Patent Description:
Ion chromatography (IC) is a well-established analytical technique and for the past <NUM> years or so has been the preferred method for the determination of inorganic anions and small organic anions. IC is also used widely for the determination of inorganic cations, as well as carbohydrates and amino acids.

In ion chromatography, dilute solutions of acids, bases, or salts are commonly used as chromatographic separation eluents. Traditionally, these eluents had been prepared off-line by dilution with reagent-grade chemicals. Off-line preparation of chromatographic eluents can be tedious and prone to operator errors, and often introduces contaminants. For example, dilute NaOH solutions, widely used as eluents in the ion chromatographic separation of anions, are easily contaminated by carbonate. The preparation of carbonate-free NaOH eluents is difficult because carbonate can be introduced as an impurity from the reagents or by adsorption of carbon dioxide from air. The presence of carbonate in NaOH eluents can compromise the performance of an ion chromatographic method and can cause an undesirable chromatographic baseline drift during the hydroxide gradient and even irreproducible retention times of target analytes. In recent years, several approaches that utilize the electrolysis of water and charge-selective electromigration of ions through ion-exchange media have been investigated by researchers to purify or generate high-purity ion chromatographic eluents. <CIT>, <CIT>, <CIT>, <CIT>,<CIT>, and <CIT> describe electrolytic devices that can be used to generate high purity acid and base solutions by using water as the carrier. Using these devices, high purity, contaminant-free acid or base solutions are automatically generated in-line for use as eluents in chromatographic separations.

With the introduction of electrolytic devices for on-line generation of pure eluents, ion chromatography was empowered to advance into a new era. It has since grown at a fast pace due to advantages of using EEGs over the conventional method of manual preparations (such as high purity eluents, excellent concentration reproducibility through precise control of a constant current, ease of use, etc.). Electrolytically generated eluents have been widely used in many areas ranging from environmental protection, biotechnology, pharmaceutical industries, power plants, and food industries, etc..

As ion chromatography evolves to utilize separation columns with smaller diameters and smaller bead sizes in the realm of Ultra High Performance Liquid Chromatography (UHPLC), the operating pressure required for the EEGs has increased. As such, there is a need for improved EEGs. <CIT> relates to a dual-membrane on-line generator for an acid or alkali solution.

In a first aspect, there is provided an eluent generation cartridge as set out in claim <NUM>.

In various embodiment of the first aspect, the eluent generation cartridge can be configured to operate at a pressure of at least about <NUM> MPa (<NUM>,<NUM> psi), such as at least about <NUM> MPa (<NUM>,<NUM> psi). In particular embodiments, the eluent generation cartridge can be configured to operate at a pressure of not greater than about <NUM> MPa (<NUM>,<NUM> psi), such as not greater than about <NUM> MPa (<NUM>,<NUM> psi).

In various embodiment of the first aspect, the plurality of reinforced membranes includes at least about <NUM> ion exchange membranes, such as not more than about <NUM> ion exchange membranes.

In various embodiment of the first aspect, wherein the membrane washer includes at least one ion exchange membranes, such as not more than about <NUM> ion exchange membranes.

In a second aspect, an electrolytic eluent generator can include an electrolyte reservoir and at least one eluent generation cartridge. The electrolyte reservoir can include a chamber containing an aqueous electrolyte solution and a first electrode. The at least one eluent generation cartridge can include a platinum mesh electrode; a polymer screen; a plurality of reinforced membranes; a membrane washer; and a spacer including a central post and an annular projection.

In various embodiment of the second aspect, the eluent generation cartridge can be configured to operate at a pressure of at least about <NUM> MPa (<NUM>,<NUM> psi), such as at least about <NUM> MPa (<NUM>,<NUM> psi). In particular embodiments, the eluent generation cartridge can be configured to operate at a pressure of not greater than about <NUM> MPa (<NUM>,<NUM> psi), such as not greater than about <NUM> MPa (<NUM>,<NUM> psi).

In various embodiment of the second aspect, the aqueous electrolyte solution includes potassium hydroxide or sodium hydroxide.

In various embodiment of the second aspect, the aqueous electrolyte solution includes methanesulfonic acid.

In various embodiment of the second aspect, the plurality of reinforced membranes includes at least about <NUM> ion exchange membranes, such as not more than about <NUM> ion exchange membranes.

In various embodiment of the second aspect, wherein the membrane washer includes at least one ion exchange membranes, such as not more than about <NUM> ion exchange membranes.

Embodiments of ultra high pressure EEGs are described herein.

