MIT researchers develop portable device for the manufacture of biopharmaceuticals on request -
For doctors on the battlefield and doctors in remote areas or parts of the developing world, get quick access to needed drugs to treat patients can be difficult.
biopharmaceuticals, which are used in a wide range of therapies, including vaccines and treatments for diabetes and cancer, are typically produced in large fermentation plants centralized. This means they must be transported to the processing site, which can be costly, lengthy and difficult to perform in areas with poor supply chains.
Now, a system of mobile products, designed for the manufacture of a range of biopharmaceuticals demand, has been developed by researchers at MIT, with funding from the Defense Advanced Agency Research Projects (DARPA).
in an article published in the journal Nature Communications , the researchers showed that the system can be used to produce a single dose of treatment from a compact containing a small droplet cells in a liquid.
in this way, the system could eventually be carried out on the battlefield and used to produce treatments to the point of care. It could also be used to make a vaccine to prevent an outbreak of the disease in a remote village, according to lead author Tim Lu, associate professor of biological engineering and electrical and computer engineering, synthetic biology and head of the group in lab search MIT electronics.
"Imagine that you were on Mars or in a remote desert without access to a full form, you can program the yeast to produce drugs to local demand," says Lu.
system is based on a programmable yeast strain Pichia pastoris, which can be induced to express two therapeutic proteins when exposed to a particular chemical trigger. researchers selected P. pastoris because it can achieve very high densities on simple carbon sources and inexpensive, and is able to express large quantities of protein.
"We have changed the yeast so that it could be more easily engineered and may include more than one therapeutic in its repertoire, "says Lu.
hormone When the researchers exposed the yeast modified to β-estradiol estrogen, the cells express recombinant human growth (rhGH). In contrast, when they exposed the cells with methanol, the yeast expressed interferon protein.
The cells are maintained in a table-top microbioreactor millimeter scale, containing a microfluidic chip, which was originally developed by Rajeev Ram, a professor of electrical engineering at MIT, and his team, and marketed by Kevin Lee - a graduate of MIT and co-author -. through a spin-off company
a liquid containing the desired chemical trigger is first introduced into the reactor, to mix with the cells
has within the reactor the mixture of cells and chemical is surrounded on three sides by a polycarbonate. on the fourth side is a soft silicone rubber membrane permeable to gas.
By pressurizing the gas above the membrane, researchers are able to gently massage the liquid droplet to ensure its contents are completely mixed.
"This ensures that one milliliter (liquid) is homogeneous, and that is important because the distribution of these small scales, where there is no turbulence, takes time surprisingly long, "said Ram, who was also a senior author of the paper.
Because the membrane is permeable to gas, it allows oxygen to circulate through the cells, while any dioxide carbon they produce can be easily extracted.
the device continuously monitors the conditions in the microfluidic chip, including oxygen levels, temperature and pH to ensure an optimal environment for cell growth. It also monitors the cell density.
If the yeast is required to produce a different protein, the liquid is simply rinsed through a filter, leaving the cells behind fresh liquid. containing a new chemical trigger can then be added to boost production of the next protein.
Although other research groups have attempted to build microbioreactors, they are not given the opportunity to retain the protein producing cells when flushing liquid are mixed with said Ram. "You want to keep the cells as they are your factory," he said. "But you also want to quickly change their chemical environment, in order to change the trigger for the production of proteins."
The researchers are studying the use of the system in combination therapies, in which multiple treatments, such as antibodies, are used together.
a combination of treatments in this way can be expensive if each requires its own production line, Lu said.
"But if you could design a single strain, or perhaps even a strain consortium that grow together to produce combinations of organic products or antibodies, that could be a very powerful way of production of these drugs at a reasonable cost, "he said.
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