Controlled microfluidic switching in arbitrary time-sequences with low drag.

The ability to test the response of cells and proteins to a changing biochemical environment is of interest for studies of fundamental cell physiology and molecular interactions. In a common experimental scheme the cells or molecules of interest are attached to a surface and the composition of the surrounding fluid is changed. It is desirable to be able to switch several different biochemical reagents in any arbitrary order, and to keep the flow velocity low enough so that the cells and molecules remain attached and can be expected to retain their function. Here we develop a device with these capabilities, using U-shaped access channels. We use total-internal reflection fluorescence microscopy to characterize the time-dependent change in concentration during switching of solutions near the device surface. Well-defined fluid interfaces are formed in the immediate vicinity of the surface ensuring distinct switching events. We show that the experimental data agrees well with Taylor-Aris theory in its range of validity. In addition, we find that well-defined interfaces are achieved also in the immediate vicinity of the surface, where analytic approaches and numerical models become inaccurate. Assisted by finite-element modelling, the details of our device were designed for use with a specific artificial protein motor, but the key results are general and can be applied to a wide range of biochemical studies in which switching is important.