The standard diagnosis of upper urinary tract cancers typically involves the removal of suspicious tissue using forceps, a procedure that is technically challenging and samples only a single region of the organ. The ureters, which transport urine from the kidneys to the bladder, measure less than five millimeters in diameter and can be up to 30 centimeters long. This size constraint limits the tools that can be used, as well as the quality and quantity of the tissue samples collected. Researchers are now working on developing microgrippers that can be utilized throughout the upper urinary tract, allowing them to capture tiny pieces of tissue from numerous locations and potentially aiding in the early detection of diseases.

A team of researchers at Johns Hopkins University (Baltimore, MD, USA) had earlier created microgrippers for the gastrointestinal tract. In their latest study, they shifted their focus to the upper urinary tract, where the complex anatomy and location pose challenges for obtaining tissue samples. The researchers designed their microgrippers to be incredibly small—less than 750 microns, smaller than the tip of a sharpened pencil. The microgrippers feature a star-like shape with six arms connected by multiple hinges, enabling them to fold into a claw-like form. Once tissue is collected, a magnet can be used to retrieve the microgrippers, which can then be analyzed together to check for cancerous samples. These microgrippers act like a loaded spring and can be produced en masse in sheets coated with food-grade wax that keeps them flat. When exposed to body temperature, the wax softens, releasing the spring’s energy, which allows the microgrippers to fold and exert enough force to pierce and grasp surrounding tissue.

Standard biopsies of the upper urinary tract typically employ a specialized ureteral catheter that guides forceps through the urinary tract to collect tissue. To assess whether the microgrippers could be compatible with this method, the researchers loaded approximately 200 microgrippers into a vial and propelled them through three different commercial catheters using compressed air. They discovered that all catheter types had similar passage rates, with about 80% of the microgrippers successfully navigating through. The team then tested the microgrippers in an ex vivo pig ureter. They deployed the microgrippers into the excised organ and incubated the ureter at body temperature for roughly ten minutes. Afterward, they used a magnet to retrieve the microgrippers, finding that most had successfully collected small clusters of tissue.

As reported in preclinical research published in the journal Advanced Healthcare Materials, the team’s analysis of the collected tissue indicated that the microgrippers could retrieve multiple layers of urothelial cells, demonstrating that this technique can yield diagnostic-quality samples. While each microgripper captures only a small amount of tissue, deploying hundreds into the upper urinary tract could collect an amount comparable to that obtained through traditional biopsy methods. However, this tissue would be gathered from various regions of the organ rather than a single localized area, which could enhance the effectiveness of the microgrippers as a screening tool. Although the current focus is on the upper urinary and gastrointestinal tracts, the microgrippers could potentially be adapted for use in other organs.

“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,” said senior study author David Gracias, Ph.D., a professor at Johns Hopkins University. “We envision using this sampling method to determine the overall health of an entire organ. Clinicians could someday use microgrippers to screen high-risk patients, potentially finding disease before symptoms develop.” 

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