JPH09119924A - Separating column for chromatography - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a separation column having micro inside diameter being employed in various chromatographs, e.g. an LC having smooth inside surface or a supercritical fluid chromatograph. SOLUTION: The separation column comprises a separation tube 1, a solid phase provided therein, a carrier tube 5 arranged concentrically to the separation tube 1, and an adapter member for holding the separation tube 1 in the carrier tube 5. This column has compatibility with a commonly employed cartridge system and realizes an extremely small inside diameter while dealing with the smoothness required for the inside surface of column.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a separation column for chromatography. The type of separation column is, for example, one used in high performance liquid chromatography or supercritical liquid chromatography applications.

[0002]

BACKGROUND OF THE INVENTION Separation columns commonly used in liquid chromatography and supercritical fluid chromatography essentially consist of tubes, the interior of which is packed with solid particles which make up the stationary phase. This packed column is equipped with special adapter parts at both ends in order to connect its tube to an analytical measuring instrument such as a chromatograph. Usually, tubes of defined material composition are used.
The most commonly used tubes are made from special steel, but other materials such as glass or plastic (PEEK) have also been used in recent years. For example, German Patent 29309
62 (DE-A-2 930 962) and European patent 6247
No. 95 (EP-A-0 624 795). The use of ceramic composites is described, for example, in German Utility Model No. 94.
05378.2 (DE-U-9405378.2).

Columns packed with a good carrier material require special properties for the inner wall of the tube. That is, the surface of the inner wall should be as smooth as possible, as well as the straightness of the tube and the concentricity of the opening. If the surface is not sufficiently smooth, the flow characteristics of the sample material separated by passing through the separation column will be adversely affected. This can lead to deviations, especially localized flow velocities in the tube, resulting in asymmetric chromatographic peaks. The surface roughness of the column tube affects not only the efficiency of the separation column but also the stability of the bed of the column packed with carrier material, the smoother the wall, the tighter the packing of the column. Become. A packing density gradient from the center to the wall of the tube can be ruled out under these conditions. . As a result, subsequent sagging of the adsorbent bed in the flow direction is prevented. A perfectly homogeneous column bed with respect to the carrier material results in a high resolution of the analytes due to the dense packing. In addition, the service life of the column is extended, thus improving the price-performance relationship.

Suitable values for the surface quality of special steel pipes are:
It is in the range of 2 microns. As the inner diameter of the tube decreases, the effect of wall surface roughness increases. The production of walls with the desired surface quality is more expensive and therefore expensive for relatively small diameter tubes. Manufacture of tubes with acceptable surface quality is very demanding and expensive, especially for tube inner diameter to outer diameter ratios (including wall thickness) of less than about 1: 3. According to the knowledge of the applicant of the present application, for example, there is currently no manufacturing process capable of producing a pipe having an inner diameter of 2 mm or less and an outer diameter of 8 mm while maintaining desired specifications (surface quality).

[0005]

OBJECTS OF THE INVENTION It is an object of the present invention to provide a separation column for chromatography in which the inner diameter of the tube is small and the above-mentioned difficulties relating to surface roughness can be essentially avoided.

[0006]

SUMMARY OF THE INVENTION The solution to the purpose of the present application is the first claim.
Provided by the invention described in the section. According to the basic principle of the invention, the separation column consists of two tubes, namely:
It consists of an outer tube (carrier tube) and an inner tube (separation tube).
The concept of a carrier tube is such that a connection to a suitable analytical system (chromatographic device) is established thereby. The carrier tube is preferably formed in both end regions so as to be compatible with the connectors and connecting parts commonly used in chromatography. A carrier tube disposed within the separation tube contains the stationary phase. The separation tube is placed inside the carrier tube by one (or more) adapters.

In accordance with the present invention, separation tubes having different inner and outer diameters, each inside the same carrier tube, typically under operating pressures of less than 400 bar, while maintaining the tightness of the system. It is possible to inject a liquid stream into the. Since the separation tube is manufactured separately from the carrier tube, the requirement for the smoothness of the inner surface of the separation tube can be achieved far more than the conventional integrally formed separation tube, the inner and outer diameters of which are , Proportional to the inner and outer diameters of each of the carrier tubes. For example, the special steel pipe is used as a separation pipe of the column according to the present invention, and thus can be stretched so that the inner diameter can be changed while maintaining the desired surface quality of the inner surface. Manufacturing costs can be significantly reduced as the reworking process required to ensure the smoothness of the inner surface is not required.

