Log-scale dose response of inhibitors on a chip

Abstract

We demonstrate the accommodation of log-scale concentration gradients of inhibitors on a single microfluidic chip with a semidirect dilution capability of reagents for the determination of the half-inhibitory concentration or IC 50. The chip provides a unique tool for hosting a wide-range of concentration gradient for studies that require an equal distribution of measuring points on a logarithmic scale. Using Matrix metalloproteinase IX and three of its inhibitors, marimastat, batimastat, and CP471474, we evaluated the IC 50 of each inhibitor with a single experiment. The present work could be applied to the systematic study of biochemical binding and inhibition processes particularly in the field of mechanistic enzymology and the pharmaceutical industry. © 2011 American Chemical Society.