CH708952A2 - Ceramic filter element for chromatographic applications, in particular HPLC applications, and chromatography, especially HPLC system, comprising a ceramic filter element. - Google Patents

Abstract

Shown and described is a chromatography system, in particular an HPLC system, a tube with two outlets and at least one filter insert for attaching to at least one of the exits. According to the invention, it is provided that the at least one filter insert contains an exchangeable ceramic frit (27). Furthermore, an exchangeable filter insert for a chromatography system is shown and described, in particular for an HPLC system, which according to the invention contains a ceramic frit (27). Further, a connection element for a chromatography system is disclosed, which includes a replaceable filter cartridge.

Description

TECHNICAL FIELD OF THE INVENTION

The field of the invention includes chromatography systems, in particular a HPLC systems.

The present invention relates to a chromatography systems, in particular an HPLC system, as well as a filter cartridge for such systems and the use of filter cartridges in said systems. Furthermore, the invention relates to a connection element for chromatography systems, in particular for the connection of a separation column tube with outgoing and access line.

BACKGROUND OF THE INVENTION

High Performance Liquid Chromatography (HPLC) is an established method for chemical analysis and separation of mixtures. The procedure is part of the standard equipment of a laboratory in research and industry. The basic principle is based on the different adhesion energy of substances to be separated on a known substrate. For analysis, a mixture of substances is dissolved in a so-called mobile phase, after which the solution is forced under pressure through a column of porous particles (stationary phase). Depending on the adsorption behavior of the various substances on the stationary phase, the constituents of the substance mixture emerge one after the other from the separation column.

In the field of HPLC, and especially for HPLC applications in the field of in vitro diagnostics, there is a need for bio-inert HPLC hardware. At no point in the HPLC apparatus should an ion exchange take place between a metal part and the sample to be analyzed by chromatography. It is also intended to avoid buildup of substances such as proteins or carryover. Thus, in particular, inert and low-drag pipe systems would be desirable.

Although stainless steel filters are pressure-stable, but not metal-free and thus not inert. Similarly, titanium filters are pressure stable but not metal free. Nevertheless, titanium filters are considered to be inert under certain conditions of use (thus, they are conditionally inert). However, titanium has the further disadvantage that it is quite expensive.

In contrast to metallic filters, ceramic filters are potentially inert. For complete sealing ceramic frits are used, which usually baked directly with a chromatography column. As a result, the ceramic filters are disadvantageously not interchangeable and not reusable. This means that usually the entire column has to be replaced. Furthermore, for caking with the column, a ceramic material is usually used which has binder portions such as e.g. Metal ions, contains. These materials may tend to crack due to shrinkage on cooling. However, cracks must be subsequently sealed with an adhesive. On the one hand, this leads to additional steps in the production, on the other hand, an adhesive material can be problematic for the inertness of Chromatographieapparatur. In order to obtain a defined porosity or structure of the ceramic frit, fillers can be used, which are burned out in the process of caking to a large extent. However, it should be remembered that always residues, i. Contaminants remain in the frit, which impairs the property of inertness.

Alternatively, the above-mentioned problems in the HPLC range, e.g. by providing complete systems including columns, fittings, filters and capillaries made entirely of plastic, especially polyaryletherketones (PAEK), e.g. Polyetheretherketone (PEEK) are made. When using pure plastic column systems only relatively low pressures on the system for packing the column or for sample transport through the column and relatively low operating pressures can be applied. This disadvantageously results in longer sample transit times.

A newly developed system provides a stainless steel tray which is completely plastic on the inside, in particular polyaryletherketone (PAEK), e.g. Polyetheretherketone (PEEK), see e.g. Revelation WO2013 / 024345. On the other hand, it is disadvantageous that, in particular, the PAEK filters or PEEK filters are inert, but they are not necessarily pressure-stable enough. Furthermore, PAEK and especially PEEK filters are brittle and usually very expensive.

Glass filters are considered more stable than PAEK, especially as PEEK, but in turn are not one hundred percent inert. Glass filters are used today only as a special solution

Sieves have less carryover due to lower material thickness than filters for the same material, but are not pressure-stable, in particular not under high-pressure conditions.

None of the aforementioned filter solutions applies in a wide range of applications as inert, metal-free and at the same time pressure-stable under high pressure conditions. High-pressure systems are used in particular at a pressure of 500 bar or more, in particular at a pressure of 1000 bar or higher.

TASK

It is therefore an object of the present invention to provide an inert, metal-free and at the same time pressure-resistant filter element. In particular, a filter element is to be provided which is inert and is stable under high pressure conditions, especially in HPLC applications. In addition, the filter should be easy to handle, in particular less brittle than PAEK filters, in particular PEEK filters, or glass filters. Furthermore, it is an object of the present invention to provide a filter element which has as little or no carryover when used. The inventive solution should in particular be inexpensive to produce. In addition, the filter element should be reusable and can be cleaned. In particular, an exchangeable filter element is to be made available. In addition, the filter for linear or turbulent flow variants should be produced and usable. In addition, it is an object of the present invention to remedy the disadvantages mentioned above and provide a filter or filter element for a chromatography system, in particular an HPLC system, which does not have the disadvantages of the prior art or at least partially avoids them.

Furthermore, it is an object of the present invention to provide an inert or bio-inert high performance liquid chromatography system (HPLC system), which does not have the disadvantages of the prior art, or at least partially avoids.

SUMMARY OF THE INVENTION

The object is achieved by a chromatography system, in particular an HPLC system, including a tube with two outputs and at least one filter insert for attaching to at least one of the outputs, which is characterized in that the at least one filter insert includes a replaceable ceramic frit.

A frit (or a ceramic frit) for the purpose of the present disclosure is conveniently a porous ceramic in the form of a monolith. The frit consists in particular of a quasi-monocrystalline or sintered, partially or fully imperial material. A frit is in particular a filter, wherein the application of the frit as a filter depends on the size of their pores.

