Automatic valve switching device and method for ion chromatography (IC) to facilitate balancing of consumables or allow normal IC operation

Abstract

An automatic valve switching arrangement is provided. A chromatographic system comprises: an electrolytic eluent generator; a first valve configured to switch between an operating position directing the output of the electrolytic eluent generator to a continuously generated trapping column and a waste position directing the output of the electrolytic eluent generator to waste; a continuously regenerated trapping column; a degasser; a sample injector comprising a sample injector valve assembly configured to switch between an operating mode directing the output of the degasser to a separation column, a loading mode for loading a sample onto the separation column, and a regenerant mode for directing the output of the degasser to a regenerant line; the separation column; a suppressor; and a detector.

Description

Technical Field

[0001] The present disclosure relates generally to the field of ion chromatography (IC), including automated valve switching arrangements for equilibration of consumables or normal IC operation. Background Art

[0002] Ion chromatography (IC) is a widely used analytical technique for the determination of anionic and cationic analytes in a variety of sample matrices. Ion exchange-based consumables need to be equilibrated before being deployed in an ion chromatography setup. These consumables include eluent generators, continuously regenerated trapping columns, analytical and guard columns, suppressors, and other consumables with ion exchange capabilities. Proper equilibration requires special plumbing setups. Consumables usually require equilibration when first installed or after a system has been shut down for an extended period of time. Summary of the invention

[0003] In a first aspect, a chromatographic system may include an electrolytic eluent generator, a first valve, a continuously regenerated capture column, a degasser, a sample injector, a separation column, a suppressor, and a detector. The electrolytic eluent generator may be configured to generate eluent electrolytically. The first valve may be configured to switch between an operating position where the output of the electrolytic eluent generator is directed to the continuously generated capture column and a waste position where the output of the electrolytic eluent generator is directed to waste liquid. The continuously regenerated capture column may be configured to remove ionic contaminants from the eluent. The degasser may be configured to remove residual gas from the eluent. The sample injector may include a sample injector valve assembly. The sample injector valve assembly may be configured to switch between an operating mode where the output of the degasser is directed to the separation column, a loading mode where the sample is loaded onto the separation column, and a regenerant mode where the output of the degasser is directed to the regenerant pipeline. The separation column may be configured to separate the components of the sample chromatographically. The suppressor may be configured to reduce the conductivity of the eluent. The detector may be configured to detect the presence of components of the sample.

[0004] In various embodiments of the first aspect, the sample injector valve assembly includes a three-position valve for switching between an operating position corresponding to an operating mode, a loading position corresponding to a loading mode, and a regenerant position corresponding to a regenerant mode.

[0005] In various embodiments of the first aspect, the sample injector valve assembly may include: a second valve for switching between a first operating position directing the output of the degasser to a third valve and a loading position directing the sample to a separation column; and a third valve for switching between a second operating position directing the output of the second valve to the separation column and a regenerant position directing the output of the second valve to a regenerant line.

[0006] In various embodiments of the first aspect, the chromatography system can further include a check valve on the regenerant line.

[0007] In various embodiments of the first aspect, the chromatography system can further include a flow restrictor between the first valve and waste.

[0008] In various embodiments of the first aspect, the chromatography system can further include a controller, wherein the controller is configured to switch the first valve to the waste position during the electrolytic eluent generator equilibration period. In certain embodiments, the controller can be further configured to switch the second valve to the regenerant position during the continuously regenerated trap column equilibration period.

[0009] In various embodiments of the first aspect, the chromatography system may further include a third valve configured to switch between an operating position for directing the output of the separation column to the suppressor and a waste position for directing the output of the separation column to waste. In a specific embodiment, the chromatography system may further include a controller, wherein the controller may be configured to switch the third valve to the waste position during the separation column equilibration time period.

[0010] In various embodiments of the first aspect, the suppressor may be a chemical suppressor.

[0011] In various embodiments of the first aspect, the suppressor can be an electrolytic suppressor. In certain embodiments, the chromatography system can further include a fourth valve configured to switch between an operating position directing an output of the detector to a regenerant line and a waste position directing an output of the detector to waste. In certain embodiments, the chromatography system can further include a controller, wherein the controller can be configured to switch the fourth valve to the waste position during a suppressor equilibration period.

