Tiny tools get a grip for better biopsies

JOHNS HOPKINS (US) — Magnetic stars—each the size of a speck of dust—can get to the body’s tightest spaces and collect tissue samples to screen for disease.

In two recent journal articles, the researchers report successful animal testing of the tiny tools, which require no power source or wires as they seize internal tissue samples.

Dozens of dust speck-sized grippers are seen here in a vial. They can be retrieved from the body magnetically once they have captured cells for biopsy. View larger. (Credit: Evin Gultepe/ Gracias Lab/JHU)


The team calls the devices “mu-grippers,” incorporating the Greek letter that stands for “micro” in scientific language. Instead of relying on electric or pneumatic power, the star-shaped tools are activated by body heat, which causes their tiny “fingers” to close on and capture cell clusters. Because the tools also contain a magnetic material, they can be retrieved through an existing body opening with a magnetic catheter.

In Gastroenterology, the researchers described using mu-grippers to collect cells from the colon and esophagus of a pig, chosen because its intestinal tract is similar to that of humans. Earlier, the team members reported in Advanced Materials that they had inserted mu-grippers through the mouth and stomach of a live animal and released them in a hard-to-access place, the bile duct, from which they obtained tissue samples.

“This is the first time that anyone has used a sub-millimeter-sized device—the size of a dust particle—to conduct a biopsy in a live animal,” says David Gracias, the associate professor of chemical and biomolecular engineering at Johns Hopkins University, whose lab developed the microgrippers.

“That’s a significant accomplishment. And because we can send the grippers in through natural orifices, it is an important advance in minimally invasive treatment and a step toward the ultimate goal of making surgical procedures noninvasive.”

More but smaller samples

Another team member, physician Florin M. Selaru, says the mu-grippers could radically change biopsies, the “gold standard” test for diagnosing cancer and other diseases. The advantage, Selaru says, is that mu-grippers can collect far more samples from many more locations. A much larger forceps used during a typical colonoscopy may remove 30 to 40 pieces of tissue to be studied for signs of cancer. But despite a doctor’s best intentions, the small number of specimens makes it easy to miss diseased lesions.

“What’s the likelihood of finding the needle in the haystack?” asks Selaru, an assistant professor of gastroenterology and hepatology. “Based on a small sample, you can’t always draw accurate inferences.

“We need to be able to do a larger statistical sampling of the tissue,” he says. “That’s what would give us enough statistical power to draw a conclusion, which, in essence, is what we’re trying to do with the microgrippers. We could deploy hundreds or even thousands of these grippers to get more samples and a better idea of what kind of or whether a disease is present.”

Although each mu-gripper can grab a much smaller tissue sample than larger biopsy tools, the researchers say each can retrieve enough cells for effective microscopic inspection and genetic analysis. Armed with this information, they say, the patient’s physician could be better prepared to diagnose and treat the patient.

Tiny surgical tools

This approach is the latest application of the Gracias lab’s self-assembling tiny surgical tools, activated by heat or chemicals. The low-cost devices are fabricated through photolithography, the same process used to make computer chips. Their fingerlike projections are made of materials that would normally curl inward, but the team adds a polymer resin to give the joints rigidity and to keep the digits from closing.

Prior to a biopsy, the grippers are kept on ice, so that the fingers remain in this extended position. An endoscopy tool then is used to insert hundreds of the tools into the area targeted for a biopsy.

Within about five minutes, the warmth of the body causes the polymer coating to soften, and the fingers curl inward to grasp tissue. A magnetic tool is then inserted to retrieve them.

Although the animal testing results are promising, the researchers say the process will require further refinement before human testing can begin.

“The next step is improving how we deploy the grippers,” Selaru says. “The concept is sound, but we still need to address some of the details. The other thing we need to do is thorough safety studies.”

The National Institutes of Health, the National Science Foundation, the Flight Attendants Medical Research Institute, and the Broad Medical Research Institute funded the research.

Source: Johns Hopkins University

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