Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 23 citations

PubMed: 35880015 DOI: 10.1016/j.crmeth.2022.100256

Miniaturized and multiplexed high-content screening of drug and immune sensitivity in a multichambered microwell chip.

Cell Rep Methods 2(7):100256

Authors: Niklas Sandström, Valentina Carannante, Karl Olofsson, Patrick A Sandoz, Elisabeth L Moussaud-Lamodière, Brinton Seashore-Ludlow, Hanna Van Ooijen, Quentin Verron, Thomas Frisk, Madoka Takai, Martin Wiklund, Päivi Östling, Björn Önfelt

Affiliations

  • Department of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, 171 65 Solna, Sweden.
  • Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, 171 65 Solna, Sweden.
  • Department of Oncology and Pathology, Science for Life Laboratory, Karolinska Institutet, 171 65 Solna, Sweden.
  • Department of Bioengineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-8656, Japan.

Abstract

Here, we present a methodology based on multiplexed fluorescence screening of two- or three-dimensional cell cultures in a newly designed multichambered microwell chip, allowing direct assessment of drug or immune cell cytotoxic efficacy. We establish a framework for cell culture, formation of tumor spheroids, fluorescence labeling, and imaging of fixed or live cells at various magnifications directly in the chip together with data analysis and interpretation. The methodology is demonstrated by drug cytotoxicity screening using ovarian and non-small cell lung cancer cells and by cellular cytotoxicity screening targeting tumor spheroids of renal carcinoma and ovarian carcinoma with natural killer cells from healthy donors. The miniaturized format allowing long-term cell culture, efficient screening, and high-quality imaging of small sample volumes makes this methodology promising for individualized cytotoxicity tests for precision medicine.

MeSH

Cells, Killer Cells, Natural, Pharmaceutical Preparations, Ovary, Neoplasms, Immunotherapy, Drug Evaluation, Preclinical, Precision Medicine, Cell Culture Techniques

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