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 semi-direct dilution capability of reagents for the determination of the half-inhibitory concentration or IC50. 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 IC50 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.

Matrix metalloproteinase-9 in a unique proteoglycan form in avian embryonic growth plate cartilage

“…Marimastat, a potent hydroxamate inhibitor of MMPs, showed 50% inhibition of the gelatinase at 10 nM, and complete inhibition at 100 nM (data not shown). Marimastat has been shown to inhibit MMP-9 in the low nM range[52]. …”

Determination of antibiotic EC50using a zero‐flow microfluidic chip based growth phenotype assay

“…Present assay system contains an integrated microfluidic chip that generates a logarithmic concentration gradient through semidirect dilution [20] in a zero‐flow environment (Fig. 1; Supporting information, Fig.…”

New Tools and New Biology: Recent Miniaturized Systems for Molecular and Cellular Biology

“…To develop an error-free system, Hong's group recently introduced a microfluidic system that can generate accurate logarithmic-scale concentration gradients (Fig. 4A) (Yun et al, 2011) and integrated this system with open-well microchambers for cell culture and dose-response assays (Hamon et al, 2013). The chip comprised 3 gradient generators (GG).…”