Abstract
A chromatography system comprising at least two pumps, a first pump which is connectable or connected with a liquid reservoir for a first fluid, and a second pump which is connectable or connected with a liquid reservoir for a second fluid, wherein the pump outlet lines from the first pump and the second pump are connected with a connection piece and, viewed in the direction of flow, a chromatography column is provided downstream of this connection piece, wherein, viewed in the direction of flow, an addition unit is provided upstream of the connection piece and a mixer switching valve and a mixer switchable by way of the mixer switching valve are provided between the connection piece and chromatography column, wherein the mixer switching valve has at least two switching positions, wherein the mixer is connectable in a first position and the mixer is bypassable in a second position.
A chromatography method in which the system is used and a conversion kit for converting a high-performance liquid chromatography system into a chromatography system for supercritical fluid chromatography are also disclosed.
Claims
1. A chromatography system comprising at least a first pump which is connectable or connected with a liquid reservoir for a first fluid, and a second pump which is connectable or connected with a liquid reservoir for a second fluid, wherein pump outlet lines from the first pump and the second pump are connected with a connection piece and, viewed in a direction of flow, a chromatography column is provided downstream of the connection piece, wherein: viewed in the direction of flow, an addition unit is provided upstream of the connection piece, and a mixer switching valve and a mixer switchable by way of the mixer switching valve are provided between the connection piece and the chromatography column, wherein the mixer switching valve has at least two switching positions, and wherein the mixer is connectable in a first position and the mixer is bypassable in a second position.
2. The chromatography system according to claim 1, wherein a flow path of a fluid in the second position of the mixer switching valve, in which the mixer is bypassable, is shorter than in the first position of the mixer switching valve, in which the mixer is connectable.
3. The chromatography system according to claim 1, wherein, viewed in the direction of flow, the addition unit is provided downstream of the first pump.
4. The chromatography system according to claim 1, wherein the addition unit comprises an injection valve, wherein the injection valve has at least two sample loop ports and two high-pressure ports for infeed and outfeed of high-pressure fluid.
5. The chromatography system according to claim 1, wherein the mixer switching valve comprises at least four ports, wherein two of said ports are connected with a mixer.
6. The chromatography system according to claim 1, wherein a chromatographic procedure with a solvent gradient is performable.
7. The chromatography system according to claim 1, wherein fluid cooling is provided for the liquid reservoir for a second fluid and the second pump.
8. The chromatography system according to claim 1, wherein the mixer is configured as a static mixer.
9. The chromatography system according to claim 1, wherein the chromatography system is controllable by way of a chromatography system controller.
10. The chromatography system according to claim 1, wherein the chromatography system is configured as a supercritical fluid chromatography (SFC) system, wherein the chromatography system has a chromatography column and, viewed in the direction of flow, at least one downstream backpressure regulator.
11. The chromatography system according to claim 1, wherein, viewed in the direction of flow, a gas-liquid separator is provided downstream of the backpressure regulator.
12. A method for carrying out a chromatographic procedure comprising the use of the chromatography system according to claim 1.
13. The method according to claim 12, wherein the liquid reservoir for a first fluid contains a first solvent which is liquid under standard conditions, and the liquid reservoir for a second fluid contains a second solvent which is gaseous under standard conditions.
14. The method according to claim 12, wherein, on application of a sample to be separated to the chromatography column, the mixer switching valve is switched into the second position and the fluid is bypassed around the mixer.
15. A conversion kit for converting a high-performance liquid-chromatography (HPLC) system into a chromatography system according to claim 1, wherein the kit includes at least one gas-liquid separator and at least one mixer switching valve.
