Microgrippers for Myriad Miniature Biopsies

Newswise — Typical diagnosis of upper urinary tract cancers requires removal of suspicious tissue with forceps, a technically challenging procedure that only samples one region of the organ. NIBIB-funded researchers are developing microgrippers that could be deployed throughout the upper urinary tract, which could grab tiny pieces of tissue at hundreds of different areas and potentially facilitate early detection of disease. Their preclinical research was recently published in the journal Advanced Healthcare Materials.

“Many cancer diagnoses result from accidental discovery through imaging or when a patient has pain or bleeding—in other words, when the tumor is large enough to see or when it starts to affect the function of the surrounding tissue,” explained senior study author David Gracias, Ph.D., a professor at Johns Hopkins University. “We’re aiming to create a new diagnostic screening paradigm that could find cancerous cells before a visible tumor develops, which could enable earlier cancer detection and jumpstart treatment.”

While Gracias and colleagues have previously developed microgrippers for the gastrointestinal tract, in this study they focused on the upper urinary tract, as its location and complex anatomy make obtaining tissue samples somewhat difficult. The ureters, which are the tubes that transport urine from the kidney to the bladder, are less than five millimeters in diameter but can be up to 30 centimeters in length. This limits both the size of the tools that can be used and the quality and quantity of the tissue samples that can be removed.

With these factors in mind, the researchers designed their microgrippers to be extremely small—less than 750 microns, or smaller than the tip of a sharpened pencil. The microgrippers are shaped like a star, comprised of six arms with multiple hinges, allowing them to fold into a claw-like shape. After they collect tissue, a magnet can be used to retrieve the microgrippers, which can be analyzed collectively to see if any of the samples that they’ve brought back are cancerous.

The microgrippers are like a loaded spring, Gracias explained. They can be manufactured by the thousands in sheets with a food-grade wax coating that keeps them flat. “After exposure to body temperature, the wax softens, which releases the energy of the spring,” Gracias said. “This allows the microgrippers to fold with enough force to pierce and grab the surrounding tissue.”

Typical biopsies of the upper urinary tract use a specialized ureteral catheter, which snakes forceps through the urinary tract to collect tissue. To understand if the microgrippers could be compatible with this technique, Gracias and colleagues loaded approximately 200 microgrippers into a vial and used compressed air to propel them through three different commercial catheters. They found that all catheter types had similar passage rates, with about 80% of the microgrippers successfully passing through. 

Gracias and his team then evaluated the microgrippers in an ex vivo pig ureter. They deployed the microgrippers into the excised organ and then incubated the ureter at body temperature for roughly ten minutes. Then they used a magnet to remove the microgrippers from the ureter, finding that most of the microgrippers had grabbed and retrieved small clusters of tissue.

Analysis of the removed tissue revealed that the microgrippers could retrieve multiple layers of urothelial cells, indicating that this technique can acquire diagnostic-quality samples. While each microgripper contains a very small amount of tissue, if hundreds are deployed into the upper urinary tract, the overall amount of tissue collected could be similar to a traditional biopsy procedure, Gracias explained. However, the tissue would be collected from many different regions of the organ instead of one localized area.

This factor could make the microgrippers an effective screening tool. Gracias likened their technique to a city survey: If all of your information comes from the same neighborhood, it’s not representative of the city population at large. “We envision using this sampling method to determine the overall health of an entire organ,” Gracias said. “Clinicians could someday use microgrippers to screen high-risk patients, potentially finding disease before symptoms develop.”

While the team is currently focused on the upper urinary and gastrointestinal tracts, the microgrippers could potentially be deployed in other organs. “Their small size and clever mechanism of action sets these microbots apart from other biopsy tools in the field,” said Jessica Falcone, Ph.D., a program director in the Division of Discovery Science and Technology at NIBIB. “Future work in live animals will help determine if this technology could someday be translated into a screening tool for humans.”

This study was supported in part by NIBIB grant R01EB017742.

This science highlight describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process—each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

Study reference: W. Liu et al. Untethered Microgrippers for Biopsy in the Upper Urinary Tract. Adv. Healthcare Mater. 2024, 2401407. https://doi.org/10.1002/adhm.202401407