Automated chemical dosing

As of the early 1990s, annual worker fatalities ran about 9 per 100,000 employees annual lost-time disabling injuries ran about 4,000 per 100,000 employees (1). Property losses increased fourfold from the 1970s (2). The trends in fatalities and property losses can probably be ascribed to the increasing complexity and productivity of the highly automated chemical plants, where personnel are isolated from processes. Whereas exposure to health and safety hazards maybe reduced, the ability of experienced operating personnel to sense process problems and to correct these problems frequently is decreased. Another aspect of process management which has tended to increase hazards is the effort to reduce the formation of wastes and undesired by-products. This effort requires dose approach to temperature and pressure limits, at which points loss of control can be catastrophic (see Process control). Process and plant safety issues have been discussed (3—8). 

Every marketed product has a level of endotoxin tolerated based on the minimum pyrogenic dose and amount of the drug to be administered as per Food and Drug Administration (FDA) guidelines [19]. However, there are none for the more advanced chemical assays described here. Indeed there are only a few highly specialized university laboratories that currently have experience in trace chemical analysis of LPS and PG. There are no commercial testing laboratories. Simplification and automation will allow more widespread availability of these methods. 

The overall process and critical activities for robotic implementation of automated HTS from intake of the researcher s benchtop assay through to the identification of a validated, optimized lead series of compounds around a bona fide chemical scaffold are shown in Fig. 2. The downstream steps of hit confirmation/ validation and structure-activity relationship (SAR) elucidation and hit to lead (HTL) have been included to emphasize that the same robotic assay used for production HTS can and should be used by the HTS team to perform high-volume hit confirmation and first-line automated dose-response analysis of confirmed hits to obtain quantitative potency (IC50) rankings to elucidate the nascent SAR of emergent hit series... 

Horizontal plating machines can be easily automated. Loaders and unloaders are usually integrated in the system. Automation of chemical analysis and dosing is incorporated with minimum cost increase. The equipment is easily linked to pre- and post-processes. Horizontal processing lends itself well to continuous production flow and reduced cycle time. 

---