Charting a course within the body

Dr. Sylvain Martel Each of us has around 100,000 kilometers of blood vessels that reach all of the organs and tissues keeping us alive. Whenever we take drugs, this vast network sees to it that the medicine makes it to all parts of the body. Chemotherapy agents tackle cancerous tumors, but these highly toxic materials also make their way everywhere else, weakening and often sickening patients. In such cases we would be better off with a vehicle that could navigate the body’s elaborate highway system, delivering treatment only to the affected area.

Sylvain Martel wanted to build that vehicle, and he has spent the last decade studying how to do so. His efforts have led to significant research results, including successful demonstration of how to modify the control functions of a magnetic resonance imaging (MRI) scanner so this device can provide imagery and guided therapy.

His work began at the Massachusetts Institute of Technology, where he helped create a miniature instrumented robot that walked on three legs at 4,000 nano-steps per second. Now, as an engineering professor at Polytechnique Montréal, he is outfitting bacteria with molecular motors so that they can maneuver directly to a particular part of the body. Acting as carriers for medication, these bacteria will move only to a specific destination like a tumor, rather than going anywhere else.

These microscopic vessels rely on electronic guidance to manipulate and detect pathogens. The initial idea was validated using several microchips fabricated in CMOS, Micragem, and Protolyne technologies with the support of CMC Microsystems. Martel has adapted it to work in conjunction with the MRI systems that are commonly used to see what is happening inside a patient.

Martel had wanted to continue work on the MIT NanoWalker when he established his own laboratory in Montreal. However, he found more support for the development of molecule-size mechanisms that could offer an unprecedented range of medical applications. While he could see the possibilities of using the MRI scanner’s magnetic field to guide probes within the body, the manufacturers of these machines do not readily share the engineering details about how these machines function.

Martel credits the research infrastructure network supported by CMC with his team’s ability to take on a multi-disciplinary array of challenges, in areas as diverse as electrical and computer engineering, mechatronics, biochemistry, biology, and physiology. “The network was instrumental in helping us move into each of these fields,” he says.

This integration of skills is reflected in the equally diverse team of graduate students that Martel has assembled to explore the inner workings of the MRI equipment and determine how it could be altered so users could manipulate tiny objects within the body. The researchers then began to map the limits of magnetic gradient strengths that could be maintained around the capillaries leading into a tumor. This restriction led to the use of MC-1 Magnetotactic Bacteria (MTB) to transport drugs towards tumors.

“Although most people would see it as a simple living organism,” he explained in an article for the International Journal of Robotics Research, “from an engineering point of view, this bacterium can be considered as a sophisticated actuator with an embedded control interface.”

Key parts of this interface are the superparamagnetic particles, known as magnetosomes, which are no larger than 50-100 microns in diameter. They play the crucial role of navigation compass for the MTB, which are driven by the long tendrils called flagella that bacteria normally use to move around.

This MTB motor, which can run between 200 and 1,000 rpm, is composed of proteins and draws power from a flow of protons. With two flagella bundles for each bacterium, a thrust force of four piconewtons can be realized, about an order of magnitude larger than the value many species of bacteria usually generate. This force likewise makes it possible for the MTB to achieve speeds of 200 microns/second, again almost 10 times more than other typical bacterium could achieve.

Martel recalls a great deal of skepticism greeting this undertaking. “We knew that it would work, but it took two years to convince people before starting the project.”

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