contents are fully mixed together.
Because the membrane is gas permeable, it allows oxygen to flow through to the cells, while any carbon dioxide they produce can be easily extracted.
If the yeast is required to produce a different protein, the liquid is simply flushed through a filter, leaving the cells behind. Fresh liquid containing a new chemical trigger can then be added, to stimulate production of the next protein.
Study in Nature Communications: Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care…