By using separation tubes having various inner diameters while keeping the outer diameter constant, the existing method can be applied to columns having the same packing material and different tube inner diameters without any difficulty. It is possible to obtain the advantage of chromatography. Therefore, the detection sensitivity, which is inversely proportional to the decrease in inner diameter, is dramatically improved while reducing the amount of solvent required and maintaining a linear flow rate.

The sleeves inserted at each end of the column are
Preferably, it is used as an adapter part that holds the separation tube in place on the carrier tube. At the same time, the separation tube is centered by these sleeves, which are preferably made of plastic.

Yet another advantage of the present invention is the reusability of the materials used. That is, the tubes can be separated from one another without any difficulty and can be recycled, i.e. returned to the production process immediately after mechanical cleaning.

In summary, the separation column according to the invention is
It follows the requirements listed in the following three categories.

1) Material characteristics of starting material a) Surface quality of inner wall b) Corrosion resistance c) Inertness of material in contact with sample d) Mechanical workability e) Stability against pressure

2) Quality of packed separation column a) High separation characteristics (efficiency) b) Appropriate signal (peak) shape, Gaussian distribution c) High detection sensitivity d) High selectivity

3) Price to performance ratio

DETAILED DESCRIPTION OF THE INVENTION FIG. 1a shows a separation column that is one embodiment of the present design. Separation column, carrier tube 5
And the inner tube is inserted therein. The inner volume 2 of the inner tube is filled with a stationary phase (not shown), for example silica gel or modified silica gel, or particles of polymeric material (reverse phase material or ion exchange material etc.). Furthermore, it is also possible to use the complete spectrum of carrier materials for chromatography. FIG. 1a shows the assembled separation column and is further shown unassembled in FIGS. 1b and 1c for a better overview of the individual parts.

The inner tubes that make up the actual separation column are held in place on the carrier tube 5 by sleeves 3 and 4. The sleeves 3, 4 are also used to center the inner tube. The sleeves 3, 4 are, in the preferred embodiment,
It comprises a plastic material, more preferably polyetheretherketone (PEEK). The PEEK material may be modified with PTFE or graphite in yet another embodiment. The material selected for the sleeve should be as resistant as possible to the solvents commonly used in chromatography.

The separation tube 1, which is arranged in a carrier tube 5 and is filled with the stationary phase, is conventionally used surrounded by plastic or fritted (heated to melt) glass (not shown). Sieve (siev
Seal both ends with e). The sieve or glass frit is inserted into the bore 7.

The sieve or frit serves the purpose of maintaining the carrier material in the packed separation tube. Furthermore, the substances eroded by the system or the contaminants contained in the liquid to be analyzed are removed before entering the column.

The carrier tube is made so that the connection to the analytical system (chromatographic device) can be established using conventional connecting components. The outer diameter of the carrier tube is especially compatible with cartridge systems on the market widely, for example the system supplied by E. Merch (compare US Pat. No. 4,737,284).

Therefore, it is possible to employ inner tubes having various inner diameters, preferably in the range between 1.00 and 3.00 mm, while maintaining the outer diameter of the carrier tube. The separation column according to the present invention can use various tube lengths. In high performance liquid chromatography,
The length of the tube preferably used is in the range between 50 mm and 300 mm. Of course, lengths other than these may be used.

Many materials have been considered for the inner tube. The following materials can be used. B) Special steel b) Special steel whose inner surface is coated with glass (glass coating tube) c) Borosilicate glass d) Ceramic composite material e) Plastic, eg PEEK.

Therefore, a number of chromatographic requirements, such as (a) operation under extreme pH conditions and salinity (corrosion resistance), (b) for example, the possibility of exhibiting reaction characteristics for tubing materials, Many materials are available to the user to accommodate the analytical inertness of a compound and handle it correctly. If special steel is used as the material for the inner tube, the tube can be stretched during the manufacturing process so that the inner diameter can be varied while maintaining the desired quality of the inner surface. The costly rework process performed to ensure the smoothness of the inner surface is no longer necessary.
There are many materials that can be considered as the carrier pipe 5, and special steel is preferably used for that purpose.

