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MIT DARPA bioreactor

Imagine a cross between one of those multi-color retractable pens and an epi-pen. But instead of colors, the device would have unlike medications. Now combine this with a tiny, droplet-sized sweatshop total of obedient unmarried-celled organisms genetically engineered to produce those medications, and you've got what a team from MIT only published in Nature Communications:A new project, with funding from DARPA, that has demonstrated the ability to synthesize multiple medications on-demand and as-needed using yeast. The discovery could presently revolutionize our ability to deliver medicine after natural disasters or to remote locations.

Let's stick with the metaphor of an epi-pen. First, the user presses the actuator, which mixes a chemical trigger into a culture of engineered Pichia pastoris cells. Upon exposure to certain chemic triggers, the cells are programmed to produce a protein: in the written report, the team used estrogen β-estradiol, which caused the cells to express recombinant human growth hormone (rHGH), and also methanol, which induced the aforementioned culture of yeast to make interferon. By controlling the concentration of the chemical trigger and the population of P. pastoris, the squad demonstrated that they could make their device produce a dose of either interferon or rHGH on control. To switch between products, they just pushed another push on the microbioreactor, which flushes out the cell civilisation with clean, sterile fluid.

"…rapid and switchable production of two biologics from a single yeast strain as specified by the operator." -Lu, Ram et al

Figure 6(a). The principal component of the microbioreactor is a polycarbonate-PDMS membrane-polycarbonate sandwiched chip with active microfluidic circuits that are equipped for pneumatic routing of reagents, precise peristaltic injection, growth chamber mixing and fluid extraction

Figure 6(a). The principal component of the microbioreactor is a polycarbonate – PDMS membrane – polycarbonate sandwiched chip with active microfluidic circuits that are equipped for pneumatic routing of reagents, precise peristaltic injection, growth bedchamber mixing and fluid extraction.  Image and caption: Lu, Ram et al

It might not be immediately credible why there's an advantage to having to tote around bacteria, rather than merely having a cartridge of whatever medication y'all need to evangelize. But consider the case of immune reactions in the field. Snake and spider bites tin be fatal without the correct handling. Antivenin is hysterically expensive, though, and it needs special storage weather to last. This device tin maintain the yeast at a temperature it likes, until called to produce the necessary substance fresh on demand.

Vaccines, also, are an awarding for the new device. Remember Balto? The Iditarod commemorates a heroic journeying to bring diphtheria antidote to a remote Alaskan village in the depths of a legendary storm. We now have a diphtheria vaccine. Senior engineer Tim Lu explains that the device could exist used to produce a vaccine to forestall a disease outbreak in a remote village. Think about what Doctors Without Borders could do if they had a steady supply of vaccines created by a milliliter-scale device like this. "Imagine you were on Mars or in a remote desert, without access to a total formulary, you could program the yeast to produce drugs on demand locally," Lu said.

MIT DARPA biopharmaceuticals on demand

Signal-of-intendance biomanufacturing employs engineered yeast and portable microbioreactors for on-demand drug production, such as in an ambulance. Credit: MIT

This project builds on prior fine art, also from MIT. The cells are held within a table-meridian microbioreactor which contains a microfluidic fleck, itself originally developed by Rajeev Ram, a professor of electrical engineering at MIT, and his squad, and then commercialized by Kevin Lee — an MIT graduate and co-author — through a spin-off company.

And then far, the system has been prototyped. The researchers are at present investigating the use of the arrangement in combinatorial treatments, in which multiple therapeutics, such as antibodies, are used together. Combining multiple therapeutics in this mode can be expensive if each product requires its own production line, Lu says. "But if you lot could engineer a single strain, or perchance fifty-fifty a consortia of strains that grow together, to manufacture combinations of biologics or antibodies, that could exist a very powerful way of producing these drugs at a reasonable cost."

(Images courtesy of MIT)