the robots were finally walking. And Nadine Dabby was struggling to contain her excitement.
It was a Friday evening in early 2008, at a lab in the California Institute of Technology in Pasadena. Dabby was working alone at an atomic force microscope when an email pinged into her inbox from her collaborator, Kyle Lund, from Arizona State University.
When she saw the email contained an attachment, the young researcher’s pulse thumped a little harder. For months, Dabby and her colleagues had been fine-tuning their experiments, and in the email Lund told her their efforts had borne fruit.
Clicking on the attachment, she saw something she had been striving toward for years: sequential snapshots of tiny robots she and her colleagues had been building moving step by step across a ‘lawn’ of molecules, mowing them down as they went.
“I was working alone at the microscope on this particular Friday evening and not getting anywhere,” recalls Dabby, who brims with enthusiasm when she speaks. “I was very excited… this was a great sign that the ‘walker’ was walking.”
the robots in question aren’t your usual construction of metal cogs and wheels. Instead, they are assembled from biological molecules: three legs made of DNA – the molecule that forms the genetic blueprint for life – and a body made of a common protein called streptavidin.
Designed a few years previously by Milan Stojanovic at Columbia University in New York City, the robots were nicknamed ‘spiders’ by scientists. They were just four nanometres across – so small that you could fit millions inside the eye of a needle.
The ingenious thing about Stojanovic’s spiders was that they harnessed the mechanisms of biology to build the shape of the robot. Embedded within the code of each DNA molecule is a naturally occurring ability to bind to other molecules of DNA in a predictable way. This specific binding pattern also determines the three-dimensional shape that the molecule assembles itself into.
Thanks to revolutions in DNA-sequencing technology, scientists can now generate their own sequences of DNA that self-assemble in this natural way, to form precisely the shapes they want.
Other studies had already shown DNA spiders could walk short distances in a random direction. In their study, published in Nature in 2010, Lund, Dabby and others were trying to guide the robot’s movement by laying down a trail of DNA ‘breadcrumbs’ for it to pick up. Several gurus in the field – Caltech’s Erik Winfree, Hao Yan from Arizona State University, Nils Walter from the University of Michigan, and Stojanovic himself – were leading the effort.
Now, late on this Friday afternoon, Lund had provided the first evidence their efforts may have paid off – a series of images captured by an immensely powerful atomic force microscope and strung together into a movie.
But Dabby reminded herself that this was far from definitive proof. “In order to prove that our walker was actually walking and not just an artefact of the microscope, we needed to either collect more images or find another method of determining what was going on,” explains Dabby. “Both Kyle and I spent three more months trying to repeat this amazing observation. But neither of us could capture another series of images like the one we had seen that February.”
At that point, she says, she suggested they try to capture images by performing a time-lapse experiment. To her way of thinking, a movie would be very difficult to attain because of interference between the surface chemistry of the ‘platform’ and the spider itself.
“So we switched tacks: we let the reaction run in solution and deposited it on the [slide] at different time points after we triggered the reaction. We were able to accumulate a lot of data showing over hundreds of controls and reactions that the walker was indeed walking over time when triggered.”
The researchers had succeeded in building robots made of DNA, and found a way to make them take roughly 50 autonomous steps along a specific path. Simple molecular robots such as these could one day be used to build molecular-scale machines that can reorganise themselves into a variety of shapes to accomplish different tasks, such as repairing damaged tissues in the body.
“You could imagine the spider carrying a drug and bonding to a two-dimensional surface like a cell membrane, finding the receptors and, depending on the local environment, triggering the activation of this drug,” Hao Yan said in a press release at the time.
For Dabby, and many others, it felt like the spider hadn’t only walked across a lawn of DNA. It had taken a short walk into the future.
the idea that humans might one day create tiny machines, one atom at a time, can be traced back to a lecture given by theoretical physicist Richard Feynman, one winter’s day in 1959.
“What would happen if we could arrange the atoms one by one the way we want them?” Feynman had asked his audience. “I can hardly doubt that when we have some control of the arrangement of things on a small scale we will get an enormously greater range of possible properties that substances can have.”
The field inspired by Feynman’s talk was dubbed nanotechnology, named after the nanometre – one billionth of a metre. Visionaries were soon dreaming of building molecular robots, or nanobots, that would enter the blood stream, as depicted in the 1966 sci-fi movie Fantastic Voyage, and fight disease.
The term ‘nanotechnology’ was soon being applied to essentially anything that made use of the properties of matter at the molecular scale. The rule of thumb is nanotechnology materials and devices have at least one dimension between 1 and 100 nanometres.