[0012] In a second aspect, a method may include: switching a first valve to a waste position directing the output of an electrolytic eluent generator to waste; allowing liquid to flow through the electrolytic eluent generator during an electrolytic eluent generator equilibration period; switching the first valve to an operating position directing the output of the electrolytic eluent generator to a continuously regenerated capture column; switching a second valve downstream of the continuously regenerated capture column to a regenerant position, wherein the regenerant position directs a downstream flow from the continuously regenerated capture column to a regenerant line; allowing liquid to flow through the continuously regenerated capture column during an equilibration period of the continuously regenerated capture column; switching the second valve to an operating position directing the downstream flow to a separation column; and verifying the operation of the chromatography system.

[0013] In various embodiments of the second aspect, the method may further include switching the third valve to a waste position that directs the output of the separation column to waste; allowing liquid to flow through the separation column during a separation column equilibrium time period; and switching the third valve to an operating position that directs the output of the separation column to a suppressor.

[0014] In various embodiments of the second aspect, the suppressor may be a chemical suppressor.

[0015] In various embodiments of the second aspect, the suppressor can be an electrolytic suppressor. In certain embodiments, the method can further include switching the fourth valve to a waste position that directs the output of the detector to waste; flowing liquid through the suppressor to the detector during a suppressor equilibration period; and switching the fourth valve to an operating position that directs the output of the detector to a regenerant line. In certain embodiments, the method can further include providing an alternate regenerant flow to the suppressor during the suppressor equilibration period.

[0016] In a third aspect, a method may include switching a valve to an equilibrium position that directs an output of an electrolysis consumable device to a waste or regenerant line; allowing liquid to flow through the electrolysis consumable device during an equilibrium time period of the electrolysis consumable device; switching a first valve to an operating position; and verifying the operation of a chromatography system.

[0017] In various embodiments of the third aspect, the electrolysis consumable device may include an electrolysis eluent generator.

[0018] In various embodiments of the third aspect, the electrolysis consumable device may include a continuously regenerated trap column.

[0019] In various embodiments of the third aspect, the electrolysis consumable device may include a separation column.

[0020] In various embodiments of the third aspect, the electrolysis consumable device may include an electrolysis suppressor. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] For a more complete understanding of the principles and advantages disclosed herein, reference is now made to the following description in conjunction with the accompanying drawings, in which:

[0022] Figure 1 An exemplary chromatography system according to various embodiments is shown.

[0023] Figure 2 A general valve flow for electrolysis consumables according to various embodiments is shown.

[0024] Figure 3 An exemplary chromatography system according to various embodiments is shown.

[0025] Figure 4An exemplary chromatography system according to various embodiments is shown.

[0026] Figure 5 Exemplary methods of preparing a chromatography system for use according to various embodiments are shown.

[0027] Figure 6 Exemplary methods of replacing electrolytic consumables according to various embodiments are shown.

[0028] It should be understood that the drawings are not necessarily drawn to scale, nor are the relationships between objects in the drawings necessarily drawn to scale. The drawings are intended to make the various embodiments of the devices, systems, and methods disclosed herein clear and easy to understand. When appropriate, the same reference numerals will be used throughout the drawings to refer to the same or similar parts. In addition, it should be understood that the drawings are not intended to limit the scope of the present teachings in any way. DETAILED DESCRIPTION

[0029] Embodiments of systems and methods for ion separation are described herein.

[0030] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described in any way.

[0031] In this detailed description of various embodiments, for purposes of explanation, numerous specific details are set forth to provide a thorough understanding of the disclosed embodiments. However, those skilled in the art will appreciate that these various embodiments may be practiced with or without these specific details. In other cases, structures and devices are shown in block diagram form. Furthermore, those skilled in the art will readily appreciate that the particular order in which the methods are presented and executed is illustrative, and it is contemplated that the order may be changed and still remain within the spirit and scope of the various embodiments disclosed herein.

