JPS62454B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to columns for chromatography.
In particular, the present invention relates to a method of packing a column with a packing material for liquid chromatography. The present invention also relates to improved liquid chromatography devices and improved methods of making and using chromatography columns. The purpose of the present invention is to completely achieve packing by applying radial pressure to the column packing material, and the structure of the present invention is to provide means for applying the radial pressure. As a result of such packing, the efficiency of the column packing material is increased and the reproducibility of chromatography is improved.
Greater uniformity in column performance both when compared to similar packed columns and over the life of a given packed column has been achieved. Characteristic aspects of the present invention are as follows. (A) A method of packing a packing material for liquid chromatography, which method comprises (i) radially expanding a column suitable for holding the packing material from its normal radius; (ii) adding the packing material; and (iii) returning the column to its normal radius and bringing it into tight contact with its packing, provided that the column is placed in a pressurized vessel and the packing material is inside the column walls. The column wall is formed from a material that allows the column wall to expand or deform during filling, the pressurized vessel is formed from a rigid material, and the column wall expansion is achieved by gas introduced inside the column wall. and the return to the normal radius of the column is achieved by removal of said gas. (B) A method of packing a packing material for liquid chromatography, which method comprises (i) radially expanding a column suitable for holding the packing material from its normal radius; (ii) adding the packing material; and (iii) returning the column to its normal radius and into tight contact with its packing, provided that the column is comprised of a rigid material having an inner coating of deformable polymeric material. The column wall is capable of expanding or deforming during packing of packing material inside the column wall, and the column wall expansion is accomplished by heating or pressurizing the column or both, and the column wall expands to its normal radius. A method in which reversion is achieved by cooling or pressure relief or both. (C) A method of packing a packing material for liquid chromatography, which method includes (i) adding the packing material to a column suitable for retaining the packing material; (ii) radially moving the column from its normal radius; (iii) returning the column to its normal radius and bringing it into snug contact with its packing, provided that the column is formed of a material capable of expansion or deformation and that the outside of the column A method in which the cam is equipped with a cam, and when the cam is rotated, the cam compresses the filler radially, and when the cam is returned to its original position, the column returns to its normal radius. (D) A method of packing a packing material for liquid chromatography, which method comprises (i) radially expanding a column suitable for holding the packing material from its normal radius; (ii) adding the packing material; and (iii) returning the column to its normal radius and bringing it into tight contact with its packing, provided that the column is formed from a rigid material and the column wall expansion is achieved by heating. , the return to normal radius is achieved by cooling. In the embodiments described above, it is preferred that the expandable or deformable material is a polymeric material and the rigid material is a metallic material. The present invention also includes a chromatography column packed with a packing material by the above-described packing method. Liquid chromatography is a method used in manufacturing and analytical chemistry. Essentially, the method involves a stationary phase interacting with a mobile phase. Typically, the stationary phase is an inert size-separating material such as a surface-active powder such as silica, alumina, or a gel-permeation chromatographic packing material.
material). This powder is contained in a chromatography column. The mobile phase, generally consisting of a carrier liquid and a sample of the chemical product to be identified, analyzed, or purified, is passed through the column. A typical utility of this method is to fix various chemical components in unknown samples. This immobilization is achieved by two things: (1) the use of a stationary phase that differentially slows the progress of different components of the sample through the column, so that each component is separated and leaves the column at a different time; (2) continuous analysis of the column effluent over a period of time. Separation is achieved when one component of the sample has a greater affinity for the stationary phase than another component.
Also, exclusion processes based on differences in sizes between molecules, such as gel permeation chromatography
separation can also be achieved by The problem remains of perfecting the uniform packing of chromatographic materials into columns. A number of techniques have been suggested, including vibration (U.S. Pat. No. 3,300,849).
