Posted in | Medical Robotics

Tiny Robots Designed to Propel Through Biological Fluids Using Ultrasound or Enzymatic Reaction

An enzyme-propelled nanorobot: urease-coated nanotubes turn into a propulsion system in a urea-containing liquid because the enzyme breaks down the urea into gaseous products. Since the tubes always have small asymmetries, the reaction products generate a current in the fluid which propels them out of the tube like a jet. (Credit : � MPI for Intelligent Systems)

Researchers anticipate that one day nanorobots and other mini-vehicles might be capable of performing vital services in medicine – for instance, by transporting pharmaceutical agents to a preferred location in the body or by conducting remotely-controlled operations.

However, so far it has been difficult to guide such micro- and nanoswimmers precisely through biological fluids such as synovial fluid, blood, or the inside of the eyeball. A team of scientists at the Max Planck Institute for Intelligent Systems in Stuttgart have proposed two new techniques to construct propulsion systems for miniature floating bodies.

With one motor, the propulsion is produced by bubbles which are made to move back and forth using ultrasound. With the other, a current generated by the product of an enzymatic reaction pushes a nanoswimmer forward.

Jet aircraft have shown the way. They burn fuel, expel the combustion products in one direction and consequently propel in the opposite direction. The team at the Max Planck Institute for Intelligent Systems in Stuttgart does it in a very similar manner - although on a much smaller scale.

The underwater-nanorobot created by them is a single-walled nanotube composed of silicon dioxide, and measuring just 220 nm in diameter. A particle of that nature would not typically be able to push itself forward in fluids. The scientists coated either only the inner or the inner and the outer surface of the nanotube with the enzyme urease which splits up urea into carbon dioxide and ammonia.

When a nanotube prepared in this fashion is launched into a fluid containing urea, the urea is broken down at the urease-coated internal wall. The reaction products produce a current in the fluid which pushes them out of the tube like a jet.

As such a nanoswimmer either is thinner at one end than at the other, or the urea is not spread evenly over its surface, this causes a thrust, so that the micro-swimmer experiences momentum in the opposite direction – as in a jet aeroplane. The nanojets clocked speeds of 10 μm/second i.e. nearly 4 cm/hour.

The Smallest Jet Engine in the World

The concept of coating a nanorobot to realize a chemical drive is not new. However, the tube currently showcased, with its 220 nm opening, represents the tiniest jet propulsion system ever to be built in the world.

Our previous record, which is still in the Guinness Book of Records, was around three-times bigger.

Samual Sanchez, Max Planck Institute for Intelligent Systems

Sanchez leads the Smart NanoBioDevices Group at the Max Planck Institute for Intelligent Systems in Stuttgart and also holds a professorship at the Institute for Bioengineering of Catalonia in Barcelona.

There is another new feature of the nanojet that researchers from the Harbin Institute of Technology in Shenzhen in China also assisted in developing - for the first time, all the materials and reaction additives used are 100% biocompatible.

"Previous chemical drives of this kind were usually based on a metallic catalyst at the surface of which hydrogen peroxide was broken down into hydrogen and oxygen molecules", says Sanchez.

Oxygen bubbles are produced in the process, which generates a push in the opposite direction. Both the gas bubbles and the hydrogen peroxide would have shortcomings if used in the human body. But this is not so with the urease-coated model having its water-soluble – and as a result bubble-free – reaction products. "Urease occurs anyway in the human organism", Sanchez explains.

The researchers at present are keen on testing the biocompatibility more precisely – and in the process test whether they can be successful in implanting such micro-tubes into a single cell.

That would be necessary, of course, in order to bring drug molecules to their destination, for example.

Samual Sanchez, Max Planck Institute for Intelligent Systems

Oscillating Bubbles Provide Thrust

Although gas bubbles were redundant in the technique specified, they form the very core of a totally new theory of propulsion for minirobos, which colleagues at the Institute in the Micro, Nano and Molecular Systems Group led by Peer Fischer suggest. However, in this approach the gas bubbles are not bubbling freely via the fluid and thus cannot harm the organism.

Instead, the researchers surround the micro-bubbles in small cylindrical chambers along a plastic strip. In order to provide the drive, the gas bubbles are made to expand and contract intermittently using ultrasound which makes them to oscillate. Since the pulsating bubbles are in chambers open only on one side, they only expand via this opening.

In this manner, they apply a force on the opposite wall of the chamber which pushes the plastic strip. To attain reasonable amount of propulsion, the team set up many chambers with air bubbles in parallel on their polymer strip.

A striking feature: the sound wave frequency needed to cause them to oscillate relied upon the size of the minute bubbles - the larger the bubbles, the smaller the equivalent resonant frequency. The research team used this connection to make their swimmer turn alternately clockwise and anti-clockwise.

To achieve that, they placed bubbles of varying sizes on the two halves of the four, long cuboid faces split lengthwise. Two different sound frequencies were then applied to a liquid to each cause all the bubbles of a certain size to oscillate. In this manner, the researchers created propulsion exclusively on one-half of the cuboid face which made it to rotate on its own axis.

This small acoustically driven rotation motor having longitudinal areas each measuring 5 mm2 in size realized up to a thousand rotations per minute in the process.

One Possibility for Steering Mini-Swimmers

"The variation in the size of the bubbles thereby enables a mini-swimmer to deliberately steer in different directions", says Tian Qiu, who also undertakes research at the Max Planck Institute in Stuttgart and played a substantial role in this study.

According to Qiu, an additional advantage of the new principle of propulsion is that even swimmers with a complex geometric structure can be coated with the wafer-thin strips along with chambers for the bubbles.

He adds that the use of ultrasound is also appropriate for optically impenetrable media such as blood. Light waves, which are also a probable control instrument for micro-drives, cannot accomplish much in this case. Going forward, the team plans to use tests in real biological media to verify whether the new drive principle is also capable of making the most of its advantages in real world situations.

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