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Updated: Nov 26, 2025

Quantitative Optical Microscopy: Measurement of Cellular Biophysical Features with a Standard Optical Microscope

Quantitative Optical Microscopy: Measurement of Cellular Biophysical Features with a Standard Optical Microscope

Published on: April 7, 2014

Phase imaging with computational specificity (PICS) for measuring dry mass changes in sub-cellular compartments.

Mikhail E Kandel^1,2, Yuchen R He^1,2, Young Jae Lee^1,3

¹Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

Nature Communications

|December 8, 2020

Summary

Phase imaging with computational specificity (PICS) uses AI to provide specific imaging of unlabeled live cells. This label-free technique enables long-term monitoring of cellular components without viability loss.

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Last Updated: Nov 26, 2025

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Area of Science:

Cell biology
Biophysics
Microscopy

Background:

Fluorescence microscopy is vital in cell biology but limited by photobleaching and phototoxicity.
Artificial intelligence (AI) shows potential in transforming imaging contrast.
Label-free imaging of live cells remains a significant challenge.

Purpose of the Study:

To introduce Phase Imaging with Computational Specificity (PICS) for high-specificity imaging of unlabeled live cells.
To demonstrate PICS's capability for long-term, label-free monitoring of cellular dynamics.
To enable quantitative measurements of cellular components without compromising cell viability.

Main Methods:

Combining quantitative phase imaging (QPI) with AI for enhanced contrast and specificity.
Developing an AI system with automatic training and real-time inference integrated into acquisition software.
Utilizing a QPI method that suppresses multiple scattering for accurate dry mass measurements.

Main Results:

PICS provides specific, quantitative information about unlabeled live cells in real-time.
Independent measurement of nucleus and cytoplasm growth over extended periods without cell death.
Accurate measurement of dry mass content in individual cell nuclei within spheroids.

Conclusions:

PICS is a versatile, quantitative technique for simultaneous, long-term monitoring of cellular components.
The method is suitable for biological applications requiring label-free imaging.
PICS overcomes limitations of traditional fluorescence microscopy for live-cell studies.