All these techniques require careful control if particle agglomeration due to size has to be avoided and homogeneous packed columns have to be obtained. Even after the column is packed,
There is a problem in maintaining the packing in proper condition during transportation and operation of the packed column. Any attempt by the prior art has superior performance,
Whether achieving column-to-column consistency of separation properties or desired stability of performance over a period of time for a single column, the goal is to produce equipment that can be used by the widest range of chromatography users. Despite the expense, they were not able to achieve sufficient success. Many of the problems mentioned above are caused by gas chromatography,
It is emphasized that this also relates to chromatography in which the sample and mobile phase are gaseous rather than liquid. In fact, in many respects these problems are associated with all-packed bed devices consisting of porous agglomerates of particles intended to be in intimate and even contact with the fluid. Such equipment includes contact beds for processing gases and liquids, packed beds used in ion exchange processes, electrophoresis processes, and the like. The invention described below is aimed at improvements in packed column manufacturing for all such processes. However, the present invention appears to have particular advantages in the field of liquid chromatography. In considering packed column methods, it is helpful to recognize four types of space, all of which may be referred to as "void volumes." These include:
(1) void volume within porous particles; (2) theoretical void volume between particles, the unavoidable type of volume resulting from a perfectly packed bed of spheres of the same size; (3) due to incomplete packing of particles. (4) The void volume represents the relatively large voids created by the integration of the voids in (3) above. The voids (4) significantly reduce the resolution of samples subjected to chromatographic analysis. The invention described below is believed to be most useful in avoiding the occurrence of void volume as described in (4) above. The present invention also tends to reduce the void volume as described in (3), further making such void volume more uniform and closer to the theoretical ideal. The void volume generally used here refers to the composite of void volumes (3) and (4). Some researchers have suggested compressing the packing of a chromatographic column by a longitudinal force, ie, a force parallel to the direction of liquid flow. However, such operations are relatively ineffective, probably because the packing material crosslinks the column and prevents its compressive forces from propagating down the length of the column.
An example of such a study is “Preparative High Pressure Liquid-Solid Chromatography” by Godbille and Devaux in the Journal of Chromatographic Science, October 1974. Description and performance of a column with an inner diameter of 8 cm
Performance of an8cmi.d.Column For
Preparative Scale High Pressure Liquid−
Accordingly, one object of the present invention is to provide a new column structure for use in chromatographic applications, which column has a high performance during its lifetime. The uniformity of its separation properties is improved. Another object of the present invention is to provide a packing for transporting chromatography packing, which packing does not have undesirable voids. Another object of the present invention is to provide an improved method for the manufacture and operation of chromatographic columns. Yet another broad object of the invention is to provide an improved method for the manufacture and operation of chromatographic columns. It is an object of the present invention to provide an improved packed column for use in fluid contacting methods, independent of the chemical nature of the packing material and the physical form of the fluid passed therethrough. It is a further object of the present invention to provide a new method for manufacturing chromatographic columns with improved inter-uniformity.A further object of the present invention is to provide a new method for manufacturing chromatographic columns with improved inter-uniformity. Still another object of the invention is to provide a method for producing a chromatographic column that is so highly reliable as to eliminate the need for preliminary testing of performance characteristics. It is an object of the present invention to provide an inexpensive, high quality chromatographic column that can be a disposable item in most commercial processing facilities. Another object of the present invention is to provide an apparatus and a processing method for re-establishing excellent sample separation performance. A further object of the invention is the production of a liquid chromatography device which can be easily filled and recovered.A further object of the invention is the production of a liquid chromatography device which can be filled with porosity and which can be easily recovered. Another object of the present invention is to provide a column that can be easily "cured" when a sample appears in the sample. Other objects of the invention will be apparent to those skilled in the art from reading the object of the invention. The above objectives are such that radial compression of the packing material within a chromatographic column during its use significantly affects the quality and uniformity of the performance characteristics of the chromatographic column so compressed. This was achieved as a result of the discovery that improvements were made. In the simplest case, the column is packed with a packing material,
Immediately before use, the cylindrical walls of the column, e.g. thin polyethylene, polytetrafluoroethylene polymers,
Alternatively, it can be compressed by external pressure acting on a wall made of a similar sheet material. This wall is surrounded by a pressure chamber and pressurized inward around the entire cylindrical bed, thereby lightly compressing the particles,
Improve uniformity across the floor. The pressure applied to this bed should preferably not exceed the lateral, radial yield point of any part of the bed, should not cause substantial destruction of the particles, and should not affect the mechanical stability of the walls. Do not exceed the maintaining pressure. If this happens, the uniformity of the cross-sectional area or shape of the bed is likely to be distorted, which is generally undesirable and makes it more difficult to achieve the desired consistency of the floor properties. There is a tendency to make it a thing. Usually good results can be achieved well below this yield point, the determination of which is only of academic importance. In some cases, this yield point may be caused by particle breakage or global change. There are many other ways in which radial pressure can be applied.