Description
[0119] In the following, preferred embodiments of the present invention are to be described by way of example with reference to four figures, without this being in any way intended to restrict the invention. In the figures:
[0120] FIG. 1 is a schematic representation of a chromatography system,
[0121] FIG. 2 is a schematic representation of a preferably usable addition unit in a first switching position,
[0122] FIG. 3 is a schematic representation of a preferably usable addition unit in a second switching position,
[0123] FIG. 4 is a schematic representation of a preferably usable mixer switching valve in a first switching position,
[0124] FIG. 5 is a schematic representation of a preferably usable mixer switching valve in a second switching position,
[0125] FIG. 6 is a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit is in a second switching position and a preferred mixer switching valve is in a first switching position,
[0126] FIG. 7 is a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit is in a second switching position and a preferred mixer switching valve is in a second switching position,
[0127] FIG. 8 is a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit is in a first switching position and a preferred mixer switching valve is in a second switching position,
[0128] FIG. 9 is a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit is in a first switching position and a preferred mixer switching valve is in a first switching position,
[0129] FIG. 10 is a schematic representation of a chromatography system configured as an SFC system.
[0130] FIG. 1 shows a schematic representation of a chromatography system 1, as may for example be configured as an HPLC system.
[0131] A suitable chromatography system 1 comprises two fluid streams, wherein a first fluid is provided by a first liquid reservoir 3 and a second fluid by a second liquid reservoir 5. The first fluid is transferred from the liquid reservoir 3 by a pump 7, which in the present case comprises two pistons 7a, 7b, into a connection piece 29. Viewed in the direction of flow, an addition unit 11 is provided upstream of the connection piece 29, wherein, in the present embodiment, said unit is disposed downstream of the pump 7. In a further embodiment, the addition unit 11 can also be disposed upstream of the pump 7.
[0132] FIGS. 2 and 3 show a preferred embodiment of an addition unit 11.
[0133] The second fluid is transferred from the liquid reservoir 5 by a pump 9, which in the present case comprises two pistons 9a, 9b, into the previously shown connection piece 29, such that, downstream of the connection piece 29, a composition is obtained which is mixed by the mixer 31 which, viewed in the direction of flow, is disposed downstream of connecting piece 29, when the mixer is connected in. The mixer is switchable by way of a mixer switching valve, which is not shown for reasons of clarity, such that the mixer 31 is connectable in a first position and the mixer 31 is bypassable in a second position.
[0134] FIGS. 4 and 5 show a preferred embodiment of a mixer switching valve, which is connected with a mixer.
[0135] In the present chromatography system 1, a chromatography column 51 is disposed downstream of the connection piece 29 and the mixer 31. In the present case, a fraction collector 61 is preferably provided downstream of the chromatography column 51.
[0136] The fraction collector 61 can be controlled by way of one or more control units, which are not shown here, wherein these control units are operatively connected with one or more detectors. Viewed in the direction of flow, the detectors are connected between chromatography column 51 and fraction collector 61.
[0137] In general, the mixer switching valve is switched into the first position and the fluid is passed through the mixer. This is in particular the case during the actual separation of the sample composition.
[0138] For application of a sample to be separated to the chromatography column, the mixer switching valve is switched into the second position and the fluid is bypassed around the mixer.
[0139] FIG. 2 describes a preferably usable addition unit 10 in a schematic representation in a first switching position.
[0140] The addition unit 10 shown in FIG. 2 comprises an injection valve 12 and a sample loop 14. The injection valve 12 shown in FIG. 2 comprises 6 ports (16, 18, 20, 22, 24, 26), wherein two ports are configured as sample loop ports (16, 18), two ports (20, 22) as high-pressure ports for the infeed and outfeed of high-pressure fluid, and two ports (24, 26) as ports for the infeed and outfeed of sample composition and/or fluid into and from the sample loop. The ports 16 and 18 are here connected with the sample loop 14 and configured as sample loop ports. The ports 20 and 22 serve as high-pressure ports for the infeed and outfeed of high-pressure fluid. A sample can be introduced into the sample loop 14 and fluid guided out of the sample loop by way of ports 24 and 26. These ports 24, 26 serve as injection and waste ports respectively. In the present embodiment, port 20 is connectable or connected in flow communication with a liquid reservoir for a first fluid and port 22 with a connection piece, wherein the liquid reservoir for a first fluid and the connection piece are not shown in FIG. 2.
