Chemists have integrated computer functions into DNA-based rolling motors, opening up a new realm of possibilities for miniature molecular robots. Nature Nanotechnology released the development, the first DNA-based engines that combine computing power with the ability to burn fuel and move in an intentional direction.

“One of our big innovations, beyond the ability of DNA engines to perform logical calculations, is finding a way to convert that information into a simple output signal – motion or no motion,” Selma says. Piranej, a PhD student in chemistry at Emory University, and first author of the paper. “This signal can be read by anyone holding a cell phone equipped with an inexpensive magnifying glass.”

“Selma’s breakthrough removes key barriers that have stood in the way of making DNA computers useful and practical for a range of biomedical applications,” says Khalid Salaita, lead author of the paper and Emory Professor of Chemistry at Emory University. Salaita is also on the faculty of the Wallace H. Coulter Department of Biomedical Engineering, a joint program of Georgia Tech and Emory.

Engines can sense chemical information in their environment, process that information, and then react accordingly, mimicking some basic properties of living cells.

“Previous DNA computers didn’t have built-in directed motion,” says Salaita. “But to achieve more sophisticated operations, you have to combine calculation and directed movement. Our DNA computers are essentially autonomous robots with sensing capabilities that determine whether they are moving or not.

Motors can be programmed to respond to a specific pathogen or DNA sequence, making them a potential technology for medical testing and diagnostics.

Another key advancement is that each engine can operate independently, under different programs, while being deployed as a group. This opens the door to a single massive array of micron-sized motors to perform a variety of tasks and perform motor-to-motor communication.

“The ability of DNA motors to communicate with each other is a step towards producing the kind of complex, collective action generated by swarms of ants or bacteria,” says Salaita. “It could even lead to emergent properties.”

DNA nanotechnology takes advantage of the natural affinity of DNA bases A, G, C and T to pair together. By moving the sequence of letters onto synthetic strands of DNA, scientists can get the strands to link together in ways that create different shapes and even build working machines.

Salaita Lab, a leader in biophysics and nanotechnology, developed the first DNA-based rolling motor in 2015. The device was 1,000 times faster than any other synthetic motor, accelerating the burgeoning field of molecular robotics. Its high speed allows a simple smart phone microscope to capture its movement by video.

The “chassis” of the motor is a micron-sized glass sphere. 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 reactive RNA, the engine fuel. The DNA legs are attracted to the RNA, but as soon as they set foot there, they erase it thanks to the activity of an enzyme which is bound to the DNA and only destroys the RNA. As the legs bind and then release from the substrate, they continue to guide the sphere.

When Piranej joined Salaita’s lab in 2018, she began working on a project to take rolling motors to the next level by integrating computer programming logic.

“It’s a major goal in the biomedical field to leverage DNA for computation,” Piranej says. “I love the idea of ​​using something innate in all of us to design new forms of technology.”

DNA is like a biological computer chip, storing large amounts of information. The basic functional units for DNA computation are short strands of synthetic DNA. Researchers can alter the “program” of DNA by altering the AGTC sequences on the strands.

“Unlike a hard silicon chip, DNA-based computers and motors can operate in water and other liquid environments,” says Salaita. “And one of the big challenges in manufacturing silicon computer chips is trying to fit more data into an ever-smaller footprint. DNA provides the ability to run many processing operations in parallel in a very small space.The density of operations that you could perform could even go to infinity.

Synthetic DNA is also biocompatible and inexpensive to manufacture. “You can replicate DNA using enzymes, copying and pasting it as many times as you want,” says Salaita. “It’s practically free.”

Limits remain, however, in the nascent field of DNA computation. A key hurdle is making the output of calculations easily readable. Current techniques rely heavily on labeling DNA with fluorescent molecules and then measuring the intensity of light emitted at different wavelengths. This method requires expensive and bulky equipment. It also limits the signals that can be read to those present in the electromagnetic spectrum.

Although trained as a chemist, Piranej began learning the basics of computer science and delving into bioengineering literature in an attempt to overcome this hurdle. She came up with the idea of ​​using a reaction well known in bioengineering to perform the calculation and associating it with the movement of rolling motors.

The reaction, known as foot-mediated strand displacement, occurs on duplex DNA – two complementary strands. The strands hug tightly against each other, except for one loose, flexible end of a strand, known as the toe plug. The rolling motor can be programmed by coating it with duplex DNA complementary to a DNA target – a sequence of interest.

When the molecular motor encounters the DNA target as it rolls along its RNA track, the DNA target binds to the duplex DNA toe plug, pulling it apart and anchoring the motor in square. The read computer simply becomes “movement” or “no movement”.

“When I first saw this concept work in an experiment, I made this sound very loud and excited,” Piranej recalls. “One of my colleagues came over and asked me, ‘Are you okay?’ Nothing compares to seeing your idea come to life like this. It’s a big moment.

These two basic “move” or “no-move” logic gates can be wired together to construct more complicated operations, mimicking the way regular computer programs rely on “zero” or “one” logic gates.

Piranej took the project even further by finding a way to bundle many different computing operations while still easily reading the output. She simply varied the size and materials of the microscopic spheres that form the chassis of the DNA-based rolling motors. For example, spheres can range from three to five microns in diameter and be made of silica or polystyrene. Each alteration provides slightly different optical properties that can be distinguished using a cell phone microscope.

The Salaita lab is working to establish a collaboration with scientists at the Atlanta Center for Microsystems Engineered Point-of-Care Technologies, an NIH-funded center created by Emory and Georgia Tech. They are exploring the potential for using DNA computing technology for home diagnosis of COVID-19 and other disease biomarkers.

“Developing devices for biomedical applications is particularly rewarding because it’s a chance to have a big impact on people’s lives,” says Piranej. “The challenges of this project made it more fun for me,” she adds.