World’s first DNA robots successfully move and deliver molecule sized cargo

In the classic 1966 American science fiction film Fantastic Voyage, a submarine crew was miniaturised and injected into a body to fix a blood clot in the brain. That’s obviously not how future medical science is going to work, but it’s not too far removed from what we’ll experience in the future, and the notion of creating microscopic machines, that don’t have shrunken humans in them, to perform complex tasks is certainly on point. Now, a recent advance where robots made from DNA were programmed to sort and deliver molecules to different specified locations represents an important step forwards in this futuristic direction, and it comes right on the heels of another announcement from another team of researchers who've managed to create the world's first Molecular Robot production line.

It’s still early days for nanotech in healthcare, but new research from a team at the California Institute of Technology (CalTech), who also recently showed off a new way to track nanobots in the body, such as this micro-rocket and these brain controlled nanobots, is showing other researchers in the space the tremendous potential of this nano sized technology.

Headed up by Anupama Thubagere and Lulu Qian the team has built robots from DNA, and programmed them to bring individual molecules to a designated location. Eventually, this technology could be used to transport molecules of many types throughout the body, and that could potentially transform everything from drug delivery to how the body fights infections to how microscopic measurements are made.

There are currently three emerging fields within DNA Nanoscience, the science of creating molecular-sized devices out of DNA, namely the self-assembly of nano-structures from DNA strands, DNA computers and storage, and DNA robotics, the latter of which is the focus of the teams study published in Science.

The central premise of DNA nanoscience is that, rather than creating molecular devices or systems from scratch, we can leverage the power of nature, which has already figured much of this out. And if, or more likely when, we finally master molecular machinery, we’ll be able to build microscopic sized robots with programmable functions and send them to places that are otherwise impossible to reach, such as the inside of a  cell or a hard to reach tumour.

In prior experiments, DNA robots demonstrated their ability to perform simple tasks, but this latest effort ramped up the level of complexity considerably, while also opening a path towards the development of general-purpose DNA robots.

“It is the first time that DNA robots were programmed to perform a cargo‐sorting task, but more important than the task itself, we showed how this seemingly complex task, and potentially many other tasks, that DNA robots can be programmed to do uses very simple and modular building blocks,” said Qian, “This is also the first example showing multiple DNA robots collectively performing the same task.”

For the new study, the researchers designed a group of autonomous DNA robots that could collectively perform a predetermined task that had them walk along a test platform, locate a molecular cargo, and deliver it to a specific location.

Each robot, which was built from a single-stranded DNA molecule of just 53 nucleotides, was equipped with “legs” for walking and “arms” for picking up objects, and they measured just 20 nanometers tall, with their walking strides being just six nanometers long, where one nanometer is a billionth of a meter. That’s tiny! For perspective, a human hair measures about 50,000 to 100,000 nanometers in diameter, so the scale we’re talking about here is ludicrously tiny.

For the cargo, the researchers used two types of molecules, each a distinct single-stranded piece of DNA and during tests the researchers placed the cargo onto a random location along the surface of a 2D self-folding “origami” DNA test platform. The walking DNA robots then moved in parallel along its surface, hunting for their cargo.

To see if a robot successfully picked up and dropped off the right cargo at the right location, the researchers used two fluorescent dyes to distinguish the molecules., but the researchers aren’t yet at the stage yet where they can program robots of this size to have built-in memory, so instead, they designed the robots to “match” their cargo.

“We designed specific drop off locations for each type of cargo. If the type matches, the drop off location will signal the robot to release the cargo, otherwise the robot will continue to walk around and search for another drop off location,” explained Qian, “you might think that the robot is not smart. But here is a key principle for building molecular machines, make individual molecules as simple as possible so they can function reliably in a complex biochemical environment, but take advantage of what a collection of molecules can do, and distribute their ‘smarts’ into different molecules.”

The researchers estimate that each DNA robot took around 300 steps to complete their tasks, or roughly ten times more than in previous efforts.

“We successfully programmed complex behaviour in DNA robots and compartmentalized each task using DNA origami,” added Thubagere.

In experiments, 80 percent of cargo molecules were sorted, so there’s room for improvement, and the team believe the failures might have been caused by the that not all molecules were correctly synthesised, or that some parts of the robot or testing platform were defective. Much more work needs to be done to figure this all out, and to test the DNA robots under different environmental conditions if we’re ever going to have these things working in our bodies, but this revolutionary new case study offers other researchers a viable methodology for the future of DNA nanoscience.

“The biggest implication that I hope the work will have is to inspire more researchers to develop modular, collective, and adaptive DNA robots for a diverse range of tasks, to truly understand the engineering principles for building artificial molecular machines, and make them as easily programmable as macroscopic robots,” said Qian.