Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology

Khoshmanesh, Khashayar, Akagi, Jin, Nahavandi, Saeid, Skommer, Joanna, Baratchi, Sara, Cooper, Jonathan M., Kalantar-Zadeh, Kourosh, Williams, David E. and Wlodkowic, Donald 2011, Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology, Analytical chemistry, vol. 83, no. 6, pp. 2133-2144.

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Title Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology
Author(s) Khoshmanesh, Khashayar
Akagi, Jin
Nahavandi, SaeidORCID iD for Nahavandi, Saeid orcid.org/0000-0002-0360-5270
Skommer, Joanna
Baratchi, Sara
Cooper, Jonathan M.
Kalantar-Zadeh, Kourosh
Williams, David E.
Wlodkowic, Donald
Journal name Analytical chemistry
Volume number 83
Issue number 6
Start page 2133
End page 2144
Total pages 12
Publisher American Chemical Society
Place of publication Washington, D. C.
Publication date 2011
ISSN 0003-2700
1520-6882
Summary Quantification of programmed and accidental cell death provides useful end-points for the anticancer drug efficacy assessment. Cell death is, however, a stochastic process. Therefore, the opportunity to dynamically quantify individual cellular states is advantageous over the commonly employed static, end-point assays. In this work, we describe the development and application of a microfabricated, dielectrophoretic (DEP) cell immobilization platform for the realtime analysis of cancer drug-induced cytotoxicity. Microelectrode arrays were designed to generate weak electro-thermal vortices that support efficient drug mixing and rapid cell immobilization at the delta-shape regions of strong electric field formed between the opposite microelectrodes. We applied this technology to the dynamic analysis of hematopoietic tumor cells that represent a particular challenge for real-time imaging due to their dislodgement during image acquisition. The present study was designed to provide a comprehensive mechanistic rationale for accelerated cell-based assays on DEP chips using real-time labeling with cell permeability markers. In this context, we provide data on the complex behavior of viable vs dying cells in the DEP fields and probe the effects of DEP fields upon cell responses to anticancer drugs and overall bioassay performance. Results indicate that simple DEP cell immobilization technology can be readily applied for the dynamic analysis of investigational drugs in hematopoietic cancer cells. This ability is of particular importance in studying the outcome of patient derived cancer cells, when exposed to therapeutic drugs, as these cells are often rare and difficult to collect, purify and immobilize.
Language eng
Field of Research 091306 Microelectromechanical Systems (MEMS)
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2011, American Chemical Society.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30040641

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