Dynamic Analysis of Tumour Cell Death Using Dielectrophoresis

Abstract

The important discovery that induction of programmed cell death in neoplastic cells is a critical event that defines tumour growth rate and response to anti-cancer therapy has provided a framework for the rationally designed, molecular anti-cancer therapeutics. The regulation of cancer cell death involves the circuitry of feedback events and rapid switches between analogue and digital responses. Such enormous complexity, with numerous variables acting at the same time, requires multiparametric and dynamic analysis at a single cell level. The opportunity to dynamically quantify individual cellular states is advantageous over the commonly employed static, end-point assays. We describe here the development and application of a microfabricated, dielectrophoretic (DEP) cell immobilisation platform for the real-time analysis of tumour cell death. We applied this technology to the dynamic analysis of haematopoietic tumour 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 labelling with cell permeability markers. Results indicate that simple DEP cell immobilisation technology can be readily applied for the dynamic analysis of investigational drugs in hematopoietic cancer cells.