Pressurization may be achieved through the use of mechanical and fluid means. Pressure can be applied from inside or outside the column. Pressure from outside the column is considered more preferable as it does not increase the complexity of the column structure. However, one of the essential advantages of the present invention is the improvement in performance and consistency of relatively large diameter columns used in preparative (as opposed to merely analytical) operations, so that particulate filler materials can be Radial compression from within is sometimes desirable in order to maximize the distribution of vectors contributing to radial compression. This may be especially true for columns with diameters less than 1 foot (30.5 cm) or even up to 10 feet (304.8 cm). (If a gas is used as the pressurized medium, the permeability of the wall material to the gas used must be considered. Coverings of materials with even less gas permeability may also be specified in some cases.) This In this connection, it may be noted that in many granular systems any force applied to a point will be attenuated to a relatively small and ineffective force at some distance from that point. In its most advantageous embodiment, the invention provides that all of the column packing material is located within the above-mentioned distance (which may be referred to as the "radius of fluidity") from the strained portion that develops the force of the column. will have a portion. As mentioned above, the pressure applied to any column must be below the radial yield point of the particulate packing material used. This yield point itself is determined by the following two factors:
It will be governed by factors such as (1) the nature of the packing material and (2) the method of packing the column. That is, a column packed using a particular operation, such as a slurry or other technique suitable for achieving a relatively densely packed column, will have a lower packing capacity than a column containing the same column packing material that is more lightly packed. Often able to withstand slightly higher pressures. Nevertheless, in many cases the above ideas are controversial. This is because there is no reason to use more expensive column packing methods if the column has to be operated in such a way that the processing advantages achieved by implementing the method of the invention are achieved. . The light tapping technique is perfectly suitable for packing the columns to be operated according to the invention. The generally satisfactory external pressure also depends on the ease with which the wall deforms, ie, the force required to push the wall towards the inner particles. The following pressure differentials have been found to be useful in a column that is 2.25 inches in diameter and about 1 foot long.

[Table] These parameters were determined in this series of experiments when the internal operating pressure of the chromatography column ranged from 3.5 to approx.
Determined in tests ranging from ⁵⁰ to about 500 psig. The present invention is a greatly improved method of avoiding packed bed voids. The present invention also provides a method for reducing the wall channeling effect, in which liquid preferentially flows through the space at the interface between the column wall and its packing material, and is in fact an excellent method for overcoming the channeling effect. Conceivable. Inflatable walls (polyethylene or EIdupont
This is especially true when organic resin walls are used, such as the organic resin walls formed from halogenated hydrocarbon polymers sold under the trademark "Teflon" by DeNemours. Although there are particular advantages that can be achieved by reducing wall channeling effects, the "radial compression" method described here gives the column the opportunity to be repressurized and to repressurize the entire volume again. be in virtually the same condition. This results in columns manufactured and operated in accordance with the present invention to be more reliable in a series of comparative experiments than all comparable liquid chromatography columns known in the art. However, this effect is extremely important even if the column is used only once. The reason is that when the column is subjected to radial compression, its packing properties are much more reliable. In fact, columns with relatively large diameters, such as approximately 2.54 cm (approximately 1
The main improvement in columns larger than 1 inch relies mostly on the uniform packing achieved by radial compression. For a given particle size, undesirable wall channeling effects in this large column were generally small compared to other imperfections in the packing arrangement. Distensible polymers include various types of elastomers and rubbers. However, it is important to remember that chemically inert surfaces are required for many chemical operations (and especially liquid chromatography analyses). Polyolefins and halogenated hydrocarbon polymers (such as Teflon) are therefore preferred. Another highly desirable property of this expandable polymer, well known in the art, is the "memory" property possessed by many plastics such as polyethylene and Teflon. This property currently depends on the ability of the filler to "forget" the shape it acquired during the initial pressurization, and on subsequent application of the filler after being perturbed by movement and shear of the polymer relative to the wall surface. It may be more appropriately expressed as the ability to take on a new shape when pressed and molded. Another aspect of the invention is the fact that high performance liquid chromatography columns (even those of the type used in high pressure liquid chromatography (HPLC)) can now be manufactured in a wide variety of shapes. . The best known prior art techniques for column packing utilized vibration at special frequencies or settling of particles from a slurry pumped through a tube. All of these techniques were essentially gravity-based sedimentation methods and were most suitable for use with elongated cylinders. The present invention can be utilized with all shapes including tubes, coils, U-shapes, etc. However, it should be understood that in many such geometries the present invention merely minimizes the inherent disadvantageous effects caused by deficiencies such as the lack of equidistant fluid paths through the geometry. be. These shapes can be oriented vertically or horizontally, the only restriction being that they are constructed in such a way that each segment can be exposed to a force vector generally directed from the outer wall toward the center of the shape. (Such conditions are referred to herein as "radial compression"). Another means of achieving the desired radial compaction is a rigid column, so to speak on the inside thereof a coating of deformable material, for example poly(tetrafluoroethylene),
The idea is to make a steel tube with a plastic coating, such as polyethylene. The coating is preferably chemically inert, with poly(tetrafluoroethylene) being the preferred coating in modern industrial materials. The coated tube is expanded, eg, by heat and/or pressure, filled with filler material, and then deflated. This contraction results in radial compression of the filler particles by the steel wall acting as a diap hragm. The particles are forced into the coating to such an extent that wall channel formation is substantially eliminated. Residual compaction may be sufficient to achieve the uniformity of filler loading described for the externally applied pressure embodiment of the present invention. There are some advantages to the use of pre-strained columns, where the chamber wall structure is formed from a relatively inflexible material such as steel. Such a column avoids any significant gradient in the pressure difference between the inlet of the column and the outer surface of the column. That is, at high column operating pressures, the packing is removed from the bottom of the column (where relatively high pressure differences can be observed with slightly structured or unstructured retention packing). There is no tendency to migrate towards the top (where the high internal pressure within the column itself is very close to the pressure exerted on the outside of the relatively slightly structured or unstructured retaining packing). Impossible. This prestrained column also has advantages in many low pressure operations. In this operation, the particles must be prestrained because they are soft, spongy, or have internal porosity, so that the strain on the particles is very closely controlled over the length of the column. must be done. As can be inferred from the above, for relatively large diameter columns where wall channeling is not a major factor, the pre-compacted metal column described above will respond to the opposing forces exerted on the surface by the particles. It can advantageously be used without a suitable intumescent material to conform to the surface of the filler particles.
This expansion reduces the void volume at the interface between the metal wall of the column and the particle agglomerate. "Swellable" as used herein means the ability to accommodate various particle irregularities on the surface of a filler agglomerate, significantly reducing the channel-forming volume between the filler and its walls. are doing. It is also possible to expand a column of polymer, fill it with packing material, and contract it to apply the appropriate radial pressure to the packing material without having to maintain external pressure. However, this operation is considered best avoided due to the unpredictable nature of the conditions encountered during transport of this column. It should be noted that such columns can nevertheless be manufactured. In fact, it is also convenient to inflate thin-walled plastic columns by a small amount before packing, this is done to remove hairs and bumps in the compacted walls, and such cosmetic This advantage facilitates the filling operation and ensures a more proper initial filling operation than methods that permanently predistort the diaphragm wall. The above advantages of the present invention relating to (a) reduction or elimination of wall channel formation and (b) more uniform packing also result in an optimization of the effectiveness of flowdistributing techniques at the head of the column. optimization). That is, channel dispersion methods known in the prior art tend to be more effective when used with columns constructed and operated in accordance with the present invention.
