Desalination system for chromatography

Abstract

To provide an analytical system.SOLUTION: An analytical system comprises: a chromatography column configured to separate a sample into one or more analytes; an ion removal device configured to remove at least ions of one charge from a mobile phase, the ion removal device fluidly coupled to an output of the chromatography column; an ion selective sensor configured to measure a signal corresponding to the activity of the ions of one charge in the mobile phase, the ion selective sensor fluidly coupled to an output of the ion removal device; an optional diverter valve that can interrupt the flow of the mobile phase; and a microprocessor configured to monitor the signal of the ion selective sensor and to either switch the optional diverter valve to interrupt the flow of the mobile phase or turn off a pump when the signal is greater than a predetermined threshold.

Description

Background Art

[0001] Combining high-speed anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) enables the direct quantification of non-derivatized carbohydrates with high sensitivity and minimal sample preparation. Compared to other chromatography techniques such as hydrophilic interaction chromatography (HILIC), HPAE has been shown to exhibit excellent resolution of oligosaccharides. Combining HPAE with a mass spectrometer (MS) enables faster and more reliable identification and peak confirmation. More importantly, it can be used to elucidate complex oligosaccharide structures. One particularly notable area is the rapidly growing glycan analysis as a result of the increasing use of biopharmaceuticals. Another important area is the evaluation of prebiotics and the properties of other oligosaccharides and polysaccharides in food and nutrition research. HPAE-PAD is an established technique in oligosaccharide and polysaccharide profiling, but HPAE-MS can provide more detailed property evaluation.

[0002] The coupling of HPAE and MS is a technical challenge. Typical alkali acetate and hydroxide eluents used for the separation of oligosaccharides are non-volatile and highly conductive, and thus not compatible with electrospray ionization (ESI) used in mass spectrometers. Therefore, a desalting device is required between the column and the ESI-MS.

[0003] The desalination suppressor employs a sandwich structure in which two cation exchange membranes separate three channels. The central channel is the eluent channel, while the adjacent side channels are regeneration channels. Electrolysis of water occurs in the regeneration channels, generating hydronium ions that pass through the cation exchange membranes. These ions continuously exchange alkaline cations in the eluent, converting alkali hydroxides and acetates into water and volatile acetic acid, which is suitable for ESI-MS. The performance of the desalination suppressor can be affected by many factors. The cation exchange membranes can become contaminated with sample matrix or precipitates of contaminants, leading to poor ion exchange and reduced desalination efficiency. Shaking of the regenerator bottle can cause the regenerator channel to become empty, potentially leading to regeneration failure. The desalination suppressor can leak and fail due to high back pressure caused by downstream clogging. If the desalination system is not functioning properly, non-volatile alkali acetates and hydroxide eluents can enter, destabilizing the ESI and causing suppressed ionization, broad peak tailing, and a complex mass spectrum. If non-volatile salts continue to flow through the ESI probe, salt deposits may accumulate in the ESI source, requiring maintenance and resulting in extended system downtime. [Overview of the project]

[0004] The analysis system comprises a pump configured to pump a mobile phase; an injection valve configured to introduce a sample into the mobile phase, which is fluid-coupled to the output of the pump; a chromatography column configured to separate a sample into one or more analytes, which is fluid-coupled to the output of the injection valve; an ion removal device configured to remove at least one ion of a single charge from the mobile phase, which is fluid-coupled to the output of the chromatography column; an ion-selective sensor configured to measure a signal corresponding to the activity of one ion of a single charge in the mobile phase, which is fluid-coupled to the output of the ion removal device; an optional diversion valve that can interrupt the flow of the mobile phase; and a microprocessor configured to monitor the signal from the ion-selective sensor and, if the signal is greater than a predetermined threshold, to switch the optional diversion valve to interrupt the flow of the mobile phase or to turn off the pump.

[0005] These and other purposes, as well as their advantages, will become apparent from the attached drawings and their descriptions.

