Portable Device Delivers Biopharmaceuticals on Demand

Biopharmaceutical drugs typically are produced through a lengthy process in large scales at dedicated bioprocessing facilities. The finished drug product must then be shipped under controlled conditions to reach the treatment site. When patients are in remote regions with limited supply chain or transportation infrastructure, the delivery can be compromised.

A portable production system, designed to manufacture a range of biopharmaceuticals on demand, could bring the manufacturing process closer to the patient, whether on a battlefield or in a remote, undeveloped region. The system, developed by researchers at MIT, with funding from the Defense Advanced Research Projects Agency (DARPA), was reported in a paper published on July 29, 2016, in Nature Communications.

In the paper, the researchers reported that the system can be used to produce a single dose of treatment from a table-top microbioreactor containing a small droplet of cells in a liquid. A programmable strain of yeast, Pichia pastoris, was induced to express one of two therapeutic proteins when exposed to a particular chemical trigger. The yeast was altered to be more easily genetically modified and could include more than one therapeutic.

When the modified yeast was exposed to estrogen β-estradiol, the cells expressed recombinant human growth hormone (rHGH). When the cells were exposed to methanol, the yeast expressed the protein interferon.

The cells are held within a millimeter-scale microbioreactor, containing a microfluidic chip. A liquid containing the desired chemical trigger is 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. To produce a different protein, the liquid is flushed through a filter, leaving the yeast cells behind. Fresh liquid containing a new chemical trigger can then be added, to stimulate production of the next protein, the researchers reported in a press statement.

Source: MIT