Moreover, the present invention makes further optimization of flow distribution devices practical and desirable since packed columns are often no longer the limiting factor in achieving good uniform distribution. “Bridglng” is a phenomenon in which the packing is arranged in a mechanical relationship with the walls of the column such that an arcuate resistance to compression of the packing in a direction generally parallel to the walls is formed. It is. One of the advantages of the present invention is that it avoids bridging resistance that inhibits effective compression of the column. However, it should be understood that by radial compaction it is also possible to improve the crosslinking phenomenon, and in that case vertical additions of fillers are separated by crosslinks that are relatively close to each other. When the crosslinks are brought into close proximity to one another, an improved chromatographic column is produced that can be operated at higher pressures with better results than columns containing the same packing operated according to the prior art. The reason is that each crosslink protects the particles below it from the pressure exerted on the crosslinks. The most advantageous use of this increased crosslinking frequency is in relatively soft, compressible filler materials such as the relatively large pore, lightly cross-crossed polymeric fillers sold under the trade name Sephadex. This is the case when using Benefits are also achieved using slightly smaller pore, more crossed materials sold under the same trade name. Such materials are very well known in the art. Less benefit is achieved for less compressible materials, and increased crosslinking is not believed to be a major contributor to the improved performance of alumina and silica type filler materials. It is believed that the improved performance of such filler materials in the practice of this invention is primarily due to factors discussed elsewhere herein. If gas is used to pressurize the column, it is desirable to use a wall material with a gas-impermeable barrier layer. Various polymeric coating materials are known to have particular resistances to the passage of particular gases and may be used.
Thin metal foils may also be incorporated between or used in conjunction with or in place of the polymeric films to form a suitable column wall structure. Figure 1 of the accompanying drawings has a wall thickness of approximately 0.076 cm (approximately 0.030 inch), a length of 30.48 cm (12 inches), and a
A polytetrafluoroethylene tube 30 is illustrated having a tube diameter of about 2 inches. FIG. 2 illustrates the storage of the tube within the filler chamber 32. FIG. FIG. 3 shows a porous glass sinter plug 38 inserted into the bottom end of the tube to better hold the tube within the filler chamber. Plug 34 is inserted into the top. Gas enters the tube through conduit 36 and plug 34 and expands as seen in FIG. Air pressure is used to cause an expansion of approximately 15% in volume. Remove plug 34. The tube is then filled with a chromatographic packing material, 60 to 200 meshes of silica-based packing. This column packing requires a necessary tapping or shaking action. A glass smelt 38 is inserted into the top of the column and an end cap 39 is bolted onto it to create a pressure chamber. FIG. 7 illustrates radial compression where gas enters chamber ³² through valve 40 to achieve initial radial compression of the tube at 250 psig. An end cap 42 is placed over the column to protect it during transport when removed from the packing chamber. The column is now ready for transport.
When the column is received, excluding the end cap, the 50
Place in a pressurized container such as Gasketed end plates 51 were tightened with bolts 52, following good practice generally known in the art in the manufacture and use of pressurized vessels. In use, the tube is externally pressurized to a pressure approximately 14 Kg/cm ² (approximately 200 psig) above the liquid chromatography operating pressure, measured at the top of the column. The same operation is repeated using a polyethylene film of medium density. The film was heated to approximately 110° C. to facilitate 15% prefill expansion. After being compressed by this heating, the film provided an excellent snug fit over the packing when the film was cooled and shrunk to form a neat packing. actually,
This adaptation allows the column to be placed at low pressures, ^e.g.
(100 psi) or less. However, this column tends to "loos up" a little during storage and requires repressurization for the illustrated assembly. Figure 10 shows wall thickness of 0.203 cm (0.08 inch), approx.