[0141] In the first switching position, a sample can be introduced into the sample loop 14, wherein this may proceed via port 24 by way of a syringe or a pump, as is known from the prior art. The sample loop 14 can be charged with a sample by an excess pressure or a reduced pressure. It can, for example, be filled by injection. Furthermore, a sample vessel can be disposed upstream of the sample loop 14 and a waste vessel downstream of the sample loop, wherein a pump, for example a peristaltic or gear pump, which draws up a sample from the sample vessel and transfers it into the sample loop 14, is disposed between the sample loop 14 and waste vessel. Fluid which is present in the sample loop prior to sample introduction is here transferred via port 26 into a waste vessel which is not shown. This fluid preferably substantially consists of the first solvent.
[0142] FIG. 3 describes a preferably usable addition unit 10 in a schematic representation in a second switching position. As described in FIG. 2, the addition unit 10 comprises an injection valve 12 and a sample loop 14, wherein the injection valve 12 comprises six ports (16, 18, 20, 22, 24, 26) which are described in greater detail in FIG. 2.
[0143] FIG. 3 shows the addition unit 10 in a second switching position in which a sample from the sample loop 14 is applied to a chromatography column. In this switching position, the sample loop 14 is switched into the flow path between a liquid reservoir for a first fluid and a connection piece. In this switching position of the injection valve 12, a fluid from a first liquid reservoir is introduced into the sample loop 14 via port 20 or port 16 and discharged into a connection piece via port 18 or port 22.
[0144] FIG. 4 describes a preferably usable mixer switching valve 30 in a first switching position. The mixer 32 shown in FIG. 4 is connected with the mixer switching valve 30 via ports 34 and 36 and lines 38 and 40. The ports 42 and 44 serve as high-pressure ports for the infeed and outfeed of high-pressure fluid. In the present embodiment, port 42 is in flow communication with a connection piece and port 44 with a chromatography column, wherein the connection piece and the chromatography column are not shown in FIG. 4.
[0145] The mixer switching valve 30 described in FIG. 4 has two switching positions, wherein, in the first position shown, the mixer 32 is connected in, such that a fluid or a fluid mixture is passed from a connection piece via the mixer 32 into a chromatography column.
[0146] FIG. 5 describes a preferably usable mixer switching valve 30 in a second switching position. The mixer 32 shown in FIG. 5 is connected with the mixer switching valve 30 via ports 34 and 36 and lines 38 and 40. The ports 42 and 44 serve as high-pressure ports for the infeed and outfeed of high-pressure fluid. In the present embodiment, port 42 is in flow communication with a connection piece and port 44 with a chromatography column, wherein the connection piece and the chromatography column are not shown in FIG. 5.
[0147] The mixer switching valve 30 described in FIG. 5 has two switching positions, wherein, in the second position shown, the mixer 32 is bypassed, such that a fluid or a fluid mixture is passed from a connection piece not via the mixer 32 but instead directly into a chromatography column.
[0148] FIG. 6 shows a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit 48 is in a second switching position and a preferred mixer switching valve 82 is in a first switching position.
[0149] The addition unit 48 comprises an injection valve 50 and a sample loop 52. The injection valve 50 shown in FIG. 6 comprises 6 ports (56, 58, 62, 64, 66, 70). The addition unit 48 and injection valve 50 are switched such that a sample can be introduced into the sample loop 52. To this end, a sample can be fed into the sample loop 52 via sample inflow line 68, which is connected with port 66 for conveying sample composition and/or fluid into and from the sample loop. The sample loop 52 is connected with the injection valve 50 via ports 62 and 64. The sample loop 52 can be charged with a sample by an excess pressure or a reduced pressure. It can, for example, be filled by injection. Furthermore, a sample vessel can be disposed upstream of the sample loop 52 and a waste vessel downstream of the sample loop, wherein a pump, for example a peristaltic or gear pump, which draws up a sample from the sample vessel and transfers it into the sample loop 52, is disposed between the sample loop 52 and waste vessel. Fluid which is present in the sample loop prior to sample introduction is here transferred via port 70 and line 72 into a waste vessel which is not shown. This fluid preferably substantially consists of the first solvent.
