AI News, Magnetic Microbots to Fight Cancer

Magnetic Microbots to Fight Cancer

Late one crisp October night in 2006, a hospital technician in Montreal slid the limp body of an anesthetized pig into the tube of a magnetic resonance imaging machine, or MRI.

On a computer screen, the bead appeared as a square white tracking icon perched on the gray, wormlike image of the scanned artery.

The microrobots would be able to travel deep inside the body, cruising our tiniest blood vessels to places that catheters can’t go and performing tasks that would be impossible without invasive procedures.

To make matters worse, today’s manufacturing techniques can’t build a motor and power source small enough to squeeze inside the capillaries—delicate vessels just a few micrometers thick—that feed a tumor.

We have designed magnetic drug carriers as small as 50 micrometers that we can steer, like the metal bead inside the pig, through large arteries and arterioles using an MRI machine.

Storytellers and scientists alike have long dreamed of miniature robots that can roam the human body, sniffing out disease and repairing organs.

You may recall the old science fiction flick Fantastic Voyage (1966), in which a submarine and its crew are shrunk to the size of a microbe and sent into the bloodstream of an eminent scientist to destroy a blood clot in his brain.

In a classic 1959 speech, he described a friend’s “wild idea” that “it would be very interesting in surgery if you could swallow the surgeon.” As Feynman’s friend imagined it, a little mechanical surgeon marches through the bloodstream to the heart and surveys its surroundings.

But while the PillCam is great at inspecting the large, easily accessible cavities of the digestive system, it’s much too big to travel elsewhere in the body.

A true medical microbot must propel and steer itself through an intricate network of fluid-filled tubes to tissues deep inside the body.

You might think that an obvious way to accomplish this task is to equip the robot with metallic particles and guide it with a magnet from outside the body.

The bulk of the machine is a powerful, doughnut-shaped superconducting magnet that generates a magnetic field up to about 60 000 times as strong as Earth’s.

The density of signals gives information about the molecular makeup of bodily tissues—distinguishing bone from blood, white matter from gray matter, tumors from healthy tissue.

Sandwiched between the main magnet and the RF coil, the gradient coils generate a magnetic field that makes the main field stronger in some places and weaker in others.

This variation changes the frequency of the protons’ signals depending on their location in the field, which allows a computer to calculate their location in the body.

The pig experiment proved the concept, but a naked 1.5-millimeter metal bead isn’t much use for transporting drugs inside the microvasculature of the human body.

To make a real medical microbot, we started with iron cobalt nanoparticles, which are more sensitive to magnetic forces than other nontoxic metal alloys.

We coated the nanoparticles in graphite to keep them from oxidizing, and then we encased them, along with molecules of the cancer drug doxorubicin, in a biodegradable polymer sac.

But that’s the limit: Propelling even tinier robots would require gradients so strong that the huge jolt of current needed to quickly fire up the coils would begin to disturb cells in the body’s central nervous system.

A distinguishable black smudge in one lobe of the liver proved that the tiny soldiers had shot through the artery, made a sharp turn at a bifurcation, and then congregated at the last waypoint.

Microcarriers may be ideal for targeting liver cancers in humans because the vessel branches that lead to the liver’s lobes are quite large—about 150 µm or wider.

But to reach tumors hidden behind networks of smaller capillaries, such as in the breast or the colon, we need microbots no thicker than a couple of micrometers.

It also has a pair of spinning, whiplike tails powered by molecular “rotary motors” that rocket it through water at speeds up to 150 times its body length per second.

Though it’s unclear what advantage this gives them, they perform the trick with a chain of iron oxide nanocrystals called magnetosomes that behave like a compass needle.

We do this with specially designed electromagnetic coils that, in addition to being less powerful than an MRI machine, allow us to orient the field by varying the amount of current passing through each coil.

When deployed in the body, they could be navigated using an MRI machine through large blood vessels, similarly to microcarriers, until narrower vessels block their path.

In my laboratory, we have already started to investigate ways of exploiting the energy properties of magnetic microbots to temporarily open up the blood-brain barrier and access tumors in the brain.

Biomedicine: Tiny medical robots are being developed that could perform surgery inside patients with greater precision than existing methods

IN THE 1966 film “Fantastic Voyage”, a submarine carrying a team of scientists is shrunk to the size of a microbe and injected into a dying man.

