Home
Resources
Publications
Nanoliter Quantitative High-Throughput Screening With Large-Scale Tunable Gradients Based on a Microfluidic Droplet Robot Under Unilateral Dispersion Mode

Nanoliter Quantitative High-Throughput Screening With Large-Scale Tunable Gradients Based on a Microfluidic Droplet Robot Under Unilateral Dispersion Mode

Yan Wei, Ying Zhu, Qun Fang

Anal Chem. 2019 Apr 16;91(8):4995-5003.

PMID: 30813716

Abstract:

Performing quantitative high throughput screening (qHTS) is in urgent need in current chemical, biological, and medical research. In this work, we developed an automated microfluidic dilution and large-scale screening system in the nanoliter range, by combining the droplet-based microfluidic robot technique with a novel unilateral Taylor-Aris dispersion-based dilution approach. The unilateral dispersion approach utilizes multiphase microfluidic design to generate a concentration gradient with fast gradient generation time, low sample/reagent consumption, and high operation efficiency over the widely used bilateral Taylor-Aris dispersion approach adopted in previous dilution systems. The present system is capable of automatically generating a large and tunable range of concentration gradients covering ca. 6 orders of magnitude in droplet arrays and achieving qHTS of a large number of different samples. We applied the microfluidic droplet system in miniaturized enzyme kinetic assay in 8-nL droplets and high-throughput quantitative screening of enzyme inhibitors with a library of 102 compounds. Only 9.8 μL of enzyme solution was consumed in 2448 droplet assays containing 102 compounds and 24 concentrations, representing an approximate 1600-fold reduction compared with multiwell plate-based assays. In the screening, dose-response curves of each tested compound were established and 4 hits (CP-471474, ilomastat, batimastat, and marimastat) were screened to have inhibitory activity to matrix metallopeptidase-9 (MMP-9), which demonstrated that the present system has the potential to provide a miniaturized qHTS platform for drug discovery.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP210755456	CP-471474		210755-45-6	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: