A novel wide-range microfluidic dilution device for drug screening

Abstract

Microfluidic dilution chip is a crucial approach to perform gradient dilution of experimental samples in many biological investigations. In this study, we developed two serial wide-range dilution chips with dilution rates of 1:1 and 1:4 on the basis of the microfluidic oscillator by designing a series chamber, which was similar to a series circuit. The size of this chamber was adjusted and mixed with the neighboring air chamber to form dilution rates by oscillatory methods. We applied this microfluidic oscillator to estimate cellular kinetics and perform an acute oxidative stress test on Caenorhabditis elegans (C. elegans) in order to further validate their effectiveness. We estimated the kinetic parameters of β-galactosidase, the biocatalyst responsible for the hydrolysis of lactose, and found out that Km was 602 ± 73 μM and kcat was 72 ± 12/s. In addition, our result of the study on acute oxidative stress of C. elegans using this novel chip was consistent with the result using 96-well plates. Overall, we believe that this novel chip can be applied to enzymatic reaction kinetics to evaluate accurately drug screening in bio-nematode models such as C. elegans. In summary, we have provided a novel microfluidic dilution chip that can form a wide range of sample concentration gradients. Our chip may facilitate drug screening, drug toxicology, and environmental toxicology.