title: Dynamic analysis of drug-induced cytotoxicity using chip-based dielectrophoretic cell immobilization technology.
abstract: 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 real-time 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.
authors.affiliation: Department of Chemistry and MacDiarmid Institute for Advanced Materials and Nanotechnology, University of Auckland, Auckland, New Zealand. kkho@deakin.edu.au
authors.forename: Khashayar
authors.initials: K
authors.lastname: Khoshmanesh
authors.forename: Jin
authors.initials: J
authors.lastname: Akagi
authors.forename: Saeid
authors.initials: S
authors.lastname: Nahavandi
authors.forename: Joanna
authors.initials: J
authors.lastname: Skommer
authors.forename: Sara
authors.initials: S
authors.lastname: Baratchi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Cooper
authors.forename: Kourosh
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.forename: Donald
authors.initials: D
authors.lastname: Wlodkowic
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018914:Cells, Immobilized / Q000187:drug effects; D003198:Computer Simulation; D003513:Cycloheximide / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation*; D017097:Electric Impedance; D004586:Electrophoresis / Q000295:instrumentation*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D056656:Lab-On-A-Chip Devices; D013696:Temperature; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D003513:Cycloheximide