In this detailed description of the various embodiments, for purposes of explanation, numerous specific details are set forth to provide a thorough understanding of the embodiments disclosed. One skilled in the art will appreciate, however, that these various embodiments may be practiced with or without these specific details. In other instances, structures and devices are shown in block diagram form.

Unless described otherwise, all technical and scientific terms used herein have a meaning as is commonly understood by one of ordinary skill in the art to which the various embodiments described herein belongs.

<FIG> illustrates an embodiment of a chromatography system <NUM>. Chromatography system <NUM> may include a pump <NUM>, an electrolytic eluent generator <NUM>, a continuously regenerated trap column <NUM>, a degasser <NUM>, a sample injector <NUM>, a chromatographic separation column <NUM>, an electrolytic suppressor <NUM>, a detector <NUM>, and a microprocessor <NUM>. Chromatographic separation column <NUM> may be in the form of a capillary column or an analytical column. A recycle line <NUM> may be used to transfer the liquid from an output of detector <NUM> to an inlet of the electrolytic suppressor <NUM>, recycle line <NUM> may be used to transfer liquid from an outlet of electrolytic suppressor <NUM> to an inlet of degasser <NUM>, and recycle line <NUM> may be used to transfer liquid from an outlet of degasser <NUM> to an inlet of continuously regenerated trap column <NUM>.

Pump <NUM> can be configured to pump a liquid from a liquid source <NUM> and be fluidically connected to electrolytic eluent generator <NUM>. In an embodiment, the liquid may be deionized water, an aqueous solution with electrolyte(s), or a mixture of an organic solvent with deionized water or with aqueous electrolyte(s) solution. A few example electrolytes are sodium acetate and acetic acid. The eluent mixture that contains an organic solvent may include a water miscible organic solvent such as, for example, methanol. Pump <NUM> can be configured to transport the liquid at a pressure ranging from about <NUM> MPa (<NUM> PSI) to about <NUM> MPa (<NUM>,<NUM> PSI). Under certain circumstances, pressures greater than <NUM> MPa (<NUM>,<NUM> PSI) may also be implemented. It should be noted that the pressures denoted herein are listed relative to an ambient pressure (<NUM> MPa to <NUM> MPa (<NUM> PSI to <NUM> PSI)). Pump <NUM> may be in the form of a high-pressure liquid chromatography (HPLC) pump. In addition, pump <NUM> can also be configured so that the liquid only touches an inert portion of pump <NUM> so that a significant amount of impurities does not leach out. In this context, significant means an amount of impurities that would interfere with the intended measurement. For example, the inert portion can be made of polyetherether ketone (PEEK) or at least coated with a PEEK lining, which does not leach out a significant number of ions when exposed to a liquid.

An eluent is a liquid that contains an acid, base, salt, or mixture thereof and can be used to elute an analyte through a chromatography column. In addition, an eluent can include a mixture of a liquid and a water miscible organic solvent, where the liquid may include an acid, base, salt, or combination thereof. Electrolytic eluent generator <NUM> is configured to generate a generant. A generant refers to a particular species of acid, base, or salt that can be added to the eluent. In an embodiment, the generant may be a base such as cation hydroxide or the generant may be an acid such as carbonic acid, phosphoric acid, acetic acid, methanesulfonic acid, or a combination thereof.

Referring to <FIG>, eluent generator <NUM> can be configured to receive the liquid from pump <NUM> and then add a generant to the liquid. The liquid containing the generant can be outputted from eluent generator <NUM> to an inlet of continuously regenerated trap column <NUM>.

Continuously regenerated trap column <NUM> is configured to remove cationic or anionic contaminants from the eluent. Continuously regenerated trap column <NUM> can include an ion exchange bed with an electrode at the eluent outlet. An ion exchange membrane interface can separate the eluent from a second electrode and contaminate ions can be swept through the ion exchange membrane towards the second electrode. In various embodiments, anion removal can utilize an anion exchange bed with a cathode at the eluent outlet separated from an anode by an anion exchange membrane. Alternatively, cation removal can utilize a cation exchange bed with an anode at the eluent outlet separated from a cathode by a cation exchange membrane. The contaminate ions can be swept out of regenerated trap column <NUM> using a recycled liquid via a recycle line <NUM> that is downstream of degas assembly <NUM>.

