Research could lead to nanosensors that recognize fibrinogen, insulin, or other biomarkers

January 14, 2016 by Anne Trafton
The atomic-force microscopy (AFM) image on the left demonstrates the physical binding between fibrinogen proteins and single walled carbon nanotubes. The right shows a trace of the AFM image with the fibrinogen in green and nanotubes in light blue.

Using carbon nanotubes, MIT chemical engineers have devised a new method for detecting proteins, including fibrinogen, one of the coagulation factors critical to the blood-clotting cascade.

This approach, if developed into an implantable sensor, could be useful for monitoring patients who are taking blood thinners, allowing doctors to make sure the drugs aren't interfering too much with blood clotting.

The new method is the first to create synthetic recognition sites (similar to natural antibodies) for proteins and to couple them directly to a powerful nanosensor such as a . The researchers have also made significant progress on a similar recognition site for insulin, which could enable better monitoring of patients with diabetes. It may also be possible to use this approach to detect proteins associated with cancer or heart disease, says Michael Strano, the Carbon P. Dubbs Professor in Chemical Engineering at MIT.

Strano is the senior author of a paper describing the method in Nature Communications. Gili Bisker, a postdoc in Strano's lab, is the paper's lead author.

A targeted search

The new sensor is the latest example of a method developed in Strano's lab, known as Corona Phase Molecular Recognition (CoPhMoRe).

This scanning electron microscopy image shows single walled carbon nanotubes, the starting material used by the researchers.

This technique takes advantage of the interactions between a given polymer and a nanoparticle surface such as that of a fluorescent , when the polymer is wrapped around the nanotube.

Certain regions of the polymers latch onto the nanoparticle surface like anchors, while other regions extend outwards into their environment. This outward-facing region, also known as the adsorbed phase or corona, has a 3-D structure that depends on the composition of the polymer.

CoPhMoRe works when a specific polymer adsorbs to the nanoparticle surface and creates a corona that recognizes the target molecule. These interactions are very specific, just like the binding between an antibody and its target. Binding of the target alters the carbon nanotubes' natural fluorescence, allowing the researchers to measure how much of the target molecule is present.

Strano's lab has previously used this approach to find recognition sites and develop nansensors for estradiol and riboflavin, among other molecules. The new paper represents their first attempt to identify corona phases that can detect proteins, which are larger, more complex, and more fragile than the molecules identified by their previous sensors.

For this study, Bisker began by screening carbon nanotubes wrapped in 20 different polymers including DNA, RNA, and polyethylene glycol (PEG), a polymer often added to drugs to increase their longevity in the bloodstream.

On their own, none of the polymers had any affinity for the 14 proteins tested, all taken from human blood. However, when the researchers tested polymer-wrapped nanotubes against the same proteins, they turned up a match between one of the modified nanotubes and fibrinogen.

"A chemist or a biologist would not be able to predict ahead of time that there should be any kind of affinity between fibrinogen and this corona phase," Strano says. "It really is a new kind of molecular recognition."

Fibrinogen, one of the most abundant proteins in human blood, is part of the blood-clotting cascade. When a blood vessel is damaged, an enzyme called thrombin converts fibrinogen into fibrin, a stringy protein that forms clots to seal the wound.

A sensor for fibrinogen could help doctors determine if patients who are taking still have enough clotting capability to protect them from injury, and could allow doctors to calculate more finely tuned dosages. It could also be used to test patients' blood clotting before they go into surgery, or to monitor wound healing, Bisker says.

Synthetic antibodies

The researchers believe their synthetic molecular recognition agents are an improvement over existing natural systems based on antibodies or DNA sequences known as aptamers, which are more fragile and tend to degrade over time.

"One of the advantages of this is that it's a completely synthetic system that can have a much longer lifetime within the body," Bisker says.

In 2013, researchers in Strano's lab demonstrated that carbon nanotube sensors can remain active in mice for more than a year after being embedded in a polymer gel and surgically implanted under the skin.

In addition to insulin, the researchers are also interested in detecting troponin, a protein that is released by dying heart cells, or detecting proteins associated with cancer, which would be useful for monitoring the success of chemotherapy. These and other sensors could become critical components of devices that deliver drugs in response to a sign of illness.

"By measuring therapeutic markers in the human body in real time, we can enable drug delivery systems that are much smarter, and release drugs in precise quantities," Strano says. "However, measurement of those biomarkers is the first step."

Explore further: Engineers synthesize antibodies with carbon nanotubes

More information: Gili Bisker et al. Protein-targeted corona phase molecular recognition, Nature Communications (2016). DOI: 10.1038/ncomms10241

Related Stories

Engineers synthesize antibodies with carbon nanotubes

November 25, 2013

MIT chemical engineers have developed a novel way to generate nanoparticles that can recognize specific molecules, opening up a new approach to building durable sensors for many different compounds, among other applications.

Nanotubes Sniff Out Cancer Agents in Living Cells

January 16, 2009

( -- A multidisciplinary team at the Massachusetts Institute of Technology (MIT) has developed carbon nanotubes that can be used as sensors for cancer drugs and other DNA-damaging agents inside living cells. The ...

Nanosensors could aid drug manufacturing

August 16, 2013

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.

Recommended for you

Nano-decoy lures human influenza A virus to its doom

October 25, 2016

To infect its victims, influenza A heads for the lungs, where it latches onto sialic acid on the surface of cells. So researchers created the perfect decoy: A carefully constructed spherical nanoparticle coated in sialic ...

New method increases energy density in lithium batteries

October 24, 2016

Yuan Yang, assistant professor of materials science and engineering at Columbia Engineering, has developed a new method to increase the energy density of lithium (Li-ion) batteries. He has built a trilayer structure that ...

Nanofiber coating prevents infections of prosthetic joints

October 24, 2016

In a proof-of-concept study with mice, scientists at The Johns Hopkins University show that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.