In Living Motion: Imaging Cellular Function in Live Tissues

By David D. Nolte

Department of Physics, Purdue University, West Lafayette, IN

Published on

Abstract

Subcellular motions inside live tissue are sensitive indicators of cellular health and cellular response to applied drugs. Digital holography volumetrically captures these motions in tissue dynamics spectroscopy for live-tissue drug screening.

When coherent light scatters from displacing objects, the phase of the light shifts according to the direction and magnitude of motion. When there are many scattering objects, moving in random directions, the phase shifts are added randomly, leading to intensity fluctuations in the scattered light. These intensity fluctuations have statistical properties that relate to the type of motion, with different fluctuation signatures for diffusive vs. directed transport, and with different frequency content for faster or slow motions.

Tissue-dynamics spectroscopy (TDS) combines dynamic light scattering with short-coherence digital holography to capture intracellular motion inside multicellular tumor spheroid tissue models. These spheroids are grown in bioreactors and have a proliferating shell of cells surrounding a hypoxic or necrotic core. The cellular mechanical activity becomes an endogenous imaging contrast agent for motility contrast imaging. Fluctuation spectroscopy is performed on dynamic speckle from the proliferating shell and the hypoxic core to generate drug-response spectrograms that are frequency vs. time representations of the changes in spectral content induced by an applied compound or an environmental perturbation. We have studied a range of reference compounds and conditions applied to multicellular tumor spheroids (MCT) to generate drug fingerprint spectrograms with potential applications in early drug discovery.

Cite this work

Researchers should cite this work as follows:

  • David D. Nolte (2012), "In Living Motion: Imaging Cellular Function in Live Tissues," https://nanohub.org/resources/14874.

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Location

Stewart Center, Purdue University, West Lafayette, IN

Tags

In Living Motion: Imaging Cellular Function in Live Tissues
  • In Living Motion: Imaging Cellular Function in Live Tissues 1. In Living Motion: Imaging Cell… 0
    00:00/00:00
  • World’s Oldest Biosensor? 2. World’s Oldest Biosensor? 24.8
    00:00/00:00
  • Moore’s Law of Electronics 3. Moore’s Law of Electronics 68.833333333333329
    00:00/00:00
  • ErooM’s Law of Pharmaceuticals 4. ErooM’s Law of Pharmaceutica… 94.2
    00:00/00:00
  • 2D Cell Culture vs. 3D Multicellular Spheroids 5. 2D Cell Culture vs. 3D Multice… 150
    00:00/00:00
  • Laser Radar (Digital Holography) 6. Laser Radar (Digital Holograph… 304.26666666666665
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  • Time Line 7. Time Line 392.16666666666669
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  • Digital Holography and Laser Ranging 8. Digital Holography and Laser R… 465.63333333333333
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  • Tumor Flythrough 9. Tumor Flythrough 535.5333333333333
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  • Volumetric Views 10. Volumetric Views 551.1
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  • Dynamic Speckle 11. Dynamic Speckle 568.86666666666667
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  • Motility Contrast Imaging (MCI) 12. Motility Contrast Imaging (MCI… 667.8
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  • Functional Imaging 13. Functional Imaging 698.16666666666663
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  • Frequency-Time Spectrogram 14. Frequency-Time Spectrogram 731.16666666666663
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  • Tissue Dynamics Spectrograms 15. Tissue Dynamics Spectrograms 778
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  • Light Scattering Mechanisms 16. Light Scattering Mechanisms 872.66666666666663
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  • Spectrogram Collage 17. Spectrogram Collage 933.26666666666665
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  • Feature Vector 18. Feature Vector 961.1
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  • Cross-correlation coefficients 19. Cross-correlation coefficients 988.76666666666665
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  • Feature Vector and Similarity Matrix (Hierarchical Clustering) 20. Feature Vector and Similarity … 1012.8666666666667
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  • Ras/Raf Pathway 21. Ras/Raf Pathway 1133.6
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  • BRAF Phenotypic Profiling 22. BRAF Phenotypic Profiling 1180.3
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  • Cell Mitosis/Division 23. Cell Mitosis/Division 1348.4
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  • MCI for Artificial Reproductive Technology 24. MCI for Artificial Reproductiv… 1467.9666666666667
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  • Personalized Medicine: 25. Personalized Medicine: 1578.4
    00:00/00:00
  • Function - Form - Motion 26. Function - Form - Motion 1681.6666666666667
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