Getting a Grip
Date: February 1, 2013
Something in our psyche loves the idea of tiny agents doing our bidding and doing it well—such as the way spy drones as small as bumblebees can whiz into a restricted area, scoop up information, and return home without a stir.
Now the potential for deploying such tools in the GI tract—and elsewhere—lights up Florin Selaru’s face. Consider the case of patients with ulcerative colitis, for example, who must undergo exploratory colon biopsies to see if chronic inflammation has crossed into cancer. Typically, endoscopists take around 30 random forceps biopsies of the colon’s mucosa.
“But what if, instead, you could deploy hundreds of metallic ‘grippers,’ each taking a fragment of tissue, with little or no trauma?” Selaru asks. A magnet would collect the grippers-plus-payload. And a day later, the molecular biology lab would report with a rare certainty whether or not the collected DNA contains cancer mutations.
This isn’t science fiction. Selaru, a gastroenterologist and molecular biologist, is some three years into a partnership with a Hopkins biomedical engineering team to develop and test miniature, self-operating biopsy tools. It began when the School of Engineering’s David Gracias asked clinicians for applications of the chemo-mechanical devices his lab created. “One thing led to another,” says Selaru. “We’re now doing the groundwork that will let us take this to patients.”
“Something was needed for pathologies that offer too little visual information,” Selaru explains. An endoscope can detect reddened mucosa, but is it early cancer or just inflammation? Only a biopsy can tell. Yet random biopsies may not adequately reflect disease. “Do you take 10 samples and call it a day?” he asks, “30? 100?” Increasing the number raises accuracy. At some point, however, damage to the mucosa becomes excessive.
Selaru cites a mathematical simulation—one helpful in oil drilling and space exploration—that shows it could take up to 1,000 samples to avoid overlooking a specific pea-sized site in the human gut. The value of the tools, then, isn’t in question.
How do they work?
Basically, Gracias’ team has layered two ultrathin metallic films—chromium and gold—each with a different intrinsic strain. The same photolithographic process that creates microchips can turn out hundreds of microgrippers on a single sheet. Normally each gripper would arch into its most stable position. That’s prevented, however, by an added third polymer layer. In practice, the devices are stored on ice, which keeps them flat. Introduce them endoscopically into the warm GI tract, though, and they curve like fingers as the polymer softens—in short, they grip.
Does the technique work? So far, yes, in lab situations. And preliminary work suggests that grippers can be guided with magnets to retrieve tissue from next-to-impossible spaces, like the biliary tree.
“There’s much to fine-tune,” says Selaru. “But we’re committed to get this all worked out. And, of course, we’re excited. The ‘grippers’ could bring a paradigm shift in disease diagnosis.” MC