For decades, scientists and fiction writers alike have been fascinated by the possibility of tiny machines that can enter a patient, travel to otherwise inaccessible regions, and then diagnose or repair problems with far less pain and with far greater precision than existing medical procedures.

More recently proponents of nanotechnology have imagined swarms of “nanobots”—tiny machines just billionths of a metre, or nanometres, across—that might fix mutations in a person's DNA or kill off cancer cells before they have a chance to develop into a tumour.

In addition, researchers are developing micro-robots, with dimensions measured in millimetres or micrometres (a human hair is around 100 micrometres in diameter), which should be able to reach more delicate areas, such as the inside of the eyes or the bloodstream.

Although the Pillcam is technically not a robot—it is a passive device that relies on the body's regular peristaltic contractions to propel it through the intestine—its success opened up the field, says Paolo Dario, a professor of biomedical robotics at Scuola Superiore Sant'Anna in Pisa, Italy.

Instead of adding a power source to the device, which increases its weight and bulk, one approach is to apply external magnetic fields to a small robotic device that contains magnetic material, allowing it to be steered simply by controlling the magnetic fields around it.

In addition, micro-robots could deliver drugs directly to veins inside the retina that have become obstructed by clots, a condition that can cause blindness and for which there is at present no reliable cure.

All of this is possible because an MRI machine contains both a large magnet that creates a strong magnetic field, and also a set of gradient coils that superimpose weaker but adjustable fields upon it.

These coils are normally used to select slices for creating three-dimensional images, but the magnetic fields they create can also be used to exert a force on a small magnetic object inside a scanner.

And the fields produced by gradient coils in a conventional MRI machine are not strong enough to pull on particles below about 250 micrometres in size, says Dr Martel, though an upgraded MRI system with more powerful coils could propel beads as small as 50 micrometres, he adds.

Because they are so tiny (only about two micrometres across), they are not strong enough to swim against the blood flow of larger vessels, though they are able to swim through vessels as little as four micrometres in diameter.

Dr Martel's idea is to use the larger magnetic beads to transport the bacteria close to a tumour, and then release them and coax them, using applied magnetic fields, to swim to the tumour and deliver a therapeutic payload.

Successful steering of the bacteria will be the subject of further tests, says Dr Sitti, but could be done via chemotaxis—a process by which small organisms follow gradients in the concentration of a particular chemical in order to find food or escape from toxic substances.

Dr Dario says medicine is “at the beginning of a new era” as open-wound surgery gives way first to minimally invasive techniques, and then to procedures that will be completely concealed and leave no visible scars.

Therapeutic robots may soon swim within the body

Imagine a microscopic machine that could swim through a person’s blood vessels on its way to delivering medicine to a cancerous tumor.

Or one that unclogs an artery to prevent a heart attack, or even performs delicate vision-saving surgery from inside the eye.

Blood, spinal fluid and other liquids make up about 60 to 65 percent of the volume of the human body.

But finding the right materials and designs to send robots swimming through even the tiniest blood vessels has proven tough.

“Microrobots can go places that larger robots can’t.” What’s more, he argues, “they can handle tools with finer precision.” Humans don’t have much experience moving things around micro-environments of the body, explains Bradley Nelson.

Before scientists could create robots to swim inside the body, they first had to solve the problem of scale.

The physics of swimming changes as an object gets smaller and smaller, Nelson observes.

(Viscosity is the thickness of a liquid.) “If you were to shrink down to the size of a [microrobot] and jump into a pool of water,” says Nelson, 'the water wouldn’t feel like water anymore.

That’s why he and other scientists have copied some of nature’s tiniest swimmers: single-celled lifeforms that infect people.

By altering the gel’s temperature, he can make his robot short and stumpy or long and needle-like.

These robots are too small to carry an engine or battery pack, notes Min Jun Kim, who led the Drexel team.

(He now works at Southern Methodist University in Dallas, Texas.) Mechanical engineers use rules of motion, energy and force to design and build machinery.

He used magnets to propel his microrobot through artificial blood vessels in a petri dish.

To treat cancer, a microswimmer that’s a longer chain could bore into a thick tumor.

He studies nanotechnology — the design and harnessing of extremely small devices — at the Chinese University of Hong Kong.

Working with robots in a real body — whether a human or a mouse — is a lot different than doing it in a petri dish under a microscope, Li explains.

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