Abstract
Laboratory Automation is today used as a routine tool in a large variety of ways for accelerated experimentation in the chemical Industries. Over the last decade interest in automation as an enabling technology for high speed synthesis, substance isolation and analytical characterization has grown rapidly. The book edited by David G. Cork and Tohru Sugawara which deals with these fields of interest consists of 11 chapters written by academic and industrial experts in the field and is divided into two main parts. The first six chapters describe several aspects of “Laboratory Automation in Chemistry Discovery” e. g., automated synthesis, reaction optimization and parallel purification techniques. Part II is entitled “Laboratory Automation in Process Chemistry” and covers laboratory information management systems, design and optimization of chemical processes, calorimetry and chemical analysis.
As automated synthesis in parallel and combinatorial chemistry especially for drug discovery has been developing for at least two decades with an accelerated pace in the last few years it seems logical to start the book with two chapters reflecting this historical background and giving an overview on some of the devices and robotic systems used in todays automated synthesis laboratories. In Chapter 1 N. Hird and B. MacLachlan give a good overview on “Robotic Workstations and Systems” and also some of the chemistries performed with the various systems. Although it is not comprehensive this market survey will be valuable especially to newcomers in the field.
Nonrobotic fluidics-based approaches which have also been used for automated synthesis are described in Chapter 2 by T. Sugawara and D. Cork. In this case instead of using moving robotic arms to carry out liquid handling, the reaction vessels are directly connected to input and output fluid lines. The Japanese company Takeda has already an impressive history about self constructed automated synthesis systems as they started with the construction of their first automated lab reactor as early as 1985. Over the last decades highly sophisticated systems for various applications in solid supported and liquid phase synthesis were developed there and are described in this chapter.
That it is not only the hardware which makes an automated system work efficiently is of course common knowledge in the automation community. As a consequent addition to the first two chapters J. S. Lindsey et al., describe in detail in Chapter 3 their approach to “An Automated Chemistry Workstation Capable of Parallel Adaptive Experimentation” with special focus on the different software modules necessary for the efficient planning and performance of automated synthesis experiments including scheduling of the whole reaction sequence and integration of design of experiments.
Chapter 4 is entitled “Automated Purification Systems” (M. R. Stabile-Harris and April Ciampoli) and briefly discusses purification of reaction products by liquid-liquid extraction and solid phase extractions using resin scavengers. Polymer-supported reagents are also described shortly as a means of producing highly pure compounds with simple filtrations as reaction work-up. Massive parallel purification of large numbers of reaction mixtures is very important in modern drug discovery units as most companies now prefer the strategy of producing pure sample compounds for biological testing compared to mixtures. Therefore Chapter 5 written by J. A. Ramieri about “Parallel Purification” is a logical supplement. In this chapter purification by multi channel HPLC systems developed at Biotage is described. However as other systems are also used extensively for HPLC purification in combination with LC-MS detection of reaction products a more general overview would have been more desirable.
Chapter 6 in which B. Warrington discusses “Future Prospects for Automation in Chemistry Discovery” is one of the very best of the whole book. He not only covers technological aspects of the current hardware and software for high throughput chemistry and its future development but also other aspects of strategic importance like the need for greater intelligence, speed and economy in chemical synthesis. High throughput syntheses in microscale reactors and the direct coupling to biological screening systems are currently a hot topic in view of lowering the preparation costs per compound. A fast feedback of results from biological test assays makes it possible in combination with splitting larger library syntheses programs into smaller portions to adjust the synthesis efforts to the most promising regions and to follow a “Learn as you go” approach for library production.
During automated experiments usually huge amounts of different data files are created. To keep track of all these data is crucial for the success of an automated laboratory and therefore Laboratory Information Management Systems (LIMS) are an integral part of an automation environment. In Chapter 7 a general introduction to various aspects of LIMS is given by C. Paszko.
Chapter 8 is entitled “Design of Chemical Processes for Automated Synthesis”. J. Otera describes an automated synthesizer which was developed for the optimization of chemical reactions. Numerous examples of successful studies on one-pot reactions and integrated chemical processes are discussed.
“Optimization of Organic Process Chemistry” (Chapter 9, J. Mills) is always done with the goal of producing larger amounts of a new chemical entity but an equally important product from these efforts is information and a thorough understanding about the reaction. With a higher efficiency in drug discovery units due to the extensive use of automation which gives rise to larger numbers of new drug candidates the pressure in chemical development departments to bring these potential drugs faster to production also rises significantly. In this struggle for higher speed and throughput innovative automation tools become crucial. J. Mills describes the basics of some valuable mathematical tools like Simplex Method, Design of Experiments (DOE) and Principal Component Analysis (PCA). He also briefly discusses some automated synthesis systems for reaction optimization. However as several different synthesizers for process chemistry were constructed during the last years a more thorough survey would have been desirable. There are also already numerous examples of the successful use of laboratory automation in process chemistry described in the literature. Therefore it is surprising that the author doesn't discuss at least some of them in more detail to illustrate the importance of this new technology to the reader.
In Chapter 10 the use of “Automated Calorimetry in Process Development” is explained by N. Evens. Besides an increased speed of development of more robust processes and the cost savings created thereby it is especially the increased process safety that makes automated calorimetry equipment extremely valuable for chemical development and production units. The author describes commercially available systems and a series of interesting case studies are presented that underline the importance of this tool to the process development chemist.
The final chapter of the book is dedicated to “Parallel Automation for Chemical Analysis” (D. T. Rossi). Important applications of parallel analytical techniques for post-combinatorial compound characterization, drug metabolism isolation and automated dissolution testing are described. Some interesting views on new developments in high throughput analytics like 96 parallel multicapillary electrophoresis and future prospects in the field of chemical analysis with lab on a chip technologies are closing the chapter.
At the end of the book a seven page index gives the possibility for a quick start into the book regarding certain topics.
The layout of the book is of good quality and therefore it is easily readable. The various aspects of different laboratory automation applications are extremely valuable for the practical work in establishing these new technologies. This is supplemented by over 350 literature citations which in some cases cover work published up to early 2001.
Although the title of the book is a little bit misleading as mostly technical applications within the pharmaceutical industry are described and not as one could assume problems more general to the chemical industry as a whole are tackled, we feel in summary that this book is highly recommendable for all practioners and newcomers to the exciting field of laboratory automation in chemical synthesis and analytics.
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