Squishy Clockwork Biobot Could Dose You With Drugs From the Inside

Photo: Sau Yin Chin. Soft and 3D-printed micromachines can be implanted in the body to deliver doses of a chemo drug.

When Swiss watchmakers invented the Geneva drive, a two-geared mechanism that produces precise ticks forward, they probably never imagined that bioengineers would one day craft a 15-millimeter version out of squishy hydrogel. But then, they weren’t trying to make a biocompatible micromachine that could be implanted in the body to deliver doses of drugs.

This strange new biobot comes from the lab of Samuel Sia, a professor of biomedical engineering at Columbia University, in New York City. It uses neither battery nor wires, and can be controlled from outside the body to deliver a dose on command. It’s a gadget well suited for this new era of personalized medicine, Sia tells IEEE Spectrum. “Doctors want to see how the patient is doing and then modify the therapy accordingly,” he says.

He has already tested the gizmo in lab mice with bone cancer, with exciting results that were published today in the journal Science Robotics. More on that experiment later.

Photos: Sau Yin Chin The researchers constructed their Geneva device layer by layer, in a process that took about 30 minutes.

Sia’s team first had to invent a type of 3D printing to fabricate their tiny Geneva drive and several other soft micromachines. They came up with a fabricator that lays down layers of a hydrogel to produce rubbery solid shapes. While human hands are required to put the pieces together, Sia says those assembly steps could be automated. And it’s pretty quick, as is: The whole process of printing and assembling one Geneva drive takes less than 30 minutes. Today’s typical 3D printers would take several hours to construct a similar device, Sia says, and most can’t handle soft materials like hydrogel.

Here’s the part that runs like clockwork! The squishy Geneva drive clicks forward when an external magnet moves a simple gear, which is just a rubbery piece with embedded iron nanoparticles (the black curved piece in the video below). With each click, one of six chambers lines up with a hole and a dose of medicine flows out. In the video, a magnet (the silver disk) keeps the device running continuously to demonstrate the mechanism, but in clinical use, a doctor could apply a magnet only when a dose is required.

You may be wondering: Could someone’s implanted micromachine be triggered accidentally by an external magnet or by a malicious person with fiendish magnetic powers? In other words, is the X-Men’s Magneto a risk factor? “Somebody walking by with a magnet won’t trigger it, but there are some cases where it’s not ideal,” Sia says. His lab is working on other ways to wirelessly drive the mechanism, including an ultrasound technique.

The hardest part of the design process was getting the material right, Sia says. Very flexible and soft materials are compatible with the body’s soft innards, unlike rigid silicon or metal devices. “But if your material is collapsing like jello, it’s hard to make robots out of it,” he says. “It has to be stiff enough to work like a tiny implantable machine.”

Image: Sau Yin Chin The pieces of the Geneva device were each printed in soft hydrogel.

The next step was in vivo.
Sia’s team wanted to see if their devices would work inside the body, with all the complications of chemistry and anatomy. Some mice with bone cancer received implanted devices that were loaded up with a chemo drug; other mice received typical chemotherapy, which floods the whole body with a toxic drug. When the team compared the effects of the device’s localized and periodic delivery of the drug to those of the typical treatment, the results were impressive. The bionic mice’s tumors grew slower, more tumor cells died off, and fewer cells elsewhere in the body suffered peripheral damage.

Photos: Sau Yin Chin Fluorescent imaging shows a chemo-delivering device inside a lab mouse.

The clinical possibilities seem obvious—oncologists could deliver more targeted and concentrated doses of powerful chemo drugs, and Sia imagines other uses, like regulating the release of hormones. But the drug delivery device is really just a proof of concept, he says. He’s not rushing out to form a startup: “We have to do the cost-benefit analysis to see if this is really a commercializable device,” he says.

He is bullish, however, on the medical potential of tiny squishy robots in general. Soft and mobile little bots could one day act as internal repair crews, doing a doctor’s work from the inside. (For more on this, check out IEEE Spectrum’s article on medical microbots.) Sia says his fabrication platform is capable of turning out a wide variety of devices. “I’m confident that we’ll find something useful,” he says.

Sia won’t say exactly what types of devices his lab is now experimenting with, except to say that they’re looking at implanted devices that move. Here’s my guess: It’s a tiny squishy micromachine that resembles a cuckoo clock.

ORIGINAL: IEEE Spectrum
By Eliza Strickland
4 Jan 2017