[0150] In the second switching position of the addition unit 48 or injection valve 50, fluid is transferred from a liquid reservoir for a first fluid via line 54 into line 60 via two high-pressure ports 56, 58 for the infeed and outfeed of high-pressure fluid. A non-return valve 74 is provided in line 60. The line 60 is connected with a connection piece 76 which is furthermore connected with an inflow line 78 for a second fluid. The common outlet line 80 is connected via port 86 with a mixer switching valve 82. The mixer switching valve 82 is connected via ports 88 and 90 with a mixer 84 and via port 92 with a line 94 which leads into a chromatography column, wherein the chromatography column is not shown in FIG. 6. In FIG. 6, the mixer switching valve 82 is in a first switching position in which a fluid or a fluid mixture is passed from the connection piece 76 via the mixer 84 into a chromatography column.
[0151] In the present embodiment, the mixer switching valve 82 is connected via ports 96 and 97 with a bypass loop 98.
[0152] In the configuration shown in FIG. 6, the chromatography column, which is not shown, can for example be equilibrated with a suitable fluid mixture before a sample is applied.
[0153] FIG. 7 shows a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit 48 is in a second switching position and a preferred mixer switching valve 82 is in a second switching position.
[0154] The portion shown in FIG. 7 therefore corresponds in many details to that shown in FIG. 6, wherein the same reference signs denote identical components, such that the explanations provided in respect of FIG. 6 also apply to FIG. 7.
[0155] As described in FIG. 6, the addition unit 48 comprises an injection valve 50 and a sample loop 52, wherein the injection valve 50 comprises six ports (56, 58, 62, 64, 66, 70) which are described in greater detail in FIG. 6. The position of the addition unit 48 and injection valve 50 is described in FIG. 6, such that reference is made thereto in order to avoid repetition.
[0156] A fluid is passed into the mixer switching valve 82 via line 60 and the connection piece 76, wherein details of the mixer switching valve 82, in particular the connection thereof with the mixer 84 and the bypass loop are described in FIG. 6.
[0157] In FIG. 7, the mixer switching valve 82 is in a second switching position in which a fluid or a fluid mixture is passed from the connection piece 76 not into mixer 84, but instead via the bypass loop 98 into a chromatography column.
[0158] The configuration shown in FIG. 7 can be for example be adopted shortly before sample application in order to ensure the mixer 84 is bypassed.
[0159] FIG. 8 shows a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit is in a first switching position and a preferred mixer switching valve is in a second switching position.
[0160] The portion shown in FIG. 8 therefore corresponds in many details to that shown in FIGS. 6 and 7, wherein the same reference signs denote identical components, such that the explanations provided in respect of FIGS. 6 and 7 also apply to FIG. 8.
[0161] As described in FIG. 6 or 7, the addition unit 48 comprises an injection valve 50 and a sample loop 52, wherein the injection valve 50 comprises six ports (56, 58, 62, 64, 66, 70) which are described in greater detail in FIG. 6.
[0162] In FIG. 8, the addition unit 48 is in a second switching position in which a sample from the sample loop 52 is applied to a chromatography column. In this switching position, the sample loop 52 is switched into the flow path between a liquid reservoir for a first fluid and the connection piece 76. In this switching position of the injection valve 50, a fluid from a first liquid reservoir is introduced into the sample loop 52 via port 56 or port 64 and discharged into the connection piece 76 via port 62 or port 58.
[0163] A fluid is passed into the mixer switching valve 82 via line 60 and the connection piece 76, wherein details of the mixer switching valve 82, in particular the connection thereof with the mixer 84 and the bypass loop are described in FIG. 6.
[0164] In FIG. 8, the mixer switching valve 82 is in a second switching position in which a fluid or a fluid mixture is passed from the connection piece 76 not into mixer 84, but instead via the bypass loop 98 into a chromatography column.
[0165] The configuration shown in FIG. 8 is adopted on application of a sample in order to ensure the mixer 84 is bypassed.
[0166] FIG. 9 shows a schematic representation of a portion of a chromatography system, wherein a preferably usable addition unit is in a first switching position and a preferred mixer switching valve is in a first switching position.
[0167] The portion shown in FIG. 9 therefore corresponds in many details to that shown in FIGS. 6, 7 and 8, wherein the same reference signs denote identical components, such that the explanations provided in respect of FIGS. 6, 7 and 8 also apply to FIG. 9.