According to the invention, the filter element is replaceable. A contaminated filter cartridge can thus be replaced by replacement without damaging the column. Other system parts can be reused. This may be many times cheaper than replacing the separation column, i. the tube. Optionally, the filter cartridge can be reused and reused after cleaning. An advantage of a ceramic material filter is that the filter is inert and can be made relatively thin in thickness.

Another advantage is that a filter consisting of ceramic, in particular a ceramic frit, shallow, i. thinner, can be designed as a plastic frit, in particular thinner than a PEEK frit. Advantageously, a ceramic frit having a thickness of less than 2 mm, in particular less than 1.0 mm, can be used as a filter. Preferably, ceramic frits are used having a thickness in the range of 0.5 mm to 2 mm, more preferably in the range of 0.6 mm to 1 mm. While a plastic frit with comparable filtering action has a thickness of about 3-5 mm or more. The lower frit volume results in a lower dead volume between sample distribution and column material.

Additional advantages and objects of the present invention will become apparent from the following description.

Such a thin replaceable ceramic frit can advantageously be used at the end of the separation column tube between the tube and connecting cable.

A chromatographic system typically includes at least one connector, preferably two connectors, for connecting the tube to a lead, preferably two leads (i.e., a drain and access lead, for example). The filter insert is for this purpose added or seated in the connecting element. The filter insert may optionally be fastened in the connecting element.

The connecting element (also called the end connection of the separation column) connects the tube (i.e., its outlets) to an outlet or access line. The ceramic frit can be pressed with the connecting element. In this case, between the ceramic frit and the connecting element is preferably an intermediate element made of a material which is softer than the material of the ceramic frit, such as e.g. Plastic to bring. This intermediate element acts as a buffer and / or seal and holds the frit in position. The intermediate element is also called holding element hereinafter. The ceramic frit is advantageously enclosed in a holding element which is e.g. designed as a ring or ring element or as a fitting insert.

The connecting element can with the aid of a closure, in particular a screw cap, attachable to the output of the separation column tube, in particular there be fixable or be pressed. By connecting fasteners and separation column, the frit can be clamped sealing, by screwing the frit can be replaced if necessary.

It is preferable to aim the sealing element to be sealing, i. liquid-tight, possibly also gas-tight, connects to the outlet of the tube. This prevents carryover and contamination of the substances to be analyzed.

Conveniently, the ceramic frit is fitted into the holding element, in particular the ceramic frit is pressed or clamped in the holding element. The fit should in particular also high pressure conditions. at more than 1000 bar under operating conditions of the novel chromatography system, withstand. A connection between the holding element and the ceramic frit is expediently non-positive and / or positive, in particular non-cohesive. The compound should preferably be solvable, i. without destroying the ceramic frit, the frit should be separable from the holding element.

The aim is the sealing element sealing (gas-tight and / or liquid-tight) to connect at the respective output of the tube.

It is preferred that the tube has on its inside a retracted inlay or a coating. Preferably, the retaining element is designed such that it can be pressed against the inlay (for example, on the front side of the tube). Preferably, the inlay made of plastic, in particular of a polyaryletherketone or a mixture of polyaryletherketones (PAEK). Also preferably, the holding element made of plastic, in particular a polyaryletherketone or a mixture of polyaryletherketones (PAEK).

By pressing the tube end and retaining member together, a sealed mass transfer path from the tube to the filter (i.e., the ceramic frit) and through the filter results.

Conveniently, a sealing ring is located on the inlay, in particular it is the inlay, and preferably inlayendständig or Røhrenendständig. This serves to reinforce the inlay at its end. Sealing ring and inlay are preferably connected to one another cohesively. The inlay and sealing material are optionally welded, in particular laser welded or glued, to produce an integral (i.e., one-piece) composite material.

The plastic used according to the invention for the holding element or the inlay is advantageously selected from the group of thermoplastics, in particular selected from fluoroplastics, polyaryletherketones (PAEK) and mixtures thereof, in particular selected from the group comprising polytetrafluoroethylene (PTFE), polyether ketone (PEK ), Polyetheretherketone (PEEK), polyetherketone ketone (PEKK), polyetheretheretherketone (PEEEK), polyetherketoneetherketone ketone (PEKEKK), and polyetheretherketoneetherketone (PEEKEK), with polyetherketone (PEK), polyetheretherketone (PEEK) and polyetherketone ketone (PEKK) being preferred, and polyetheretherketone (PEEK) most preferred.

The inlay and / or the holding element are preferably made of plastic, particularly preferably of a PAEK or mixtures containing them. With this material combination, a good tightness (liquid seal and gas seal) can be achieved.

The ceramic material of the ceramic frit is ceramic or partially ceramic. The ceramic material of the ceramic frit consists in particular of carbides, nitrides and / or oxides (or other), one or more elements selected from the group consisting of boron, aluminum, silicon, germanium, zirconium, cerium, rare earths (or others). The ceramic material of the ceramic frit is preferably selected from the group consisting of silicon carbide, silicon nitride, silicon oxide, zirconium oxide, zirconium carbide, titanium oxide, titanium carbide and mixtures thereof.

The chromatography system conveniently includes two filter cartridges, wherein each of the filter cartridges can be attached or attached to one output of the tube.

Advantageously, a replaceable ceramic frit can be used as a precolumn in a chromatography system, in particular in an HPLC system. This is an inexpensive solution because the ceramic frit can be replaced regularly when loaded with contaminants, while the main column can continue to be used after the ceramic frit has been replaced or cleaned.

Optionally, the holding element, in particular when designed as a retaining ring, one of an end face of the ceramic frit projecting flange, in particular a flange, form.