[0032] All literature and similar materials cited in this application, including but not limited to patents, patent applications, papers, books, monographs, and internet web pages, are expressly incorporated by reference in their entirety for any purpose. Unless otherwise described, all technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which the various embodiments described herein belong.

[0033] It should be understood that there is an implicit "about" before the temperatures, concentrations, times, pressures, flow rates, cross-sectional areas, etc. discussed in the present teachings, so that there are slight and insubstantial deviations within the scope of the present teachings. In this application, unless otherwise specifically stated, the use of the singular includes the plural. Moreover, the use of "comprise / comprises / comprising", "contain / contains / containing", and "include / includes / including" are not intended to be limiting. It should be understood that the foregoing general description and the following detailed description are merely exemplary and illustrative and do not limit the present teachings.

[0034] As used herein, "a" or "an" may also mean "at least one" or "one or more." Moreover, the use of "or" is inclusive, such that the phrase "A or B" is true when "A" is true, "B" is true, or both "A" and "B" are true. In addition, unless the context requires otherwise, singular terms shall include pluralities and plural terms shall include the singular.

[0035] A "system" describes a set of real or abstract components comprising a whole, wherein each component interacts or relates to at least one other component within the whole.

[0036] Proper balancing of ion exchange based consumables such as eluent generators, continuously regenerated trap columns, analytical and guard columns, and suppressors requires special plumbing setup and is usually performed manually prior to analysis, manually and as a separate setup. Consumables usually require balancing when first installed and after prolonged system shutdown.

[0037] The systems and methods disclosed herein solve multiple problems associated with balancing ion exchange based consumables. When first installed, the system may take several days to install and achieve acceptable performance due to the various balancing routines that need to be performed as specified for the consumables. Subsequent replacement of consumables by the user will require prompt hands-on work to ensure that the consumables are balanced according to the written procedures. In addition, system performance may be impaired after restarting the system after a long shutdown. In order to achieve good performance, a certain degree of balancing is required, and this increases hands-on time. In addition, the pressure contribution of various consumables may not be very obvious and requires the user to take additional steps for diagnosis.

[0038] Figure 1An embodiment of a chromatography system 100 is shown. The chromatography system 100 may include a pump 102, an electrolytic eluent generator 104, a continuously regenerated trap column 106, a degasser 108, a sample injector 110, a chromatographic separation device 112, an electrolytic suppressor 114, a detector 116, and a microprocessor 118. The chromatographic separation device 112 may take the form of a capillary column or an analytical column. A pipeline 120 may be used to transfer liquid from the output of the detector 116 to the inlet of the regenerant channel of the electrolytic suppressor 114. A pipeline 124 may be used to transfer liquid from the outlet of the regenerant channel of the electrolytic suppressor 114 to the inlet of the regenerant channel of the continuously regenerated trap column 106. A recirculation line 126 may optionally be used to transfer liquid from the outlet of the continuously regenerated trap column 106 to the inlet of the degasser 108 or may be directed to waste. When configured with flow of the regenerant stream from a continuously regenerating trap column, liquid from the outlet of the degasser 108 may be directed to waste 128 .

[0039] Pump 102 can be configured to pump liquid from a liquid source 132 such as deionized water and be fluidically connected to an electrolytic eluent generator 104. Pump 102 can be configured to deliver liquid at a pressure ranging from about 20PSI to about 15,000PSI. In some cases, a pressure greater than 15,000PSI can also be implemented. It should be noted that the pressure indicated herein is listed relative to ambient pressure (13.7PSI to 15.2PSI). Pump 102 can take the form of a high pressure liquid chromatography (HPLC) pump. In addition, pump 102 can also be configured to make liquid only contact the inert part of pump 102, so that a significant amount of impurities will not be filtered out. In this context, "significant" means the amount of impurities that will interfere with the expected measurement results. For example, the inert part can be made of polyetheretherketone (PEEK) or at least coated with a PEEK lining, which does not filter out a significant amount of ions when exposed to liquid.

