Biodynamic imaging for phenotypic profiling of three-dimensional tissue culture

Hao Sun, Daniel Merrill, Ran An, John Turek, Daniela Matei, David D. Nolte

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Three-dimensional (3-D) tissue culture represents a more biologically relevant environment for testing new drugs compared to conventional two-dimensional cancer cell culture models. Biodynamic imaging is a high-content 3-D optical imaging technology based on low-coherence interferometry and digital holography that uses dynamic speckle as high-content image contrast to probe deep inside 3-D tissue. Speckle contrast is shown to be a scaling function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Cellular responses of 3-D multicellular spheroids to paclitaxel are compared among three different growth techniques: rotating bioreactor (BR), hanging-drop (HD), and nonadherent (U-bottom, UB) plate spheroids, compared with ex vivo living tissues. HD spheroids have the most homogeneous tissue, whereas BR spheroids display large sample-to-sample variability as well as spatial heterogeneity. The responses of BR-grown tumor spheroids to paclitaxel are more similar to those of ex vivo biopsies than the responses of spheroids grown using HD or plate methods. The rate of mitosis inhibition by application of taxol is measured through tissue dynamics spectroscopic imaging, demonstrating the ability to monitor antimitotic chemotherapy. These results illustrate the potential use of low-coherence digital holography for 3-D pharmaceutical screening applications.

Original languageEnglish (US)
Article number016007
JournalJournal of Biomedical Optics
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Keywords

  • Three-dimensional tissue growth
  • biodynamic imaging
  • biological relevance
  • biomedical imaging
  • cellular dynamics
  • digital holography
  • drug development
  • drug discovery
  • dynamic light scattering
  • high-content imaging
  • low-coherence interferometry
  • pharmaceutical
  • physiological effects of paclitaxel
  • speckle

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering

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