In an embodiment with flange ring on the retaining ring of the retaining ring is stepped in particular frontally stepped, wherein the inner ring side of the retaining ring corresponds in its axial thickness of the ceramic frit thickness. Due to the above flange ring, the filter insert according to the invention can be slipped onto a tube, in particular its inlay. This is particularly advantageous for frequent replacement of the filter cartridge. Because in this case the filter insert can be attached in advance to the tube. Thereafter, the tube end can be inserted with the attached filter insert in the connecting element and optionally screwed.

The said holding element can be further enclosed in a sleeve, which clasps the holding element. The collar is preferably made of metal and e.g. designed as a metal ring.

If the retaining element, e.g. if it is designed as a retaining ring, additionally in a cuff, especially a metal ring, taken hold, this creates additional stability and support for the filter cartridge. This is particularly advantageous when the filter cartridge is often removed and reinstalled, e.g. for his cleaning.

The sleeve is spaced from the end face of the tube, in particular the end face of the tubular jacket in such a way that allows a sealing pressing between the holding element and the inlay

The sealing pressure should in particular and mainly between inlay and retaining ring, but not between the tube shell and retaining ring or sleeve.

Furthermore, the use of a replaceable ceramic frit as a precolumn in a chromatography system, in particular in an HPLC system, according to one of the preceding claims, is disclosed.

According to the invention, the object mentioned by an interchangeable filter cartridge for a chromatography system with filter, in particular for a HPLC system, solved by the filter includes a ceramic frit.

The ceramic frit is preferably enclosed in a retaining ring. The retaining ring is preferably a plastic retaining ring (in particular made of PAEK).

Preferably, the ceramic frit of the filter cartridge with the retaining ring (in particular the plastic retaining ring) is pressed. This creates a frictional connection between the ceramic frit and retaining ring.

The holding element for a filter made of ceramic frit is preferably made of plastic, in particular of a thermoplastic, preferably of a semi-crystalline thermoplastic, in particular a polyaryletherketone (PAEK) or of a mixture comprising at least one polyaryletherketone.

The holding element for holding the filter is preferably enclosed in a cuff. The collar is preferably made of metal, in particular an inert metal, preferably made of titanium, a titanium alloy, steel or stainless steel.

In one embodiment, the retaining element as a retaining ring, in particular as a plastic retaining ring, configured, which is optionally comprised of a metal ring.

If the holding element, in particular if designed as a retaining ring, comprises of a metal ring, this promotes the dimensional stability of the filter insert even at high operating pressure of the chromatography system. In addition, this can be granted a simple operation when replacing the filter cartridge.

In general, the filter can be enclosed in a connecting element of a chromatography system. The filter is preferably first received in a holding element and possibly additionally taken together with the holding element in a sleeve before it is enclosed in the connecting element.

The connector includes a passageway for connecting the interior of a separation column tube to the interior of an exit or access conduit for mass transfer. Furthermore, the connecting element includes a fastening part for fastening the connecting element to an outlet of the separating column tube and a fastening part for a feeder or access line.

In one embodiment of the invention, the holding element is preferably designed as a fitting insert as a plastic fitting insert, which is received in the connecting element. The connecting element is preferably made of metal, in particular stainless steel.

The invention further discloses a connecting element for a chromatography system, in particular an HPLC system. The fastener includes a fastener for attachment to an exit of a separation column tube, a passageway for interconnecting, inter-connecting the interior of the separation column tube with the interior of an exit or access conduit, with a replaceable filter cartridge inserting a ceramic frit as a filter in the passageway includes.

The filter insert according to the invention and thus the chromatography system according to the invention can be part of an in-vitro diagnostic system or a liquid handling system. Chemical analysis systems and preparative instruments are examples of such liquid handling systems and optionally in vitro diagnostic systems.

Further advantages and objects of the present invention will become apparent from the following description.

BRIEF DESCRIPTION OF THE FIGURES

Further advantages and features of the invention will become apparent from the following detailed description with reference to the figures. It shows schematically, not to scale true representation: <Tb> FIG. 1: <SEP> an HPLC column with filter insert and connecting parts and, by way of example, a connected capillary on one side of the column; <Tb> FIG. 2: <SEP> a detail II of FIG. 1 with filter insert; <Tb> FIG. 3: <SEP> a filter cartridge of FIGS. 1 and 2, a) in plan view and b) in section; <Tb> FIG. 4: <SEP> a filter insert according to FIGS. 1 to 3 in oblique view in three variants of a filter: a) homogeneously porous filter, b) filters with passage capillaries, c) further filters with passage capillaries; <Tb> FIG. 5: <SEP> another HPLC column with filter insert and connecting parts and, by way of example, a connected capillary on one side of the column; <Tb> FIG. 6: <SEP> a detail VI of FIG. 5 with filter insert; <Tb> FIG. 7: <SEP> a filter cartridge of Figures 5 and 6 in section. <Tb> FIG. 8 <SEP> a filter insert according to Fig. 5-7 in oblique view with three variants of a filter: a) homogeneous porous filter, b) filters with Durchgangsskapillaren, c) another filter with Durchgangsskapillaren; <Tb> FIG. 9 <SEP> a connector with fit ring insert and filter embedded therein; <Tb> FIG. 10 <SEP> one end of a HPLC column with connector and filter cartridge.

DETAILED DESCRIPTION OF THE FIGURES

In the following, the same reference numerals for the same or functionally identical elements (in different figures). An additional apostrophe can be used to distinguish between several identical, similar, functionally identical or functionally similar elements.

