The Dispensing Well Plate: A Novel Device for Nanoliter Liquid Handling in Ultra High-Throughput Screening

摘要

This article reports on a novel dispensing system for the massive parallel delivery of liquid volumes in the range of 50 nL. Due to the similarity of the device to conventional micro-well plates used for the storage of liquids, the device has been termed “dispensing well plate” (DWP). In contrast to other known micro dispensers, the DWP can consist of up to 1,536 dispensing units in parallel, all of which hold different reagents. The dispensing units can be arranged very closely at the pitch of conventional micro-well plates (2.25 mm or 4.5 mm). Driven by pneumatic actuation, a fixed volume of different liquids can be dispensed simultaneously and contact-free into micro-well plates or onto flat substrates. Because of this, the liquid handling in many chemical, biochemical, and pharmaceutical applications—especially within high-throughput screening (HTS)—can be sped up by a factor of 10 to 100. In our article, the basic operation principle of the device is presented, and experimental evidence of its extraordinary performance is given: a reproducibility of 2% to 5% and a homogeneity within individual droplet arrays of 1% to 2% has been measured, as well as viscosity independent performance for liquids in the range from 1 to 5 mPas. The applicability of the DWP technology within HTS is demonstrated by performing a miniaturized kinase assay at 1 μL assay volume in a 1536-well plate format.