Patent Application
20110259831
The present invention relates generally to processing columns and, in particular, to a tracking regulator system and method for processing columns.
Processing columns are used in many industrial processes at various pressure ratings. For example, the use of large scale chromatography to purify raw materials, intermediates and end products is common in many industrial segments including pharmaceutical products, biopharmaceutical products, nutraceutical products, food and beverage products, household products, personal care products, petroleum products, chemical products and other specialty products. In addition, certain industries, such as the biopharmaceutical industry, require the use of multiple chromatographic purification steps for every product made.
Processing columns typically require both the formation and maintenance of a homogenous bed of particulate substrate material (such as polymeric or silica gel based chromatography medias) within the column. For the sake of efficiency, the arrangement of particulate material inside the column should be as homogeneous as possible. In addition, empty volumes between the bed of particulate substrate material and the column inlets and outlets must be avoided. The state of the art in large-scale column chromatography utilizes a technology referred to as “dynamic axial compression” to address these issues. In dynamic axial compression, an adjustable position piston head is used to compress the substrate particulate material, usually of a size between 5 and 100 microns, within the column. The piston head is dynamically moved by means of pneumatic or hydraulic pressure. The force on the piston may be applied externally of the column via a rod or internally by pressuring the column on one side of the piston.
In processing column applications, fluctuations in the substrate bed volume occur due to settling, shrinking and swelling of the bed material, especially when such material is of a compressible nature and the shrinking or expansion of the bed is due not only to hydraulic forces of flow through the bed, but from the added effect of pH, solvent concentration or salt concentration. Another problem is that the operation of eluent pumps is not free of pulsations. This results in a variable mechanical stress on the bed as well.
A need therefore exists for a system and method that maintains the bed integrity by compensating for dynamic changes in bed pressure based on real time monitoring of the process liquid flow pressure.
While the embodiment of the system and method of the present invention is described below in terms of liquid chromatography, it is to be understood that the invention is not so limited and that it may alternatively be applied to other processes involving processing columns such as filtration, solid phase synthesis, capture and adsorption as well as other types of chromatography, including gas and supercritical fluid.
An embodiment of the system of the present invention is indicated in general at 10 in
A substrate bed 36 of particulate material is positioned between the bottom surface of the piston head and the bottom plate. The bed 36 may alternatively be a single piece (monolithic or membrane) bed or a liquid suspension of cells (such as is used in fermentation using yeast, or a bioreactor using plant of animal cells). The substrate bed 36 may be porous or non-porous and may include polymeric material or gel, including a base structure that is constructed from cellulose, methacrylate, divinyl benzene, silica, zeolite, titanium or is of the type used in any other separation medium.
The system includes a sensing diaphragm 42 that is in fluid communication with port 34 of the processing column 12 via a capillary line 44 containing a fluid such as air or a liquid. The system also includes a tracking regulator 50 which features a pressure sensing input 51 that is in fluid communication with the sensing diaphragm 42 via a liquid-filled line 52. As will be explained in greater detail below, the tracking regulator also allows a bias pressure to be added to the pressure acting on the piston head 16 based on the process liquid flow pressure feedback provided by sensing diaphragm 42.
A hydraulic liquid reservoir 54 communicates with the inlet of a hydraulic pump 56 via line 58, while the outlet of the pump communicates with a hydraulic fluid inlet 60 of the tracking regulator 50 via line 62. The tracking regulator is also in fluid communication with the hydraulic liquid reservoir 54 via a hydraulic fluid drain port and line, indicated at 63 and 64, respectively. The tracking regulator 50 also features a hydraulic fluid outlet 65 that is in fluid communication with the piston pressure chamber 26 of the processing column via line 66. The operation of pump 56 is controlled by electronic controller 68. Electronic controller 68 may be a microprocessor or any other electronic control device known in the art.
In operation, a set bed pressure Ps for the substrate bed 36 is selected and entered into controller 68. This initiates the operation of pump 56 so that hydraulic liquid from reservoir 54 is directed to the piston pressure chamber 26 through lines 58 and 62, tracking regulator 50 and line 66. As a result, the piston pressure chamber is pressurized with the hydraulic liquid and piston head 16 is pushed downward with the selected set bed pressure Ps so as to compress or pack the particulate material of substrate bed 36.