[0006] The accompanying drawings, incorporated into and forming part of this specification, illustrate embodiments and, together with the general description presented above and the detailed descriptions of embodiments presented below, illustrate the principles of this disclosure. [Brief explanation of the drawing]

[0007] [Figure 1] This is a schematic diagram of a typical HPAE-PAD / MS system. [Figure 2] This is a schematic diagram of an embodiment. [Figure 3] This is a schematic diagram of an embodiment. [Figure 4] This is a schematic diagram of an embodiment. [Figure 5] This is a schematic diagram of the system in Example 1. [Figure 6] This is a schematic diagram of the system in Example 1 for testing conductivity readings. [Figure 7] This is a schematic diagram of the system in Example 2. [Figure 8] This is the calibration of potassium ISE using calibration standards 1, 2, 5, 10, and 20 mM potassium acetate for Example 2. [Figure 9] This is a graph showing the relationship between ISE voltage and potassium concentration in Example 2. [Figure 10] This graph shows the ISE voltage and conductivity when the desalination unit is turned off to operate with 10 mM KOH. [Figure 11] This graph shows the ISE voltage and conductivity when the desalination unit is turned off for operation using 5mM KOH / 5mM KOAc. [Figure 12] This is a schematic diagram of the system in Example 4. [Figure 13] This is a graph of conductivity measured before and after the cation suppressor in Example 4. [Figure 14] This is a schematic diagram of the system in Example 5. [Figure 15] This is a plot of conductivity against the sodium concentration from the NaOH eluent in Example 5. [Figure 16] This is a plot of conductivity against the sodium concentration from the NaOAc / NaOH eluent of Example 5. [Figure 17] This is a plot of the response time of the conductivity detector that senses sodium concentration in Example 5. [Modes for carrying out the invention]

[0008] Some eluents used for separation contain non-volatile salts that are not suitable for electrospray ionization mass spectrometry (ESI-MS). Examples include alkali acetate and hydroxide eluents used for the separation of oligosaccharides. A suppressor is required to convert the non-volatile salts into water or volatile acids (e.g., acetic acid). If the suppressor fails, the non-volatile salts enter the MS, causing the MS to shut down and requiring extensive repairs to the mass spectrometer. The described system and method provide a way to detect when the suppressor has failed and allow intervention to prevent damage to the MS.

[0009] In some embodiments, the analysis system comprises a pump configured to pump a mobile phase; an injection valve configured to introduce a sample into the mobile phase, and fluid-coupled to the output of the pump; a chromatography column configured to separate a sample into one or more analytes, and fluid-coupled to the output of the injection valve; an ion removal device configured to remove at least one ion of a single charge from the mobile phase, and fluid-coupled to the output of the chromatography column; an ion-selective sensor configured to measure a signal corresponding to the activity of one ion of a single charge in the mobile phase, and fluid-coupled to the output of the ion removal device; an optional diversion valve that can interrupt the flow of the mobile phase; and a microprocessor configured to monitor the signal from the ion-selective sensor and, if the signal is greater than a predetermined threshold, to switch the optional diversion valve to interrupt the flow of the mobile phase or to turn off the pump.

[0010] The eluent conditions used for oligosaccharide separation typically involve a gradient of alkali acetate (e.g., up to 200–400 mM NaOAc) in a constant alkali hydroxide (typically 100 mM NaOH). Figure 1 shows a schematic diagram of a typical HPAE-PAD / MS system. The column outlet is connected to an electrochemical cell for the PAD, which is then connected to an electrolytically regenerated desalination unit (Thermo Fisher Scientific). A conductivity detector can be connected at the desalination unit outlet to monitor conductivity before the effluent enters the MS. However, conductivity readings do not provide information about the precise composition of the effluent, which is a mixture of acetic acid and alkali acetate solutions of different concentrations. Therefore, the conductivity signal cannot effectively provide an indicator of whether the desalination unit is functioning properly (Figure 1 and Example 1). The device described presents real-time monitoring of the effluent with an effective indicator.

