HTS automation

The next step in complexity and functionality in HTS automation can be defined as the workcell concept, in which several different instruments serving the four main functions are integrated into a relatively dense array on a fixed framework that includes some robotic mechanism for transporting plates from one instrument to... 

All separations were performed on an Applied Biosystems Model 270A-HT automated capillary electrophoresis system. All separation media were prepared using Milli-Q water and filtered through 0.22- m filters obtained from Gelman Sciences... 

HTS is usually carried out it multiwell plates and the industry has settled on certain standard formats. One key standard is that most screening assays are carried out in 96 (8 12) or 384 (16 24) well plates with a standard footprint. This standard is important because most automation is optimized for use with these plates and attendant assay volumes in the 100 pL range. Furthermore, source plates containing test compound are typically stored in a similar configuration, allowing for more efficient transfer of test compound from the source plate to the assay plate. Various types of plates are available to match different assay formats, including... 

Out of the work with HT-XPIPE it became clear to the consortium that there was a need to expand the automated molecular replacement protocol embodied in HT-XPIPE to handle scenarios in which either the target was a new project or ligand-binding caused a packing change in the protein that... 

The chip micro reactor ([R 6]) was only one part of a complex serial-screening apparatus [20]. This automated system consists of an autosampler (CTC-HTS Pal system) which introduces the reactant solutions in the chip via capillaries. A pumping system (p-HPLC-CEC System) serves for fluid motion by hydro dynamic-driven flow. A dilution system [Jasco PU-15(5)] is used for slug dilution on-chip. The detection system was a Jasco UV-1575 and analysis was carried out by LC/MS (Agilent 1100 series capLC-Waters Micromass ZQ). All components were on-line and self-configured. 

In the current era neutral compounds are important simply because there are so many of them especially in screening collections made in automated chemistry for HTS. Other things being equal, a compound with an ionizable moiety is preferred to a neutral compound. By definition a neutral compound will not give an acid or basic pJCj value. Some essentially neutral compounds can form aqueous unstable salts. This most commonly occurs when an extremely poorly basic compound is dissolved in organic solvent and the salt is precipitatated, e.g. by bubbling in HCl gas. 

HTS is most simply defined in terms of throughput. The use of automation to achieve high throughput is a natural, but not inevitable, consequence in the quest for... 

A comprehensive listing of all the vendors that offer HTS instrumentation and platforms is beyond the scope of this chapter, but most vendors maintain informative websites and there are three professional organizations that disseminate useful information about automation platforms for HTS on the world wide web, the Society for Biomolecular Sciences (www.sbsonline.com), the Association for Laboratory Automation (www.labautomation.org), and the Laboratory Robotics Interest Group (www.lab-robotics.org). The latter maintains an online forum where vendors and experienced users often provide immediate and useful guidance. 

The most complex automated systems are used almost exclusively by centralized HTS operations in large pharmaceutical companies and are referred to as ultra HTS (uHTS) platforms. They typically consist of the same four functional instruments, but have the capacity to process several hundred plates per extended workday. They often incorporate a modular design philosophy with multiple duplicate instruments for enhanced capacity that offer some functional redundancy. The mechanism for moving plates from one instrument module to another is often, but not always, a continuous track-way that resembles an industrial assembly line rather than the robotic arm typically used in a workcell system [5-8],... 

Successful management of a central HTS operation requires a discipline of process control that extends beyond the automation systems. The progression of HTS projects must be carefully guided and tracked through several milestones designed to ensure that a steady and predictable stream of robust assays are available for transfer to the automation platforms and that sufficient bulk reagents and consumable supplies will arrive in time to support the HTS campaigns. 

The demands for protein reagents and cells for HTS have already prompted several companies to adopt automated systems for protein purification [10, 11],... 

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