Friday, September 30, 2016

Emory's 'Rolosense' rolling to finals of Collegiate Inventors Competition

“I think the advantage we have with our technology is that it's so simple," says Aaron Blanchard, left (a PhD student in Emory's Laney Graduate School and Coulter Department of Biomedical Engineering at Georgia Tech and Emory), shown using the Rolosense with his advisor, Emory chemist Khalid Salaita. 

By Carol Clark

The first rolling DNA motor – the biological equivalent of the invention of the wheel for the field of DNA machines – is headed from its origins in an Emory University chemistry lab to the finals of the 2016 Collegiate Inventors Competition in Washington D.C.

Kevin Yehl and Aaron Blanchard make up one of six teams of graduate students who will be flown to the finals in early November. Yehl and Blanchard developed the DNA motor (dubbed Rolosense), and its application as a chemical sensor, in the laboratory of their advisor – Emory chemist Khalid Salaita.

Blanchard is a PhD student in Emory's Laney Graduate School and the Coulter Department of Biomedical Engineering (BME) at Georgia Tech and Emory, while Yehl recently graduated from Laney and the BME department.

The entries of the elite student teams represent the most promising inventions from U.S. universities. “Their ideas will shape the future,” wrote Michael Oister, CEO of the National Inventors Hall of Fame, in a letter announcing the finalists.

The Collegiate Inventors Competition annually gives out about $100,000 in cash prizes and is considered the foremost program in the country encouraging invention and creativity in undergraduate and graduate students. The competition also promotes entrepreneurship, by rewarding ideas that hold value for society.

The Rolosense is 1,000 times faster than any other synthetic DNA motor. Its speed means a simple iPhone microscope can capture its movement through video, giving it potential for real-world applications, such as disease diagnostics.

Kevin Yehl sets up a smart-phone microscope to get a readout for the particle motion of the rolling DNA-based motor.

"It's exciting," Yehl says. "Previous winners have gone on to start companies with their inventions and become successful scientists. It will be great to get feedback from the judges on the Rolosense."

The judges will include inductees to the National Inventors Hall of Fame, officials from the U.S. Patent and Trademark Office, and scientists from the global healthcare firm AbbVie.

Some of the best discoveries involve serendipity, and that was the case for the Rolosense. Yehl was working last year as a post-doctoral fellow in the Salaita lab, which specializes in visualizing and measuring mechanical forces at the nano-scale. He was conducting experiments using enzymatic nano-particles – micron-sized glass spheres. “We were originally just interested in understanding the properties of enzymes when they’re confined to a surface,” Yehl says.

During the experiments, however, he learned by accident that the nano-particles roll. That gave him the idea of constructing a rolling DNA-based motor using the glass spheres.

The field of synthetic DNA-based motors, also known as nano-walkers, is about 15 years old. Researchers are striving to duplicate the action of nature’s nano-walkers. Myosin, for example, are tiny biological mechanisms that “walk” on filaments to carry nutrients throughout the human body. 

So far, however, mankind’s efforts have fallen far short of nature’s myosin, which speeds effortlessly about its biological errands. Some synthetic nano-walkers move on two legs. They are essentially enzymes made of DNA, powered by the fuel RNA. These nano-walkers tend to be extremely unstable, due to the high levels of Brownian motion at the nano-scale. Other versions with four, and even six, legs have proved more stable, but much slower. In fact, their pace is glacial: A four-legged DNA-based motor would need about 20 years to move one centimeter.

 A cell phone app is in the works.
The Rolosense design mows over these limitations. Hundreds of DNA strands, or “legs,” are allowed to bind to the sphere. These DNA legs are placed on a glass slide coated with the reactant: RNA.

The DNA legs are drawn to the RNA, but as soon as they set foot on it they destroy it through the activity of an enzyme called RNase H. As the legs bind and then release from the substrate, they guide the sphere along, allowing more of the DNA legs to keep binding and pulling.

“The Rolosense can travel one centimeter in seven days, instead of 20 years, making it 1,000 times faster than other synthetic DNA motors,” Salaita says. “In fact, nature’s myosin motors are only 10 times faster than the Rolosense, and it took them billions of years to evolve.”

The researchers next demonstrated the Rolosense could be used to detect a single DNA mutation by measuring particle displacement. Yehl simply glued lenses from two inexpensive laser pointers to the camera of an iPhone to turn the phone’s camera into a microscope and capture videos of the particle motion.

The simple, low-tech method could come in handy for doing diagnostic sensing in the field, or anywhere with limited resources.

Nature Nanotechnology published the work on the rolling DNA motor. The researchers have filed an invention disclosure patent for the concept of using the particle motion of the Rolosense as a sensor for everything from a single DNA mutation in a biological sample to heavy metals in water.

Yehl has since left Emory for a position at MIT, but he continues to work with Salaita and Blanchard on refining the Rolosense.

Blanchard, who has a background in computer coding, is integrating the data analysis of the Rolosense into a smart phone app that will provide a readout of the results.

“I feel really fortunate as a graduate student to be working on this project,” Blanchard says. “As the molecular detection field grows, I think that Rolosense will grow with it.”

For their demonstration during the finals, Yehl and Blanchard plan to hand the judges smart phones and samples of water (including some containing lead), and let the judges use Rolosense to test the samples.

“It can be easy to dazzle with complex technologies like a robot,” Blanchard says, “but I think the advantage that we have with our technology is that it’s so simple. We can let the judges see for themselves how they can use Rolosense to quickly learn something useful, like whether a water source is contaminated with a heavy metal.”

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