Degasser <NUM> may be used to remove residual gases in eluents. In an embodiment, a residual gas may be hydrogen and oxygen. Degasser <NUM> may include a tubing section that is gas permeable and liquid impermeable such as, for example, amorphous fluoropolymers or more specifically Teflon AF. The flowing liquid can be outputted from degasser <NUM> to sample injector <NUM> with a substantial portion of the gas removed. The gas can be swept out of degasser <NUM> using a recycled liquid via a recycle line <NUM> that is downstream of electrolytic suppressor <NUM>. The recycled liquid containing the residual gas can also be outputted from degasser <NUM> and directed to the continuously regenerated trap column <NUM>.

Sample Injector <NUM> can be used to inject a bolus of a liquid sample into an eluent stream. The liquid sample may include a plurality of chemical constituents (i.e., matrix components) and one or more analytes of interest.

Chromatographic separation column <NUM> can be used to separate various matrix components present in the liquid sample from the analyte(s) of interest. Typically, chromatographic separation column <NUM> may be in the form of a hollow cylinder that contains a packed stationary phase. As the liquid sample flows through chromatographic separation column <NUM>, the matrix components and target analytes can have a range of retention times for eluting off of chromatographic separation column <NUM>. Depending on the characteristics of the target analytes and matrix components, they can have different affinities to the stationary phase in chromatographic separation column <NUM>. An output of chromatographic separation column <NUM> can be fluidically connected to the electrolytic suppressor <NUM>.

Electrolytic suppressor <NUM> can be used to reduce eluent conductivity background and enhance analyte response through efficient exchange of eluent counterions for regenerant ions. Electrolytic suppressor <NUM> can include an anode chamber, a cathode chamber, and an eluent suppression bed chamber separated by ion exchange membranes. The anode chamber and/or cathode chamber can produce regenerate ions. The eluent suppression bed chamber can include a flow path for the eluent separated from the regenerant by an ion exchange barrier and eluent counterions can be exchanged with regenerate ions across the ion exchange barrier. The cathode chamber or anode chamber can be supplied a recycled liquid via a recycle line <NUM> that is downstream of conductivity detector <NUM>. An output of electrolytic suppressor <NUM> can be fluidically connected to detector <NUM> to measure the presence of the separated chemical constituents of the liquid sample.

As illustrated in <FIG>, the fluidic output of the eluent from detector <NUM> is recycled to electrolytic suppressor <NUM> via recycle line <NUM>, the fluidic output of the electrolytic suppressor <NUM> is recycled to degasser <NUM> via recycle line <NUM>, the fluidic output from degasser <NUM> is recycled to continuously regenerated trap column <NUM> via recycle line <NUM>, and the fluidic output of the continuously regenerated trap column <NUM> flows to waste.

Detector <NUM> may be in the form of ultraviolet-visible spectrometer, a fluorescence spectrometer, an electrochemical detector, a conductometric detector, a charge detector, or a combination thereof. Details regarding the charge detector that is based on a charged barrier and two electrodes can be found in US Pre-Grant Publication No. <NUM>. For the situation where recycle line <NUM> is not needed, detector <NUM> may also be in the form of a mass spectrometer or a charged aerosol detector. The charged aerosol detector nebulizes the effluent flow and creates charged particles that can be measured as a current proportional to the analyte concentration. Details regarding the charged aerosol detector can be found in <CIT>; and <CIT>.

An electronic circuit may include microprocessor <NUM>, a timer, and a memory portion. In addition, the electronic circuit may include a power supply that are configured to apply a controlling signal, respectively. Microprocessor <NUM> can be used to control the operation of chromatography system <NUM>. Microprocessor <NUM> may either be integrated into chromatography system <NUM> or be part of a personal computer that communicates with chromatography system <NUM>. Microprocessor <NUM> may be configured to communicate with and control one or more components of chromatography system such as pump <NUM>, eluent generator <NUM>, sample injector <NUM>, and detector <NUM>. The memory portion may be used to store instructions to set the magnitude and timing of the current waveform with respect to the switching of sample injector <NUM> that injects the sample.

<FIG> illustrates the operation principle of an electrolytic eluent generator cartridge <NUM>. The cartridge can include a high-pressure eluent generation chamber <NUM> and a low-pressure electrolyte reservoir <NUM>. In various embodiments, the high-pressure generation chamber <NUM> can operate pressures greater than about <NUM> MPa (<NUM>,<NUM> psi), such as at least about <NUM> MPa (<NUM>,<NUM> psi), even at least about <NUM> MPa (<NUM>,<NUM> psi), but not greater than about <NUM> MPa (<NUM>,<NUM> psi), such as not greater than about <NUM> MPa (<NUM>,<NUM> psi).

