THANKS to Hollywood, we already know how to navigate our way around the nanoworld. As they tell it in the movies, all you need to do is board a submarine and prepare to be miniaturised. Now that nanotechnology has become a reality, it is tempting to think that Hollywood-style vehicles capable of swimming through a patient鈥檚 bloodstream are just around the corner.
It鈥檚 not all plain sailing, though. Nanotech researchers have been warning for years that the potential benefits of small-scale technology will remain a pipe dream until they overcome some of the basic problems of working at small scales. When it comes to moving through liquids, propulsion, momentum, gravity and many other familiar aspects of the everyday world change almost beyond recognition at the nanoscale.
In fact, conditions are so hostile that materials scientists have had to develop technologies that are a far cry from ordinary vehicles. 鈥淵ou wouldn鈥檛 think about making a railroad train out of something as heavy as lead and trying to move it using electrostatic charges,鈥� says , a materials scientist at the Pennsylvania State University in University Park. 鈥淏ut that鈥檚 exactly the kind of thing we鈥檙e doing at the nanoscale.鈥�
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Now that researchers are starting to make inroads into these problems, the advent of tiny vehicles delivering drugs to specific pathogens within a patient鈥檚 bloodstream doesn鈥檛 seem so far-fetched. Nanoswimmers could be used to clean up the environment too, or sent through solutions to build structures from the bottom up.
When you get down to the micro and nanoscale, viscosity, surface interactions and Brownian motion rule. Forget gliding with ease down a river and imagine instead trying to swim through a pool of thick molasses while someone fires cannonballs at random around you.
The way a body moves through a given fluid is characterised by the ratio of inertial to viscous forces in the moving fluid. The movement of a person swimming through water is mainly impeded by the inertia of the fluid they are moving through. If you were a bacterium, however, the viscosity of water would be the biggest hindrance. 鈥淚t would be like swimming in something a million times more viscous than water,鈥� says , a physicist at the University of Sheffield in the UK.
As well as making things very hard work, large viscous forces make swimming at the nanoscale tricky in another way. You can get a good idea of this by stirring tar and corn syrup a few times to get partial mixing. If you then stir in the opposite direction, you can unmix them. This would be impossible with runnier fluids.
For nanoswimmers, this rules out many of the swimming actions that would work at a larger scale. 鈥淎nything that involves flapping won鈥檛 work,鈥� says Jones. 鈥淚f I waved my arms up and down, for example, I鈥檇 go one way on the upstroke and back again on the downstroke. I鈥檇 just be wriggling around on the spot.鈥�
Many bacteria break this symmetry by moving tail-like filaments called flagella. Some twirl rigid, corkscrew-shaped flagella, while others set up travelling waves that move along the flagella from one end to the other. In 2005, a group led by at the School for Industrial Physics and Chemistry in Paris, France, caused a stir when they first showed that they could reproduce similar travelling waves in artificial microswimmers ().
At around 10 micrometres long, Bibette鈥檚 artifical swimmers were roughly one-fifth the size of spermatozoa. Their bodies were red blood cells and their tails consisted of a chain of magnetic particles glued together by DNA. Using an oscillating magnetic field, the researchers induced travelling waves that enabled the swimmers to race along at around 6 or 7 micrometres per second. They could also steer them by varying the orientation of the magnetic field.
The big drawback of this approach, however, is that the motion depends entirely on the external magnetic field, so the swimmers all have to move in the same direction. 鈥淚t would be nice to have swimmers that could move independently,鈥� says R茅mi Dreyfus, who worked on the project before moving to New York University, 鈥渂ut I don鈥檛 think we can do that with our system.鈥�
A much better idea would be an autonomous engine that can harness the chemical energy in its surroundings. Enter Jones and his colleague Ramin Golestanian. In July, their team published details of an experimental system that can do just that ().
The researchers took polystyrene balls about 1 micrometre wide and coated one hemisphere with a platinum catalyst. They then dunked the balls in a weak solution of hydrogen peroxide, which the platinum breaks down to form oxygen and water. The reaction produces more molecules than it consumes, so the platinum-coated side of the sphere is bombarded more heavily than the uncoated side. 鈥淲ithout the reaction the sphere wiggles around but it doesn鈥檛 go anywhere because on average it has got the same number of particles hitting it on every side,鈥� says Jones. 鈥淲e鈥檙e breaking that symmetry by creating more collisions on one side than the other, and that鈥檚 pushing the sphere along.鈥�
Though their microswimmers are also buffeted at random by molecules, Jones and Golestanian found that they spread through a solution 30 times faster than they would by diffusion. It鈥檚 a promising start, but the spheres still swim around uncontrollably.
Sniffing swimmers
Other groups have suggested ways around this problem. Working with chemist Thomas Fischer of Florida State University in Tallahassee, Mallouk and his colleague Ayusman Sen can control the movement of magnetic nanorods. They use a series of magnetic stripes on the surface of a garnet film to direct the rods in two dimensions. That鈥檚 fine for some lab-on-a-chip applications, but not for a fantastic voyage through the bloodstream.
A more promising approach to getting swimmers moving in three dimensions is a chemical guidance system. The idea is for nanomachines to 鈥渟niff鈥� their way up or down a chemical gradient. Mallouk and Sen鈥檚 group has just succeeded in demonstrating it for the first time in a non-biological system by persuading nanorods made from gold and platinum to swim towards a source of hydrogen peroxide. Electrochemical reactions at the gold and plantinum ends of the rods cause electrons to flow through the metal, which attracts hydrogen ions in the solution to move along the outside of the rods. This creates enough force to pull the rods along, with the rods moving faster as the concentration of hydrogen peroxide increases.
Moving in one direction is still tricky for a very small swimmer, however, because the Brownian motion of surrounding molecules continually knocks them off course. Nanorods overcome this using the same approach as bacteria. The rods and bacteria set off in a random direction and travel for roughly the same distance between collisions. If they happen to be heading towards the fuel source, however, the reaction speeds up so they accelerate and go further before the next knock, gradually meandering towards their goal.
Importantly, this random walk approach could work with any chemical that affects the rate of reaction. And just as well. Hydrogen peroxide is a no good as a fuel for many potential applications. You couldn鈥檛 use it in someone鈥檚 bloodstream, for example.
Even though catalytic engines can work in principle, Brownian motion becomes a bigger issue the smaller you go, so what works for microscale bacteria might not work well for objects a thousand times smaller. This might place an ultimate limit on the ability to steer freely. 鈥淔lagellum-driven bacteria are the smallest free motors in nature,鈥� says Sen. 鈥淓verything smaller is on a track or in a membrane. That鈥檚 a good lesson for us.鈥� Even if all goes according to plan, the first fantastic voyage through the body could prove a far bumpier ride than Hollywood imagined.
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