[0040] Eluent is a liquid containing acid, alkali, salt or its mixture, and can be used for eluting analyte by chromatographic column. In addition, eluent can comprise a mixture of liquid and water miscible organic solvent, wherein the liquid can comprise acid, alkali, salt or its combination. Electrolytic eluent generator 104 is configured to generate product. Product refers to the acid, alkali or salt of the specific species that can be added to the eluent. In one embodiment, product can be alkali, such as cationic hydroxide, or product can be acid, such as carbonic acid, phosphoric acid, acetic acid, methanesulfonic acid or its combination.

[0041] Reference Figure 1 The eluent generator 104 may be configured to receive the liquid from the pump 102 and then add the product to the liquid. The liquid containing the product may be output from the eluent generator 104 to the inlet of the continuously regenerated trap column 106.

[0042] The continuously regenerated capture column 106 is configured to remove cation or anion pollutants from the eluent. The continuously regenerated capture column 106 may include an ion exchange bed with an electrode at the eluent outlet. The ion exchange membrane stack can separate the eluent from the second electrode, and the pollutant ions can be swept toward the second electrode by the ion exchange membrane stack. The ion exchange membrane stack may include one or more ion exchange membranes. In various embodiments, anion removal can utilize anion exchange beds, wherein the cathode at the eluent outlet is separated from the anode by anion exchange membrane. Alternatively, cation removal can utilize cation exchange beds, wherein the anode at the eluent outlet is separated from the cathode by a cation exchange membrane.

[0043] Degasser 108 can be used to remove residual gases. In one embodiment, the residual gases can be hydrogen and oxygen. Degasser 108 can include a gas permeable and liquid impermeable pipe section, such as an amorphous fluoropolymer or more specifically Teflon AF. The flowing liquid can be output from degasser 108 to a sample injector 110 where a significant portion of the gas is removed.

[0044] Sample injector 110 can be used for injecting a large dose of liquid sample into the eluent stream. The liquid sample can include multiple chemical compositions (i.e., matrix components) and one or more analytes of interest. Sample injector 110 can include automatic sampler 134, sample loop 136, and multi-way valve 138. Automatic sampler 134 can extract a sample from a sample container. Multi-way valve 138 can be in a first position to allow sample to fill sample loop 136 to the desired volume. After filling sample loop 136, multi-way valve can be switched to a second position, and the eluent stream can drive the sample to the chromatographic separation device 112.

[0045] The chromatographic separation device 112 can be used to separate various matrix components present in the liquid sample from one or more analytes of interest. Typically, the chromatographic separation device 112 can take the form of a hollow cylinder containing a filled stationary phase. When the liquid sample flows through the chromatographic separation device 112, the matrix components and the target analyte can have a certain range of retention times to elute from the chromatographic separation device 112. According to the characteristics of the target analyte and the matrix components, they can have different affinities to the stationary phase in the chromatographic separation device 112. The output of the chromatographic separation device 112 can be fluidically connected to an electrolytic suppressor 114.

[0046] The electrolytic suppressor 114 can be used to reduce the eluent conductivity background and enhance the analyte response by effectively exchanging the eluent counter ions for the regenerant ions. The electrolytic suppressor 114 may include an anode chamber, a cathode chamber and an eluent suppression bed chamber separated by an ion exchange membrane. The anode chamber and / or the cathode chamber may produce regenerative ions or transport supplied regenerant ions. The eluent suppression bed chamber may include a flow path for the eluent separated from the regenerant by the ion exchange barrier, and the eluent counter ions may be exchanged with the regenerative ions across the ion exchange barrier. The output of the electrolytic suppressor 114 may be fluidically connected to a detector 116 to measure the presence of separated chemical components of the liquid sample.

[0047] The detector 116 may be in the form of a UV-visible spectrometer, a fluorescence spectrometer, an electrochemical detector, a conductivity detector, a mass spectrometry detector, or a combination thereof.

