Combinatorial dispensing as a fast and efficient means to create complex screens

Liquid handling robots carry out tasks from simple plate filling to complex operations such as creating reagent cocktails from multiple stock solutions. The latter task is conceptually a combinatorial process where each cocktail is created by combining a subset of stock solutions in user-defined volumes. General-purpose liquid handlers can perform this task, but their hardware lacks the inherent properties needed to exploit the combinatorial nature of the problem at hand. Here we present the use of non-contact dispensing technologies to create complex screens at low volume and high density. Our approach is based on the "inkjet printer principle" where a block of dispensers (print head) travels over a multi-well plate (paper) to deliver the reagents (inks) in a user-defined pattern. Impact-induced mixing and the lack of tip contamination remove the need for extensive tip washing or the use of large numbers of disposable tips. As an example, protein crystallization screening is used to demonstrate the technology. This application requires the creation of complex mixtures from many stock solutions with a great diversity of viscosities and surface tensions. In addition, dispense volumes cover a range from 50 nL to 50 microL, illustrating its utility in low-volume high-density screening.