When the liquid chromatography process is initiated, process fluid (in this case, first a mobile phase liquid and later the liquid solution of crude material to be chromatographed) travels into the column through the process fluid port 34, passes through the substrate bed 36 and then through the process fluid passage 22 and out of the column. While this mode operation, with the process fluid port 34 serving as the column inlet and the process fluid passage 22 serving as the column outlet, will be assumed going forward, it should be understood that the flow may alternatively be routed to travel in the reverse direction with the liquid entering the column through the process fluid passage 22 and exiting the column through process fluid port 34.
As a result of the process fluid flowing through the substrate bed 36, a flow pressure Pf acts on the bottom side of the piston head 16 in addition to the set bed pressure Ps. Left unaddressed, as in typical prior art systems with locked pistons, the piston head 16 would be unable to travel upward so as to reduce the additional flow pressure acting on the substrate bed 36. In the case of dynamic axial compression columns, especially with the use of soft and compressible substrate bed media, normal operation can require operating at high flow rates through the bed. This may require an increased piston pressure setting to keep the piston from moving. The increased piston pressure setting can be tolerated by the bed material as long as it is hydraulically cushioned by the incoming flow. When the flow rate is reduced or stopped, however, such piston pressure can exert physical pressure on the media that is beyond its physical ability to support, resulting in over compression of the media which closes the internal pore structure as well as resulting in breakage of the media substrate. As will now be explained, the system of
The controller 68 is calibrated so that the pressure provided to the inlet of the tracking regulator 50 through line 62 actually equals the set bed pressure Ps or an amount slightly above the maximum anticipated operating or process flow pressure Pfmax. This amount, preferably around 1-2 psi above Pfmax, is the overpressure point, the use of which will be explained below. The tracking regulator is calibrated so that, absent the flow of liquid through port 34, only hydraulic fluid sufficient to provide the set bed pressure Ps is provided to the piston pressure chamber 26.
When the process fluid flow through the column is initiated, sensing diaphragm 42 senses the pressure of the fluid flowing through process fluid port 34 via capillary 44 and provides a sensed pressure input to the tracking regulator 50 via liquid-filled line 52. Tracking regulator 50 responds by increasing the amount of hydraulic fluid delivered from line 62 to the piston pressure chamber 26 through line 66 in proportion to the pressure sensed by the sensing diaphragm 42. Tracking regulator 50 is calibrated so that the additional hydraulic fluid, and thus pressure, delivered to the piston pressure chamber 26 causes the total bed pressure Pt acting on the top side of the piston head 16 to equal the set bed Ps pressure plus the process fluid flow pressure Pf acting on the bottom side of the piston head. In other words, the tracking regulator adjusts the pressure that the piston head 16 applies to the substrate bed 36 according to the following equation:
P
t
=P
s
+P
f
where:
The sensing diaphragm 42 senses both increases and decreases in the process fluid flow pressure. Any increases in the flow of fluid into the column, which result in corresponding increases in the flow pressure Pf acting on the bottom side of the piston head 16, are reflected by the pressure sensed at port 34 by the sensing diaphragm and communicated to tracking regulator 50. The tracking regulator 50 reacts by increasing the pressure within the piston pressure chamber 26 so that the total bed pressure Pt acting on the piston head continues to match the process flow pressure Pf plus the set bed pressure Ps.
When the flow of processing fluid into the column through port 34 decreases, this information is transmitted to the tracking regulator via the sensing diaphragm 42, as described previously. The tracking regulator 50 responds by releasing pressure from piston pressure chamber 26 through line 66 and hydraulic fluid drain line 64. As a result, the hydraulic fluid travels back to the hydraulic fluid reservoir. The amount of fluid released is proportional to the pressure decrease sensed by the sensing diaphragm, and thus the tracking regulator. As a result, the total bed pressure Pt is reduced corresponding to the reduction of the process fluid flow pressure Pf. In other words, the tracking regulator 50 reacts by decreasing the pressure within the piston pressure chamber 26 so that the total bed pressure Pt acting on the piston head continues to match the process flow pressure Pf plus the set bed pressure Ps.
When the flow of processing fluid into the column through port 34 reaches a level corresponding to the overpressure point, again as detected by the sensing diaphragm 42 via port 34, the tracking regulator, releases pressure from piston pressure chamber 26 through line 66 and hydraulic fluid drain line 64. As a result, the hydraulic fluid travels back to the hydraulic fluid reservoir. The amount of fluid released is such that the differential pressure added to the set bed pressure decreases so that it equals Pfmax. As a result, the tracking regulator 50 reacts by decreasing the pressure within the piston pressure chamber 26 so that the total bed pressure Pt acting on the piston head matches the maximum anticipated process flow pressure Pfmax plus the set bed pressure Ps.
In view of the above, the tracking regulator enables the total bed pressure to track the process fluid flow pressure so that the integrity of the substrate bed is maintained. Due to the purely fluid and mechanical linkages between port 34 and the tracking regulator 50, the responsiveness of the tracking regulator is nearly instantaneous, thus minimalizing the chances of risk to the substrate material.
As indicated in phantom at 70 in
Suitable sensing diaphragms 42 and tracking regulators 50 are known in the art. As an example only, the SJS series regulator and 42 MW welded diaphragm instrument isolator available from Tescom Corporation of Elk River, Minn., are suitable for use as the tracking regulator 50 and sensing diaphragm 42, respectively. Preferably, the sensing diaphragm features a flow-through cell design rather than a t-off design, which may require some modification of off the shelf diaphragm instrument isolators.
In an alternative embodiment of the system of the present invention, indicated in general at 110 in
An external driving column 125 is supported above the column 114 and contains a driving piston 127. A piston pressure chamber 126 is formed between the top of the driving column and the driving piston head.
A substrate bed 136 of particulate material is positioned between the bottom surface of the piston head and the bottom plate. The bed 136 may alternatively be a single piece (monolithic or membrane) bed or a liquid suspension of cells (such as is used in fermentation using yeast, or a bioreactor using plant of animal cells). The substrate bed 136 may be porous or non-porous and may include polymeric material or gel, including a base structure that is constructed from cellulose, methacrylate, divinyl benzene, silica, zeolite, titanium or is of the type used in any other separation medium.
The system of
A hydraulic liquid reservoir 154 communicates with the inlet of a hydraulic pump 156 via line 158, while the outlet of the pump communicates with a hydraulic fluid inlet 160 of the tracking regulator 150 via line 162. The tracking regulator is also in fluid communication with the hydraulic liquid reservoir 154 via a hydraulic fluid drain port and line, indicated at 163 and 164, respectively. The tracking regulator 150 also features a hydraulic fluid outlet 165 that is in fluid communication with the piston pressure chamber 126 of the external driving column via line 166. The operation of pump 156 is controlled by electronic controller 168. Electronic controller 168 may be a microprocessor or any other electronic control device known in the art.
The components of the system of
As indicated in phantom at 170 in
The system and method of the present invention may be used with any fluid processing process and associated column that features an internal piston head that applies a pressure to a bed. Examples of such fluid processes and equipment include, but are not limited to, chromatography columns (liquid, supercritical fluids, gas), capture columns, flow through synthesizer columns and bioreactor/fermentor columns (in which case the bed is a liquid suspension of cells). Such processes may be used in a variety of applications including, but not limited to, biological and chemical applications.
The present invention therefore offers a pressure tracking system that maintains integrity of the bed by the nearly instantaneous adjustment of the system hydraulic pressure to exceed the process fluid pressure by the set bed pressure. Fluctuations in the bed volume, due to settling, shrinking and swelling are automatically remedied by either adding hydraulic liquid to the piston pressure chamber or relieving liquid back to the hydraulic fluid reservoir.
While the preferred embodiments of the invention have been shown and described, it will be apparent to those skilled in the art that changes and modifications may be made therein without departing from the spirit of the invention, the scope of which is defined by the appended claims.
