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The challenge of bioseparations is to isolate and purify identified products from the dilute product broth produced from cell culture. Innovation in bioseparations technology is increasingly driven by the requirements imposed by the growing importance of production on a process scale of injectable-grade products, and economic pressures to improve the efficiency of downstream processing. As in other areas of technical change, science does not necessarily precede new technology: progress results from a complex and messy mixture of advances in understanding, ingenious ideas, novel techniques and chance discoveries. What is certain is that close interaction between academics and practitioners, biological scientists and process engineers is needed to solve the problems of bioseparations. The Second International Conference on Separations for Biotechnology at Reading, UK, in September 1990 set out to provide a critical multidisciplinary forum for the discussion of bioseparations. This volume contains the papers presented at the meeting. The meeting was organised around six themes with oral and poster presentations on the science and practice of bioseparations technology, and the same structure has been kept for this book. We have also included the texts of the keynote review paper by Professor Alan Michaels and the introductory review papers specially commissioned for the conference. Within each part of this book the review paper is followed by the contributed papers grouped alphabetically by their first author. All the original papers published here were accepted for publication after scientific refereeing.

Separation processes in biotechnology are of increasing industrial importance since they entail the major costs of bioprocessing especially when high purity is required. Chromatography and membranes are two of the most important technologies used for direct treatment of fermentation broths as well as for high resolution steps in product purification. The theoretical foundations of chromatographic and membrane processes are well understood for the case of small molecules. Nevertheless there is a need to adapt and further develop that knowledge to the processing of large biological molecules. This is being achieved with the contribution of other areas like molecular biology and materials science. The objective of this NATO Advanced Study Institute is to present an updated treatment of the fundamentals of chromatographic and membrane processes with special relevance in bioprocessing.This volume collects the lectures presented at this Institute. The lectures are arranged in five chapters. Chapter I deals with chromatographic processes covering topics like equilibrium, kinetics and contacting devices. Membrane processes and some applications in biotechnology are treated in chapter 2. Chapter 3 is devoted to affinity chromatographic and membrane processes. Chapter 4 considers the current developments on chromatographic supports and membranes both from the constitutive materials and form points of view. Scale-up, optimization and reaction/separation integration are the topics covered in chapter 5. We are very grateful to all lecturers and participants that made possible this Institute. Financial support from NATO Scientific Affairs Division, INIC, JNICT, FLAD, University of Ac;ores and DRT Ac;ores is gratefully acknowledged.

The use of aqueous two-phase systems for the partitioning of macromolecules, organelles and cells was originally developed by Per-Ake Albertsson in Sweden in the mid-fifties [1-3]. These systems were initially applied to separations of plant organelles and viruses but their use has now extended into most areas of cell biology and biochemistry [4,5]. Since 1979 biennial International Conferences on Partitioning in Aqueous Two-Phase Systems have been held in Los Angeles (1979), Sheffield (1981), Vancouver (1983) and Lund (1985). The 5th conference was held in Oxford from 23-28 August 1987 and was entitled'Advances in Separations Using Aqueous Phase Systems in Cell Biology and Biotechnology'. It is the formal presentations from this meeting which comprise this volume. In contrast to earlier books on phase partitioning [4,5] this volume contains, for the first time, worldwide contributions from over sixty partitioners from a variety of scientific disciplines, thereby providing a detailed overview of the widespread application and potential of bioseparations using phase partitioning. Disciplines include Biophysics, Biochemistry, Cell Biology, Microbiology, Biotechnology and Process Engineering, in both academic and commercial establishments. These biennial conferences allow advances in these diverse partitioning fields to be reviewed and compared; they also provide an opportunity for those considering using phase partitioning to obtain information, advice and contacts. Attendance has grown steadily over the years and 140 scientists came to Oxford. The conference consisted of ten symposia on areas of application of partitioning which have been organised as specific chapters in this volume.

This book is based on the contributions to the IFAC-Workshop'Mass Spectro­ metry in Biotechnological Process Analysis and Control'held in Graz, Austria from 23 to 24 October 1986. The idea to organize this workshop and further to prepare these proceedings was stimulated by the following facts. Biotechnological processes urgently need better on-line instrumentation. Mass spectrometry (MS) offers a great potential to especially analyse gases and volatile compounds. It is, however, considered that this potential by far is not exhausted. The main reason for this is that MS often still is considered to be a very expensive technique requiring the permanent attention of a MS expert. In addition methods have not yet been developed to a user friendly state. On-line MS-methods are available to a certain extent, but need further development. To stimulate such development an interdisciplinary effort is necessary. Needs of industrial and university users and experience of physicists and instrument manufacturers have to be brought into a hopefully fruitful discussion. An introductory article describes the bioprocess background including a brief summary of the state of the art in bioprocess sensor and parameter estimation development, and the potential MS offers for bioprocess monitoring. In the first chapter on'Instrumentation and Gas Analysis'a general overview on some developments in MS-instrumentation is given initially by Schmid. Then the presently available instrumentation for bioprocess monitoring is discussed by instrument manufacturers (Winter; Schaefer and Schultis; Bartman).