Electrically controlled DNA robot arm is 100,000 times faster – millisecond moves enable molecular factories

Scientists at the Technical University of Munich (TUM) have developed a novel electric propulsion technology for nanorobots. It allows molecular machines to move a hundred thousand times faster than with the biochemical processes used to date. This makes nanobots fast enough to do assembly line work in molecular factories.

The DNA nanobot is shaped like a gearshift, with an extendible arm that ranges from 25 to more than 400 nanometers long that’s attached to a 55-by-55-nanometer platform.

Friedrich Simmel, a biophysicist at the Technical University of Munich, and his colleagues could swivel their DNA robotic arm 360 degrees in a matter of milliseconds. To lock the arm down in particular positions, the team built latches made of short, single-stranded DNA into the platform.

Such quick, efficient DNA nanobots could someday help move tiny cargo, such as molecules or nanoparticles, in a nanofactory that manufactures new types of materials.

Up and down, up and down. The points of light alternate back and forth in lockstep. They are produced by glowing molecules affixed to the ends of tiny robot arms. Prof. Friedrich Simmel observes the movement of the nanomachines on the monitor of a fluorescence microscope. A simple mouse click is all it takes for the points of light to move in another direction.

“By applying electric fields, we can arbitrarily rotate the arms in a plane,” explains the head of the Chair of Physics of Synthetic Biological Systems at TU Munich. His team has for the first time managed to control nanobots electrically and has at the same time set a record: The new technique is 100 000 times faster than all previous methods.

DNA-Origami Robots
Scientists around the world are working on new technologies for the nanofactories of the future. They hope these will one day be used to analyse biochemical samples or produce active medical agents. The required miniature machines can already be produced cost-effectively using the DNA-origami technique.

The only reason these molecular machines have not been deployed on a large scale to date is that they are too slow. The building blocks are activated with enzymes, strands of DNA or light to then perform specific tasks, for example to gather and transport molecules.

However, traditional nanobots take minutes to carry out these actions, sometimes even hours. Therefore, efficient molecular assembly lines cannot, for all practical intents and purposes, be implemented using these methodologies.

Electronic Speed Boost
“Building up a nanotechnological assembly line calls for a different kind of propulsion technology. We came up with the idea of dropping biochemical nanomachine switching completely in favor of the interactions between DNA structures and electric fields,” explains TUM researcher Simmel, who is also the co-coordinator of the Excellence Cluster Nanosystems Initiative Munich (NIM).

The principle behind the propulsion technology is simple: DNA molecules have negative charges. The biomolecules can thus be moved by applying electric fields. Theoretically, this should allow nanobots made of DNA to be steered using electrical impulses.

Robotics under the microscope
To determine whether and how fast the robot arms would line up with an electric field, the researchers affixed several million nanobot arms to a glass substrate and placed this into a sample holder with electrical contacts designed specifically for the purpose.

Each of the miniature machines produced by the lead author Enzo Kopperger comprises a 400 nanometer arm attached to a rigid 55 by 55 nanometer base plate with a flexible joint made of unpaired bases. This construction ensures that the arms can rotate arbitrarily in the horizontal plane.

In collaboration with fluorescence specialists headed by Prof. Don C. Lamb of the Ludwig Maximillians University Munich, the researchers marked the tips of the robot arms using pigment molecules. They observed their motion using a fluorescence microscope. They then changed the direction of the electric field. This allowed the researchers to arbitrarily alter the orientation of the arms and control the locomotion process.

“The experiment demonstrated that molecular machines can be moved, and thus also driven electrically,” says Simmel. “Thanks to the electronic control process, we can now initiate movements on a millisecond time scale and are thus 100 000 times faster than with previously used biochemical approaches.”

Progress to a Nanofactory
The new control technology is suited not only for moving around pigments and nanoparticles. The arms of the miniature robots can also apply force to molecules. These interactions can be utilized for diagnostics and in pharmaceutical development, emphasizes Simmel. “Nanobots are small and economical. Millions of them could work in parallel to look for specific substances in samples or to synthesize complex molecules – not unlike an assembly line.

Science – A self-assembled nanoscale robotic arm controlled by electric fields

Electrically driving a DNA arm
Most nanoelectromechanical systems are formed by etching inorganic materials such as silicon. Kopperger et al. improved the precision of such machines by synthesizing a 25-nm-long arm defined by a DNA six-helix bundle connected to a 55 nm-by-55 nm DNA origami plate via flexible single-stranded scaffold crossovers (see the Perspective by Hogberg). When placed in a cross-shaped electrophoretic chamber, the arms could be driven at angular frequencies of up to 25 Hz and positioned to within 2.5 nm. The arm could be used to transport fluorophores and inorganic nanoparticles.

The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer–by–55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Förster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.

Processes that occur at the nanometer scale have a tremendous impact on our daily lives. Sophisticated evolved nanomachines operate in each of our cells; we also, as a society, increasingly rely on synthetic nanodevices for communication and computation. Scientists are still only beginning to master this scale, but, recently, DNA nanotechnology (1)—in particular, DNA origami (2)—has emerged as a powerful tool to build structures precise enough to help us do so. On page 296 of this issue, Kopperger et al. (3) show that they are now also able to control the motion of a DNA origami device from the outside by applying electric fields.


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