[0011] Examples of ion removal devices (desalination devices) include suppressors. In the case of a self-regenerating suppressor, a constant current is applied to the electrodes to induce water electrolysis, and hydrogen or hydroxide ions are continuously supplied to suppress the eluent. The suppressor can be designed to remove ions of a single charge, or ions of both positive and negative charges. In some embodiments, the ion removal device is configured to remove only ions of a single charge. In some embodiments, the ion removal device is configured to remove ions of both charges. The ions to be removed are typically counterions of the eluent. In some embodiments, the ions of a single charge are selected from the group consisting of lithium, sodium, potassium, cesium, and rubidium.

[0012] Ion-selective sensors are configured to measure a signal corresponding to the activity of a single-charge ion in the mobile phase. Embodiments of ion-selective sensors include ion-selective electrodes (ISEs) and pH sensors. In some embodiments, the ion-selective sensor detects an increase in salt concentration in the effluent of an ion removal device. A combination ion-selective electrode (ISE) of alkaline cations in the eluent can be housed in a flow cell. The ISE continuously monitors the alkaline cation concentration in the effluent. The output potential of the ISE is proportional to the concentration of the selected ion in the solution. In some embodiments, the output of the ISE can be used to trigger a flow diversion valve when the electrode response exceeds a setpoint, switching the valve position and preventing non-volatile eluent from entering the mass spectrometer. For example, a potassium electrode can accurately detect millimolar levels of potassium ions at pH > 2. In some embodiments, the ion-selective sensor is a potassium electrode, and the signal corresponds to a potassium activity value, with a predetermined threshold corresponding to potassium activity values ​​from 0.1 mM to 0.35 M (Figure 2). Examples of predetermined threshold values ​​include 0.1mM~0.2mM, 0.2mM~0.3mM, 0.3mM~0.4mM, 0.4mM~0.5mM, 0.5mM~0.6mM, 0.6mM~0.7mM, 0.7mM~0.8mM, 0.8mM~0.9mM, 0.9mM~1mM, 1mM~1.25mM, 1.25mM~1.5mM, 1.5mM~1.75mM, 1.75mM~2mM, 2mM~5mM, 5mM~10mM, 1 Examples include 0mM-15mM, 15mM-20mM, 20mM-25mM, 25mM-50mM, 50mM-75mM, 75mM-100mM, 100mM-125mM, 125mM-150mM, 150mM-175mM, 175mM-200mM, 200mM-225mM, 225mM-250mM, 250mM-275mM, 275mM-300mM, 300mM-325mM, and 325mM-350mM. In some embodiments, the threshold is 1.75mM. In some embodiments, the output of the ISE can be used to turn off the pump and prevent the non-volatile eluent from entering the mass spectrometer. The data demonstrate that changes in potassium concentration within the range of interest in the presence of acetic acid can be adequately detected by ISE (Example 2).In some embodiments, the ion-selective sensor comprises a solid electrode, and the ion-selective sensor does not leach an ion-exchange reagent.

[0013] In some embodiments, the ion-selective sensor is a hydronium electrode (pH sensor, Figure 3). When the desalter is functioning properly, the pH of the effluent is in the range of 2-3. If the desalter cannot convert >99% of the alkali acetate and alkali hydroxide into acetic acid and water, the alkali ions present in the effluent increase, the concentration of the alkali acetate rises, and ultimately, this leads to an increase in pH. The change in pH can be identified by the pH sensor and can be used as an indicator of the status of the desalter (Example 3). Since the pH of the stream is acidic, the pH sensor is not interfered with by alkali ions (e.g., sodium ions) and can provide reliable measurements. Under normal operating conditions, while the effluent from the desalter continuously flows into the MS, the pH sensor continuously monitors the pH of the effluent. The pH reading provides an indicator regarding the status of the system. In some embodiments, the output of the pH sensor is used as a mechanism to trigger a diverter valve and switch the valve position when the pH exceeds a set value, thereby preventing the non-volatile eluent from entering the mass spectrometer. In some embodiments, the predetermined threshold is selected from pH values in the range of 2-4, such as 2, 2.5, 3, 3.5, and 4. Since the flow path to the MS is closed and the flow path to the waste is open, the salt-containing effluent is not directed to the MS. If the desalter cannot convert >99% of the alkali acetate and alkali hydroxide into acetic acid and water, the reading of the pH sensor exceeds 3. In some embodiments, the output of the pH sensor is used to turn off the pump and prevent the non-volatile eluent from entering the mass spectrometer.

