Label-free live cell imaging by Confocal Raman Microscopy identifies CHO host and producer cell lines

Biotechnol J. 2017 Jan;12(1):1600037. doi: 10.1002/biot.201600037. Epub 2016 Sep 23.

Abstract

As a possible viable and non-invasive method to identify high producing cells, Confocal Raman Microscopy was shown to be able to differentiate CHO host cell lines and derivative production clones. Cluster analysis of spectra and their derivatives was able to differentiate between different producer cell lines and a host, and also distinguished between an intracellular region of high lipid and protein content that in structure resembles the Endoplasmic Reticulum. This ability to identify the ER may be a major contributor to the identification of high producers. PCA enabled the discrimination even of host cell lines and their subclones with inherently higher production capacity. The method is thus a promising option that may contribute to early, non-invasive identification of high potential candidates during cell line development and possibly could also be used for proof of identity of established production clones.

Keywords: Chinese hamster ovary cells; Label-free detection; Raman microscopy; Single cell analysis.

MeSH terms

  • Adalimumab / genetics
  • Adalimumab / metabolism
  • Amine Oxidase (Copper-Containing) / genetics
  • Amine Oxidase (Copper-Containing) / metabolism
  • Animals
  • CHO Cells / cytology*
  • CHO Cells / ultrastructure*
  • Cluster Analysis
  • Cricetulus
  • Endoplasmic Reticulum / ultrastructure
  • Humans
  • Lipids / chemistry
  • Metals / chemistry
  • Microscopy, Confocal / methods*
  • Molecular Imaging / methods
  • Principal Component Analysis
  • Protein Engineering / methods*
  • Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spectrum Analysis, Raman / methods

Substances

  • Lipids
  • Metals
  • Proteins
  • Recombinant Proteins
  • Amine Oxidase (Copper-Containing)
  • Adalimumab