Fig. 1 shows a separation column, in particular a chromatography column. The separation column includes a hollow, especially cylindrical, tube 9. To the tube, i. At their exits 10, 10 (made, for example, as capillary outlets), access lines 13 can be connected via connecting elements 11, 11. The tube 9 serves to receive a stationary phase (not shown) in the tube interior 12 and can be traversed by a mobile phase (not shown). The tube interior 12 thus forms a passage. If a mixture of substances is added to the mobile phase, the different constituents of the substance mixture separate into fractions transported at different rates due to a different distribution of the components between the stationary and the mobile phase. Both ends 14, 14 of the tube 9 are connected to connecting elements 11, 11 or connectable. These connecting elements 11, 11, serve to connect a supply or a discharge line 13 (shown by way of example only one of the two lines) for sample material to the tube 9. For ease of assembly can be formed on the tube 9 and the connecting elements 11, 11 tool engagement points, which favor the holding and thus the screwing of tube 9 and connecting element 11, 11. For example, each tube end region 14, 14 has a thread (here in particular an external thread 19) which can be screwed to a mating thread (here in particular an internal thread 21) of the connecting element 11, 11. Alternatively, other types of connection could be used, such as a pull-out plug-in mechanism (e.g., with hooking).

Each connecting element 11, 11 has two connection points 23 and 25; a first connection point 23 is used for attachment to the tube 9 and a second connection point 25 serves for attachment to an access or exit line 13. A connecting element 11, 11 thus serves to connect the tube 9 with an access or exit line 13 , When assembled, it is possible to feed the tube 9 with sample material and to withdraw and analyze the material transported and separated by the tube passage. A connecting element 11, 11 includes at least one continuous main body 15, in particular made of metal, a fitting insert 17, 17 and optionally an exchangeable filter 27. The main body 15 has at least the two connection points 23 and 25, which via an intermediate bridge region 24th connected to each other. Preferably, the two connection points 23 and 25 of a connecting element 11 are arranged coaxially with each other. Each connection point 23, 25 may be provided with a thread, in particular an internal thread 21, or another attachment structure. The fitting insert 17, 17 is also called compact here. Advantageously, the fitting insert 17,17 is made of a plastic. The fitting insert 17, 17 has a passage opening 18, to which the outlet or access line 13 can be attached.

In Fig. 1, filters 27, 27 are shown, which are the tube passage 12 upstream and downstream. The filters 27, 27 are fitted into the connecting element 11, 11, preferably in such a way that the filters 27, 27 are removable, i. interchangeable, are. The filters 27, 27 abut the tube end region 14, 14. That the filters 27, 27 in particular abut the front end of the tube end regions 14, 14. Optionally, the filters may wholly or partially penetrate into the tube 9 or its end region 14, 14 (this is not shown in the figures).

The filter 27, 27 is advantageously enclosed in a filter holder 26. The filter holder 26 is used in particular for holding the frit and for sealing. The filter holder is preferably made of plastic, preferably a PAEK or mixtures thereof, in particular PEEK. Optionally, the filter and filter holder can be further accommodated in a sleeve 28, in particular a metal sleeve, more preferably a stainless steel sleeve. Preferably, the sleeve is configured as a kind of cylindrical metal sheath. The sleeve 28 stabilizes and reinforces the filter holder 26. Filter 27, filter holder 26 and possibly sleeve 28 together form, in particular, a filter insert.

In Figs. 1 and 2, a longitudinal section through the tube 9 and the screwed fasteners 11, 11 is shown. The tube 9 includes a jacket 29, in particular of metal, which is advantageously covered with an inlay 31 substantially over its entire inner side. The tube 9 preferably consists at least of a metal jacket 29 and an inlay 31. The ends 14 of the tube 9 have end faces. Surfaces that are visible in the axial (i.e., axial direction of the tube) plan view are referred to herein as end surfaces. The metal shell 29 of the tube thus has end face 32. The tube jacket is preferably made of a metal or a metal alloy, particularly preferably made of stainless steel. The inlay 31 is preferably made of a plastic material (e.g., PAEK, especially PEEK). The inlay 31 is expediently made of a plastic tube, which is retracted or inserted into the metal shell 29. Optionally, the outer diameter of the inlay 31 may be designed slightly smaller than the inner diameter of the metal shell 29, in particular by a maximum of 100 microns, preferably by a maximum of 50 microns, more preferably by a maximum of 5 microns. Alternatively, the inlay 31 may be applied as a coating on the inside of the tubular jacket 29. Inlay 31 and metal shell 29 are approximately the same length, wherein the inlay 31 is dimensioned such that in the operational or mounted system, a pressure between inlay 31 and filter cartridge or filter 27 is.

As can be seen from the enlarged illustration in FIG. 2, a peripheral recess 33 can be formed on the inside of the shell 29 on the inside of the shell, which is covered with a sealing ring 35. The sealing ring 35 is thus terminal at least on the outside on the lateral surface of the inlay 31. The contact surfaces between inlay 31 and sealing ring 35 are advantageously welded or optionally glued together, thereby forming an integral, i. one-piece or cohesive, composite. If the sealing ring 35 is introduced into the recess 33 by injection molding, a material bond (i.e., a cohesive connection) may possibly form during injection molding production, which may make additional welding unnecessary, depending on the application. Advantageously, the recess is open on the front side, so that the sealing ring 35 may optionally form an end face 36 with the inlay 31. A remaining edge region of the tubular jacket 29 can form a kind of web 39 radially outward. Optionally, the inlay 31 and / or sealing ring 35 are slightly in front of the axial extension, e.g. preferably 0.1 mm to 2 mm, over the edge of the tubular jacket 29, i. the web 39, out, so that inlay 31 and sealing ring 35 are compressed under pressing force and can form a gas-tight passage with the filter element or the filter 27 and its socket 26 and / or sleeve 28 (or alternative the fitting insert 17) as a counterpart.

