Healthcare (Commonwealth Union) – Scientists at the University of Toronto’s Faculty of Applied Science & Engineering have created a groundbreaking microfluidic platform designed to forecast cancer cell behavior and aggressiveness, paving the way for more precise and personalized cancer treatments.
The platform, named the Recoverable-Spheroid-on-a-Chip with Unrestricted External Shape (ReSCUE), was developed under the leadership of Edmond Young, an associate professor in the department of mechanical and industrial engineering. It enables researchers to recover and release tumoroids—patient-derived tumor cells—for detailed analysis and characterization.
This innovation provides researchers with an unprecedented ability to control and manipulate tumor shapes, a largely untapped area of cancer research with significant potential for advancing the field.
Sina Kheiri, a PhD graduate and co-lead author of the study published in Advanced Materials indicated thatthere are many platforms available for in vitro modeling of spheroids—three-dimensional clusters of cells that replicate tissues and miniature tumors.
He indicated however, that a significant challenge in cancer research has been the lack of control over the shape, recovery, and positioning of these cancer organoids. As a result, researchers often work with tumor-on-a-chip models that are difficult to analyze, as they remain fixed to the device and can only be examined using optical microscopy.
The platform also allows researchers to cultivate cancer organoids in various shapes, addressing a critical gap in current in vitro cancer modeling. According to Kheiri, much of the existing research focuses on spherical tumors, even though tumors within the body often assume a wide range of shapes.
He pointed out that in many invasive cancers, tumor shapes are rarely spherical. Kheiri further indicated that for instance, a recent study involving 85 breast cancer patients found that only 20 percent of tumors were spherical. If modeling studies are restricted to spherical tumor shapes, they miss a significant portion of the diversity and complexity of real-life tumors. This limits their ability to fully understand cancer cell behavior across the broader spectrum of tumor morphologies.
Kheiri’s PhD research was co-supervised by Edmond Young and Eugenia Kumacheva, a professor in the Department of Chemistry within the Faculty of Arts & Science, who is also cross-appointed to the Institute of Biomedical Engineering. Kumacheva’s lab developed a biomimetic hydrogel used as a scaffold in the multi-layer ReSCUE platform, enabling patient-derived cancer cells to grow and organize as they would in human tissue.
The platform’s development involved collaboration with David Cescon, a clinician scientist and breast medical oncologist at the Princess Margaret Cancer Centre, as well as an associate professor in the Institute of Medical Science at the Temerty Faculty of Medicine. Cescon’s team provided the cancer cells used to create breast cancer organoids for the research.
Kheiri’s discovery of the link between tumor shapes and cancer cell behavior came unexpectedly. While refining the microfluidic platform, he noticed that some patient-derived tumoroids were forming positive curvatures, influenced by the shape of the microwell. This insight opened new avenues for understanding the relationship between tumor geometry and cellular behavior.
“I was playing with the aspect ratio of the microwells and observed that when the wells had a more rod-like or elongated shape, rather than a circular or disc shape, the tissues formed cellular strands at the regions with positive curvature,” he explained. “I didn’t see that in tumoroids from the same cancer-cell sample that formed a spherical shape.
“So, we started to make different shapes and analyze the effects of shape or curvature on cancer behaviour.”
The team studied disk-, rod-, and U-shaped tumoroids and observed increased cell activity and proliferation in regions with positive curvatures—areas where the tumor shape is convex and curves outward.
This suggests that cells in these convex regions may exhibit more invasive growth compared to areas of the tumor with flat curvatures.
