Advances in Biochemical Engineering/
Biotechnology, Vol. 68
Managing Editor: Th. Scheper
© Springer-Verlag Berlin Heidelberg 2000
Multistage Magnetic and Electrophoretic Extraction
of Cells, Particles and Macromolecules
K.S.M.S. Raghavarao 1 , Marc Dueser 2 , Paul Todd 2
1 Department of Food Engineering, Central Food Technological Research Institute (CFTRI),
Mysore-570 013, India
2 Department of Chemical Engineering, University of Colorado, Boulder, CO-80809-424, USA
E-mail: raghava@cscftri.ren.nic.in
Improved techniques for separating cells, particles, and macromolecules (proteins) are increasingly important to biotechnology because separation is frequently the limiting factor for
many biological processes. Manufacturers of new enzymes and pharmaceutical products
require improved methods for recovering intact cells and intracellular products. Similarly
isolation, purification, and concentration of many biomolecules produced in fermentation
processes is extremely important. Often such downstream processing contributes a large
portion of the product cost. In conventional methods like centrifugation and even modern
methods like chromatography, scale-up problems are enormous, making them uneconomical
and prohibitively expensive unless the product is of very high value. Therefore there has been
a need for efficient and economical alternative approaches to bioseparation processes to
eliminate, reduce, or facilitate solids handling. Magnetic and electric field assisted separations may hold considerable potential for providing a future major improvement in bioseparation technology.
In the present review the merits and demerits of the existing methods are discussed. We
present mainly our own research on the development of unified multistage extraction
processes that are versatile enough to handle cells and particles as well as macromolecules as
described below. We describe multistage methods, namely ADSEP (Advanced Separator),
MAGSEP (Magnetic Separator), and ELECSEP (Electrophoretic Separator), for quantitatively
separating cells, particles, and solutes by using magnetically and electrophoretically assisted
extraction processes. To the best of our knowledge, multistage magnetic and electrophoretic
separations have not been reported in the earlier literature. The theoretical underpinnings of
these separations are crucial to their success and to the identification of their advantages over
other separation processes in particular applications. Hence mathematical modeling is
stressed here, presenting our own models while also reviewing models reported in the
literature. We also present suggestions for future work while analyzing the scale-up and
economic aspects of these extraction processes. Commercial uses of the magnetic and
electrophoretic processes, having both ground- and space-based research elements, also are
presented in this review.
Keywords. Magnetic extraction, Electrophoretic extraction, Aqueous two-phase extraction,
Multistage extraction, Counter-current distribution
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
2
Cell and Particle Separations . . . . . . . . . . . . . . . . . . . . . 144
2.1
Magnetic Extraction . . . . . . . . . . . . . . . . . . . . . . . . . . 144
2.1.1 Existing Methods – Brief Summary . . . . . . . . . . . . . . . . . . 145
2.1.2 Multistage Magnetic Method . . . . . . . . . . . . . . . . . . . . . 148
2.1.3 Theory and Mathematical Models . . . . . . . . . . . . . . . . . . 153
Biotechnology, Vol. 68
Managing Editor: Th. Scheper
© Springer-Verlag Berlin Heidelberg 2000
Multistage Magnetic and Electrophoretic Extraction
of Cells, Particles and Macromolecules
K.S.M.S. Raghavarao 1 , Marc Dueser 2 , Paul Todd 2
1 Department of Food Engineering, Central Food Technological Research Institute (CFTRI),
Mysore-570 013, India
2 Department of Chemical Engineering, University of Colorado, Boulder, CO-80809-424, USA
E-mail: raghava@cscftri.ren.nic.in
Improved techniques for separating cells, particles, and macromolecules (proteins) are increasingly important to biotechnology because separation is frequently the limiting factor for
many biological processes. Manufacturers of new enzymes and pharmaceutical products
require improved methods for recovering intact cells and intracellular products. Similarly
isolation, purification, and concentration of many biomolecules produced in fermentation
processes is extremely important. Often such downstream processing contributes a large
portion of the product cost. In conventional methods like centrifugation and even modern
methods like chromatography, scale-up problems are enormous, making them uneconomical
and prohibitively expensive unless the product is of very high value. Therefore there has been
a need for efficient and economical alternative approaches to bioseparation processes to
eliminate, reduce, or facilitate solids handling. Magnetic and electric field assisted separations may hold considerable potential for providing a future major improvement in bioseparation technology.
In the present review the merits and demerits of the existing methods are discussed. We
present mainly our own research on the development of unified multistage extraction
processes that are versatile enough to handle cells and particles as well as macromolecules as
described below. We describe multistage methods, namely ADSEP (Advanced Separator),
MAGSEP (Magnetic Separator), and ELECSEP (Electrophoretic Separator), for quantitatively
separating cells, particles, and solutes by using magnetically and electrophoretically assisted
extraction processes. To the best of our knowledge, multistage magnetic and electrophoretic
separations have not been reported in the earlier literature. The theoretical underpinnings of
these separations are crucial to their success and to the identification of their advantages over
other separation processes in particular applications. Hence mathematical modeling is
stressed here, presenting our own models while also reviewing models reported in the
literature. We also present suggestions for future work while analyzing the scale-up and
economic aspects of these extraction processes. Commercial uses of the magnetic and
electrophoretic processes, having both ground- and space-based research elements, also are
presented in this review.
Keywords. Magnetic extraction, Electrophoretic extraction, Aqueous two-phase extraction,
Multistage extraction, Counter-current distribution
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
2
Cell and Particle Separations . . . . . . . . . . . . . . . . . . . . . 144
2.1
Magnetic Extraction . . . . . . . . . . . . . . . . . . . . . . . . . . 144
2.1.1 Existing Methods – Brief Summary . . . . . . . . . . . . . . . . . . 145
2.1.2 Multistage Magnetic Method . . . . . . . . . . . . . . . . . . . . . 148
2.1.3 Theory and Mathematical Models . . . . . . . . . . . . . . . . . . 153