Test Compound and Reagent Dispensing
According to Elaine Heron, Ph.D., Labcyte’s CEO, successful kinase screening campaigns in any format require precise liquid handling, robust assays, and sensitive detection methods combined to produce accurate results.
“The dirty little secret about compound dispensing in assays is that when performing transfers using a plastic pipette and an intermediate dilution, five to ten percent of the compounds in a given library are often lost,” Dr. Heron reported. She further explained that Labcyte’s technology addresses this specific problem by very precisely dispensing low volumes onto assay plates.
“Our system also allows people to save money by reducing the size of assays with better results,” Dr. Heron added. Labcyte’s Acoustic Droplet Ejection (ADE) technology, which is embodied in its Echo 555 liquid handler, enables dispensing of test compounds in extremely low volumes for screening and compound titration applications.
ADE works by transmitting sound waves through microplate wells containing test compounds. The pressure generated by a focused acoustic wave creates upswelling at the fluid surface, thereby causing a droplet to fly upward from the liquid surface. These droplets are then captured by the assay plate, which is suspended upside down over the source plate.
For the Echo systems, the size of the droplet is 2.5 nL; higher droplet volumes are attained by rapidly ejecting multiple droplets. Since there is no contact between the ejection mechanism and the sample, the technology is particularly suited to biological assays in which precise transfers are critical and cross-contamination interferes with accurate results.
According to Labcyte, its contact-free approach means that no tips or washing are needed, and compounds are not lost by adsorption onto plastic surfaces. The ability to accurately transfer 2.5 nL droplets allows miniaturization of assays to 384-, 1,536-, and 3,456-well formats economically, and with less solvent and plastic waste, Dr. Heron said.
In January, Labcyte acquired Deerac Fluids, a provider of liquid-handling systems that enable dispensing of a wide variety of liquids in 0.05–50 µL volumes. According to Dr. Heron, Deerac’s systems “expand the range of low-volume liquid-handling systems we are able to offer our customers.”
Deerac’s technology consists of a feed-back-controlled, air-displacement technology originally developed at Trinity College, Dublin. For the microHTS-format kinase-assay applications described at the workshop, Labcyte’s ADE-based dispensers were used to add test compounds to the assays and the Deerac products to add reagents.
Corning Life Sciences worked closely with Labcyte to develop the compound-assay plates that allow ADE-based dispensing with Echo systems. For these assay configurations, the plates containing the wells in which the assays are performed are upside down over the right-side up Echo source plates. “The 1,536-well flat-bottomed plates are made of an acrylic olefin copolymer that is acoustically clear, meaning that an acoustic signal can transfer the Echo system signal clearly,” explained Kim Titus, business development manager for Corning Life Sciences.
These source plates, she added, were developed with a well-geometry design that allows accurate transfer to the center of the assay plate wells, reducing the chance that test drugs will “jump into wells where you don’t want them.”