Arbitrarily Accessible 3D Microfluidic Device for Combinatorial High-Throughput Drug Screening

Abstract

Microfluidics-based drug-screening systems have enabled efficient and high-throughput drug screening, but their routine uses in ordinary labs are limited due to the complexity involved in device fabrication and system setup. In this work, we report an easy-to-use and low-cost arbitrarily accessible 3D microfluidic device that can be easily adopted by various labs to perform combinatorial assays for high-throughput drug screening. The device is capable of precisely performing automatic and simultaneous reagent loading and aliquoting tasks and performing multistep assays with arbitrary sequences. The device is not intended to compete with other microfluidic technologies regarding ultra-low reaction volume. Instead, its freedom from tubing or pumping systems and easy operation makes it an ideal platform for routine high-throughput drug screening outside traditional microfluidic labs. The functionality and quantitative reliability of the 3D microfluidic device were demonstrated with a histone acetyltransferase-based drug-screening assay using the recombinant Plasmodium falciparum GCN5 enzyme, benchmarked with a traditional microtiter plate-based method. This arbitrarily accessible, multistep capable, low-cost, and easy-to-use device can be widely adopted in various combinatorial assays beyond high-throughput drug screening.

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

“…Microfluidic constructs, as is the main case for most of the fabricated 3D bioprinted liver devices, have been commonly used by pharmaceutical companies. The generation of suitable drug and gene carriers as well as the emergence of different microfluidic devices allowing the investigation of the effects of drugs under conditions reproducing the biological system has been widely described . The most common liver‐on‐a‐chip models for drug screening are for testing acute drug toxicity .…”

Microfluidic and Paper-Based Devices for Disease Detection and Diagnostic Research

“…These devices do not require external pumps or tubing, so they are easy to control and use. The enzymatic assays mainly focus on identifying specific inhibitors and use arrays with hydrophobic coatings to create the small droplets [ 178 , 179 ]. These small droplets function as single microreactors that contain a substrate and an inhibitor capable of low limit of detection enzyme kinetics.…”

“…These small droplets function as single microreactors that contain a substrate and an inhibitor capable of low limit of detection enzyme kinetics. Chen et al used fluorescence as an analytical output to measure the effectiveness of histone acetyltransferase inhibitors on Plasmodium falciparum enzymes [ 178 ]. Conversely, Cho et al relied on secondary ion mass spectroscopy technique to measure protein kinase activity after exposure to inhibitors [ 179 ].…”

Recent Advancements towards Full-System Microfluidics

“…A serious drawback for traditional microfluidic systems is the need for experienced users and the complexity of a typical setup, which includes tubing, valves and pumps. In their recent paper to this special issue, the Guan group presented an efficient high-throughput drug screening platform capable of quantitative combinatorial assays based on an arbitrarily accessible 3D microfluidic device [ 44 ]. The device featured automatic and simultaneous reagent loading and aliquoting tasks and performing multistep assays with arbitrary sequences and freedom from regular fluid handling systems, making it easy to operate; ideal for routine high-throughput drug screening outside traditional microfluidic labs.…”