Journal of Laboratory Automation

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Recent advances in microfabrication techniques, sensing methods, and miniaturization have enabled automated analysis of samples using microfluidic systems. Each unique application requires successful custom development of integrated lab-on-a-chip devices. This involves design, analysis and characterization of individual components, (pumps, valves, mixers, separators, sensors) and the integrated system. In this regard, first-principle-based simulations of the underlying complex multiphysics phenomena can provide detailed understanding of device function. An overview of modeling and simulation-based analysis for the design and development of microfluidic devices is presented. In particular, we highlight some key factors affecting the performance of lab-on-a-chip systems such as surface tension effects, analyte dispersion, Joule heating, and mass transport limitations, and delineate the parameters that influence them. The limitations of these modeling techniques and future needs are discussed.

Methods for the rapid determination of the enantiomeric excess (ee%) of organic substrates, especially for HTS, are often the “bottleneck” in a process. For this purpose, a new process of entirely automated sample preparation and the determination of ee% using electrospray ionization-mass spectrometry (ESI-MS) has been developed. Various substrates and new auxiliaries were explored to enhance the methodical scope. In combination with a very versatile liquid-handling system (HTS-PAL) and a comprehensive processing equipment, a multitude of standardized reaction vessels can be managed with the presented system. As an example of use, the ee% determination of I-phenylethanole via ESI-MS is compared to state-of-the-art GC analysis. In addition, a HTS suitable data processing network was constructed that allows postrun data manipulation and the automated data transfer to analysis and visualization templates with a maximum amount of automation.

High throughput robotic systems have been used since the 1990s to carry out biochemical assays in microtiter plates. However, before the application of such systems in industrial fermentation process development, some important specific demands should be taken into account. These are sufficient oxygen supply, optimal growth temperature, minimized sample evaporation, avoidance of contaminations, and simple but reliable process monitoring. A fully automated solution where all these aspects have been taken into account is presented. It is basically an arrangement of connected apparatuses (rail-mounted robotic arm, liquid handlers, sealer, shakers, fluorescence reader, etc.) that are integrated into a climatic chamber. Its readiness for use is demonstrated for the cultivation of Saccharomyces cerevisiae. This automation system permits to prepare, run, and monitor 768 aerobic micro-scale fermentations in parallel and without the need for any manual intervention. Although the applied quasi-continuous culture fluorescence measurement technique repeatedly requires a short interruption of the shaking process, this does not have a significant influence on the performance of cell culture experiments.

In the mid-1990s, HTS labs were built with high-end automation for screening 10,000s of compounds. Compound Management labs continued to manually pick samples and invest in standalone equipment. The bottleneck for screening shifted from testing samples to the distribution of compounds. To solve this problem, Merck & Co., Inc. developed an automated compound distribution center. The facility uses automation from The Automation Partnership and a Merck-developed compound ordering system to provide solid and solution samples to Merck scientists worldwide.

Cell-based assays for identification of biologically active small molecules from chemical libraries are becoming increasingly popular for HTS aimed at a variety of drug targets. Functional assays require good coordination between several independent processes during the run. This article describes our custom designed, fully automated Thermo LAS robotic system with integrated FLIPR^TETRA and several additional peripheral elements such as a BioTek ELX washer unit, a PE Evolution pipettor, and PE FlexDrop dispenser. The Thermo LAS robotic control software, Polara, ensures that each and every plate of sensitive cells in a large batch experiences the same procedure as an individual plate assayed in the hands of a scientist. Such robotic systems can process hundreds of plates a day and require large-scale automated support for cell preparation. The TAP SelecT is an automated robotic system that can plate 100– 300 plates of cells per day with defined accuracy and precision. In addition to plating cells, SelecT can also pass and expand cell lines. Here, we present a case study of a GPCR-mediated Ca-flux assay, where this robotic team enables high-throughput logistics even for an extremely sensitive cell-based assay.

The technology and techniques used when automating laboratory activities have been developed and documented for more than 40 years. Work performed under the subject of “laboratory automation” has progressed from pioneering achievements in data acquisition and instrument control to multicomponent, fully integrated systems resembling manufacturing plants. If the field is to move forward, we need to organize the practices of those applying automation and computing technologies to laboratory activities, and to formulate a course of study. This JALA Guest Editorial seeks to initiate a dialog on the definition and development of the field of “Laboratory Automation Engineering.”