[0048] The electronic circuit can include a microprocessor 118, a timer and a memory section. In addition, the electronic circuit can include a power supply configured to apply a control signal respectively. The microprocessor 118 can be used for controlling the operation of the chromatographic system 100. The microprocessor 118 can be integrated into the chromatographic system 100 or be a part of a personal computer that communicates with the chromatographic system 100. The microprocessor 118 can be configured to communicate with one or more parts of the chromatographic system (such as pump 102, pump 130, eluent generator 104, sample injector 110 and detector 116) and control it. The memory section can be used for storing instructions, to set the magnitude and timing of the current waveform with respect to the switching of the sample injector 110 that injects the sample.

[0049] After the first installation or long-term storage, the ion exchange material may seep out a leachate that is oligomeric or ionic in nature. Since these compounds can remain in the downstream ion exchange components, they may cause system startup time delays and in some cases may exceed the capacity of the downstream components, resulting in performance problems such as reduced sensitivity, retention of peaks of interest resulting in poor peak shape, and increased background and noise. The solution to the above problems is to balance the consumables by following the prescribed protocols, which are usually performed on the consumables on a separate basis and then re-laid into the system before use. These are additional steps that the user must perform and increase hands-on time. Whenever consumables must be replaced on the IC system, they need to be balanced before use, and this also adds a lot of downtime and labor. Failure to implement the required balancing steps may contaminate downstream consumables with leachate and may cause serious performance problems and additional downtime. Errors in following the prescribed steps may also increase system downtime. Problems with system startup after a delayed shutdown period may also be a common problem encountered in the art.

[0050] Additionally, it may be desirable to measure the pressure contribution of a consumable to the overall system pressure as an indicator of certain issues and compromised performance with that consumable. For electrolyzers with a separate regenerant path containing the electrodes, this path also needs to be repaved and flushed with a reagent or aqueous stream in order to prepare the consumable to be deployed on the system for standard operation. Facilitating the regeneration aspect is another challenge from a piping configuration perspective and currently requires user hands-on time. These issues can be addressed by a valve adjustment process that allows for easy deployment of the balancing method, and the system can resume normal operation after the required steps have been performed to ensure excellent performance of the IC system. While the embodiments discussed show specific valve configurations, it will be apparent from this disclosure that other valve configurations available in the industry may be used.

[0051] refer to Figure 2 , the consumable 202 that needs to be balanced is located upstream of the valve 204. In the first position 206, the valve 204 can direct the flow from the consumable to the balance setting, and then send it to the waste liquid or as a water stream for regenerating the regenerant path for the electrolysis device. The second position 208 on the valve restores the normal laying or operation of the IC system. Therefore, the valve adjustment process can realize the automatic deployment of ion chromatography. The balance step can be adjusted for the consumables, and for each individual consumable, a specific setting is required. The optional reagent 210 can be delivered to the electrolysis consumables to regenerate the regenerant path. The systems and methods disclosed herein can be deployed in an automatic manner through the method of the chromatographic software that controls the operation of the system. Therefore, the hands-on time and labor associated with these settings can be significantly reduced or eliminated. By providing a balanced valve adjustment setting for the consumables upstream of the facility, the overall balance time can be reduced, allowing the system to start with minimal downtime.

[0052] Figure 3 An exemplary ion chromatography system 300 is shown. Six-way two-position valve 340 is installed between eluent generator 104 and continuously regenerated trapping column 106, as shown. In a first position (not shown), valve 340 delivers the output of eluent generator 104 to continuously regenerated trapping column 106. In a second position, valve 340 delivers the output of eluent generator 104 to restrictor 342, such as the restrictor rated as 2000psi or other user-selected values, which is then transferred to waste liquid. The prescribed balance of eluent generator 104 can be implemented and delivered to waste liquid, and valve 340 can be switched to resume normal operation then. In various embodiments, the waste liquid from valve 340 can be delivered to an optional detector 350. In this way, the balance of eluent generator 104 can be monitored to ensure the sufficient balance of eluent generator 104. Other waste streams may similarly be directed to an optional detector, such as detector 350 or a separate detector, to monitor the waste stream and ensure a satisfactory balance of each component.

