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small pores that the filtrate must pass through to get to this point, some organic materials may be prone
to foaming in this situation. While some foaming may be acceptable, excessive amounts of foaming may
cause problems in the downstream processing of the filtrate leaving this device.
The last aspect to consider in using this solid-liquid separation device in the application proposed, is the
shear experienced by molecules present in the filtrate as it passes through the cake and septum of the
device. There will be some amount of shear as the liquid passes through small pores of the device and is
thus separated from the solids that were originally present. In addition, some biological solutions may
experience foaming tendencies on the vacuum side of this device. Both of these effects may adversely
affect some shear sensitive biological molecules processed in this fashion.
Even though there are a number of considerations for using this new technology to develop new
continuous chromatography systems, the potential of having a feasible continuous chromatography
system that can process at a rate of 1 to 3 liters per minute for a few thousand dollars is very exciting.
Applications in DNA Purification
In addition to the affinity chromatography applications outlined above, this same processing method could
be applied to other difficult pharmaceutical purifications in analogous ways. One such application is DNA
purification (DNA vaccine production and for gene therapies) using the properties of crystalline calcium
silicate hydrates and their abilities to bind to different degrees, Genomic DNA, open-circular plasmid, and
conformationally constrained supercoiled plasmid.
A number of recent studies have concentrated on the abilities of hydrated calcium silicates to preferential
absorb Genomic DNA, open-circular plasmid, or conformationally constrained supercoiled plasmid.
These materials were also shown to absorb impurities from upstream processing without significant
absorption of supercoiled plasmid under certain conditions (1). This referenced paper illustrates a new
and reviews existing information on the purification of nucleic acids using these types of materials instead
of traditional chromagraphic media. Beyond this, it also notes the ability of these materials to perform
separation on lipoproteins, triglycerides, cholesterols, phospholipids, glycolipids, and glycoproteins from
mammalian blood, plasma fluids. Of course the advantage of using materials instead of traditional
chromagraphic materials is their inherent lower costs.
The properties of crystalline calcium silicate hydrates used in this manner could improve the cost
effectiveness of purifications if done in a traditional column mode, but even more efficient and scaleable
operations could be envisioned if these are used in a mixing and filtration mode as we illustrated earlier.
Although studies have been done on these materials in a batch mixing and filtration operations, it is
feasible that a continuous mixing and filtration system could be devised, as outlined above, producing
cost effective, high volume purifications. The key element here would be replacing the batch mixing, or
absorption, time in the tank with the residence time in the tank as mentioned earlier.
Conclusion
Chromatography and related techniques are of ever growing importance in the development and
manufacture of new drugs especially those dependent on biological production processes. Growing out
of tedious batch methods, this powerful separation technique is ideal for research work, but can facilitate
significant bottlenecks when applied to larger scale production processes. The key in capitalizing on the
purification possibilities of this method, yet insuring that its use does not insert unwanted cost and
complexity into the final production process, is to implement a continuous version of this technique into
operation. The use of the Disposable Rotary Drum Filter in affinity and analogous chromatography
applications is one such step in this direction.
References
(1) Michael A. Winters, Jesse D. Richter, Sangeetha L. Sagar, Ann L. Lee, and Russel J. Lander; Plasmid
DNA Purification by Selective Calcium Silicate Adsorption of Closely Related Impurities; Biotechnol.
Prog.; 2003; 19(2) pp 440 447.
(2) Schweitzer, P.A., Handbook of Separation Techniques for Chemical Engineers, McGraw-Hill,
New York 1979, pp. 4-3 4-54.
(3) Kossik, J., (2002). "New Approaches to Four Unit Operations based on the use of the Disposable
Rotary Drum Filter, Solid-Liquid Separations for Biochemical Processing Session, FIFTEENTH ANNUAL
TECHNICAL CONFERENCE, American Filtration & Separations Society (AFS), April 9-12, 2002, MOODY
GARDENS HOTEL, GALVESTON ISLAND, TEXAS.
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