Nanosensors could aid drug manufacturing

Chemical engineers find that arrays of carbon nanotubes can detect flaws in drugs and help improve production

MIT chemical engineers have discovered that arrays of billions of nanoscale sensors have unique properties that could help pharmaceutical companies produce drugs — especially those based on antibodies — more safely and efficiently.

Using these sensors, the researchers were able to characterize variations in the binding strength of antibody drugs, which hold promise for treating cancer and other diseases. They also used the sensors to monitor the structure of antibody molecules, including whether they contain a chain of sugars that interferes with proper function.

“This could help pharmaceutical companies figure out why certain drug formulations work better than others, and may help improve their effectiveness,” says Michael Strano, an MIT professor of chemical engineering and senior author of a recent paper describing the sensors in the journal ACS Nano.

The team also demonstrated how nanosensor arrays could be used to determine which cells in a population of genetically engineered, drug-producing cells are the most productive or desirable, Strano says.

Lead author of the paper is Nigel Reuel, a graduate student in Strano’s lab. The labs of MIT faculty members Krystyn Van Vliet, Christopher Love and Dane Wittrup also contributed, along with scientists from Novartis.

Testing drug strength

Strano and other scientists have previously shown that tiny, nanometer-sized sensors, such as carbon nanotubes, offer a powerful way to detect minute quantities of a substance. Carbon nanotubes are 50,000 times thinner than a human hair, and they can bind to proteins that recognize a specific target molecule. When the target is present, it alters the fluorescent signal produced by the nanotube in a way that scientists can detect.

Some researchers are trying to exploit large arrays of nanosensors, such as carbon nanotubes or semiconducting nanowires, each customized for a different target molecule, to detect many different targets at once. In the new study, Strano and his colleagues wanted to explore unique properties that emerge from large arrays of sensors that all detect the same thing.

The first feature they discovered, through mathematical modeling and experimentation, is that uniform arrays can measure the distribution in binding strength of complex proteins such as antibodies. Antibodies are naturally occurring molecules that play a key role in the body’s ability to recognize and defend against foreign invaders. In recent years, scientists have been developing antibodies to treat disease, particularly cancer. When those antibodies bind to proteins found on cancer cells, they stimulate the body’s own immune system to attack the tumor.

For antibody drugs to be effective, they must strongly bind their target. However, the manufacturing process, which relies on nonhuman, engineered cells, does not always generate consistent, uniformly binding batches of antibodies.

Currently, drug companies use time-consuming and expensive analytical processes to test each batch and make sure it meets the regulatory standards for effectiveness. However, the new MIT sensor could make this process much faster, allowing researchers to not only better monitor and control production, but also to fine-tune the manufacturing process to generate a more consistent product.

“You could use the technology to reject batches, but ideally you’d want to use it in your upstream process development to better define culture conditions, so then you wouldn’t produce spurious lots,” Reuel says.

Measuring weak interactions

Another useful trait of such sensors is their ability to measure very weak binding interactions, which could also help with antibody drug manufacturing.

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