Micro- and Nanotechnologies
Technology development for micro and nanofluidic devices
A microfluidic technology based upon the use of “fluid walls” was recently introduced to address the lack of uptake of traditional microfluidic devices in biomedicine. Reasons cited for this lack of uptake include technical complexity, high failure rates due to gas-bubbles altering flows and affecting cells in micro-channels, the questionable bio-compatibility of materials like polydimethylsiloxane used to make devices, the inaccessibility of cells growing in them, and – probably the most important – biologists cannot use their familiar culture dishes and microscopes. The new technology reshapes fluid interfaces between two immiscible liquids (cell-growth medium and a bio-inert fluorocarbon, FC40) in a standard cell-culture dish, to form arrays of isolated liquid chambers. Each aqueous chamber is separated from its neighbours by transparent liquid walls of FC40. At the microscale, these fluid walls prove to be strong, pliant, and resilient. We now extend this fluid-shaping technology to create complicated circuits that can have almost any imaginable 2D shape, and demonstrate the power of the approach through a range of dynamic biological assays, in which cells migrate up concentration gradients established by diffusion. In one, primary mouse macrophages from the bone marrow are imaged as they migrate over polystyrene towards a chemo-attractant. More complex circuits in which cells are given a choice between different competing chemo-attractants allow analysis of the decisions those cells make. In another, a steep gradient over less than 100 µm is generated by diffusion between two laminar streams as they flow through a conduit (width 500 µm, height 50 µm); bacterial cells (Pseudomonas Aeruginosa) growing in the conduit then migrate over glass towards an antibiotic. Finally, circuits with fluid-walls are built within wells of 96-well plates, to demonstrate that this technology can be seamlessly incorporated into standard high-throughput workflows based on microplates. All these circuits are built in minutes on virgin Petri dishes or standard plastics. The fluid walls allow direct access to any part of the circuit, they can even be reconfigured during the experiment, and cells can be recovered through them at any stage for analysis.