High-throughput imaging: Focusing in on drug discovery in 3D

Methods. 2016 Mar 1;96:97-102. doi: 10.1016/j.ymeth.2015.11.013. Epub 2015 Nov 21.

Abstract

3D organotypic culture models such as organoids and multicellular tumor spheroids (MCTS) are becoming more widely used for drug discovery and toxicology screening. As a result, 3D culture technologies adapted for high-throughput screening formats are prevalent. While a multitude of assays have been reported and validated for high-throughput imaging (HTI) and high-content screening (HCS) for novel drug discovery and toxicology, limited HTI/HCS with large compound libraries have been reported. Nonetheless, 3D HTI instrumentation technology is advancing and this technology is now on the verge of allowing for 3D HCS of thousands of samples. This review focuses on the state-of-the-art high-throughput imaging systems, including hardware and software, and recent literature examples of 3D organotypic culture models employing this technology for drug discovery and toxicology screening.

Keywords: 3D image analysis software; 3D tissue culture; High-content screening; High-throughput imaging; Multicellular tumor spheroids; Organoids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Discovery
  • Drug Screening Assays, Antitumor*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Hepatocytes / ultrastructure*
  • Humans
  • Image Processing, Computer-Assisted / statistics & numerical data*
  • Imaging, Three-Dimensional / instrumentation
  • Imaging, Three-Dimensional / methods*
  • Small Molecule Libraries / pharmacology
  • Software
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Spheroids, Cellular / ultrastructure*

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries