Finite element modelling and design of a concentration gradient generating bioreactor: application to biological pattern formation and toxicology.

This paper describes the use of a microfluidic gradient maker for the toxicological analysis of some conventional biomolecules such as hydrogen peroxide and a local anaesthetic, lidocaine on different cell cultures, human endothelial cells and myoblasts, respectively. The microfluidic device was designed and simulated using COMSOL Multiphysics and the concentration gradient in the microfluidic network was analysed through a fluid-dynamic and mass-transport study. Subsequently the device was fabricated with soft lithography, casting PDMS in a master to obtain channels about 250 microm deep. Hydrogen peroxide was tested on human endothelial cells, while lidocaine was tested on C2C12 myoblasts and an analysis was performed using propidium iodide staining followed by an imaging processing routine to obtain quantitative dose-response profiles in the gradient maker. The results show that the Gradient Maker (GM) bioreactor is a more sensitive method for detection of cell toxicity, and compared with testing of drug toxicity using microwells with individual cell cultures, allows one shot testing with a single cell culture exposed to a large number of concentrations. Moreover, the Gradient Maker was also modelled in order to realise biological pattern formation using two morphogenes acting as activator and inhibitor with varying diffusion rates.