A research team led by Raju Tomer, professor of biological sciences at Columbia University, announced on June 10 the development of a new microscope lens design that aims to enhance 3D tissue imaging while reducing costs and complexity. The details were published in the journal Nature Biotechnology.
The need for high-resolution, three-dimensional images of intact tissues is growing in biology and medicine. Such images are used to map neural circuits, characterize diseases, and support artificial intelligence models for diagnostics. Traditional approaches require tradeoffs: oil-immersion lenses offer sharp images but are costly and limited in depth, while air lenses can image deeper but struggle with clarity when samples are chemically treated for transparency.
The new solution from Tomer's group is called HySIL (Hybrid Solid–Liquid Optics). It combines a simple curved solid lens with a matched immersion liquid so they function as one optical system. This enables affordable air lenses to deliver high-resolution images across large tissue samples without changing hardware or preparation methods.
To demonstrate the technology, the team built SCOPE—a modular device that attaches to existing light-sheet microscopes—and an advanced version called Super-SCOPE. These tools were integrated into a compact projector-based light-sheet microscope (pLSM) developed by Tomer's group in 2024 and now commercially available as SLICE. The researchers tested their devices on whole mouse, salamander, and cavefish brains; lab-grown miniature human brain tissues; and intact human cancer biopsies for next-generation pathology studies.
Jack Glaser, co-founder and CEO of MBF Bioscience who co-authored the paper, said, "A new optical concept only changes a field if labs without specialized optics expertise can actually use it day to day. What HySIL gives us is the rare combination of lower cost and higher performance in the same instrument. Engineering that into a robust, well-supported light-sheet system makes it something working labs can rely on across neuroscience, cancer research, developmental biology, and pathology." Hanina Hibshoosh, professor at Columbia University Irving Medical Center who also contributed to the study, said, "Examining 3D images of tissues lets you see the whole tissue architecture, not just the cross-section that pathology has traditionally been limited to. Tools like pLSM-SCOPE that make this kind of imaging affordable and accessible will become increasingly important as AI helps us analyze ever-larger amounts of tissue data for diagnosis and prognosis."
The research was supported by grants from the National Institutes of Health. Columbia University has filed patent applications related to these technologies. Tomer has served as a paid consultant for MBF Bioscience regarding implementation efforts.
