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  3. Hybrid Solid-liquid Optics Enable Scalable, High-resolution, Multi-immersion Light-sheet Microscopy.
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Hybrid Solid-Liquid Optics Enable Scalable, High-Resolution, Multi-Immersion Light-Sheet Microscopy.

Cheng Gong1,2, Pauline Affatato1, Matt Fay3

  • 1Departments of Biological Sciences, Columbia University, New York, NY, USA.

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|November 24, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Researchers developed a new imaging framework (HySIL) and devices (SCOPE/Super-SCOPE) to enable affordable, high-resolution 3D imaging of large biological samples. This advances scalable, data-driven discovery in modern biology.

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Area of Science:

  • Biophysics
  • Optical Engineering
  • Cell Biology

Background:

  • High-content 3D imaging is crucial for data-driven biological discovery.
  • Current methods using immersion or air objectives have limitations in scalability, cost, and resolution for large samples.

Purpose of the Study:

  • To develop a scalable and affordable high-resolution 3D imaging solution for molecular to organ scales.
  • To overcome the limitations of traditional microscopy objectives in imaging intact, cleared, or expanded biological specimens.

Main Methods:

  • Introduction of the Hybrid Solid-Liquid Immersion Lens (HySIL) framework, combining solid optics with index-matched liquid.
  • Development of SCOPE and Super-SCOPE objective-agnostic imaging devices based on HySIL.
  • Integration with a low-cost light-sheet microscopy (LSM) platform.

Main Results:

  • Achieved submicron lateral resolution (<0.75 μm) with long working distances (>30 mm) using inexpensive air objectives.
  • Demonstrated scalable, subcellular-resolution volumetric mapping of diverse biological samples, including brains, organoids, and histopathology.
  • Enabled multi-immersion and multi-color imaging capabilities.

Conclusions:

  • HySIL and SCOPE provide an accessible foundation for scalable, high-resolution volumetric imaging.
  • The developed system significantly advances data-driven biological discovery by enabling detailed mapping of large biological structures.
  • Offers a cost-effective alternative for high-content 3D imaging in research and diagnostics.