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

Journal: Nature communications
Published Date:

Abstract

Due to its specificity, fluorescence microscopy has become a quintessential imaging tool in cell biology. However, photobleaching, phototoxicity, and related artifacts continue to limit fluorescence microscopy's utility. Recently, it has been shown that artificial intelligence (AI) can transform one form of contrast into another. We present phase imaging with computational specificity (PICS), a combination of quantitative phase imaging and AI, which provides information about unlabeled live cells with high specificity. Our imaging system allows for automatic training, while inference is built into the acquisition software and runs in real-time. Applying the computed fluorescence maps back to the quantitative phase imaging (QPI) data, we measured the growth of both nuclei and cytoplasm independently, over many days, without loss of viability. Using a QPI method that suppresses multiple scattering, we measured the dry mass content of individual cell nuclei within spheroids. In its current implementation, PICS offers a versatile quantitative technique for continuous simultaneous monitoring of individual cellular components in biological applications where long-term label-free imaging is desirable.

Authors

  • Mikhail E Kandel
    Quantitative Light Imaging Laboratory, Department of Electrical and Computer Engineering, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
  • Yuchen R He
    Beckman Institute for Advanced Science and Technology, The University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Young Jae Lee
    Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Taylor Hsuan-Yu Chen
    Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Kathryn Michele Sullivan
    Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Onur Aydin
    Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • M Taher A Saif
    Department of Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; mgazzola@illinois.edu saif@illinois.edu.
  • Hyunjoon Kong
    Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
  • Nahil Sobh
    Beckman Institute for Advanced Science and Technology, The University of Illinois at Urbana-Champaign, Urbana, IL 61801.
  • Gabriel Popescu
    Quantitative Light Imaging Laboratory, Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, Illinois 61801, USA.