Leveraging the IncuCyte Technology for Higher-Throughput and Automated Chemotaxis Assays for Target Validation and Compound Characterization

SLAS Discov. 2018 Feb;23(2):122-131. doi: 10.1177/2472555217733437. Epub 2017 Sep 28.

Abstract

Chemotaxis is the directional movement of cells in response to a chemical stimulus and is vital for many physiological processes, including immune responses, tumor metastasis, wound healing, and blood vessel formation. Therefore, modulation of chemotaxis is likely to be of therapeutic benefit. Hence, a high-throughput means to conduct chemotaxis assays is advantageous for lead evaluation and optimization in drug discovery. In this study, we have validated a novel approach for a higher-throughput, label-free, image-based IncuCyte chemotaxis assay encompassing various cell types, including T cells, B cells, mouse Th17, immature and mature dendritic cells, monocyte THP-1, CCRF-CEM, monocytes, neutrophils, macrophages, and MDA-MB-231. These assays enable us to visualize chemotactic cell migration in real time and perform kinetic cell motility studies on an automated platform, thereby allowing us to incorporate the quantitative studies of cell migration behavior into a routine drug discovery screening cascade.

Keywords: automated chemotaxis platform; automation or robotics; cell trafficking; cell-based assays; compound characterization; higher throughput; imaging technologies; immunoassays; kinetic cell motility; target validation.

MeSH terms

  • Animals
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Chemotaxis / drug effects*
  • Dendritic Cells / drug effects
  • Drug Discovery / methods*
  • Drug Evaluation, Preclinical / methods
  • High-Throughput Screening Assays / methods*
  • Macrophages / drug effects
  • Mice
  • Monocytes / drug effects
  • Neutrophils / drug effects
  • Pharmaceutical Preparations / administration & dosage*

Substances

  • Pharmaceutical Preparations