The eluent generation chamber <NUM> contains a perforated platinum (Pt) electrode <NUM>. The electrolyte reservoir <NUM> can contain a Pt electrode <NUM> and an electrolyte solution. In various embodiments, the electrolytic eluent generator cartridge <NUM> can produce a base, such as KOH, electrode <NUM> can be a cathode where hydroxide ions can be formed, and electrode <NUM> can be an anode. In other embodiments, the electrolytic eluent generator cartridge <NUM> can produce an acid, such as carbonic acid, phosphoric acid, acetic acid, methanesulfonic acid, electrode <NUM> can be an anode where hydronium ions can be formed, and electrode <NUM> can be a cathode. The eluent generation chamber <NUM> can be connected to the electrolyte reservoir <NUM> by means of an exchange connector <NUM> which can permit the passage of ions of only one charge from the electrolyte reservoir <NUM> into the high-pressure generation chamber <NUM>. The exchange connector <NUM> can also serve the critical role of a high-pressure physical barrier between the low-pressure electrolyte reservoir <NUM> and the high-pressure generation chamber <NUM>. In various embodiments, where the electrolytic eluent generator cartridge <NUM> is a base generator, the exchange connector <NUM> can permit the passage of cations while substantially preventing the passage of anions from the electrolyte reservoir <NUM> into the generation chamber <NUM>. In alternate embodiments where the electrolytic generator cartridge <NUM> is an acid generator, the exchange connector <NUM> can permit the passage of anions while substantially preventing the passage of cations from the electrolyte reservoir <NUM> into the generation chamber <NUM>.

In various embodiments, the eluent generation chamber <NUM> and the ion exchange connector <NUM> can be assembled into an eluent generation cartridge.

To generate a KOH eluent, deionized water can be pumped through the eluent generation chamber <NUM> and a DC current can be applied between the electrode <NUM> and electrode <NUM>. Under the applied electric field, the electrolysis of water can occur at both the electrode <NUM> and electrode <NUM> of the device <NUM>. Water can be oxidized to form H+ ions and oxygen gas at electrode <NUM> in the electrolyte reservoir <NUM>: H2O → <NUM>+ + <NUM>/<NUM> O2↑+ 2e-. Water can be reduced to form OH- ions and hydrogen gas at electrode <NUM> in the KOH generation chamber <NUM>: <NUM> H2O + 2e-→ <NUM> OH- + H2↑. As H+ ions, generated at the anode <NUM>, displaces K+ ions in the electrolyte reservoir <NUM>, the displaced ions can migrate across the cation exchange connector <NUM> into the eluent generation chamber <NUM>. These K+ ions can combine with hydroxide ions generated at the cathode <NUM> to produce the KOH solution, which can be used as the eluent for anion exchange chromatography. The concentration of generated KOH can be determined by the current applied to the generator cartridge <NUM> and the carrier water flow rate through the generation chamber <NUM>.

To generate a methanesulfonic acid eluent, deionized water can be pumped through the eluent generation chamber <NUM> and a DC current can be applied between the electrode <NUM> and electrode <NUM>. Under the applied field, the electrolysis of water can occur at both the electrode <NUM> and electrode <NUM> of the device <NUM>. Water can be oxidized to form H+ ions and oxygen gas at the electrode <NUM> in the KOH generation chamber <NUM>: H2O → <NUM>+ + <NUM>/<NUM> O2↑+ 2e-. Water can be reduced to form OH- ions and hydrogen gas at the electrode <NUM> in the electrolyte reservoir <NUM>: <NUM> H2O + 2e-→ <NUM> OH- + H2↑. As OH- ions, generated at the electrode <NUM>, displaces methanesulfonate ions in the electrolyte reservoir <NUM>, the displaced ions can migrate across the anion exchange connector <NUM> into the eluent generation chamber <NUM>. These methanesulfonate ions can combine with hydronium ions generated at the electrode <NUM> to produce the methanesulfonic acid solution, which can be used as the eluent for cation exchange chromatography. The concentration of generated methanesulfonic acid can be determined by the current applied to the generator cartridge <NUM> and the carrier water flow rate through the generation chamber <NUM>.