The tube end region 14, 14 is preferably screwed to the connecting element 11, 11. The end face 36, 36 of the inlay 31 may abut the edge of the filter 27 and / or its socket 26. The end face of the sealing ring 35 expediently abuts, at least in part, the socket 26 of the filter 27. The socket 26 of the filter 27 is advantageously made of a plastic material, such as e.g. PAEK, in particular PEEK. The contact surfaces between 31 inlay and socket 26 and / or sealing ring 35 and socket 26 on the one hand, socket 26 and fitting insert 17 on the other hand each form an annularly closed pressure area. When screwing tube 9 and connecting element 11, 11 thus meet plastic surfaces (especially PAEK surfaces such as PEEK surfaces) to each other, which liquid-tight under appropriate contact pressure, possibly gas-tight, close and a transport passage from the tube 9 via the filter 27 and the form optional fitting insert 17 in the outlet or access line 13.

Inlayaussenseitig can when screwing the tube shell 29 and the respective connecting element 11 or 11 meet, but this need not be. Optionally, the end face 32 of the tubular jacket 29 meets the sleeve 28 (preferably a metal sleeve) to press them again under pressure on the fitting insert 17. However, it is preferred that the metal collar touches neither the metal shell of the column nor the fitting insert. The metal collar serves in particular to limit the deformation of the plastic socket 26.

By screwing or pressing of tube 9 with or on connecting element 11, 11 thus creates a liquid-tight (possibly gas-tight) passage passage, which from the interior of the inlay 31 through the filter 27, into a fine passage opening 18 in the fitting insert 17 and thus leads to a departure or access channel 13.

On the opposite side of the passage opening 18 to the filter 27, the fitting insert 17 is designed such that a supply line or a discharge line can be used in a liquid-tight manner (possibly gastight). Advantageously, a supply or discharge line has a metal shell and an inner lining made of plastic. The second connection point 25, 25 of the connecting element 11, 11 is designed such that both components of the supply or discharge line 13 when connecting to the connecting element 11, 11 preferably on the same material or the same material surfaces meet (eg plastic on plastic or metal Metal). This means that the inner lining, which is advantageously made of plastic, with the fitting insert 17 is liquid-tight, possibly gas-tight, connectable (eg via pressing pressure) and the jacket, which is advantageously metallic, (form-fitting) with metallic portions of the connecting element 11, 11th , in particular liquid-tight (possibly gas-tight), is connectable.

The filter insert with filter 27 and socket 26 and optionally sleeve 28 abuts the fitting insert 17. The fitting insert 17 filter side expediently has a funnel-shaped recess, i. a funnel 55, which tapers towards the passage opening 18. Advantageously, the funnel region 55 remains free of filter material, so that a flowing medium distributed on entry into the filter area 27 to the entire filter diameter and with the most homogeneous speed over the entire radial region of the filter 27 into the tube 9 and / or passes from the tube. 9 coming out at the exit from the filter area 27 without area congestion can flow into and through the passage opening 18.

Where the filter cartridge with filter 27 and socket 26 and optionally sleeve 28 abuts the fitting insert 17, there may optionally be the filter insert (filter 27, socket 26 and if present sleeve 28) embedded in a recess of the fitting insert 17 (not shown ). However, a funnel 55, as described above, is preferably present below the area of the filter 27.

The fitting insert 17 has on the side facing away from the filter 27, for example, a cylindrical recess 58, which recess 58 serves to receive a supply or discharge line. Inner lining of the supply and discharge line and fitting insert 17 should be able to form a positive press connection of plastic material on plastic material here. Following recess 58, the connecting element 11, on the inside, expediently has a section 59 with a metallic surface for the positive reception of an access or exit duct 13. The access duct 13 is preferably inserted into a connection part 60 with a tapered fit 61, which is e.g. for screwing access or outlet line 13 with the connecting element 11 is used to produce a snug fit in the connecting element 11. The access or exit line 13 preferably includes a lining or inlay 62 (eg made of PAEK, such as PEEK) in a capillary 63. The capillary 63 of the access or exit line 13 can at least in the region of the connection part 60 with a metallic shell 69, which encloses and supports the incoming capillary 63 over a certain range. Section 59 and fit 61 are preferably funnel-shaped or cone-shaped, in order to provide a form-fitting and optionally liquid-tight and / or gas-tight connection. In particular, the cone 61 may be made of metal to produce a metal-to-metal seal with the connecting element 11.

In detail, the connecting element 11 is preferably designed as follows: The metal jacket 15 comprises the fitting insert 17, which can be inserted from the first end 23 and thereby abuts against a first inner shoulder 56 of the metal jacket 15. In the cavity of the first end 23 of the fitting insert 17, this following the filter insert (with filter 27, filter holder 26 and possibly sleeve 28) and turn this following the tube end portion 14 is non-positively inserted (preferably by screwing into a present in the cavity thread 21st ). In the cavity of the second end 25 may - preferably below - a discharge line or access line 13 are non-positively inserted (preferably by screwing into a present in the cavity thread).

In Fig. 3, a filter cartridge with filter 27 and socket 26 is shown. Filter 27 and filter holder 26 form expediently a cylindrical filter insert. The filter 27 is essentially formed of a porous ceramic frit. The filter holder 26 is made of, for example, a plastic, in particular PAEK, e.g. PEEK with which the ceramic frit can be pressed or pressed in without damage to form a replaceable and easy-to-handle filter element. Optionally, the plastic frit may be further received in a metal collar 28 (not shown in FIGS. 3 and 4). In Figs. 4a, 4b and 4c filter cartridges with filters 27, 27, 27 and socket 26 are shown. The filter used here consists, for example, of a homogeneously porous ceramic frit 27 (FIG. 4 a), a ceramic frit 27 with essentially straight capillary passages in a ceramic block (FIG. 4 b) or a ceramic frit 27 with im Substantially straight capillary passages in a bundle of ceramic rods (Figure 4c), which bundle may be bonded to an inner sleeve 71.

The maximum pore diameters of the capillary passages for filters 27 or 27 are preferably in the range from 0.01 μm to 100 μm, preferably from 0.5 μm to 2 μm.

