• Microsystems   A mini-submarine to fight cancer?

A mini-submarine to fight cancer?

No scientist really believes in nanorobots that can swim around and perform surgery anywhere in the human body. However, micro-robots that could help perform tasks in the human body are slowly entering the realm of possibility.
At present, the only way to perform minimally invasive procedures in the body is by using an endoscope. Endoscopy is versatile, reliable and functionally expandable. In 2001 the Federal Food and Drug Administration (FDA) licensed the PillCam, the first swallowable capsule endoscope produced by the Israeli company Given Imaging that is fitted with a camera. “The PillCam is already in its seventh generation,” reports Homi Shamir, CEO of Given Imaging. The latest system is optimised for colon and oesophagus examination in particular. “We are currently looking into the possibilities of a remote-controlled capsule,” says Homi Shamir. The endoscope developed by Siemens Healthcare and Olympus Medical System is also grappling with the problem of autonomous navigation.
In 2008, Philips developed a system for targeted drug dispensing, which enables doctors to achieve more with a lower dose of active ingredient, and reduces side effects. The IntelliCap is swallowed and carried by peristalsis to the stomach and colon, continuously measuring the pH value of its environment in the process. This value is highest in the stomach and then decreases. Based on measured pH values and basic knowledge of the average speed of movement, the smart pill pinpoints its current location to within a few centimetres. A microelectronically controlled pump then releases a drug at the target site in the required dosage and manner. In addition to the pH value, it can also measure temperature and transmit it wirelessly to an external database, thereby combining both diagnostics and therapy. Matthew Harris of Philips Research: “The smart pill is regularly used by pharma companies for research purposes.”

The human body’s network of fluid-filled vessels provides the answer to this problem. Virtually every organ can be reached via these pathways, so there is a realistic possibility that one day micro-robots will be able to swim to the required locations.
Thus far, research groups have been mainly working with magnetic fields. Firstly, a magnetic micro-robot can move relatively precisely through the body using a magnetic field, and secondly a current can be induced in the robot via the magnetic field, enabling it to carry on moving. Another option for fuelling the micro-robot is so-called energy harvesting. It has already been shown that heart pacemakers can operate using energy obtained from the blood temperature or the pulse.

A gift from mother nature
The most progress in this area, not only on the drive mechanism, has been made by the group headed by Prof. Sylvain Martel of the École Polytechnique in Montreal: “Mother Nature has done a good job, so we work with what she has given us.” Taking a bacterium that already incorporates an efficient flagellum drive, the scientist used magnetic nanoparticles to turn it into a magnetotactile bacterium (MTB). This type of bacteria is harmless to humans and does not divide in the human body. “Unfortunately, bacteria are temperature-sensitive,” says Prof. Martel. The advantage is that they can be produced in large numbers relatively easily. This bacterium is controlled externally via the magnetic fields of an MRI, which also simultaneously monitors the MTBs.
In Montreal the delivery of active ingredients to the body can already be controlled. The team glued biodegradable polymer particles, about 150 nm in size and loaded with an active ingredient, to these MTBs.

Prof. Bradley Nelson and his team at the ETH Zurich have developed artificial bacteria. Here again the micro-robots are moved using the magnetic gradients of an external magnetic field. “I can imagine that one of the first application areas will be the eye, because here the micro-robot can be monitored externally using a video camera, and access is easy and creates fewer technical problems.” The artificial ABF (Artificial Bacteria Flagella) has a flagellum made of indium, gallium, arsenic and chrome. The head of the artificial bacterium is made of magnetic nickel, among other things. The ABF can swim and rotate in all directions at 20 µm/s. “I estimate that speeds in excess of 100 µm/s should be possible,” says Bradley Nelson confidently. Polystyrene microbeads have already been transported successfully.
Prof. Christian Karnutsch of Karlsruhe University wants to develop micro-robots for use in cancer therapy. “Nautilos” for example will one day seek out and destroy cancer cells and viruses in the human bloodstream. “To do this, Nautilos needs to combine three components no bigger than 0.5 mm: the drive and communication train, the diagnostic system and the therapeutic system,” says Christian Karnutsch. “Drive and communication concepts already exist.” However, these systems are still much too large. 

The micro-robot on a human hair. Source: ETHZ

Capillary effects will draw the blood into the Nautilos, where the diagnostic unit equipped with antibodies of the most common types of cancer will be located in its micro-laboratory. The cancer cells bind themselves to the corresponding antibodies and the result is measured by sensor. The problem remains how to get rid of the cancer cells in order to reset the system to zero. The power will be produced using energy harvesting.
ARES, a completed EU project, developed actuators based on shape memory alloys. The acronym ARES stands for Assembling Reconfigurable Endoluminal Surgical Robots, in other words, the creation of a modular robot from swallowable parts that coalesce in the stomach itself for the purpose of diagnosis and microsurgery. Demonstrators have been tested in an artificial stomach.
In the follow-up project, ARAKNES (Array of Robots Augmenting the KINematics of Endoluminal Surgery), the partners plan to develop usable systems.

Unlike ARES, which was a purely scientific project, several firms are also involved: Italian company MicroTech and German companies KARL STORZ Microelectronics and novineon Healthcare Technology Partners.
novineon is already contributing its experience from the recently completed Vector project, in which endoscope capsules are actively controlled by the doctor. “An external, robot-controlled magnet guides the capsule,” explains Prof. Marc Schurr, Managing Director of novineon. “There will certainly be further research projects, as the market potential is huge.”
“In the Neuroboid collaborative project we are trying to develop an intelligent, multi-functional endoscope. A preliminary study by BMBF is already underway,” says Dr. Cleopatra Charalampaki, Senior Physician at Graz University Clinic. The operation microsystem will one day record and remove brain tumours at cellular level. The module under development will provide 1,000x magnification, enabling clusters to be identified. In addition to optical measuring procedures, the module will also be able to analyse spectroscopically and haptically, assisted by a database. “The tissue will be removed by laser, and the lower the number of tumour cells remaining, the better the chances for the patient’s long-term survival,” explains Charalampaki. The system is controlled by micro-robotic manipulators. Cleopatra Charalampaki is the project’s medical coordinator, while Siemens is acting as technical and administrative coordinator. A further 17 partners from research and industry are also involved in the project.
Closest to the ‘market’ are the teams headed by Sylvain Martel and Cleopatra Charalampaki, since Martel has already tested the procedure on live animals and Charalampaki has worked with patients’ tumour material. Bradley Nelson anticipates clinical trials in eye treatment within three to eight years, while the expected timeframe for the Neuroboid project is four to five years.
Dr. Barbara Stumpp

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German Summary
An Nanoroboter, die irgendwann im menschlichen Körper herumschwimmen und chirurgische Aufgaben erledigen, glaubt eigentlich kein Wissenschaftler. Aber Mikroroboter, die hilfreich im menschlichen Körper agieren könnten, rücken langsam in den Bereich des Absehbaren. Der deutschsparchige Beitrag ist nachzulesen unter www.meditec-international.com/medi0611micro