Stacked ion exchange membranes are the heart of electrolytic eluent generators. To generate pure eluents on-line for ion chromatography, both physical and chemical properties of the membranes are critical for the quality and the performance of the electrolytic eluent generators. Beyond these two, there is another key factor: the stacked membrane continuity that determines the operational voltage when a constant current is applied on an electrolytic eluent generator. The membrane continuity issue can occur during EGC assembly and operation, resulting in poor production yield and unsatisfactory performance due to the over-voltage problem. Herein is disclosed a new configuration consisting of a top membrane washer and a disk-containing spacer to resolve the challenges encountered from high torque force during assembly and applications under high pressure conditions. This novel configuration can be utilized to overcome the over-voltage problem during cartridge assembly with a high-torque force application. Furthermore, this configuration can be used to assemble EGC KOH and MSA cartridges successfully and enable these cartridges capable of generating pure eluents electrolytically under an ultra-high pressure.

<FIG> illustrate an eluent generation cartridge <NUM> not claimed but useful for understanding the invention. The eluent generation cartridge <NUM> can include a platinum mesh electrode <NUM>, a polymer screen <NUM>, a plurality of ion exchange membrane stacks <NUM>, <NUM>, and <NUM>, and a spacer <NUM>. Spacer <NUM> includes an annular projection <NUM> that forms a seal with ion exchange membrane <NUM> while allowing the electrolyte solution to contact ion exchange membrane <NUM> in the space <NUM> inside the annual projection <NUM>.

The plurality of ion exchange membranes <NUM>, <NUM>, and <NUM> are compressed by the spacer <NUM>. A torque force is applied onto a compression bolt (not shown). Then, the compression force is transferred to the ion exchange membranes <NUM>, <NUM>, and <NUM> through the spacer <NUM>, and the spacer <NUM> with the annular projection <NUM> near the perimeter is pushed down for seal. The compression of the membranes <NUM>, <NUM>, and <NUM> by the annular projection <NUM> results in a membrane deformation, as shown in <FIG>. The deformation varies from the perimeter to the center. The membrane near the center is deformed the most, which can cause the entire membrane <NUM> to bulge into space <NUM>, creating a void <NUM> between membranes <NUM> and <NUM>. The membrane deformation can be small for a moderate torque force, with a negligible impact on the stacked membranes continuity during assembly and operation. However, when a high torque force is required for ultra-high pressure EEG cartridges, the membrane discontinuity during the torque process can become an issue. The void formed during compression for ultra high pressure can lead to an electrical discontinuity resulting in voltage spikes and increased resistance.

<FIG> illustrate an eluent generation cartridge <NUM> in accordance with the claimed invention. The eluent generation cartridge <NUM> includes a platinum mesh electrode <NUM>, a polymer screen <NUM>, a plurality of ion exchange membrane stacks <NUM> and <NUM>, a membrane washer <NUM>, and a spacer <NUM>. Spacer <NUM> includes an annular projection <NUM>, similar to spacer <NUM>, and a central post <NUM>. The electrolyte solution can contact membrane stack <NUM> and membrane washer <NUM> in the annular space <NUM> between the annular projection <NUM> and the central post <NUM>.

In various embodiments, the plurality of ion exchange membrane stacks <NUM> and <NUM> can include a number of ion exchange membranes, at least a portion of which can be reinforced membranes. In various embodiments, the total number of ion exchange membranes, including reinforced and non-reinforced ion exchange membranes, can be at least about <NUM> ion exchange membranes. Generally, the ion exchange membrane stacks <NUM> and <NUM> together may include not greater than about <NUM> ion exchange membranes.

In various embodiments, the membrane washer <NUM> can include one or more ion exchange membranes. Generally, the membrane washer <NUM> may include not more than about <NUM> ion exchange membranes.

As shown in <FIG>, the membrane washer <NUM> can deform into the annular space <NUM> during compression forming a gap <NUM> between membrane washer <NUM> and ion exchange membrane <NUM>. However, the electrolyte solution <NUM> can flow into the gap <NUM>, avoiding the discontinuity seen in the embodiment shown in <FIG>.

Claim 1:
An eluent generation cartridge (<NUM>) comprising:
a platinum mesh electrode (<NUM>);
a polymer screen (<NUM>); and being characterized by:
a plurality of ion exchange membrane stacks (<NUM>, <NUM>) comprising a plurality of reinforced membranes;
a membrane washer (<NUM>); and
a spacer (<NUM>) including a central post (<NUM>) and an annular projection (<NUM>),
wherein the membrane washer (<NUM>) is deformable into an annular space (<NUM>) between the annular projection (<NUM>) and the central post (<NUM>) during compression such that a gap (<NUM>) is formed between the membrane washer (<NUM>) and the adjacent ion exchange membrane stack (<NUM>).