For medics on the battlefield and doctors in remote or developing parts of the world, getting rapid access to the drugs needed to treat patients can be challenging.
Biopharmaceutical drugs, which are used in a wide range of therapies including vaccines and treatments for diabetes and cancer, are typically produced in large, centralized fermentation plants. This means they must be transported to the treatment site, which can be expensive, time-consuming, and challenging to execute in areas with poor supply chains.
Now, researchers at MIT have developed a portable production system, designed to manufacture a range of biopharmaceuticals on demand.
In a paper published in the journal Nature Communications, the researchers demonstrate that the system can be used to produce a single dose of treatment from a compact device containing a small droplet of cells in a liquid.
In this way, the system could ultimately be carried onto the battlefield and used to produce treatments at the point of care. It could also be used to manufacture a vaccine to prevent a disease outbreak in a remote village.
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, the researcher says.
The system is based on a programmable strain of yeast, Pichia pastoris, which can be induced to express one of two therapeutic proteins when exposed to a particular chemical trigger. The researchers chose P. pastoris because it can grow to very high densities on simple and inexpensive carbon sources, and is able to express large amounts of protein.
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.
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.
The device continuously monitors conditions within the microfluidic chip, including oxygen levels, temperature, and pH, to ensure the optimum environment for cell growth. It also monitors cell density.
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.
Although other research teams have previously attempted to build microbioreactors, these have not have not had the ability to retain the protein-producing cells while flushing out the liquid they are mixed with.
