Corporate Banner
Satellite Banner
Biologics & Bioprocessing
Scientific Community
Become a Member | Sign in
Home>News>This Article

Nanosensors Could Aid Drug Manufacturing

Published: Friday, August 23, 2013
Last Updated: Friday, August 23, 2013
Bookmark and Share
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.

Antibodies are usually coated with long sugar chains through a process called glycosylation. These sugar chains are necessary for the drugs to be effective, but they are extremely hard to detect because they interact so weakly with other molecules. Drug-manufacturing organisms that synthesize antibodies are also programmed to add sugar chains, but the process is difficult to control and is strongly influenced by the cells’ environmental conditions, including temperature and acidity.

Without the appropriate glycosylation, antibodies delivered to a patient may elicit an unwanted immune response or be destroyed by the body’s cells, making them useless.

“This has been a problem for pharmaceutical companies and researchers alike, trying to measure glycosylated proteins by recognizing the carbohydrate chain,” Strano says. “What a nanosensor array can do is greatly expand the number of opportunities to detect rare binding events. You can measure what you would otherwise not be able to quantify with a single, larger sensor with the same sensitivity.”

This tool could help researchers determine the optimal conditions for the correct degree of glycosylation to occur, making it easier to consistently produce effective drugs.

Mapping production

The third property the researchers discovered is the ability to map the production of a molecule of interest. “One of the things you would like to do is find strains of particular organisms that produce the therapeutic that you want,” Strano says. “There are lots of ways of doing this, but none of them are easy.”

The MIT team found that by growing the cells on a surface coated with an array of nanometer-sized sensors, they could detect the location of the most productive cells. In this study, they looked for an antibody produced by engineered human embryonic kidney cells, but the system could also be tailored to other proteins and organisms.

Once the most productive cells are identified, scientists look for genes that distinguish those cells from the less productive ones and engineer a new strain that is highly productive, Strano says.

Potential applications such as monitoring drug-producing cells are what make the new technology exciting, says Lara Mahal, an associate professor of chemistry at New York University, who was not part of the research team.

“It’s potentially very powerful as a way of being able to select out colonies,” Mahal says. “Production is something that people are very interested in monitoring. You can have all of these cells growing in the same environment, yet they don’t show the same behavior.”

The researchers have built a briefcase-sized prototype of their sensor that they plan to test with Novartis, which funded the research along with the National Science Foundation.

“Carbon nanotubes coupled to protein-binding entities are interesting for several areas of bio-manufacturing as they offer great potential for online monitoring of product levels and quality. Our collaboration has shown that carbon nanotube-based fluorescent sensors are applicable for such purposes, and I am eager to follow the maturation of this technology,” says Ramon Wahl, an author of the paper and a principal scientist at Novartis.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,700+ scientific posters on ePosters
  • More than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Viruses Join Fight Against Harmful Bacteria
Engineered viruses could combat human disease and improve food safety.
Friday, September 25, 2015
Protein Found to Play a Key Role in Blocking Pathogen Survival
Calprotectin fends off microbial invaders by limiting access to iron, an important nutrient.
Wednesday, August 26, 2015
Firms “Under-invest” in Long-Term Cancer Research
Tweaks to the R&D pipeline could create new drugs and greater social benefit.
Thursday, July 30, 2015
Freshly Squeezed Vaccines
Microfluidic cell-squeezing device opens new possibilities for cell-based vaccines.
Saturday, May 23, 2015
Recruiting The Entire Immune System To Attack Cancer
Stimulating both major branches of the immune system halts tumor growth more effectively.
Wednesday, April 15, 2015
MIT Chemists Devise Novel Way to Manufacture Peptide Drugs
New, fast synthetic method enables manufacture of peptides in hours, which could boost drug development.
Wednesday, March 19, 2014
Researchers Use Nanoparticles to Deliver Vaccines to Lungs
Particles that deliver vaccines directly to mucosal surfaces could defend against many infectious diseases.
Tuesday, October 01, 2013
MIT Team Receives $10.4 Million Biomanufacturing Grant from DARPA
With the grant, MIT’s Biomanufacturing Research Program aims to develop new technologies that can rapidly manufacture biologic drugs on the battlefield.
Thursday, September 19, 2013
Bringing a New Perspective to Infectious Disease
Enlisted in the fight against HIV, MIT engineers and scientists contribute new technology, materials and computational studies.
Thursday, February 07, 2013
A Safer Way to Vaccinate
Polymer film that gradually releases DNA coding for viral proteins could offer a better alternative to traditional vaccines.
Monday, January 28, 2013
Oscillating Microscopic Beads Could be Key to Biolab on a Chip
MIT team finds way to manipulate and measure magnetic particles without contact, potentially enabling multiple medical tests on a tiny device.
Tuesday, September 25, 2012
DARPA and NIH to Fund ‘Human Body on a Chip’ Research
MIT-led team to receive up to $32 million to develop technology that could accelerate pace and efficiency of pharmaceutical testing.
Wednesday, July 25, 2012
Scientific News
Enzyme Malfunction May be Why Binge Drinking Can Lead to Alcoholism
A new study in mice shows that restoring the synthesis of a key brain chemical tied to inhibiting addictive behavior may help prevent alcohol cravings following binge drinking.
New Treatment for Obesity Developed
Researchers at the University of Liverpool, working with a global healthcare company, have helped develop a new treatment for obesity.
New Protein Found in Immune Cells
Immunobiologists from the University of Freiburg discover Kidins220/ARMS in B cells and demonstrate its functions.
New Approach to Treating Heparin-induced Blood Disorder
A potential treatment for a serious clotting condition that can strike patients who receive heparin to treat or prevent blood clots may lie within reach by elucidating the structure of the protein complex at its root.
Antibody Treatment Efficacious in Psoriasis
An experimental, biologic treatment, brodalumab, achieved 100 percent reduction in psoriasis symptoms in twice as many patients as a second, commonly used treatment, according to the results of a multicenter clinical trial led by Mount Sinai researchers.
Promising Drug Candidate to Treat Chronic Itch
In a new study, scientists from the Florida campus of The Scripps Research Institute (TSRI) describe a class of compounds with the potential to stop chronic itch without the adverse side effects normally associated with medicating the condition.
Escape Prevention
Studying flu virus structure brings us a step closer to a permanent vaccine.
13 Ways to Stop an Unseen Force from Disrupting Weighing
Download a free Mettler Toledo paper to discover how to halt static’s negative effects before the next weigh-in.
Inroads Against Leukaemia
Potential for halting disease in molecule isolated from sea sponges.
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,700+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos