Liquid purification or separation – Processes – Chromatography
Reexamination Certificate
2000-07-26
2004-05-18
Therkorn, Ernest G. (Department: 1723)
Liquid purification or separation
Processes
Chromatography
C210S198200
Reexamination Certificate
active
06736973
ABSTRACT:
The invention pertains to a porous self-supporting structure comprising at least two porous components A and B, an article comprising a porous self-supporting structure comprising at least two porous components A and B, a housing for use in the article of the invention, end-fittings for use in the article of the invention as well as a process for manufacturing a porous self supporting structure of the present invention.
BACKGROUND OF THE INVENTION
Liquid chromatography is one of the most important tools for sample analysis as well as for the isolation or purification of compounds Chromatography works basically via an interaction of molecules dissolved in a liquid phase (mobile phase) and a solid phase (stationary phase). An almost ideal chromatographic process performs an efficient compound separation, sometimes of large sample volume, within very short time. A conventional chromatographic process is carried out by passing a liquid phase containing sample to be separated through a stationary phase (matrix). Since different compounds interact differently with the stationary phase the travelling time is different and as a consequence, a separation occurs. Conventional stationary phases are built in form of porous beads providing a high enough active surface for the interactions. They are packed in columns normally few centimeters long and few millimeters wads and fixed by porous frits on both ends. Because of their porosity and structure, the beads have rather low mechanical stability. When chromatographic separation systems are scaled up for commercial purposes, more matrix volume is required and thus large columns have to be employed. The combination of high flow rates and larger bed height (i.e. hydrostatic pressure) results in high pressure decrease across the matrix causing compression of the matrix material. This changes the column characteristics due to lower overall porosity and inhomogeneitics. One of the attempts to overcome this problem is incorporation of short columns with large cross-sectional area. However, uneven distribution of the sample over the cross-sectional area and a large dead volume still cause problems. The design of a chromatographic column using horizontal flow solves the problems related to the back pressure by employing a cylinder shaped column as disclosed by Saxena (U.S. Pat. Nos. 4,627,918, 4,676,898 and 4,840,730). The separation matrix is placed between two tube-shaped porous frits of different diameters. The mobile phase passes through the outer porous frit through the matrix. Since the height of the matrix bed is small the hydrostatic pressure does not play an important role. In addition, the bed thickness is low which causes only low back pressures.
Due to the particle structure however, two inherent drawbacks regarding efficiency and speed of the separation remain unsolved: neither the entire bed volume is used for the separation due to the voids (space between the particles) nor the separation time sufficiently short due to diffusion limitations inside one side closed particle pores.
A first attempt to overcome both of the above mentioned problems was introduced by Hjerten et. al J. Chromatogr., 473 (1989) 273-275, WO 90/07965 by polymerising a mixture of acrylic acid and methylenebisacrylamide for the production of a stationary phase. The resulting polymer plug contains channels which are large enough to permit a hydrodynamic flow. The polymer itself is, however, very soft and should by highly compressed before usage. On large scales, this leads to a drawback, since the compression produces non-uniform channels within the plus resulting in less than ideal column efficiency. Almost at the same time the so-called “membrane chromatography” war discovered by Svee et al. (U.S. Pat. Nos. 4,889,632 4,923,610 and 4,952,349). The used membranes have a rigid structure comprising bimodal pore-size distribution of open channels and as such excellent hydrodynamic characteristics resulting in short separation times. Although in principle the size of the membrane is non-limited, mechanical instability and irregular sample distribution limit the application of such units on large scale processes.
Another approach was introduced by Frechet and Svec (U.S. Pat Nos 5,334,310 and 5,453,185) by polymerising( monomers to a rigid porous plug within an empty chromatographic steel column of limited diameter. The porous plug has similar characteristics to those of the above mentioned membranes. The high back pressure of the plug however, determines the upper limit of the flow rate which together with a small column diameter prevents applications on preparative level. Josic et. al. disclosed rigid porous tubes based on methacrylates (WO-A-96/06158) where a mobile phase passes the bed in radial direction resulting in much lower back pressure even at elevated flow rates. This design enables a very fast separation on a semi-preparative level.
During tire bulk polymerisation of plugs of large diameter or tubes of large thickness a considerable amount of heat is generated Since the monomer mixture has a relatively low heat conductivity, the temperature within the mixture increases dramatically during the polymerisation (Peters E. C., F. Svec, J. M. J. Frechet, Chem. Mater., 9 (997) 1898) Since the pore size distribution is temperature dependent (Svec and Frechet, Chem. Mater., 7 (1995) 707), the resulting polymer has a variable structure and cannot be used for good chromatographic separations. Peters et. al., Chem. Mater., 9 (1997) 1898, suggested the polymerisation by slow addition of monomers mixture showing that the temperature increase is much lower and that the pore size distribution is only slightly affected, No separation efficiency of such a column however is presented. In addition, this approach prolongs the time for completion of the polymerisation and requires a very precise addition of the monomer mixture in order to avoid temperature increase.
Another way to control or decrease the amount of heat generated is the addition of polymeric particles of the same pore structure into the monomer mixture. Since the particle diameter is typically in the range of microns, monomers can diffuse into their pores and polymerise resulting in a non-homogeneous pore size distribution. To avoid changes in the polymer structure, pores of the particle should be filled with the inhibitors. If the concentration of the particles is too high, the inhibitor inhibits also the polymerisation of monomer mixture around the particles.
On the other hand, if the amount of polymeric particles added to the polymerisation mixture is too low, the particles can settle down in the mould during the polymerisation. In this way the local concentration of the particles in the monomer mixture in the upper part of the mould is low, thus the generated heat is again very large. It is therefore extremely difficult to prepare large porous polymers with a well defined pore size distribution.
Thus, it is an object of the present invention to produce a large scale rigid porous polymer media with well defined uniform pore characteristics.
It is further an object of the present invention to produce large scale rigid porous polymer media exhibiting low back pressures even at high flow rates.
It is still another object of the present invention to produce large scale rigid porous polymer media from large variety of monomers.
It is another object of the present invention to produce large scale rigid porous polymer media in an easy and inexpensive way.
These and further objects of the present invention will be evident from the following description of the present invention as well as from the given examples.
DISCLOSURE OF THE INVENTION
To achieve foregoing and other objects and in accordance with the purpose of the present invention as embodied and broadly described herein, the present invention is directed to a chromatographic unit comprising a porous polymer tube haling a large thickness and housing for the porous polymer tube. The resulting unit can be applied as a chromatographic column, for different bioconve
Barut Milos
Josic Djuro
Podgornik Ales
Strancar Ales
BIA Separations d.o.o.
Jacobson & Holman PLLC
Therkorn Ernest G.
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