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

Scientists have figured out how to make their own molecules from scratch

ETH Zurich/Lucio Isa

And the possibilities are huge.
A new technique for making artificial molecules in the lab has been developed by researchers in Switzerland, and it opens up the possibility of new micro-robots and other microscopic structures being produced for a specific task - such as delivering medicine into targeted areas in the body - in a way that closely mimics the body's natural processes.

"So far, no scientist has succeeded in fully controlling the sequence of individual components when producing artificial molecules on the micro-scale," said lead researcher, Lucio Isa from ETH Zurich.

The process to create these artificial molecules starts with microspheres made of polymer or silica - 1 micrometre in diameter - which are placed side-by-side in tiny indentations and engraved in polymer templates. The indentations set the form of the finished object and heat is then used to bond the spheres together.

The team says this new procedure is more effective than other micro-3D printing technologies because it enables scientists to build single micro-structures from multiple materials. This means they can arrange artificial molecules in the sequence and with the geometry of their choosing.

It also enables them to precisely define magnetic, non-magnetic, and differently charged areas. Small rods, tiny triangles, and basic 3D objects can be created, though the research team wants to expand the capabilities of the process further.

The researchers say the practical benefits of the process could range from

• self-propelled micro-carriers that move in an external electric field and micro-mixers for lab-on-a-chip applications, to (eventually) 
• micro-robots for biomedical applications which are able to grab, transport, and release other specific micro-objects.

They also think their new technique could be used to assemble larger 'superstructures' for use in areas such as photonics (light-based signal processing).

Thanks to the level of control the team has managed to develop, the process is extremely versatile. "In principle, our method can be adapted to any material, even metals," said Isa.

"The full programmability of our approach opens up new directions not only for assembling and studying complex materials with single-particle-level control but also for fabricating new microscale devices for sensing, patterning, and delivery applications," concludes the study, which has been published in the journal Science Advances.

ORIGINAL: Science Alert
DAVID NIELD
8 APR 2016

“Soft” (and miniaturized) robots. Micro-robots will move like biological organisms

Simulation of euglenid movement. (Credit: SISSA)

Increasingly small robots can carry out their functions even inside the human body. No, this isn't a sci-fi dream. The technology is almost ready. However there is still one condition they must meet to be effective: these devices need to have the same "softness" and flexibility as biological tissues. Share This:

4 This is the opinion of scientists like Antonio De Simone, from SISSA (the International School for Advanced Studies of Trieste) and Marino Arroyo from the Polytechnic University of Catalonia, who have just published a paper in the Journal of the Mechanics and Physics of Solids. Taking inspiration from unicellular water micro-organisms, they studied the locomotion mechanisms of "soft robots." Forget cogwheels, pistons and levers: miniaturized robots of the future will be "soft."

"If I think of the robots of tomorrow, what comes to mind are the tentacles of an octopus or the trunk of an elephant rather than the mechanical arm of a crane or the inner workings of a watch. And if I think of micro-robots then I think of unicellular organisms moving in water. The robots of the future will be increasingly like biological organisms" explains Antonio De Simone. De Simone and his team at SISSA have been studying the movement of euglenids, unicellular aquatic animals, for several years. One of the aims of De Simone's research -- which has recently been awarded a European Research Council Advanced Grant of 1,300,000 euro -- is to transfer the knowledge acquired in euglenids to micro-robotics, a field that represents a promising challenge for the future.

Micro-robots may in fact carry out a number of important functions, for example for human health, by delivering drugs directly to where they are needed, re-opening occluded blood vessels, or helping to close wounds, to name just a few. To do this, these tiny robots will have to be able to move around efficiently.

"Imagine trying to miniaturize a device made up of levers and cogwheels: you can't go below a certain minimal size. Instead, by mimicking biological systems we can go all the way down to cell size, and this is exactly the direction research is taking. We, in particular, are working on movement and studying how certain unicellular organisms with highly efficient locomotion move." In their study, De Simone and Arroyo simulated euglenid species with different shapes and locomotion methods, based chiefly on cell body deformation and swelling, to describe in detail the mechanics and characteristics of the movement obtained. "Our work not only helps to understand the movement mechanism of these unicellular organisms, but it provides a knowledge base to plan the locomotion system of future micro-robots." De Simone and Arroyo's paper has been selected to appear in the special issue of the J. Mech. Phys. Solids. Sources


SISSA


ORIGINAL: Zeit News

December 12, 2013