Steel pipe 6 with inner diameter d ₁ of 0.635 cm (approximately 0.25 inch)
0 (316 stainless steel) is shown as an example. The tube is placed in a heat exchanger 61, shown schematically, heated to 25-85°C. At the same time, a slurry of 10 micron silica-based chromatographic packing material is flowed down the column and the packing material is allowed to settle by well-known slurry techniques. The combination of the pressurized slurry and heated tube expands the tube during the filling operation to substantially a diameter d ₂ as seen in FIG. 11. When the tube is returned to room temperature as shown in Figure 12,
It compresses the filling radially according to the invention. A metal tube 62 having a wall 64 coated with approximately 0.001 inch of polytetrafluoroethylene polymer 66 is most preferred where wall channeling effects are to be avoided or minimized. This polymer 66 is expandable under radial compression and substantially conforms to the shape of the filler material 69 at the interface 68, thereby avoiding any undesirable wall channel formation. The columns described in Figures 10-13 are compatible with and include end fittings like other columns sold in the chromatography industry and are shipped pre-compressed for immediate use. be done. This radial compression is permanent: they usually do not require any further compression steps as long as the same packing is in the column. A number of simple mechanical means to achieve the required radial compression may be used. These are advantageously assembled to reduce the cross-sectional area of the column over the length of the column, ie from the inlet end fitting to the outlet end fitting. The contraction of the heat-expanded tube is a kind of mechanical means, where the tube itself is the radial compression means. In another aspect of the invention, a flexible walled tube formed from foil, plastic film, etc. is distorted by external means such as a cam or the like device until it assumes an annular to non-circular cross-section. However, devices such as cams force the shape of the wall to change so that its cross-sectional area decreases. The reduction in cross-sectional area is typically a small change of 2-5%, but this is effective in well-packed columns, and reductions of more than about 10% are rarely necessary. FIG. 15 illustrates a column equipped with such mechanical pressurization means. Column 80 consists of tubing formed from 0.030 mil (0.000075 cm) thick polytetrafluoroethylene. It is in its normal position shown with a solid line around it (here the cam is at wall 8
Four cams 82 are provided. These cams are connected to the flexible column wall 81
extends over the entire length of. If radial compression is desired, the cam is rotated to the position defined by the dotted line and the cam compresses the filler 86 so that the desired amount of radial compression is achieved. An expandable polymer surface at the interface between the column wall and the packing material is advantageous as in another embodiment of the invention. It is not part of this invention to discuss in detail the well-known aspects of mechanical techniques utilized in devising various means to ensure proper compression. Those skilled in the art will be able to devise many rapid operation devices that can be implemented in accordance with the teachings of the present invention. However, in general it is preferable to have at least two to three different pressurization sites in any given column, although one pressurization site may be sufficiently effective for short columns. FIG. 15 also illustrates the desired wide range radial compression. Obviously the vectors emanating from the pressure points created by the cams are not strictly radial. Although they nevertheless have a substantial, effective net effect, the effect is radial and operates well within the term "radial compression" as used herein. There are numerous other means of providing a source of strain-inducing pressure in this packed bed. For example, the bed may be wrapped in a jacket, into which a low melting point alloy, such as Woods Metal, may be poured, pressurized, cooled and solidified under pressure. Metals that expand upon cooling are preferred. The alloy can be melted, recompressed, and refrozen if recompression is necessary to heal, refill, or repair the filler. Another method is to wrap a helical wire or tube or a series of circular grooves around the column and use thermal, pneumatic or mechanical means to vary the size of the tubes and grooves to create a strain or break in the column. This results in a decrease in area. Improved flow path dispersion is always achieved when using superior