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Imaging Biological Samples with Optical Microscopy

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Optical microscopy uses optic principles to provide detailed images of samples. Antonie van Leeuwenhoek designed the first compound optical microscope in the 17th century to visualize blood cells, bacteria, and yeast cells. In 1830, Joseph Jackson Lister created an essentially modern light microscope. The 20th century saw the development of microscopes with enhanced magnification and resolution.
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Related Experiment Video

Updated: Jan 10, 2026

Single Plane Illumination Module and Micro-capillary Approach for a Wide-field Microscope

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Published on: August 15, 2014

Hybrid Solid-Liquid Optics Enable Scalable, High-Resolution, Multi-Immersion Light-Sheet Microscopy.

Cheng Gong^1,2, Pauline Affatato¹, Matt Fay³

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

Biorxiv : the Preprint Server for Biology

|November 24, 2025

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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Last Updated: Jan 10, 2026

Single Plane Illumination Module and Micro-capillary Approach for a Wide-field Microscope

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Published on: August 15, 2014

Light-sheet Microscopy for Three-dimensional Visualization of Human Immune Cells

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Published on: June 13, 2018

A Guide to Build a Highly Inclined Swept Tile Microscope for Extended Field-of-view Single-molecule Imaging

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Published on: April 8, 2019

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.