Professor Raju Tomer's team at Columbia University has cracked a problem that has frustrated researchers for decades: how to see deep inside tissue with crystal clarity without spending a fortune on equipment that only specialists can operate. The solution, called HySIL—short for Hybrid Solid–Liquid Optics—pairs a simple curved lens with a precisely matched liquid, letting the two function as one continuous optical system, and it upends the entire economics of 3D tissue imaging.
For years, researchers have faced an impossible choice. Oil-immersion lenses deliver the sharpest images but cost thousands of dollars, can only penetrate a few millimeters deep, and require fussy sample preparation. Cheaper air lenses can reach centimeters into a tissue sample but produce blurred images when used with the chemical treatments that make tissues transparent for 3D viewing. That trade-off between sharpness and accessibility has hobbled progress in fields ranging from neuroscience to cancer research.
The breakthrough, published in Nature Biotechnology, comes from treating the immersion liquid not as a passive filler but as an active optical component. By doing so, the Tomer lab created a modular device called SCOPE that clips directly onto existing light-sheet microscopes—the kind many labs already own. The team also built a higher-resolution variant called Super-SCOPE. In 2024, they incorporated HySIL into an even more compact projector-based microscope called SLICE, which is now available commercially through their industry partner MBF Bioscience.
The impact ripples across biology. Working with collaborators spanning neuroscience, developmental biology, and pathology, the team demonstrated SCOPE on whole mouse, salamander, and cavefish brains for mapping neural circuits; lab-grown miniature human brain tissues for studying disease and development; and intact human cancer biopsies. Each application revealed something impossible to see with traditional two-dimensional slides: the full three-dimensional architecture of tissue, not just a thin cross-section.
That shift matters immensely for pathology. For decades, doctors have analyzed tissue by slicing it thin, mounting it on glass slides, and staring down a microscope at flat images. But disease—whether cancer spreading through tissue or developmental abnormalities—reveals itself in three dimensions. Hanina Hibshoosh, professor of pathology and cell biology at Columbia University Irving Medical Center and a co-author on the paper, explained that tools like SCOPE "let you see the whole tissue architecture, not just the cross-section that pathology has traditionally been limited to."
The broader significance stretches beyond hospitals. As researchers gain easier access to high-resolution 3D tissue images, they can train the next generation of artificial intelligence models for disease detection and diagnosis. What once required a specialized optics lab—expensive equipment, expert technicians—can now happen in teaching labs, clinics in remote areas, or resource-limited settings where it's needed most. Jack Glaser, co-founder and CEO of MBF Bioscience, highlighted the rarity of what HySIL delivers: "lower cost and higher performance on the same instrument."
Tomer himself framed it plainly: "We've broken a long-standing trade-off in microscopy between performance and accessibility." The implications are still unfolding, but one thing is clear—the microscope revolution just became accessible to far more of the world.