flow path dispersion means at the column inlet, as described above, and this dispersion is maintained with remarkable fidelity over the entire length of the novel radial compression column of the disclosed type. Ru. It has been found that it is usually most desirable to strain the packed column before wetting the column, ie, before starting the liquid chromatography operation. When prepacked columns, such as those made with polymeric walls, must be used, they are often "relaxed" somewhat over a period of time after initial packing. That is, if they are conveniently repressurized before wetting them, the resulting force is retained in the columns during use. The term "diaphragm" as used herein refers to a movable column wall portion that can strain the packing within the column. Many complex structures can be used to achieve these results. It is not necessary that all of the column walls be movable, as may be suggested in the examples below, and it is often sufficient to impart strain along a single linear position along the column wall. Such strain can also be applied by pressing on a significant number of sites distributed over the column surface. A wall that uses all of this technique is a "diaphragm" according to the common usage of the term herein. This wall may be on the inside, for example in the center of the column, and may be movable towards the outer wall of the column. Nevertheless, it is generally desirable to use one of the relatively simple structures described herein. There are other ways to properly fill the filler using repetitive compressive forces. One is to rotate a mechanically balanced column around its axis at high speeds, pushing the packing particles outwardly against the outer wall of the column. It may indeed be necessary to have a follower device (mechanical or hydraulic) located on the axis so that it expands to the extent necessary to fill all the spaces left by the outwardly moving particles. unknown. This device is considered a mechanical equivalent to the present invention since it uses radial compression and reduction of the effective cross-sectional area of the filler. Although in this condition the primary force will be directed outward, the centrifugal force device is considered merely a means to achieve radial compression. In such conditions, compression and absorption of the void volume created by the compression cannot be accomplished in one operation, and the use of an on-axis follower is required to absorb the void volume. This tracking device is needed to avoid the packing material moving towards the outer wall of the column and creating a central void. Furthermore, a donut-shaped column, ie a column with a hollow axial hole, could be constructed. Not only could pressure be generated from either the inner or outer cylindrical wall, but this wall could also be used to improve the heat exchange properties of the device. Generally, the term "radial compression" is meant to describe compression in which the compressive force is oriented primarily in a direction perpendicular to the flow of liquid through the column.
That is, in a typical state of a cylindrical column, the compressive force is directed toward the center of the cylinder.

[Brief explanation of the drawing]

Figures 1-9 of the accompanying drawings illustrate the parts of the column and the steps used to form the novel compressed column, illustrating the steps used to form the externally pressurized column. Figures 10-13 schematically illustrate the steps used in accordance with the present invention to form a column with an external compression cylinder lined with a "deformable polymer coating." Figures 14a and 14b schematically illustrate various configurations of chromatography tubes that can be advantageously filled according to the invention. These exemplify novel aspects of column configuration made possible by the practice of the present invention. It is stated for. That is, conical shape (Fig. 14a), bent shape (Fig. 14a)
Fig. b) or other shapes with elongated channels (which cannot be filled reliably using prior art packing methods), show. FIG. 15 schematically shows a cross-section of a cylindrical column provided with compression means acting mechanically around the cylindrical column. 30...Tube, 32...Filling chamber, 34
... Plug, 36 ... Conduit, 38 ... Glass smelt, 39 ... End cap, 40 ... Valve, 4
2... End cap, 50... Pressurized container, 51...
...End plate with gasket, 52...Bolt,
60... Steel pipe, 61... Heat exchanger, 62... Metal tube, 64... Wall, 66... Polymer, 68... Interface, 69... Filler material, 80... Column, 81
... flexible column wall, 82 ... cam, 84 ...
Wall, 86... filler.

