Generating nonlinear chemical gradients in microfluidic devices by biased mixer input design*

Cell migration can be driven by chemical gradients. Our ability to precisely emulate and control the aspects of the biophysical environment (manipulate chemical gradients) is crucial to studying cell function. We present five microfluidic designs for generating non-linear gradients by passing the chemical through a combination of bifurcated, trifurcated, and mixing channels that split, mix, and recombine the flows to produce incremental dilutions into a common chamber. The non-linearity was introduced by adding bias to the mixers inputs. The study began with a 1:1 mixing ratio that generated a reference linear gradient in the chamber, followed by 2:1, 3:1, 4:1, and 5:1 mixing ratios that generated non-linear gradients. The bias was introduced by altering the input channel widths. Both COMSOL simulations and wet-lab experiments were used to study the chemical profiles across and along the gradient chamber.

ELW and OMA contributed as co-first authors.