[0053] Next, the output stream from the continuously regenerated trap column 106 can be delivered to the degasser 108 and then to the sample injector 310. Instead of a standard 6-way 2-position valve, the injection valve 338 can be a 7-way 3-position valve. In the 3rd position of the valve, the additional 7th port is connected to the pump flow and can be used during the balance of the consumables. The 7th port can be connected to the waste liquid on the regenerant line 122. In order to ensure that the flow is delivered in the correct direction, a check valve 344 is deployed on the regenerant line between the electrolytic suppressor 114 output port and the continuously regenerated trap column 106 regenerant inlet port. Therefore, this configuration can be used to regenerate the continuously regenerated trap column 106 with the help of the established regenerant flow to provide water for the electrolysis reaction.

[0054] The injection valve in the 1st position can load the sample, and the eluent is directly delivered to the column. The injection valve in the 2nd position can inject the sample similar to the standard setting, and the eluent is delivered to the column via the sample loop for analysis. In the 3rd position, the eluent pumped through the continuously regenerated capture column 106 is delivered to the regenerant side of the continuously regenerated capture column 106 and delivered to waste. This configuration will help to balance the continuously regenerated capture column 106 before resuming normal operation in the 1st or 2nd position.

[0055] Next, the eluent is delivered to the chromatographic separation device 112 and then to the valve 346, which in this embodiment is shown as a three-way valve with two positions. In position one, the valve delivers the eluent from the chromatographic separation device 112 to the electrolytic suppressor 114 eluent inlet port. In the second position, the eluent from the chromatographic separation device 112 is delivered to the waste. The second position is used to balance the chromatographic separation device 112 before standard operation. The advantage of this arrangement is that any leachate from the chromatographic separation device 112 is flushed into the waste rather than into the downstream consumables.

[0056] The suppression eluent from the eluent output port of the electrolytic suppressor 114 is delivered to the detector 116 and then to the three-way two-position valve 348. In the first position, the suppression eluent is delivered to the regenerant channel of the electrolytic suppressor 114 to provide the water required for the electrolytic reaction. In the second position, the suppression eluent from the eluent output port of the electrolytic suppressor 114 is delivered through the detector 116 and is delivered to the waste liquid. When installed, the electrolytic suppressor 114 can be balanced in this setting. An optional regenerant stream (not shown) can be deployed to flush the suppressor regenerant channel.

[0057] Figure 3 Another benefit of the embodiment is that as each consumable is routed to waste, the downstream pressure can be easily obtained by subtracting it from the total system pressure. Figure 3 Embodiments provide consumable pressure contributions and can be used for troubleshooting purposes when system pressure rises due to consumable problems. This can provide valuable diagnostic information. In addition, quickly flushing consumables and sending them to waste can ensure good system performance.

[0058] Figure 4 A simplified setup is shown, where only two valves (valves 340 and 338) are deployed to allow equilibration of the eluent generator 104 and the continuously regenerated trap column 106, as previously discussed. This is not required when a) the chromatographic column does not leach significantly to alter performance, and b) the suppressor used is not Figure 3 This setup may be useful when using a chemical suppressor in a setup with a different column or suppressor. Additionally, in such cases, the user can perform equilibration of the column and suppressor in manual mode.

[0059] Figure 5 A method 500 of preparing a chromatography system for use is shown. At 502, balancing of the system can be initiated. In various embodiments, a user interface can provide a user with options for balancing the system. A human user can initiate balancing of the system through the user interface, such as by pressing a button. Balancing can also be performed in an automated manner by programming the balancing before starting the system and then resuming normal operation in a fully automated manner.

[0060] refer to Figure 5 At 504, the system may close the valve (e.g. Figure 3 The valve 340 of the embodiment of the present invention is switched to a balanced position. In various embodiments, the balanced position can direct the effluent of the electrolytic eluent generator to waste liquid. At 506, the electrolytic eluent generator can be balanced. In various embodiments, the pump can supply deionized water to the eluent generator within the equilibrium time according to the established protocol. In various embodiments, the established protocol can be provided by the manufacturer of the chromatography system or the eluent generator, or the protocol can be provided by the user.

