How Scientists Adapted an Ancient Art Form to Create Nanoscopic Medical Tools

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Holly Greenberg was a 24-year-old graduate student in the mechanical engineering lab at Brigham Young University (BYU) when she stumbled on the idea that folded paper cranes might have any relevance to her work.

Greenberg was interested in compliant mechanisms – that is, objects whose motion comes from bending, folding, and twisting. One of her best friends was an origami prodigy who taught her some basic techniques. “Some people read a lot of papers for grad school. I folded a lot of paper,” Greenberg says.

Colorful T-rex and Venus flytrap figures, along with books of origami patterns, began to populate the laboratory’s shelves. And Greenberg, along with her professors, realized that the ancient art of paper-folding might apply to other realms, including the design of medical instruments and devices.

It was a marriage of art and engineering, a 1,000-year-old practice applied to cutting-edge technology. “Origami artists discovered new ways of doing things that we never would have stumbled on using the methods we’d been using forever,” says Larry Howell, PhD, professor of mechanical engineering and associate academic vice president at BYU.

By the time Greenberg entered the lab in 2010, scientists and engineers across the world were already using origami principles – chiefly, the idea that something large could be folded into a compact shape, then expanded again – in the design of automobile airbags and rocket shields.

Zhong You, PhD, now professor of engineering science at the University of Oxford, had worked on a collapsible heart stent to treat aortic aneurysms, which used origami principles to fold from a 30-mm diameter to a scant 7-9-mm for ease of insertion, then deployed to its full size once inside the aorta.

And Robert J. Lang, PhD, a physicist and world-renowned origami expert, had designed a pouch for medical instruments, using origami to fold a flat material so that sterile surfaces would not come in contact with non-sterile surfaces when it was being used. Lang was consulting with government agencies, private companies and universities, including BYU, on ways to apply origami principles and techniques to a range of projects.

“The thing that origami contributes to medicine as well as other fields is deterministic shape-change,” Lang says, meaning devices that change shape in a specific and intentional way rather than simply crumpling like a shirt stuffed into a drawer. “As origami has become more recognized, part of the engineer’s toolbox, more people working on medical problems have seen it and made that connection: Oh, this could be useful.”

The National Science Foundation caught the buzz and in the early 2010s funded a series of grants related to origami: a day-long workshop on the design of DNA origami, a project on programmable “intelligent” origami, and one, at BYU, on applying origami principles to non-paper materials.

The team at BYU created an origami-style “bellows” that could provide a sterile sheath for the curved arm of an X-ray machine as it was pivoted in different directions. They used origami to design a better-fitting adult diaper that conformed to the body’s curves.

“One of the first patterns we played with was something called the chomper,” says Spencer Magleby, PhD, professor of mechanical engineering at BYU and associate dean of undergraduate education. An origami chomper looks like a beak or mouth; when squeezed from the sides, it opens and closes as if it’s biting.

The same principle could be used to make a tiny instrument for laparoscopic surgery, operated with a cable to pinch closed for insertion, then opened and manipulated once inside the body. The BYU team called it an oriceps (origami-inspired surgical forceps).

At Pennsylvania State University, where Mary Frecker, PhD, directs the Center for Biodevices, her team began working on a device that could be inserted through an endoscope to treat abdominal tumors with radiofrequency ablation – an electrical current that causes tumor cells to vibrate, heat up, and die.

Frecker’s team used origami techniques to make a probe tip composed of tiny needles that could compact for insertion, then fan out like a 3D peacock tail once inside the tumor. They called it the “chimera,” a Greek word referring to a creature composed of incongruous parts.

Such origami-inspired devices have some advantages over traditional instruments: simplicity of design means fewer moving parts and fewer opportunities for bacteria to gather in hinges or joints, as well as lower manufacturing costs.

If medical instruments and stents could be made smaller, the surgeries themselves would be less invasive and disruptive to the body; healing might be faster and less complicated.

“The application [of origami in medicine] has risen in concert with the rise in laparoscopic surgery,” says Lang. “You want to go in through a tiny little hole; once you’re inside, you want to spread out, whether with stents that spread out a blood vessel or retractors that open up to move organs out of the way. That’s where origami has played a role.”

Using origami in medical applications also presents challenges. Traditional origami is based on using paper, but devices intended for use in the body must be made of materials that are biocompatible.

Then there’s the question of activation. “How are you going to make it move once it gets to the destination?” asks Lang. “Is it a motor, a lever, is it electrically activated?” Some origami-inspired devices deploy when they reach a certain temperature, but that temperature must also be compatible with the human body.

Greenberg left BYU 10 years ago and now works in business development at Chevron. Her origami experiments are limited to folding napkins with her children while they wait for dinner at a Chinese restaurant.

But around the world – at Oxford, Penn State, and BYU, at labs in Israel, China, Japan, and elsewhere – researchers continue to explore how origami might apply to medical devices and procedures: a folded biocompatible sheet embedded with chemotherapy drugs that could unfurl inside the body; a miniscule stent, just 0.5 mm in diameter, for treating glaucoma; and a branch of DNA nanotechnology that involves “knitting” DNA into 3D structures that could be used, for example, in bioimaging and “smart” drug delivery, bringing chemotherapy directly into target cancer cells.

“The interest in origami-inspired medical devices has grown quite a bit” in the last decade, says Frecker, whose team is now working on an origami-inspired product to protect doctors who do sinus surgeries from exposure to aerosol droplets from their patients.

At this point, most origami-inspired medical applications remain in the research or prototype stage. It can take years to raise funds, garner a manufacturer’s interest, and gain FDA approval. “It’s moving gradually from the labs into companies,” says Howell. “That just takes time.”

The basic principles of origami – deriving motion from creasing and uncreasing; converting something flat to something three dimensional; reducing something large to something small by folding it; using simple techniques to yield complex results – have changed the way biomedical engineers look at their work.

For Frecker, those concepts have also changed the way she views the world. “I never realized how ubiquitous origami is until I started working on it in my research,” she says. “It’s everywhere.”

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