Automation platform

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. 

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. 

Vinarov, D.A. and Markley, J.L. (2005) High-throughput automated platform for nuclear magnetic resonance-based structural proteomics. Expert Review of Proteomics, 2 (1), 49-55. 

Gulf of Mexico, Main Pass Block 41, Platform C, Fire Unmanned automated platform, cause of accident unknown. 

The use of automated platforms can decrease the manual workload and increase sample throughput during the primary separation step, but further advancement is still required to reduce the long times to develop rugged analytical assay for daily-use bioanalytical applications. 

Plastic substrates are now utilized for both nucleic acid and protein microarrays. In particular, plastic microarrays have been introduced for high-throughput applications based upon the microtiter plate which is the standard automation platform. 

In the 1980s, an analytical technique was developed for the study of chromium speciation in natural waters based on the atomization of electrodeposited species on graphite tubes.79 Two independent automated platforms consisting of an ultraviolet (UV) on-line unit and a chelation/preconcentration/... 

Advances in solid-phase oligosaccharide synthesis led to the development of an automated platform that was first demonstrated by Peter Seeberger and coworkers in 2001 using a modified peptide synthesizer [38], Automated washing, deprotection, and glycosylation steps dramatically reduced the time and labor usually attributed to solution- and solid-phase synthesis of oligosaccharides. 

The automated solid-phase synthesis of oligosaccharides was first reported in 2001 [38], A peptide synthesizer was modified to enable solid-phase oligosaccharide synthesis. The synthesizer was equipped with a cooling system for low-temperature glycosylations. As in the case with other automated platforms, a combination of new technologies and synthetic methods were developed, and distinctive breakthroughs were achieved. Many state-of-the-art synthetic and analytical methods were adopted and adjusted over the years. The first decade of automated solid-phase oligosaccharide synthesis relied on the development of new methods to access complex structures (Fig. 7.3). 

This chapter discusses in more detail the operational informatics systems and their integration with compound management and HTS instrumentation. It then covers various aspects of screening data analysis such as statistical methods to define hits, quality considerations, reporting, visualization, and cheminformatics-driven analysis and mining of HTS data. We start from the assumption that the HTS assay has been optimized and miniaturized on an automation platform and that the assay has been validated to deliver robust and reproducible high quality results—the prerequisite of a successful HTS campaign. 

M. Kullolli, W. S. Hancock, and M. Hincapie, Automated platform for fractionation of human plasma glycoproteome in clinical proteomics, Anal. Chem., 82 (2010) 115-120. 

Although commercial assays for direct serum analysis of rTj are available, kit procedures are not as convenient as are those for other thyroid hormones and no rTs method has been adapted to an automated platform because this measurement has no recognized diagnostic value. In comparison with the reference method described by Chopra,the typical kit procedure is relatively fast it requires a 3-hour incubation at room temperature, followed by polyethylene glycol precipitation and centrifugation. The entire procedure requires less than 6 hours to perform. 

PCR multiplexing and post-PCR automation make this platform attractive to laboratories. The throughput is less scalable than the previous platforms described, but can process up to 22 samples plus two controls. The starting PCR uses approximately 50 ng of DNA. After PCR, the automated platform takes 4 hours until the first results, with 30 minutes for each subsequent sample. 

The detection of kappa or lambda messenger RNA via an in situ hybridization reaction provides an alternative to the immunohistochemical detection of cytoplasmic kappa or lambda light chain (Fig. 6.4C and D). This technique allows for a much cleaner reaction product because it is only demonstrated where there is mRNA for kappa and lambda and not protein. Several immunohistochemical standards now provide an automated platform for the performance of this in situ hybridization reaction. This allows for this technique to enter routine performance and can be accomplished in approximately 5 hours. 

High-throughput screening automation exists at a variety of levels, from manual to semi-automated to fully automated turnkey systems (83). However, the types of equipment tend to be similar, and the way in which the screening process is integrated dictates the level of automation. For a brief discussion on the advantages and disadvantages of automated platforms versus workstations, see refs. 84 and 85. 

All the high-throughput screening automation platforms tend to have the same limited number of basic operations a method moving around microplates, dispensing liquids, a series of detectors, and incubators. The methods... 

Not all laboratories have the resources to build fully integrated screening platforms and support them. Additionally, not all assays can be modified to work on an automated platform. For example, a particular detector may not be available in a format that can be integrated. Most screening laboratories will use workstation approaches in addition to fully automated platforms to enable assay flexibility. Unlike the automated platforms, where plates are processed in a serial manner, plates are batched together, "a stack," in workstation approaches. Workstation approaches replaces the robot with a human, and as long as... 

Figure 1 Commercial automation platforms for high-throughput synthesis and formulation, (a) The Symyx core module (CM) synthesis platform, (b) The Chemspeed Swing SLT platform. Images reproduced with permission from Freeslate Inc. and Chemspeed Technologies, respectively.

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