The filter cartridges shown in FIGS. 3 and 4 are suitable for use with sleeve 28 similar to the embodiments in FIGS. 1 and 2. Alternatively, the socket 26 can be wider, so that the sleeve 28 is omitted. The use of a sleeve 28 shows its advantage, however, in that the dimensions of the filter insert are adjustable during its production and thereby a replacement of the filter cartridge is granted.

In FIGS. 5 and 6, in a second exemplary embodiment, in contrast to the first exemplary embodiment according to FIGS. 1 and 2, the tube end region 114 is designed without a web. In addition, the inlay 31 is extended relative to the tube 109 and designed to protrude beyond it, wherein preferably for reinforcement a sealing ring 35, the inlay 31 is circumferentially peripherally mounted on the shell side. Here, the sealing ring 35 is preferably welded terminally with the lateral surface of the inlay 31. The filter cartridge, which preferably consists of filter 27 (i.e., frit) and filter holder 126 (or filter, filter holder and optional sleeve), is slipped over inlay 31 and sealing ring 35. In particular, the filter holder 126 has a stepped end face, whose radially outer side region 175 projects beyond the radially inner side region 177, wherein the frit 27 is made substantially flush with the radially inner side region 177 of the stepped end face of the filter holder 126. That Frit 27 and radially inner side portion 177 of the stepped end face of the filter holder 126 form a common, preferably planar end face, which is surmounted by the radially outer side portion 175 of the stepped end face of the filter holder 126 in the axial direction, whereby over the frit 27, a cylindrical recess is formed , which is suitable for mounting on a protruding inlay 31 with sealing ring 35.

In Fig. 7, a filter cartridge with filter 27 and socket 126 is shown. Filter 27 and filter holder 126 form expediently a cylindrical filter insert with flange 179 on the filter holder 126. The shape of the socket 126 is used in particular to cooperate with a tube end portion 114, 114 with protruding inlay 31. The filter 27 is - as previously shown with reference to FIGS. 3 and 4 - formed essentially of a porous ceramic frit. Again, for example, the filter holder 126 is made of a plastic, in particular PAEK, such as e.g. PEEK, with which the ceramic frit can be pressed without damage to form a replaceable and easy-to-handle filter element. Optionally, the ceramic frit, which is preferably enclosed in plastic, can be further accommodated in a sleeve, which can be designed in particular as a metal sleeve (not shown in the figures). In Figs. 4a, 4b and 4c filter cartridges with filters 27, 27, 27 and filter holder 126 are shown. The filter used here consists, for example, of a homogeneously porous ceramic frit 27 (FIG. 4 a), a ceramic frit 27 with essentially straight capillary passages in a ceramic block (FIG. 4 b) or a ceramic frit 27 with im Substantially straight capillary passages in a bundle of ceramic rods (Figure 4c), the bundle with an inner sleeve 71, eg a ceramic band, plastic band, or metal band may be included. Preferably, the bundle of ceramic rods is thermally baked.

The filter cartridges shown in FIGS. 7 and 8 are suitable for use similar to the embodiments in FIGS. 5 and 6. Alternatively, the socket 126 could be further incorporated in an additional sleeve (not shown in the figures). The use of a cuff would offer the same advantages as shown above with respect to Figs. 1-4.

Fig. 9 shows a connecting element 211 with a passage and an inserted fitting insert 226, which also takes over the task of a holding element, characterized in that the filter 27 is embedded in the fitting insert 226. In Fig. 10, this connecting element 211 is shown in conjunction with a separating tube 209. By connecting or, in particular, by screwing the tubular jacket 229 to the connecting element 211, the filter 226, which is a ceramic frit, is pressed against the front edges of the tubular jacket 229. The edge 230 of the fitting insert 226, which encloses the filter 27, is pressed under screwing force for sealing against the ring seal 235. The seal 235 is designed as a ring seal, which surrounds the inlay 231 and rests against the inside of the tube jacket 229. Seal 235 and optionally Inlayende protrude advantageously slightly above the end face of the tube shell 229, which results in a good compression seal as soon as the connecting element 211 is screwed onto the tube end. Between the fitting element 226 and the end face 250 of the filter 203 facing away from the tube jacket 229, a collecting funnel gap 250 can be cut out, as usual between the fitting element and the filter and shown here.

filter materials

In principle, any ceramic material can be used as a filter or frit material if it exhibits some release effect, i. when the ceramic material has interactive properties.

An interactive property in the chromatographic domain is understood to mean an interaction between the analyte (i.e., the material to be separated) and the stationary phase (i.e., the solid or liquid part in the column which does not move). The interactions that mainly occur are adsorption, distribution, ion exchange, and size exclusion.

Interactive properties are achieved in particular by derivatization of the ceramic material. By derivatization is meant the chemical alteration of the surface by adsorptively or covalently with e.g. functional molecules is occupied. The ceramic part can also be used without derivatization, but in the biochromatography area this does not always work. Optionally, therefore, the ceramic part is treated accordingly prior to its use. The process includes at least one wet chemical process or gas phase processes in which a compound is adsorbed and / or chemically bonded to the ceramic surface. Example: In the case of the so-called "end capping", the part to be processed is dissolved in a solution of at least one organosilane (or another compound), possibly in a solvent such as e.g. Toluene, possibly with a catalyst such. aqueous hydrochloric acid, inserted over minutes to hours in the solution and / or possibly also heated. After cleaning with e.g. Solvent and drying, the part is usable.

In SiO2 the release effect is already present, i. instrinsich. With SiO2 frits, therefore, no derivatization treatment is necessary.

