Adaptation of liquid handlers to the automation of combinatorial organic chemistry

High throughput screening has been at the forefront of laboratory automation for several years, resulting in rapid and efficient biological testing. More recent efforts have focused on automating the synthesis of new candidates for screening, particularly through the use of combinatorial methods. Traditional robotic liquid handlers have been designed for delivery of aqueous samples for biological assays, but they are not necessarily suitable for delivery of the organic solvents and reagents for synthesis. Additionally, screening applications are often run by a dedicated operator or teams of operators, while apparatus for combinatorial organic synthesis may be used by a large and heterogeneous group, often located at more than one site. Several of the problems related to conversion of conventional liquid handlers for use in organic synthesis are discussed below. The Hamilton Microlab 2200 liquid handler is currently used in our laboratory to perform many liquid handling tasks, including product distribution and reagent delivery for both solution- and solid-phase chemistry. Many hardware and software modifications have been incorporated into the system to adequately support the needs of organic and combinatorial chemistry. For example, we have incorporated user-friendly software with built-in calibration and error recovery routines, a flexible worktable and convenient carriers for various racks. By using a universal deck layout and common carriers, we can provide identical systems at several sites. Our methods are not specific to the Hamilton Microlab, and application to other liquid handlers will be discussed.