Implanting Fully Working Microbots in Humans

While the mention of additive manufacturing typically brings to mind all the work being done with 3D printing, there are breakthroughs in the biomedical field in additive manufacturing that do not involve conventional 3D printers.

After eight years of research, overcoming one challenge after another, a team of researchers led by Sam Sia, professor of biomedical engineering at Columbia Engineering, has developed a way to manufacture microscale-size machines, or what is a Geneva device essentially. And they manufactured these devices, or microrobots, solely from biomaterials that have freely moving parts and can be safely implanted in the body and activated wirelessly.

The team figured out a way to layer hydrogels, a soft, biocompatible material that over the past half century has been studied extensively. They have subsequently been used not only in the medical field but in a variety of other fields from agriculture to cosmetics.

Fabrication and complete assembly of a Geneva drive or microrobot. (Left) Layer-by-layer fabrication of support structures and assembly of gear components. (Right) Complete device after layers have been sealed. Image: Sau Yin Chin/Columbia Engineering.

“We think this opens the door to another whole new class of implantable devices, namely, you can think about making small devices out of biological materials, not made of metal or silicon, so that they are biocompatible,” Sia said. “You don’t need a battery on board because we move the components wirelessly, in this case using magnetism. We’re really excited about this because we’ve been able to connect the world of biomaterials with that of complex, elaborate medical devices.”

Overcoming Obstacles

Although there are various wireless modes of activation of implantable biomedical microelectromechanical systems, most involve electronic components that are not biocompatible, according to the researchers in a published study of their work. The paper, whose lead author Sau Yin Chin worked with Sia, described the innovative manufacturing technique in the online journal Science Robotics in January.

The development evolved from Sia’s work in microfabricating biomaterials, which started out in single layers. “So being able to do that in three dimensions and to form complex, intricate patterns layered on top of each other and layer them in alignment gave us the ability to do things we couldn’t do before, such as making three-dimensional devices. You definitely can’t do that with one layer,” Sia said.

But it wasn’t easy, and it wasn’t quick. “It seemed like we worked on this for a long time,” Sia acknowledged. “There were always challenges. But we ended up knocking them over one by one. Overall, it was a lot of little things that we had to overcome to come up with a platform that was rapid and robust.”

Some of the key challenges were figuring out how to power small robotic devices without using toxic batteries; how to make small, biocompatible moveable components that were not silicon, which has limited biocompatibility; and how to communicate wirelessly once the devices are implanted.

For instance, the biological materials are soft and squishy, not like metal or silicon. So traditional materials processing techniques can’t be used. “You won’t be able to form the solid structures like that so we had to overcome that and do it in a way where we were able to achieve the properties of mechanical devices,” Sia explained. “We came up with a mechanism where we still use materials that are stiff enough but we actually use the squishiness to our advantage because they actually can bend.”

Then the team developed a simple yet flexible and rapid setup for assembling layers of polymerized hydrogels, and each layer could contain different biomaterial compositions and device components. Although some researchers working in the field use 3D printers to print biomaterials, the team felt there were too many limitations with that approach. “Here we use photo patterning,” Sia said. An entire layer patterned using light is exposed through a mask, and then the layers are precisely aligned and stacked one on top of the other.

“We came up with some tricks like that in order to get a device out of this soft material,” Sia said, adding, “We had a lot of challenges like that and that’s why it took us a long time but we ended up getting this to work.”

The team demonstrated that this fabrication strategy can be used to generate components and structures typically found in mechanical systems, such as a simple gate valve component, gated linear manifold device, a spinning toothed rotor, and a spinning gear with multiple reservoirs. This means that the manufacturing platform has a number of potential implantable applications, including precision drug delivery, stents, and other larger devices from catheters to cardiac pacemakers.

In collaboration with a surgeon/medical researcher, the team tested one application, the drug delivery system, on mice with bone cancer and found that tumor growth was limited when the cancer drug was delivered adjacent to the cancer, and less toxicity was found compared to chemotherapy administered throughout the body.

Sia said whether there is value in using the new manufacturing technique for various applications will need to be explored application by application, taking into consideration other factors such as economics and safety. “In a vacuum, there are are definitely advantages that such a device would provide [but] it’s one thing to do a proof of concept. What we were trying to do was to come up with a platform that at least will allow you to start thinking about those possibilities. Over time, it will be less about whether or not one can do it. It will be more about options and choosing the methodology where the cost and any safety concerns are justified by the incredible value such a device would provide.”

Nancy Giges is an independent writer.