The end of a column which is an embodiment of the present invention is shown in FIGS. 2a and 2b. Here, FIG. 2a illustrates a state during assembly, and FIG. 2b illustrates a final assembly. The inner tube 11 is fixed in the carrier tube 15 by a sleeve 13,
At the same time it is centrally located. Sleeve 13
Has a conical outer shape adapted to each conical diameter of the carrier tube 15. The sleeve 13 is pushed to the right in Fig. 2a until flush with the end of the inner pipe, and the inner pipe 11 is attached as shown in Fig. 2b.

If, instead of the tube 11 shown here, one wishes to insert an inner tube with a different diameter into the carrier tube 15 (without deformation), this is simply the wall thickness of the separating tube. It can be implemented just by changing it or by using another sleeve. It will be appreciated that the group of parts shown in FIG. 2b on the left side of the column will also be similar on its right side.

Further details of one embodiment of the present invention are shown in FIG.
Shown in a and 3b. The embodiment shown here essentially corresponds to the embodiment given in FIG. 2b, in addition to this, another sealing means 20 comprising a sieve according to the invention is shown. The sealing means 20 is (in addition to the sleeve 13) the inner tube 11 when the column is used in a chromatograph.
This is to ensure that the liquid carried through does not enter the area between the inner tube 11 and the outer tube 15. FIG. 3 b is an enlarged view of the sealing means 20.

Explaining according to the complete assembly of the column shown in FIG. 3a, the lower end surface of the sealing means is the inner tube 11
Above it, it is laid flat on the sleeve 13 and on the shoulder inside the carrier tube 15. A sieve 21 is included in the sealing means 20, by means of which contaminant particles can be suppressed and furthermore a uniform distribution of the liquid flowing into the inner tube can be guaranteed. A back cut is visible at the connection of the carrier tube 15. If a force is applied to the sealing means 20 in connecting the column to the chromatograph, the sealing material, which is completely pressed by the applied pressure, is pushed into the back cut 22 and thus the sealing effect is further improved. As a result, the sealing element with the sieve will be held in a better position in place on the tube.

The encapsulation element 20 may be made of PTFE, for example. Special steel is a suitable material for the sieve used for the sealing element. However, the versatility of other porous materials may also be exploited.

As already mentioned in connection with FIGS. 2a and 2b, the separation column according to the invention is compatible with the cartridge system widely used internationally. For example,
If a value of 8 mm was chosen for the outer diameter of the end of the carrier tube, the separation column would be similar to the cartridge system commercially available from Macherey-Nagel as E. Merck.
It is also compatible with the better-supplied one (trademark "manuCART"). Therefore, the groove 24 is, for example, “manuCA
Helps hold corresponding fittings (half shell) from the "RT" system (compare US Pat. No. 4,737,284). Furthermore, the parts shown in FIG. 3a in relation to an embodiment of the invention are shown to one another on an exact scale.

As described above, the present invention sufficiently satisfies or exceeds the requirement for smoothness for chromatographic applications, which has an outer diameter of 8 mm and an inner diameter of 2 mm or less, and despite its minute inner diameter. It creates a compatible separation tube. In addition, the separation tube according to the present invention has a relatively simple structure, is cost-effective in its manufacture, and has no restriction on the tube length. Furthermore, on the one hand, the selected sealing principle ensures that there is no leakage, even against the high pressures traditionally used in chromatography, and on the other hand, the sealing means allow the chromatographic It is designed so that there is no dead volume appearing in the system. Various dead volumes are undesired for chromatography because they lead to a reduction in chromatographic separation performance. Finally, by mounting the separation tube according to the invention, no radial forces are exerted on the inner tube which influence the chromatographic ratio. Therefore, it is possible to avoid the narrowing of the inner diameter of the separation tube due to the conventional connection of the attachment.

If the development of the design example of the present invention is further advanced,
It can be foreseen that the outer surface of the inner tube 11 will be machined at both ends to a distance of approximately 5 mm. By this method, it is possible to carry out the conventional processing for the same arrangement shape of each sleeve regardless of the tolerance of the inner diameter with respect to the outer diameter.
An additional advantage seen in that respect is that after the drawing step nothing special has to be done with regard to the quality of the outer surface of the inner tube.

Although the embodiments of the present invention have been described in detail above, examples of each embodiment of the present invention will be shown below. (Embodiment 1) In a separation column used for chromatography such as liquid chromatography or supercritical chromatography, the separation column is equipped with a separation tube in which a stationary phase is packed, and the separation tube is concentrically arranged. A separation column including a carrier tube surrounded by the tube and an adapter member for holding the separation tube in the carrier tube. (Embodiment 2) The separation column for chromatography of Embodiment 1 in which the adapter member includes a sleeve. (Embodiment 3) The separation column for chromatography according to Embodiment 2, wherein the sleeve is made of a plastic material. (Embodiment 4) The chromatographic separation column of Embodiment 3 wherein the plastic material contains polyether ether ketone (PEEK). (Embodiment 5) The separation column for chromatography as described above, wherein the sleeve has a conical shape, and the carrier tube has a corresponding conical opening inside thereof. (Embodiment 6) The separation column for chromatography as described above, wherein the separation tube is made of steel. (Embodiment 7) The aforementioned separation column for chromatography, wherein the separation tube is made of ceramic or ceramic composite material. (Embodiment 8) The separation column for chromatography as described above, wherein the separation tube is made of glass-coated special steel. (Embodiment 9) The separation column for chromatography as described above, which is provided with a sealing means that is installed flat on the separation tube and the sleeve. (Embodiment 10) The aforementioned separation column for chromatography, wherein the sealing means is provided with a sieve. (Embodiment 11) The separation column for chromatography as described above, which is a separation tube having an outer diameter of about 8 mm in its end region. (Embodiment 12) The separation column for chromatography as described above, wherein the end of the separation tube is machined.

[0032]

As described above, according to the present invention, it is possible to maintain the sealing property in the chromatographic system and reduce the inner diameter of the column without deteriorating the characteristics (smoothness) of the inner surface of the column. it can. Furthermore, unlike the conventional configuration, each element can be removed,
Mechanical cleaning and material reuse is possible. By maintaining the quality of the surface characteristics even for columns with small diameters,
The chromatographic peak and column efficiency can be improved.

[Brief description of the drawings]

FIG. 1a is a cross-sectional view of a separation column for chromatography which is an embodiment of the present invention.

1b is a cross-sectional view of the carrier tube of FIG. 1a in a pre-assembled state.

1c is a cross-sectional view of the separation tube and sleeve of FIG. 1a in an unassembled state.

FIG. 2a is a partial detailed view of a separation column for chromatography according to an embodiment of the present invention before being incorporated.

FIG. 2b is a diagram showing a final assembled state of FIG. 2a.

FIG. 3a is a partial detailed view of a separation column for chromatography according to an embodiment of the present invention, which includes a sealing unit.

FIG. 3b is a partially enlarged view of FIG. 3a.

[Explanation of symbols]

 1, 11: Separation tube 5, 15: Carrier tube 3, 4, 13: Sleeve 20: Sealing means 21: Sieve

Claims (12)

[Claims] 1. A separation column used in a chromatograph, comprising a separation tube, wherein the separation tube is provided with a stationary phase, a carrier tube concentrically surrounding the separation tube, and the separation in the carrier tube. A separation column for chromatography, which comprises an adapter member for holding a tube. 2. The separation column for chromatography according to claim 1, wherein the adapter member includes a sleeve. 3. The chromatographic separation column according to claim 2, wherein the sleeve is made of a plastic material. 4. The plastic material comprises polyetheretherketone (PEEK).
A separation column for chromatography according to the item. 5. The chromatographic separation as claimed in claim 2, wherein the sleeve has a conical shape and the carrier tube has a corresponding conical opening in its interior. column. 6. The separation column for chromatography according to claim 1, wherein the separation tube is made of steel. 7. The separation tube according to claim 1, wherein the separation tube is made of ceramic or ceramic composite material.
A separation column for chromatography according to the item. 8. The separation tube is made of glass-coated special steel, and the separation tube is made of glass.
A separation column for chromatography according to the item. 9. The separation column for chromatography according to any one of claims 2 to 8, further comprising a sealing means installed flat on the separation tube and the sleeve. 10. The separation column for chromatography according to any one of claims 1 to 9, wherein the sealing means is provided with a sieve. 11. A separation tube having an outer diameter of about 8 mm in its end region.
A separation column for chromatography according to the item. 12. The separation column for chromatography according to any one of claims 1 to 11, wherein an end of the separation tube is machined.