[0014] In some embodiments, the ion-selective sensor comprises an ion-selective flow cell. The ion-selective flow cell has a flow cell inlet and a flow cell outlet. The ion-selective flow cell includes the ion-selective sensor, and the flow cell inlet is fluidly coupled to the outlet of the ion removal device.

[0015] In some embodiments, when the ion selection sensor detects a signal exceeding a predetermined threshold, the diversion valve can interrupt the flow of the mobile phase. The diversion valve has a first valve inlet, a first valve outlet, and a second valve outlet. The diversion valve has a first state and a second state. In the first valve state, the first valve inlet is fluidly coupled to the first valve outlet and not fluidly coupled to the second valve outlet. In the second valve state, the first valve inlet is fluidly coupled to the second valve outlet and not fluidly coupled to the first valve outlet. The diversion valve is upstream of the MS. This may be immediately upstream of the MS, or before the ion selection sensor, or before the ion removal device. The diversion valve can interrupt the flow of the mobile phase and replace it with another liquid, such as water, by switching from the first state to the second state. In some embodiments, the second outlet of the first splitting device is fluidly connected to the first valve inlet of the diversion valve. In some embodiments, either the first or the second valve outlet of the diversion valve is fluidly connected to the mass spectrometer.

[0016] The microprocessor is configured to monitor the signal of the ion selection sensor and, when the signal is greater than a predetermined threshold, switch an optional diversion valve to interrupt the flow of the mobile phase or turn off the pump. This can prevent the mobile phase with too many ions from entering the MS.

[0017] In some embodiments, the flow is split at the outlet of the desalination unit using a first splitting device, such as a micro-tee. The first splitting device comprises a first inlet, a first outlet, and a second outlet. The first inlet is fluid-coupled to the first and second outlets, respectively, and the first inlet is also fluid-coupled to an ion removal device. The first outlet of the splitting device is connected to an ion-selective sensor, such as a combination ion-selective electrode (ISE) for alkaline cations in the eluent, housed in a flow cell or pH sensor. In some embodiments, the second outlet of the splitting device is connected to a flow-dividing valve, which is then connected to an MS. The valve is typically open to the MS and typically closed to the flow path for waste disposal. Under normal operating conditions, the effluent from the desalination unit continuously flows into the MS, while the ion-selective sensor continuously monitors the alkaline cation concentration in the effluent. Since the function of the desalination unit is to exchange alkaline cations in the eluent for hydronium ions, a high concentration of alkaline cations indicates that the desalination unit is not functioning. Since the output potential of the ion-selective sensor is proportional to the concentration of the selected ion in the solution, the output of the ion-selective sensor can be used to trigger a flow diversion valve when the electrode response exceeds a set value, switching the valve position and preventing non-volatile eluent from entering the mass spectrometer. For example, a potassium electrode can accurately detect millimolar levels of potassium ions at pH > 2. Data show that changes in potassium concentration within the range of interest in the presence of acetic acid are well detectable by the ISE (Example 2). The ratio of flow rates through the MS and ISE can be adjusted through back pressure tubing. The length of the connection between the desalination outlet and the MS inlet does not need to be significantly altered to accommodate additional micro-tees and flow diversion valves, so no large variations occur in the setup.

[0018] In some embodiments, the flow is divided using a first splitting device, such as a microtee, located at the outlet of the desalination unit. The first splitting device comprises a first inlet, a first outlet, and a second outlet. The first inlet is fluid-coupled to the first and second outlets, respectively, and the first inlet is also fluid-coupled to an ion removal device. The first outlet of the splitting device is connected to a cation suppressor and then to a conductivity sensor. In some embodiments, the second outlet of the splitting device is connected to a flow divider valve and then to an MS. The valve is typically open to the MS and typically closed to the flow path for waste (Figure 7). After the altered eluent, containing a mixture of acetic acid and alkali acetate, enters the cation suppressor, the acetate ions are exchanged for hydroxide ions, and the mixture is converted to alkali hydroxide and water. An increase in alkali cation concentration due to a desalination unit failure can be directly detected by the conductivity sensor against a low conductivity background from the DI water. As shown in Example 4, the conductivity before the Dionex CERS cation suppressor does not reflect a direct correlation with the various concentrations of the altered eluent, whereas the conductivity after the Dionex CERS cation suppressor shows a linear relationship between sodium concentration and conductivity response. In Example 5, the embodiment was demonstrated in a Thermo Scientific Dionex ICS-6000 system with a desalination unit, and conductivity was measured before and after a Dionex CERS 1-mm prototype cation suppressor. This embodiment presents a reliable solution for monitoring the amount of alkali cations in the flow, which is a direct indicator of desalination performance.