The inventive filter inserts include filters 27, 27, in particular according to the embodiment filter 27, 27 or 27 as stated above, from as pure as possible ceramic materials, which are essentially no fillers or filler residues or admixtures include. Examples of filter materials are e.g. oxidic, carbidic and nitridic ceramics and mixtures thereof, in particular aluminum oxide, silicon carbide, zirconium oxide, titanium oxide, titanium carbide, silicon nitride, and mixtures thereof. The purity of said filter materials or mixtures thereof is preferably at least 98% by weight, preferably at least 99% by weight, more preferably at least 99.9% by weight. The purity here is the mole fraction of a desired substance to the entire mixture. Ideally, the purity would be 1, i. 100 wt% if no impurities are present.

In particular, salt-like admixtures (such as salts) in the filter materials are undesirable which lower the melting point, e.g. Boric acid or boron trioxide, and oxides, carbonates, halides or other salts of alkali and / or alkaline earth metals, since these could be dissolved out of the frit material and interfere with the analysis of the chromatographically separated substances.

Optionally, it may be necessary during the manufacturing process of the filter 27, 27, in particular 27, 27 or 27, admixtures, e.g. as fillers to influence the porosity of the frit. For this purpose, preference is given in the preparation process to organic admixtures which consist only of carbon, hydrogen, oxygen, nitrogen and / or silicon and therefore leave no residue on ignition in the finished and ready-to-use filter and lead to correspondingly pure filter frits of the abovementioned purity.

As such admixtures, polymer particles such as, for example, polyamides, polycarbonates, epoxy resins can be used in the filter production. The form of the admixtures as a solid may include fibers, spherical particles or the like. Also admixtures in liquid form or sol-gel-like form are conceivable.

The temperatures to be used in the production process are for sintering mainly in the temperature range of 1000 ° C to 3500 ° C, usually between 1600 ° C and 3000 ° C, but especially between 1700 ° C and 2600 ° C, depending on the material. The said organic admixtures are annealed without residue.

In summary, it is found that the filter insert according to the invention combines the following advantages in comparison to known ceramic frits:

Use as a guard column

According to a particularly advantageous embodiment, the filter insert according to the invention, in particular if it is e.g. a SiO2 frit filter included, used as a guard column. The purpose of the frit is firstly to retain the stationary phase (i.e., the release agent) in the separation column 9 or 109, and secondly to effect as a precolumn a first or pre-separation of the substance mixture to be analyzed. For example, SiO 2, especially sintered silica gel, exhibit guard column functionality.

In this context, the interchangeability of the filter element according to the invention is advantageous. As a result, the separation column can be equipped with a precolumn function as needed.

A guard column system can be used to protect columns from the deleterious effects of chemical contaminants or microparticles by sticking in the guard column. It is known to use pre-column systems as upstream, separate cartridges. The new filter insert according to the invention, on the one hand, keeps the filling of the separating column in place and, on the other hand, due to its filtering effect, ensures that the protected main column has a longer service life or, less frequently, has to be replaced. New only the filter 27 can be replaced by the inventive filter cartridge is replaced. It is stated that the exchangeability of the frit makes it possible to use the filter insert according to the invention also as a precolumn. Thus, the filter according to the invention, especially if it also functions as a guard column, helps to save costs and material.

In summary, it is found that the filter insert according to the invention, in its function as a guard column, at least combines the following advantages:

While specific embodiments have been described above, it will be apparent that various combinations of the illustrated embodiments may be used so far as the embodiments are not mutually exclusive.

While the invention has been described above with reference to specific embodiments, it is obvious that changes, modifications, variations, and combinations may be made without departing from the spirit of the invention.

LIST OF REFERENCE NUMBERS

[0093] <tb> 9 <SEP> Tube, i.e. separation column <tb> 10, 10 <SEP> Output at the tube end or tube output <tb> 11, 11 <SEP> Connector <Tb> 12 <September> Tube Affairs <tb> 13 <SEP> outgoing line or access line <tb> 14, 14 <SEP> Tube End Area <Tb> 15 <September> body <tb> 17, 17 <SEP> Fitting insert <Tb> 18 <September> through opening <tb> 19, 19 <SEP> male thread <tb> 21, 21 <SEP> Female thread <tb> 23 <SEP> first connection point <Tb> 24 <September> bridge area <tb> 25 <SEP> second connection point <tb> 26 <SEP> Holding element, especially filter holder or holder for filters <tb> 27, 27, 27, 27, 27, 27 <SEP> Filter, especially ceramic frit <tb> 28 <SEP> Cuff or metal ring <tb> 29 <SEP> Tube sheath, in particular metal sheath <tb> 31 <SEP> Inlay or coating <tb> 32 <SEP> End face of the tubular jacket <Tb> 33 <September> recess <Tb> 35 <September> sealing ring <tb> 36 <SEP> Face of the inlay <tb> 37 <SEP> Face of the seal ring <Tb> 39 <September> Steg <tb> 55 <SEP> Hopper region (preferably in the fitting insert) <tb> 56 <SEP> Abutting surface in the connecting element <tb> 58 <SEP> Recess in the fitting insert <tb> 60 <SEP> Connection part for access line <tb> 61 <SEP> Taper fitting, in particular of metal <tb> 62 <SEP> Inner lining or inlay of the access line or outlet line, in particular of plastic <tb> 63 <SEP> Capillary of the inlet or outlet line <tb> 69 <SEP> Capillary reinforcement, in particular of metal <tb> 71 <SEP> Inner sleeve, e.g. metal band <tb> 109 <SEP> tube, i.e. separation column <tb> 114, 114 <SEP> Tube End Area <Tb> 126 <September> Filter Mount <tb> 129 <SEP> Tube sheath, in particular metal sheath <tb> 132 <SEP> End face of the tubular jacket <175> <SEP> radially outward-side region of the filter holder <tb> 177 <SEP> radially inward area of the filter holder <Tb> 179 <September> filter flange <tb> 209 <SEP> tube, i.e. separation column <Tb> 211 <September> connecting element <tb> <SEP> Fitting insert, especially with recess (serves here <tb> <SEP> also as socket or holder for filters) <Tb> 229 <September> tube envelope <tb> 230 <SEP> bordering edge of the fitting insert <Tb> 231 <September> inlay <Tb> 235 <September> sealing ring <tb> 250 <SEP> funnel-shaped gap

