Make it simple: long-term stable gradient generation in a microfluidic microdevice.

Abstract

Microfluidics-based gradient generators have been used for various biological applications, specifically chemotaxis in cell culture. However, the ability to generate and maintain long term gradients alongside the ability to quickly switch solutions is a challenge of the current microfabricated systems. In this study, a simple flow-driven microfluidic system was developed to achieve long-term stable concentration gradients. Computational modelling was performed to highlight the fluid dynamics as well as to verify the ability of maintaining stable gradients over 7 days. Numerical simulation was analysed to evaluate the static pressure, velocity magnitude and wall shear stress distribution in the chamber. A microdevice fabricated with polydimethylsiloxane (PDMS), using a standard soft lithography technique is presented. It consists of eight parallel microchannels (5 μm × 30 μm × 1,800 μm) linking source and sink chambers; a syringe pump drives fluid through the sink chamber, advection/diffusion from source to sink establishes a gradient. A gradient of a fluorescent dye was generated under the low flow control at 1-10 μl/h of a simple syringe pump equipped with a pulsation damper that was comparable to a pulseless microfluidic pump. Concentration gradients were formed in 1 h and stable from 2 h out to 5 days and consuming less than 1.0 ml of solution. This study focuses on a novel solution to achieve a long-term microfluidic gradient generator using simple engineering techniques of biomedical microdevices.