By this definition, the field of nanotechnology has exploded. In 2011, the journal Nature Nanotechnology noted that the number of scientific papers published on nanotech grew from about 8,000 in 1991 to about 87,000 in 2009.
Nanotechnology has already made its way into our homes. The U.S.-based Project on Emerging Nanotechnologies (a partnership between think tank Woodrow Wilson International Centre for Scholars and the Pew Charitable Trusts) has gathered a list of more than 1,000 nanotech consumer products already available, from the surfaces on hair straightening devices to cleaning products.
Until recently, the concept of building more complicated atomic-scale structures remained largely science fiction. But now, that futuristic vision appears to be inching closer to reality. And, like the work done by Dabby and her colleagues, some of the most exciting developments are arising from labs where researchers are using the principles, or even the very mechanisms, employed by the real nanotechnology expert: nature.
the iridescence of a butterfly wing, a gecko’s ability to walk up walls and the intricate beauty of a seashell all owe their remarkable properties to nanostructures, says Max Lu, leader of the functional nanomaterials group at the Australian Institute for Bioengineering & Nanotechnology in Brisbane.
“There are endless examples,” says Lu, whose areas of expertise include the molecular engineering of nanomaterials for clean energy and environmental applications. “In many ways in nanotechnology, what we are trying to do is learn from nature. For example, I recently I read an article on the nanostructure of the skin of desert lizards, which have the remarkable ability to harvest moisture from the air. Now that would be useful if humans wanted to develop a membrane with those properties.”
Natural nanotechnology has been refined over billions of years. From ‘machines’ that translate the genetic code, to the intricate mechanisms that rotate tail-like flagella on bacteria, biology works at the nano-scale. Our own bodies, Lu points out, house multitudes of natural nano-machines.
And remarkably, each natural nano-machine essentially assembles itself. Based on their chemical make-up, molecules such as DNA and proteins fold up into three-dimensional shapes that determine their function. And then those folded-up molecules organise themselves into more complicated structures capable of performing complex tasks, again using naturally occurring bonds between molecules as the glue to hold them together.
In recent years, research that harnesses these biological approaches to building nano-machines has become a hot topic. In May 2012, for example, researchers from Harvard University’s Wyss Institute for Biologically Inspired Engineering developed a system for building complex nanostructures out of short strands of DNA that fit together like Lego building blocks.
Each of the ‘blocks’ in this case is built of single-stranded DNA. One block will only connect with another if its DNA sequence is complementary. This means a series of blocks can assemble by themselves into specific shapes that are determined by the DNA sequences chosen by the researchers.
Scientists have already used these building blocks to construct letters, numbers and emoticons, but think they could also be used to create nano-scale devices to deliver drugs to disease sites.
One of the most prominent people in this field of self-assembling nanotechnology is Reza Ghadiri, a chemist from the Scripps Research Institute in California, who won the 1998 Feynman Prize for Nanotechnology for constructing molecular structures through the use of self-organisation.
Ghadiri says that while this approach is still in its infancy, remarkable progress is being made. “It isn’t science fiction,” he says. “Nature has shown you can build these things. Nature obviously is a guide, and you can marvel at how well these things can function – intricate, complex machinery.”
while dabby and her colleagues were building their DNA robots, across the country at Tufts University, outside Boston, a group of researchers led by Charlie Sykes were working on a machine that was even smaller. Sykes was trying to make an electrical motor formed from a single molecule of a type of chemical found in spirits like brandy.
Late summer in 2010, Sykes was in his first-floor office when the phone rang. On the line was graduate student Heather Tierney, calling from the lab in the basement where she had seen the first evidence that their experiments were working.
Other researchers had built single-molecule motors, but up until Sykes and Tierney’s results, the motors had been driven by chemical energy or light. Sykes and his colleagues were trying to get their motor to work using electricity, which they think offers significant advantages when it comes to practical applications.
Earlier experiments with molecular motors had been performed in chemical solutions, where large numbers of molecules are set spinning at the same time, Sykes explains. “Unlike those, we were interested in exciting them one at a time. When you get down to nano-scale control of things, electricity is the way to go.”
Downstairs is the scanning tunnelling microscope lab where Sykes’ team performed their experiments. Working with such tiny molecules, the researchers needed to go to great lengths to protect their experiments from the outside world. Foot-thick walls and quadruple-glazed windows surround the lab, keeping noise out. Inside a large stainless steel vacuum chamber is a smaller vessel cooled to minus 200 degrees Celsius, which in turn contains an even colder vessel cooled a further 60 degrees. The low temperatures help slow a molecule’s rotations enough that it can be measured.