Claims (26)

A chromatography system, in particular an HPLC system, comprising a tube (9, 109) having two outlets (10, 10) and at least one filter insert for attaching to at least one of the outlets, characterized in that the at least one filter insert includes a replaceable ceramic frit (27, 27, 27, 27, 27, 27). 2. Chromatographiesystem according to claim 1, characterized in that it comprises at least one connecting element (11, 11, 211) for connecting the tube (9, 109, 209) with a connecting line (13), wherein the ceramic frit (27, 27 , 27, 27, 27, 27) in the connecting element (11, 11, 211) sits or is received. 3. Chromatographiesystem according to claim 2, characterized in that the connecting element (11, 11, 211) by means of a closure (21), in particular a screw cap, at the output (10, 10, 210) attachable, in particular can be fixed or pressed is. 4. Chromatographiesystem according to any one of the preceding claims, characterized in that the ceramic frit (27, 27, 27, 27, 27, 27) in a holding element (26, 126 , 226), eg designed as a ring or ring element (26, 126) or as a fitting insert (226) is bordered. 5. Chromatographiesystem according to claim 4, characterized in that the holding element (26, 126, 226), which encloses the ceramic frit, in a connecting element (11, 211) sits. 6. Chromatographiesystem according to any one of claims 4 or 5, characterized in that the ceramic frit (27, 27, 27, 27, 27, 27) in the holding element (26, 126, 226) is fitted, in particular that the ceramic frit in the holding element (26, 126, 226) is pressed or clamped in this. 7. Chromatographiesystem according to any one of claims 4-6, characterized in that the holding element (26, 126, 226) sealingly to the tube (9, 109, 209) at the output (10, 10) connects. 8. Chromatography system according to one of the preceding claims, characterized in that the tube (9, 109, 209) includes a tube jacket (29, 129) with an inlay (31), wherein, insofar as a holding element is present, the holding element (26, 126, 226) is preferably pressed against the inlay (31). 9. Chromatographiesystem according to claim 8, characterized in that the inlay (31) consists of plastic, in particular a PAEK. 10. Chromatographiesystem according to any one of claims 8 or 9, characterized in that a sealing ring (35) on the inlay (31) is present, in particular the inlay (31) lies around. 11. Chromatography system according to one of claims 4-10, characterized in that the holding element (26, 126, 226) consists of plastic, in particular a PAEK. 12. A chromatography system according to any one of the preceding claims, characterized in that the ceramic material of the ceramic frit is selected from the group consisting of silicon carbide, zirconium oxide, titanium oxide, titanium carbide, silicon nitride, silicon oxide and mixtures thereof. 13. Chromatographiesystem according to any one of the preceding claims, characterized in that it comprises two filter cartridges, each of the filter cartridges on each an output (10, 10) can be added or deposited. 14. Chromatography system according to one of the preceding claims 4-13, characterized in that the holding element (126) one of an end face of the ceramic frit (27, 27, 27, 27, 27) projecting flange ( 179). 15. The chromatography system according to claim 14, characterized in that the retaining element is designed as a retaining ring, wherein the retaining ring (126) is stepped frontally formed, wherein the inside of the retaining ring (126) corresponds in its axial thickness of the ceramic frit thickness. 16. Chromatographiesystem according to any one of the preceding claims 4-13, characterized in that the holding element (26), which can be referred to as a first holding element, in a second holding element (28) is taken, wherein the second holding element is preferably made of metal and eg is designed as a metal ring. 17. Chromatographiesystem according to the preceding claim 14, characterized in that the second holding element (28) from the end face of the tube (9), in particular the end face of the tubular jacket (29, 129) is spaced. 18. Use of a replaceable ceramic frit as precolumn in a chromatography system, in particular in an HPLC system, according to one of the preceding claims. 19. Replaceable filter cartridge for a chromatography system, in particular an HPLC system, comprising a filter (27, 27, 27, 27, 27, 27), characterized in that the Filter includes a ceramic frit 20. Interchangeable filter insert according to claim 19, characterized in that the filter is enclosed in a holding element (26, 126, 226). 21. Interchangeable filter insert according to claim 20, characterized in that the holding element (26, 126, 226) is made of plastic, in particular of a thermoplastic, preferably of a semi-crystalline thermoplastic, in particular a polyaryletherketone or of a mixture comprising at least one polyaryletherketone. 22. Interchangeable filter insert according to one of claims 19 or 21, characterized in that the holding element (26, 126, 226), which can be referred to as a first holding element, is enclosed in a second holding element (28), preferably by the two holding element ( 28) is included. 23. Interchangeable filter insert according to claim 22, characterized in that the second holding element (28) made of metal, in particular an inert metal, preferably made of titanium, a titanium alloy, steel or stainless steel. 24. Interchangeable filter insert according to one of claims 21-23, characterized in that the filter, in particular via the holding element (26, 126, 226) and optionally via the second holding element (28), is enclosed in a connecting element. 25. Replaceable filter insert according to claim 24, characterized in that the connecting element includes - a passage for connecting the interior of a separation column tube (9, 109, 209) to the interior of a waste or access line (13) - A fastening part (21) for attachment to an output (10, 10, 110) of the separation column tube (9, 109, 209). 26. Connecting element (11, 211) for a chromatography system, in particular an HPLC system, comprising A fastening part (21) for attachment to an outlet (10, 10, 110) of a separating column tube, A passage for connecting the interior of the separation column tube (9, 109, 209) to the interior of a drain or access duct (13), characterized in that a replaceable filter insert is inserted in the passage, wherein the filter insert includes a ceramic frit (27, 27, 27, 27, 27, 27).