MIT researchers have developed a novel system for manufacturing biopharmaceutical drugs on demand in resource-limited environments.
Researchers from MIT have developed a novel biopharmaceutical production system that can manufacture a variety of biopharmaceutical drugs on demand to provide treatment in resource-limited environments.
The system was developed to produce a single dose of treatment from a portable, compact device containing a small droplet of cells in a liquid. The technology is based on a programmable strain of yeast that can be used to produce therapeutic proteins when exposed to a chemical trigger. Tim Lu, associate professor of biological engineering at MIT and senior author on the work, said this device can produce biopharmaceutical drugs with unprecedented speed and efficiency.
"The microbioreactor platform enables high-density growth of yeast, which we've engineered to be efficient at producing biologic drugs," Lu said. "This system is efficient both in terms of speed and titer, thus allowing for the production of dose-level amounts of drugs in a short amount of time."
This particular strain of yeast, known as Pichia pastoris, can be used to express one of two therapeutic proteins and was chosen because it can grow to very high densities on basic, inexpensive carbon sources. Lu and his colleagues believe this device could provide a novel solution for clinics in remote locations where the resources and infrastructure needed to create vaccines and therapies are limited.
"Existing vaccines and therapeutics are made in large factories at high scale cost," Lu said. "We envision that our technology will enable distribution and portable biomanufacturingin regions that do not have good infrastructure, allowing for important vaccines and therapeutics to be produced on demand. In addition, because our technology enables rapid production of different biological drugs, it could be used to rapidly prototype and manufacture vaccines and therapeutics against emerging pathogens. Eventually, one could imagine that in the future, this kind of biomanufacturingcould be performed locally in hospitals, homes, and other settings."
The cells are housed in a millimeter-scale microbioreactorthat contains a microfluidicchip. There's also a liquid containing the desired chemical trigger inside, which can be fed into the reactor to mix with the cells. Inside the reactor, the cell and chemical mixture is surrounded on three sides by polycarbonate, while the fourth side is a flexible, gas-permeable silicone rubber membrane. The gas-permeable membrane allows for oxygen to flow through the cells while extracting any carbon dioxide produced.
The device can then continuously monitor the conditions within the microfluidicchip, including temperature, acidity or basicity, and oxygen levels to foster an ideal environment for cell growth. Lu said this device could be revolutionary as it provides perfusion capabilities in a portable device.
"This device is the first instrumented microbioreactorwith perfusion capability," Lu said. "There are large-scale perfusion bioreactorsthat are capable of continuous production, but those systems are not portable and may not easily support the rapid medium change-over necessary for flexible production. Perfusion is critical as it allows us to continuously feed the cells, and thereby realize exceedingly high cell densities. This allows us to retain cells while changing the induction medium."
Microfluidic deviceslike this one have long been a staple in research settings, and recently researchers have begun to explore their potential to provide services in resource-limited areas. Lab-on-a-chip devices have enabled researchers to diagnose and treat patients outside of the traditional laboratory setting, giving way to many different emerging technologies with exciting potential.
As Lu and his colleagues move forward with their research, they hope to integrate a few different platforms that could take this proof-of-concept into the regulatory and approval process where a practical device can be developed--a process that could take a few years to accomplish.
"For this system to see widespread use, we would like to integrate analytics and purification platforms with it," Lu said. "Then we would seek regulatory approval for the platform. These steps may take at least several years to carry out."
Kristopher Sturgis is a contributor to Qmed.
Like what you're reading? Subscribe to our daily e-newsletter.
[Image courtesy of MIT]