Inside the final layer of this scientific Russian Doll is the scanning tunnelling microscope – 10cm high, suspended on three springs that protect it from vibrations. Without them, a truck passing a block away would interfere with the measurements, Sykes says. The microscope’s fine metal tip provides an electrical charge to a single thioether molecule resting on a copper surface, making the molecule rotate.
The device’s output is a series of data-points in a spreadsheet, which could be graphed as a “line with spikes in it,” Sykes explains. “The height of the spike tells you which direction it’s going in.”
The researchers wanted to show that they could make the molecule spin in such a way that, over time, it spun in one direction more than the other. To do this, they needed to count about half a million of these rotational events – by hand. Each line on the graph had to be measured by computer and then checked by an army of graduate students, undergraduates and even high school students working in three-hour shifts. To make sure nobody allowed their enthusiasm to start skewing their measurements, all the students who performed the measurements were ‘blinded’ to the particular experimental set-up that had produced the results.
After all that work, the positive findings that day in 2010 generated a “mixture of excitement and celebration,” Sykes recalls. “The experiment had been going for five years. But to be sure, we still had to do a lot of control experiments, and there was pressure because we knew there were other groups working on this same thing and we didn’t want to get scooped.” The work paid off – the results of the paper were published in Nature Nanotechnology in September 2011.
down the track, single-molecule motors could have a range of applications. Coating the insides of tiny ‘microfluidic’ tubes with a layer of such motors could help propel fluids, Sykes says. Microfluidics are used in a host of areas, from DNA diagnostics and molecular biology, to optics and the development of fuel cells.
In the long term, these single-molecule motors could have charges applied at either end, turning them into tiny sources of light, Sykes says. “They could also be turned into tiny antennae to convert between electromagnetic signals and mechanical signals, or between optical and electrical signals.”
Sykes also points out that the molecular motor is versatile enough to be engineered into larger molecular devices. In fact, a few months after his group published their results, scientists in the Netherlands reported that they’d used a similar scanning tunnelling microscope to drive a molecular ‘car’ across a surface.
Tibor Kudernac, from the University of Twente, and his colleagues built their molecular car using four rotary elements arranged in a way that would be familiar to anyone who has seen underneath a regular vehicle. Electrons passed from the microscope’s tip to the molecule, serve as ‘fuel’ – with 10 electric bursts, they were able to make the car move six nanometres forward along the copper surface.
Although the structure of the four-wheeled molecule is completely new, the inspiration again came from nature, says Kudernac. Each of the cells relies on molecular machinery that “walks inside our body” to perform vital tasks such as carrying cargo from one part of a cell to another, he says.
“In the distant future, you could envisage using [a molecular car] as a small carrier of cargo in our bodies,” he says. “You could imagine a molecule that can bind to cell surfaces and use them as a road to walk or roll along.
“This was the first demonstration of an emerging functionality combining four motors to create directional motion. Now it’s up to our imagination what we can do with it.”
FOR REZA GHADIRI, some of the most exciting potential applications of the kind of molecular devices being constructed today will be in the medical field.
Like the self-assembly techniques of the DNA researchers, his group has had success using small protein fragments that assemble themselves into rings, tubes and other shapes.
“We have made rings of peptides that self-assemble into a nanotube that have some material applications, for example, to disrupt biological membranes,” he says. “We have had quite a good success in making antiviral agents against hepatitis C virus based on them.”
Looking ahead, he can imagine using synthetic or self-assembled structures made of protein to help bones heal or to guide the differentiation of cells into specific tissues. “Eventually you could have a whole series of therapies based on self-assembly of small molecules,” Ghadiri says.
Biological systems are capable not only of assembling themselves into machines based on their molecular structures: they are also capable of responding to their environments. Recently, scientists have begun looking at ways to mimic this. In January this year, one group published experimental results showing that nanoparticles encapsulated in a deformable shell might be able to repair surfaces similar to the way white blood cells work in the body. In their approach, dubbed ‘repair-and-go’, a flexible capsule filled with a solution of nanoparticles could find cracks in a surface, stop to repair defects by releasing the nanoparticles, and move on to the next defect.
If nanotechnologists can harness this capacity for self-repair, the potential applications would be truly astounding. To illustrate the point, Dabby recalls the disappointment that struck in 2009 when NASA’s Mars rover ‘Spirit’ became stuck in a sand trap on the surface of the Red Planet.
“We spent 10 years making that rover,” Dabby says. “What if you could make materials that could reconfigure themselves to get out of that hole, or a cell-phone screen that could repair itself when you drop it? By looking at biology and applying it to nanotechnology, we’re verging on some really cool stuff.”