Liquid purification or separation – With means to add treating material – Chromatography
Reexamination Certificate
2001-09-14
2003-08-26
Therkorn, Ernest G. (Department: 1723)
Liquid purification or separation
With means to add treating material
Chromatography
C210S456000, C210S656000
Reexamination Certificate
active
06610200
ABSTRACT:
THE TECHNICAL FIELD
The present invention concerns a system for adsorption (capture) of a compound that is present in a liquid flow that pass through a fluidised bed. The invention also concerns various parts of this system, such the as a predistributor, a distributor, a vessel, a tilting device etc. The invention also concerns processes that are adapted to these parts.
By the term “capture” or “adsorption” is contemplated that the compound becomes bound to the particles of the fluidised bed by covalent bonds or affinity bonds, or by physically entrapment within the particles. The binding may be more or less reversible. Affinity bonds include binding caused by bioaffinity interaction, ionic interaction, hydrophobic interaction etc.
Binding as described above has previously been used for removal and/or purifying: a) the compound that becomes bound to the particles or b) a compound remaining in the liquid, or c) the liquid as such. In case of item a) the particles have been further processed in order to release and possibly further purify the bound compound. In case of items b) and c) the liquid has been further processed, for instance in order to recover or remove some other compound present therein.
Previous vessels for the above-mentioned processes have been in form of cylindrical columns equipped with meshes at the outlet end (collector end) and at the inlet end (distributor end).
The collector arrangement typically has contained a plate covered with a mesh on the side facing the vessel interior and a collector chamber with one or more outlet openings in the column end piece at the opposite side.
The distributor arrangement typically has contained a distribution chamber with one or more inlet tubes and a relatively thin perforated plate covered by a mesh resting on distance holders on the side facing the vessel interior. The major functions of the meshes have been to hinder fluidised particles from escaping the vessel and as a support for particles packed to a bed.
U.S. Pat. No. 4,450,082 describes a predistributor/distributor system for packed beds.
The meshes used at either end of the vessel have had pore sizes smaller than the particles used to form the bed (packed bed or fluidised bed).
Particles with densities greater than the liquid have been combined with upward flow and with the distributor placed at the lower and the collector at the upper end of the vessel. Particles with densities lower than the liquid have been combined with downward flow and with the distributor placed at the upper and the collector at the lower end of the vessel. After adsorption in a fluidised bed mode the particles have been allowed to sediment before release of the captured (adsorbed) compound (packed bed mode).
The term “release” includes desorption.
Capture of compounds in beds that are fluidised by an upward liquid flow is described in WO 9100799 (Upfront Chromatography), WO 9218237 (Amersham Phamacia Biotech AB), WO 9520427 (Amersham Pharmacia Biotech AB), WO 9717132 (Amersham Pharmacia Biotech AB), WO 9833572 (Amersham Pharmacia Biotech AB) and U.S. Pat. No. 4,976,865 (Sanchez et al, CNRS).
Drawbacks of Previous Techniques (Distributor Design)
In many applications a severe blockage has been experienced of the inlet and outlet meshes. The main reason has been clogging of feed material into the meshes, e.g. cells, cell debris, aggregates etc. This leads to an increased back pressure and maldistribution of the incoming fluid. The effect will be channeling in the bed disturbed plug flow and eventually the bed will collapse.
I similar effect is caused by air bubbles that are present in the feed stream.
Meshes have a mechanical instability. Even if installed as planar, they will tend to stretch and become wavy-like. Non-planar meshes tend to disrupt a plug flow profile created by a traditional distributor.
Distribution system in existing columns contains horizontal surfaces. It has been experienced that this type of surfaces often are difficult to clean from adhering material, for instance cell and cell debris in case the feed material contains fermentation broths and the like containing sticky components. Critical column parts are the horizontal surface of the bottom end piece and surface of the perforated plate (distribution plate) facing the bed where there are “dead zones”, i.e. zones with no active flow of liquid and consequently no continuous rinsing.
Drawbacks Without Predistribution
When the area of the distributor is increased and/or the distributor area is divided into modules with separate distribution chambers, there is a risk for uneven distribution of flow across the area of the distributor. This problem becomes particular important in case plug flow is desired in fluidised beds.
Drawbacks of Prior Art Vessel Designs With Respect to Emptying
The traditional way of emptying vessels used in packed bed as well as in fluidised bed has been to empty either from the top or from the bottom while keeping the vessel in an upright position. Bottom emptying many times has been trough a valve in the side wall just above the bottom. Previous methods have been rather complicated, many times leaving bed residues in the vessels requiring extra cleaning.
Drawbacks of Previous Designs of Reactor Vessels (Fluidised Mode Versus Packed Bed Mode)
If the bed is eluted and/or washed in an expanded mode the volume of liquid needed will typically be at least twice the packed bed volume, i.e. much more than for the same procedure in packed bed mode. The reason is that the liquid in an expanded bed will be highly turbulent when a lighter buffer is trying to displace the denser sample. In respect of process economics, the consumption of washing buffer should be kept as low as possible.
The Objectives of the Inventive Aspects
To get a sanitary distributor design with a minimum of dead zones and horizontal surfaces.
To generate the essential plug flow profile without using a thin perforated plate and a mesh in which the pore size is less than the particle size.
To reduce the risk for blockage of the distributor system by increasing the smallest passage area considerably compared to columns in which meshes are included.
To facilitate plug flow characteristics in chromatographic beds.
To get a simple and mechanical robust construction which can stand an industrial environment.
To be scaleable (consistent performance) from small laboratory columns/vessels to industrial columns/vessels.
To have systems in which the need for large volumes for washing and for release is lowered by making it easier to change from packed to fluidised mode and the reverse.
To provide a system that facilitates emptying of vessels used for capturing compounds to particles in packed or fluidised bed mode.
By the term “essential plug flow” is contemplated a plate number ≧5 for an expanded bed/fluidised bed. The method for measuring plate number is given in the experimental part.
REFERENCES:
patent: 4450082 (1984-05-01), Tanouchi
patent: 4871463 (1989-10-01), Taylor et al.
patent: 4976865 (1990-12-01), Sanchez et al.
patent: 278687 (1990-05-01), None
patent: 19718652 (1998-04-01), None
patent: 0 201 640 (1986-11-01), None
patent: 63231262 (1988-09-01), None
patent: WO 9520427 (1995-08-01), None
patent: WO 9534359 (1995-12-01), None
patent: WO 9833572 (1998-08-01), None
Translation of DD 278 687 PTO 03-2028 Mar. 2003 pp. 1-9.*
Translation of DE 19, 718, 652 PTO-03-2029 Mar. 2003 pp. 1-29.*
Translation of Japan Patent 63-231262 PTO 03-2030 Mar. 2003 pp. 1-19.
Gebauer Klaus
Leijon Patrik
Tärnström Anders
Amersham Biosciences AB
Ronning, Jr. Royal N.
Ryan Stephen G.
Therkorn Ernest G.
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