Claims (1)

[Claims] 1. A method for packing a packing material for liquid chromatography, which method comprises the steps of: (i) expanding a column suitable for holding a packing material radially from its normal radius; (ii) (iii) returning the column to its normal radius and bringing it into snug contact with the packing, provided that the column is placed in a pressurized vessel and the column of packing material is The column wall is formed from a material that allows the column wall to expand or deform when filled inside the wall, the pressurized container is formed from a rigid material, and the column wall expansion is a gas introduced inside the column wall. A method, characterized in that the return to the normal radius of the column is achieved by removal of said gas. 2. The method of claim 1, wherein the column wall is provided with a plug, a gas conduit and a gas outlet pot. 3. A method for packing a packing material for liquid chromatography, which method includes (i) expanding a column suitable for holding a packing material radially from its normal radius; (ii) adding the packing material. , and (iii) returning the column to its normal radius and bringing it into snug contact with its packing material, provided that the column is made of a rigid material with an inner coating of deformable polymeric material and the packing material The column wall is capable of expanding or deforming upon filling of the inside of the column wall, and the column wall expansion is accomplished by heating or pressurizing the column, or both, and the return of the column to its normal radius is A method characterized in that it is achieved by cooling and/or pressure relief. 4. A method of packing packing materials for liquid chromatography, which involves (i) adding the packing material to a column suitable for holding the packing material, (ii) compressing the column radially from its normal radius. and (iii) returning the column to its normal radius and into tight contact with its packing, provided that the column is formed of an expandable or deformable material and that a cam is provided on the outside of the column. Equipped with
A method characterized in that when the cam is rotated, the cam compresses the filler radially, and when the cam is returned to its original position, the column returns to its normal radius. 5. A method according to any one of claims 1 to 4, wherein the expandable or deformable material is a polymeric material. 6. The method according to claim 5, wherein the polymeric material is polyethylene or poly(tetrafluoroethylene). 7. A method for filling a packing material for liquid chromatography, which method comprises: (i) retaining the packing material; (ii) adding packing material; and (iii) returning the column to its normal radius and in tight contact with the packing material. characterized in that the column is formed from a rigid material, column wall expansion is achieved by heating, and return to normal radius is achieved by cooling.8. The method according to any one of claims 1 to 7, wherein the metal material is stainless steel. 9 The method according to claim 8, wherein the metal material is stainless steel. 10 The filling material for liquid chromatography is In a packed column, the steps of (i) expanding the column radially from its normal radius suitable to hold the packing material, (ii) adding the packing material, and (iii) expanding the column to its normal radius are as follows: the column is placed in a pressurized vessel and the column wall expands or deforms during the filling of the packing material inside the column wall. the column wall is formed from the material obtained, the pressurized vessel is formed from a rigid material, column wall expansion is achieved by gas introduced inside the column wall, and return of the column to its normal radius is achieved. A column for chromatography, characterized in that it is obtained by the method achieved by the removal of said gas. The column for chromatography according to item 10. 12. In a column packed with a packing material for liquid chromatography, the step of: (i) expanding the column suitable for holding the packing material radially from its normal radius; , (ii) adding a packing material, and (iii) returning the column to its normal radius and in tight contact with the packing, provided that the column has an inner coating of deformable polymeric material. The column wall can be expanded or deformed when the packing material is packed inside the column wall, and the column wall expansion is achieved by heating or pressurizing the column, or both. A column for chromatography, characterized in that the return to the normal radius of the column is achieved by cooling or pressure relief or both. 13 In a column packed with a packing material for liquid chromatography, (i) adding the packing material to a column suitable for retaining the packing material; (ii) compressing the column radially from its normal radius; and (iii) returning the column to its normal radius and into tight contact with its packing, provided that the column is formed of an expandable or deformable material and that a cam is provided on the outside of the column. Equipped with
A column for chromatography, characterized in that it is obtained by a method in which when the cam is rotated, the cam compresses a packing material radially, and when the cam is returned to its original state, the column returns to its normal radius. 14. The chromatography column according to any one of claims 10 to 13, wherein the expandable or deformable substance is a polymeric substance. 15 Claim 14 in which the polymeric material is polyethylene or poly(tetrafluoroethylene)
Column for chromatography described in section. 16 In a column packed with a packing material for liquid chromatography, (i) radially expanding the column suitable for holding the packing material from its normal radius; (ii) adding the packing material. and (iii) returning the column to its normal radius and into tight contact with its packing, provided that the column is formed from a rigid material and column wall expansion is accomplished by heating, A column for chromatography, characterized in that the return to a normal radius is achieved by cooling. 17. The chromatography column according to any one of claims 10 to 16, wherein the rigid material is a metal material. 18. The chromatography column according to claim 17, wherein the metal material is stainless steel.