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Scanless temporal focusing enables high-speed three-dimensional quantitative phase microscopy
Peter So1,2, Yuechuan Lin2,3, Xiang Zhang2,3
1Laser Biomedical Research Center, G. R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Research Square
|April 27, 2026
Summary
Quantitative phase microscopy (QPM) now offers high-speed, label-free 3D imaging. This new temporal focusing QPM (TF-QPM) provides sub-micron optical sectioning for fast, detailed biological and physical system analysis.
Area of Science:
- Biophysics
- Optical Imaging
- Microscopy
Background:
- Quantitative phase microscopy (QPM) is crucial for label-free imaging of biological and physical systems.
- Achieving high-speed, 3D QPM with strong optical sectioning presents a significant challenge.
Purpose of the Study:
- To introduce a novel single-shot reflection-mode temporal focusing QPM (TF-QPM) system.
- To enable high-speed, label-free, 3D phase-sensitive volumetric imaging with enhanced optical sectioning.
Main Methods:
- Developed a single-shot reflection-mode temporal focusing QPM (TF-QPM) technique.
- Extended temporal focusing principles for label-free phase-sensitive imaging.
- Utilized camera speed limitations for high frame rate acquisition (3,709 Hz).
Main Results:
- Achieved sub-micron optical sectioning without mechanical scanning.
- Obtained diffraction-limited 3D imaging with 402 nm lateral and 920 nm axial resolution.
- Demonstrated high-speed volumetric imaging at 3,709 Hz with reduced speckle noise.
- Enabled precise 3D particle tracking and characterization of fast dynamics.
- Showcased histology-level resolution in intact tissues with virtual staining capabilities.
Conclusions:
- TF-QPM is a scanless, high-speed platform for rapid, label-free volumetric imaging.
- The technology offers a significant advancement over existing QPM techniques.
- TF-QPM provides a viable alternative to traditional sectioning workflows in tissue imaging and beyond.
