Such a configuration permits interrogation of highly complex genetic models in a variety of backgrounds. An ADE system is fully integrated with existing laboratory processes and platforms to facilitate execution of PCR and quantitative PCR (qPCR) reactions. With growing needs for throughput and consistency, we find that traditional aspiration-and-dispense liquid-handling robots no longer have the required speed, quality, or reproducibility.We present an adaptation and installation of an acoustic droplet ejection (ADE) liquid-handling system for ultra-high-throughput screening of genetically engineered models.

These highly complex models of human disease often require increasingly convoluted genetic analysis. Genetically engineered animal models are major tools of a drug discovery pipeline because they facilitate understanding of the molecular and biochemical basis of disease. The results of this study also support the requirement for thorough mixing during serial compound dilutions prepared for high-throughput lead optimization strategies using traditional liquid handlers. The data confirmed the importance of establishing robust QC procedures for dose-response generation in addition to accuracy and precision determinations for each instrument, and they validated the use of nanoliter pipettors for dose-response testing. This study compared representative automation procedures done on a variety of liquid dispensers, including manual, traditional, and nanodispense volumes. Moreover, an intermediate dilution step in aqueous solution might result in compound precipitation at high concentrations. However, nanoliter dispensing technology allows for the conservation of compound, reduces compound carryover from well to well through discrete dispenses, and eliminates the need for intermediate compound dilution steps to achieve a low final DMSO assay concentration. For example, standard gravimetric measurements are unreliable for testing the accuracy of nanoliter liquid dispenses.

Although traditional automated liquid handlers are still considered the standard platform in many laboratories, nanoliter dispensers are becoming more common and pose new challenges for routine quality control procedures. One challenge in evaluating the performance of liquid handlers is identifying and validating a robust method for testing dispense volumes across different instruments. With the advancement of high-throughput biomolecular screening techniques to the lead optimization stage, there is a critical need to quality control (QC) dose-response curves generated by robotic liquid handlers to ensure accurate affinity determinations.

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