[0061] At 508, the system can switch the valve after the eluent generator to the normal operating position and the valve after the continuously regenerated trap column (eg, Figure 3 The valve 338 of the embodiment is switched to the equilibrium position. In various embodiments, the equilibrium position can direct the flow downstream of the continuously regenerated capture column to the regeneration line, such as Figure 3The continuously regenerated trap column may be equilibrated at 510. In various embodiments, a pump may supply deionized water to an eluent generator, which may supply eluent to the continuously regenerated trap column during an equilibration time according to an established protocol. At 512, the system may switch a valve located after the continuously regenerated trap column to a normal operating position.

[0062] In various embodiments, it may be necessary to balance the separation column and / or the suppressor. In other embodiments, it may not be necessary to balance the separation column and suppressor, such as if the separation column does not leach significantly and / or when the suppressor is a chemical suppressor rather than an electrolytic suppressor. Optionally, at 514, the system may adjust the valve located after the separation column, such as Figure 3 The valve 346 of the embodiment is switched to the equilibrium position. In various embodiments, the equilibrium position can direct the flow animal downstream of the separation column to waste. Optionally, at 516, the separation column can be balanced. In various embodiments, the pump can supply deionized water to the eluent generator, and the eluent generator can generate the eluent flow to the separation column within the equilibrium time according to the established protocol.

[0063] Optionally, at 518, the system can switch the valve after the separation column to the normal operating position and the valve after the electrolytic suppressor (e.g. Figure 3 The valve 348 of the electrolytic suppressor is switched to a balanced position. In various embodiments, the balanced position can direct the effluent of the electrolytic suppressor to waste. Optionally, at 520, the electrolytic eluent generator can be balanced. In various embodiments, the pump can drive the eluent flow through the column and to the suppressor within the equilibrium time according to the established protocol. Optionally, at 522, the system can switch the valve located after the electrolytic suppressor to a normal operating position.

[0064] At 524, the system may prompt a human user or robot to load a validation sample and the human user may load the validation sample. In various embodiments, the sample may be loaded after equilibration of the electrolytic consumables. In other embodiments, the system may prompt the user and at 502, the user may load the sample at the start of equilibration, which would eliminate the need for a human user to return to the chromatography system between equilibration and validation. At 526, the system may perform a validation routine to ensure that the system is operating within the required range.

[0065] In various embodiments, the system can measure pressure after balancing of various components to determine the pressure contribution

[0066] Figure 6A method 600 of preparing a chromatography system for use after replacing an electrolytic consumable device is shown. The electrolytic consumable device can be an electrolytic eluent generator, a continuously regenerated capture column, a separation column, an electrolytic suppressor, etc. At 602, a human user can replace the electrolytic consumable device and start balancing the electrolytic consumable device. In various embodiments, the system can provide a user interface for starting balancing of the device, and the human user can start balancing, such as by selecting the device and pressing a button to start balancing.

[0067] At 604, the system can switch the valve located downstream of the electrolysis consumable to a balanced position. In various embodiments, the balanced position can direct the effluent of the electrolysis consumable device to a waste liquid or to a regenerant pipeline. At 606, the electrolysis consumable device can be balanced. In various embodiments, the system can drive the flow through the electrolysis consumable device by a pump within the equilibrium time according to the established protocol. In various embodiments, the established protocol can be provided by the manufacturer of the chromatographic system or the eluent generator, or the protocol can be provided by the user. At 608, the system can switch the valve located downstream of the electrolysis consumable to a normal operating position.

[0068] At 610, the system may prompt a human user to load a validation sample and the human user may load the validation sample. In various embodiments, the sample may be loaded after the electrolytic consumable device is equilibrated. In other embodiments, the system may prompt the user and at 602, the user may load the sample when equilibration is initiated, which would eliminate the need for the human user to return to the chromatography system between equilibration and validation. At 612, the system may perform a validation routine to ensure that the system is operating within the required range.

