Developing "Chips” for the Prediction of Cytotoxicity

	A microfluidic chip for cell handling and analysis

This project will address the scientific and technological challenges associated with the conception and design of an integrated device or "chip" to carry out complete cytotoxicity assays based on mammalian cells. The initial focus will be on an assay that determines the systemic or organ-specific cytotoxicity of chemicals. In combination with biokinetic (ADME) data these matter can be used in the prediction of acute toxicity in lab animals or humans.

 

Currently, the majority of testing laboratories in the EU carry out cytotoxicity assay manually, using typically 6 to 384 well microtiter plate formats. After seeding of the well-plates, the cell culture is treated with the test chemical and incubated for a number of hours or days. The degree of toxicity is then determined by measuring a particular cytotoxic "endpoint", such as membrane integrity of metabolism. Often the objective is to produce a dose-response curve from which, for example, an IC50 value can be extracted (i.e. the concentration of test chemical at which the viability of half of the cell population is compromised).

Application in Commercial Products

There are a number of commercial products that target the automation and miniaturisation of cell-based assays. Some of these utilise a micro-fluidic chip (e.g. desk-top analyser from Agilent Technologies), but their function is usually limited to the analysis of treated cells (e.g. cytometry), neglecting the preceding steps in the assay. A number of companies offer "workstation" solutions which can carry out many different assay steps and which can handle standard microtiter plate formats (e.g. cell-assay workstations from Caliper Life Sciences). However, to achieve a more satisfactory level of functionality and throughput, users must resort to large, sophisticated and costly test platforms (e.g. JRC cytotoxicity test facility).

 

his project will identify and demonstrate how selected nanobiotechnologies can be exploited to deliver more functionally rich, highly integrated and holistic solutions to carry out cytotoxicity testing of chemicals. Both existing know-how and the most radical of new ideas will be considered and elaborated with the aim of making a quantum leap in the cell-on-chip concept.