MIT chemical engineers have developed arrays of carbon nanotube sensors that can detect single protein molecules as they are secreted from cells. Credit: MIT
For the first time ever a sensor will be able to detect single protein molecules as they are secreted by cells or even a single cell.
Engineers from the Massachusetts Institute of Technology (MIT) have developed sensors— made of chemically modified carbon nanotubes— that could help scientists detect very small amounts of protein when tracking viral infections, monitoring cells’ manufacturing of useful proteins or revealing food contamination.
Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT, said the sensors will greatly improve the detection of proteins in patients.
“We hope to use sensor arrays like this to look for the ‘needle in a haystack’,” Strano said in a statement. “These arrays represent the most sensitive molecular sensing platforms that we have available to us technologically.
“You can functionalize them so you can see the stochastic fluctuations of single molecules binding to them,” he added.
Strano’s lab previously developed sensors that can detect several types of molecules, all based on modifications of carbon nanotubes—hollow, nanometer-thick cylinders made of carbon that naturally fluoresce when exposed to laser light.
They turned these nanotubes into sensors by coating them with DNA, proteins or other molecules that can bind to a specific target.
After the target is bound the nanotubes fluorescence changes in a measurable way.
In the recent study the research team was able to use chains of DNA called aptamers to coat the carbon nanotubes.
Past efforts using DNA aptamers were stymied because of the difficulty of getting the aptamer to stick to the nanotude while maintaining the configuration it needs to bind to its target.
Markita Landry, a former MIT postdoc who is now an assistant professor at the University of California at Berkeley, was able to add a “spacer” sequence between the section of the aptamer that attaches to the nanotube and the section that binds to the target.
This allowed each region the freedom to perform its own function.
The researchers were able to successfully demonstrate sensors for a signaling protein—RAP1—and a viral protein—HIV1 integrase. They believe the approach could work for several other proteins.
They also set up an array of the sensors on a microscope slide to monitor protein production of single cells. The research team found that when a single bacterial, human or yeast cell is placed on the array, the sensors can detect whenever the cell secretes a molecule of the target protein.
“Nanosensor arrays like this have no detection limit,” Strano says. “They can see down to single molecules.”
However, the sensors take longer to sense the molecules with fewer present.
Juyao Dong, a former MIT graduate student, said there are a number of applications the sensors could be used for.
“This platform will open a new path to detect trace amounts of proteins secreted by microorganisms,” Dong said in a statement. “It will advance biological research [on] the generation of signal molecules, as well as the biopharmaceutical industry’s [efforts to monitor] microorganism health and product quality.”
The sensors could be used to test cells engineered to help treat disease.
Researchers are also working on an approach where doctors could remove a patient’s own cells, engineer them to express a therapeutic protein and place them back in the patient.
“We think these nanosensor arrays are going to be useful tools for measuring these precious cells and making sure that they’re performing the way that you want them to,” Strano said.
According to Strano, the arrays could also be used to study viral infection, neurotransmitter function and a phenomenon called quorum sensing, which allows bacteria to communicate with each other to coordinate their gene expression.
The study appeared in Nature Nanotechnology.
