A Multi-Well Concentration Gradient Drug Delivery Microfluidic Device For High-Content And High-Throughput Screening

Abstract

<p>A microfluidic device capable of drug delivery to multiple wells in a concentration gradient was designed for automated high content and high throughput screening. The design was proposed to utilize a nanoporous polycarbonate membrane to spatially and temporally control drug dosage from the microchannels below to the wells above. Microchannels were to hold to the drugs or reagents, while wells were to culture cells. An array of 16 wells was to fit in the equivalent area of a single well of a 96 well plate. Two simpler devices were created to validate electrokinetic drug delivery to a single well and to characterize cell proliferation and viability in micro-wells. The first device tested drug delivery to a single well with methylene blue dye at applied voltages of 100V, 125V, and 150V. It was validated that the dosage of dye could be controlled by increasing the voltage and by increasing the duration the voltage was applied. The second devices were a series of 9-well arrays, each testing a different diameter (1.2 mm – 0.35 mm). These devices were cultured with MCF-7 breast cancer cells over 5 days. At the end of the 5 day study, all diameters except for 0.5 mm and 0.35 mm measured a cell viability of 99% and exhibited cell growth patterns similar to coverslip glass controls. The proposed integrated cell culture and drug delivery device could have application towards early stage drug discovery and could have compatibility with lab equipment originally designed for well plates.</p>