Claims

1. A chromatography system comprising: an electrolytic eluent generator configured to electrolytically generate an eluent; a first valve configured to switch between an operating position directing an output of the electrolytic eluent generator to a continuously regenerated trap column and a waste position directing the output of the electrolytic eluent generator to waste; a continuously regenerating trap column configured to remove ionic contaminants from the eluent; a degasser configured to remove residual gas from the eluent; a sample injector comprising a sample injector valve assembly configured to switch between an operating mode directing an output of the degasser to a separation column, a loading mode loading a sample onto the separation column, and a regenerant mode directing the output of the degasser to a regenerant line; The separation column is configured to chromatographically separate components of the sample; a suppressor configured to reduce the conductivity of the eluent; and A detector is configured to detect the presence of a component of the sample.

2. The chromatography system of claim 1 , wherein the sample injector valve assembly comprises a three-position valve for switching between an operating position corresponding to the operating mode, a loading position corresponding to the loading mode, and a regenerant position corresponding to the regenerant mode.

3. The chromatography system of claim 1, wherein the sample injector valve assembly comprises a second valve for switching between a first operating position and a loading position, wherein In the first operating position, the second valve directs the output of the degasser to a third valve, and in the loading position, the second valve directs the sample onto the separation column; and a third valve for switching between a second operating position and a regenerant position, wherein in the second operating position the third valve directs the output of the second valve to the separation column, and in the regenerant position the third valve directs the output of the second valve to a regenerant line.

4. The chromatography system of claim 1, further comprising a check valve on the regenerant line.

5. The chromatography system of claim 1, further comprising a flow restrictor between the first valve and waste.

6. The chromatography system of claim 3, further comprising a controller, wherein the controller is configured to switch the first valve to the waste position during an electrolytic eluent generator equilibration period.

7. The chromatography system of claim 6, wherein the controller is further configured to switch the third valve to the regenerant position during a trap column equilibration period of continuous regeneration.

8. The chromatography system of claim 3, further comprising a fourth valve configured to switch between an operating position directing the output of the separation column to the suppressor and a waste position directing the output of the separation column to waste.

9. The chromatography system of claim 8, further comprising a controller, wherein the controller is configured to switch the fourth valve to the waste position during a separation column equilibration period.

10. The chromatography system of claim 1, wherein the suppressor is a chemical suppressor.

11. The chromatography system of claim 3, wherein the suppressor is an electrolytic suppressor.

12. The chromatography system of claim 11, further comprising a fifth valve configured to switch between an operating position directing the output of the detector to a regenerant line and a waste position directing the output of the detector to waste.

13. The chromatography system of claim 12, further comprising a controller, wherein the controller is configured to switch the fifth valve to the waste position during a suppressor equilibration period.

14. A method for preparing a chromatography system as claimed in any one of claims 3, 6-9, 11-13, the method comprising: switching the first valve to a waste position that directs an output of the electrolytic eluent generator to waste; flowing liquid through the electrolytic eluent generator during an electrolytic eluent generator balancing period; switching said first valve to an operating position for directing said output of an electrolytic eluent generator to a continuously regenerated trap column; switching a third valve downstream of the continuously regenerated trap column to a regenerant position that directs downstream flow from the continuously regenerated trap column to a regenerant line; flowing a liquid through the continuously regenerating trap column during an equilibration period of the continuously regenerating trap column; switching the third valve to an operating position directing the downstream flow to a separation column; and Verify the operation of the chromatography system.

15. The method of claim 14, further comprising: switching a fourth valve to a waste position that directs the output of the separation column to waste; flowing a liquid through the separation column during a separation column equilibration period; and The fourth valve is switched to an operating position directing the output of the separation column to a suppressor.

16. The method of claim 15, wherein the suppressor is a chemical suppressor.

17. The method of claim 15, wherein the suppressor is an electrolytic suppressor.

18. The method of claim 17, further comprising: switching the fifth valve to a waste position that directs an output of the detector to waste; flowing liquid through the suppressor to the detector during a suppressor equilibration period; and The fifth valve is switched to an operating position to direct the output of the detector to a regenerant line.

19. The method of claim 18, further comprising providing an alternate regenerant flow to the suppressor during the suppressor equilibration period.

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