4
Scale-Up and Economic Aspects
A limited number of biotechnological applications are available at present
where magnetic extraction techniques were successfully used both in a laboratory and large-scale. Recent developments such as new methods of generating
high magnetic field gradients and availability of reasonably priced efficient and
superconducting magnets enabled the use of magnetic extraction technology
even on a large-scale [1]. Batch HGMS machines are in commercial use and continuous separators are also developed [1]. Some of the following are already
commercialized or have very high possibility in near future.
Magnetic affinity adsorbents are now widely accepted in immunoassay
techniques [145, 146]. The main advantage of magnetic separation here is to
eliminate the need for centrifugation with its many associated disadvantages
[145]. Further magnetic separations are cheaper, faster, allow many samples to
be handled simultaneously, and help to lend the process towards automation.
Ease of conjugation of magnetic immunomicrospheres having the required size
with antibodies paved the way for large-scale immunological cell sorting [1].
Development of new polymers simplified the handling of water insoluble
enzymes and use of immobilized magnetic enzymes for reaction on a largescale has been investigated [1]. Performance data in simple and complex
matrices for the process-scale cell separation with the help of bioreceptor
ferrofluids and HGMS was reported [147].
Commercially introduced by Dynal A/S (Oslo, Norway) and Miltenyi Biotech
(Bergish Gladbach, Germany), immunomagnetic cell separation has become an
established method for cell analysis in clinical diagnostics. Its low price makes it
an alternative to flow-cytometry and very handy for the rare cellular events [148].
On analyzing the available information, it appears that electro-extraction
may pose more scale-up problems when compared to magnetic extraction for
cells, particles, and macromolecules. However, the actual situation varies
depending on the application and each method has its own advantages and
disadvantages. For instance, the advantages of using the magnetic rather than
electric field are: no need for medium modifications, no biological effects in the
range of practical static magnetic field intensities, no joule heating and therefore no flow distortion and thus no need for a complex cooling system [149]. On
the other hand, the disadvantages are: its complex interaction with paramagnetic and ferromagnetic labels, adding to the cost of research and development and its dependency on chemical reagents antibodies and magnetic colloids while all other methods are based on cellular immunoreactivity [44].
Practically no reports are available in the literature up to the present date
regarding economic aspects of magnetic and electro-extractions. One report
was available on costing, albeit based on 1977 data, of a HGMS unit for cleaning
of wastewater from a steel mill [150]. However, we are optimistic about the
prospects for the electrophoretic methods in processing of cells and macromolecules due to two main factors. As a source of energy, electrons are cheap
and equilibrate quickly. As a force, electric fields are tunable to a very fine
degree and involve no moving parts. Small-scale applications are already
Multistage Magnetic and Electrophoretic Extraction of Cells, Particles and Macromolecules
181
Scale-Up and Economic Aspects
A limited number of biotechnological applications are available at present
where magnetic extraction techniques were successfully used both in a laboratory and large-scale. Recent developments such as new methods of generating
high magnetic field gradients and availability of reasonably priced efficient and
superconducting magnets enabled the use of magnetic extraction technology
even on a large-scale [1]. Batch HGMS machines are in commercial use and continuous separators are also developed [1]. Some of the following are already
commercialized or have very high possibility in near future.
Magnetic affinity adsorbents are now widely accepted in immunoassay
techniques [145, 146]. The main advantage of magnetic separation here is to
eliminate the need for centrifugation with its many associated disadvantages
[145]. Further magnetic separations are cheaper, faster, allow many samples to
be handled simultaneously, and help to lend the process towards automation.
Ease of conjugation of magnetic immunomicrospheres having the required size
with antibodies paved the way for large-scale immunological cell sorting [1].
Development of new polymers simplified the handling of water insoluble
enzymes and use of immobilized magnetic enzymes for reaction on a largescale has been investigated [1]. Performance data in simple and complex
matrices for the process-scale cell separation with the help of bioreceptor
ferrofluids and HGMS was reported [147].
Commercially introduced by Dynal A/S (Oslo, Norway) and Miltenyi Biotech
(Bergish Gladbach, Germany), immunomagnetic cell separation has become an
established method for cell analysis in clinical diagnostics. Its low price makes it
an alternative to flow-cytometry and very handy for the rare cellular events [148].
On analyzing the available information, it appears that electro-extraction
may pose more scale-up problems when compared to magnetic extraction for
cells, particles, and macromolecules. However, the actual situation varies
depending on the application and each method has its own advantages and
disadvantages. For instance, the advantages of using the magnetic rather than
electric field are: no need for medium modifications, no biological effects in the
range of practical static magnetic field intensities, no joule heating and therefore no flow distortion and thus no need for a complex cooling system [149]. On
the other hand, the disadvantages are: its complex interaction with paramagnetic and ferromagnetic labels, adding to the cost of research and development and its dependency on chemical reagents antibodies and magnetic colloids while all other methods are based on cellular immunoreactivity [44].
Practically no reports are available in the literature up to the present date
regarding economic aspects of magnetic and electro-extractions. One report
was available on costing, albeit based on 1977 data, of a HGMS unit for cleaning
of wastewater from a steel mill [150]. However, we are optimistic about the
prospects for the electrophoretic methods in processing of cells and macromolecules due to two main factors. As a source of energy, electrons are cheap
and equilibrate quickly. As a force, electric fields are tunable to a very fine
degree and involve no moving parts. Small-scale applications are already
Multistage Magnetic and Electrophoretic Extraction of Cells, Particles and Macromolecules
181