[0168] As described in FIG. 6, 7 or 8, the addition unit 48 comprises an injection valve 50 and a sample loop 52, wherein the injection valve 50 comprises six ports (56, 58, 62, 64, 66, 70) which are described in greater detail in FIG. 6.
[0169] In FIG. 9, the addition unit 48 is in a second switching position in which a sample from the sample loop 52 is applied to a chromatography column. In this switching position, the sample loop 52 is switched into the flow path between a liquid reservoir for a first fluid and the connection piece 76. In this switching position of the injection valve 50, a fluid from a first liquid reservoir is introduced into the sample loop 52 via port 56 or port 64 and discharged into the connection piece 76 via port 62 or port 58.
[0170] A fluid is passed into the mixer switching valve 82 via line 60 and the connection piece 76, wherein details of the mixer switching valve 82, in particular the connection thereof with the mixer 84 and the bypass loop are described in FIG. 6.
[0171] In FIG. 9, the mixer switching valve 82 is in a first switching position in which a fluid or a fluid mixture is passed from the connection piece 76 via the mixer 84 into a chromatography column.
[0172] The configuration shown in FIG. 9 is adopted once the sample to be applied has passed through the mixer switching valve 82, wherein this position is where possible switched immediately after passage of the sample to be applied. Furthermore, during the actual separation, i.e. after application of the sample, the switching position in FIG. 6 is set, for example in order to introduce a further sample into the sample loop 52.
[0173] FIG. 10 is a schematic representation of a chromatography system 100 with a gas-liquid separator 130 which is suitable for supercritical fluid chromatography.
[0174] Such a system is described by way of example using supercritical CO.sub.2, wherein methanol is shown as an exemplary solvent. Obviously, systems in which other solvents, preferably organic solvents are applied, or other supercritical fluids are used, have a similar structure.
[0175] As shown in FIG. 10, the respective fluids are kept in storage containers, in particular the gas that is still used in a supercritical state is provided in a storage tank 102 and the solvent is provided in a storage tank 104, and they can be conveyed out of the storage tanks 102, 104 to the further components of the system by way of a pump 106, 108 respectively. In the system 100 described here, a preparation stage (110, 112) is preferably provided in each fluid inflow line, by way of which the fluids can be temperature controlled. Further, leveling of the pressure fluctuations indicated by the pumps can also be provided. Accordingly, this preparation stage can be designed, for example, as a heat exchanger or as a pump. An addition unit 114, for example an injector, is provided in the solvent line via which a mixture to be separated is introduced into system 100, before the CO.sub.2 and solvent are introduced into a connection piece 116 and fed to a chromatography column 118. FIGS. 2 and 3 show a preferred embodiment of an addition unit 114. A switchable mixer 117 is provided between the connection piece 116 and the chromatography column 118, which mixer is switchable by way of a mixer switching valve, which is not shown for reasons of clarity, such that the mixer 117 is connectable in a first position and the mixer 117 is bypassable in a second position. FIGS. 4 and 5 show a preferred embodiment of a mixer switching valve, which is connected with a mixer.
[0176] In the present system 100, two analysis units are disposed downstream of the chromatography column 118, wherein a sample discharge unit 120 is connected with a mass spectrometer 122 and a UV detector 124 is provided downstream of the sample discharge unit. Downstream of the analysis unit, a device for providing an additional volume 125 is shown in the present case which in particular serves to increase the run time of the liquid so as to be able to evaluate the results, for example, of the mass spectrometer 122. The backpressure regulator 126 provided in the line downstream of the means for providing an additional volume 125 maintains the respective pressure which is required for the fluid to remain in a supercritical state. Downstream of the backpressure regulator 126, a heat exchanger 128 is provided that prevents the aerosol from freezing during the expansion process. Subsequently, the aerosol is introduced into a gas-liquid separator 130 according to the invention, wherein the gas in the system is discharged via an outlet 132.
[0177] The liquid is introduced into a fraction collector 134 and fractionated therein. The solvent contained in the fractionated samples can be removed from the samples.
[0178] The features of the invention disclosed in the preceding description, as well as in the claims, figures and exemplary embodiments, may be essential both individually and in any combination for realizing the invention in its various embodiments.
