When making protein drugs like antibodies or insulin, one of the most expensive steps is the purification step: separating the protein from the bioreactors used to make it. This step can account for half of the total cost of making protein.

To keep costs down, MIT engineers devised a new way to do this purification. Their approach, which uses special nanoparticles to rapidly crystallize proteins, could help make protein medicines cheaper and more accessible, especially in developing countries.

"This work uses bioconjugated functionalized nanoparticles as templates to enhance protein crystal formation at low concentrations," said Kripa Varanasi, professor of mechanical engineering at MIT and senior author of the new study. "Our goal is to reduce the cost so that the manufacture of this drug becomes affordable in developing countries."

The researchers demonstrated that their method could be used to crystallize lysozyme (an antibacterial enzyme), and insulin. They believe it could also be applied to many other useful proteins, including antibody drugs and vaccines.

MIT graduate student Caroline McCue is the lead author of the study and Dr. Henri-Louis Girard is also a co-author of the paper.

Antibodies and other protein medicines are part of a growing list of biologics medicines, which also include molecular medicines such as DNA and RNA, as well as cell-based therapies. Most protein drugs are produced by living cells such as yeast in large bioreactors.

Once these proteins have been produced, they must be separated from the reactor, usually through a process called chromatography. Chromatography, which separates proteins based on their size, requires special materials, making the process very expensive.

Varanasi and his colleagues decided to try a different approach, based on protein crystallization. Researchers often crystallize proteins to study their structure, but the process is considered too slow for industrial use and doesn't work well at low concentrations of protein. To overcome these hurdles, Varanasi's lab began using nanoscale structures to speed up crystallization.

In previous work, the lab has used nanoscale features to create materials that repel water or modify interfaces for injecting highly viscous biopharmaceuticals. In this case, the researchers want to tune the nanoparticles so that they locally increase the concentration of proteins on the surface and provide a template for the proteins to align correctly and form crystals.