[0019] In some embodiments, a capillary-type cation suppressor (such as the Dionex CCES300) can be used to minimize the flow diversion (e.g., 10 μL / min) from the stream entering the mass spectrometer.

[0020] In some embodiments, instead of a cation suppressor coupled to a conductivity sensor, an integrated cation suppressor and conductivity sensor can be used, in which the suppressor is equipped with a sensor electrode for detecting conductivity (Figure 4). The structure of the integrated cation suppressor and conductivity sensor can be similar to that of the Dionex Electrolytic pH Modifier (Thermo Fisher Scientific), and it is possible to add a pair of sensor electrodes placed near the exit of the device.

[0021] In some embodiments, the analytical system further comprises a second splitting device having a second inlet, a third outlet, and a fourth outlet. The second inlet is fluid-coupled to the third and fourth outlets, respectively. The second inlet is also fluid-coupled to the outlet of a chromatography column. The third outlet is fluid-coupled to an ion removal device. The fourth outlet is fluid-coupled to an electrochemical detector. The second splitting device is configured to split the mobile phase introduced into the second inlet such that a third portion of the mobile phase flows to the third outlet and a fourth portion of the mobile phase flows to the fourth outlet.

[0022] A method for analyzing a sample using a mass spectrometer and a chromatography system involves several steps. The sample is injected into the chromatography column of the chromatography system. A mobile phase is introduced into the chromatography column to separate the sample into one or more analytes that elute from the chromatography column at different times. The mobile phase is introduced from the chromatography column into an ion removal device. At least one ion of charge is removed from the mobile phase in the ion removal device. After removing the ions in the ion removal device, the mobile phase is divided into a first part and a second part. The first part is passed to an ion-selective sensor. The signal is measured by the ion-selective sensor. The second part is passed to a mass spectrometer if the signal from the ion-selective sensor falls below a predetermined threshold.

[0023] In some embodiments, the method includes passing a second portion to a diversion valve and passing the second portion from the diversion valve to a mass spectrometer, provided that the signal from the ion-selective electrode falls below a predetermined threshold.

[0024] In some embodiments, the method further includes determining that a signal from an ion-selective sensor exceeds a predetermined threshold, and then stopping the flow of a second portion from a diversion valve to a mass spectrometer. The diversion valve is then switched so that the second portion flows from the diversion valve to a waste reservoir.

[0025] In some embodiments, the method further includes determining that a signal from an ion-selective sensor exceeds a predetermined threshold, and then stopping the flow of the second portion from passing to the mass spectrometer.

[0026] In some embodiments, the method further includes dividing the mobile phase into a third and a fourth part after it has been introduced into a chromatography column and before at least one ion of charge is removed in an ion removal device. The third part is introduced into an electrochemical detector. One or more analytes are measured in the electrochemical detector. The fourth part is introduced into an ion removal device.

[0027] In this case, all ranges are inclusive and can be combined. That is, a reference to a value indicated by a range includes all values ​​within that range. For example, the range defined as 400-450 ppm includes 400 ppm and 450 ppm as independent embodiments. The ranges of 400-450 ppm and 450-500 ppm can be combined to form the range of 400-500 ppm.

[0028] In this disclosure, the singular forms “a,” “an,” and “the” include the plural forms, and references to specific numbers include at least that specific number unless the context explicitly indicates otherwise. Thus, for example, references to “a certain material” refer to at least one such material and its equivalents known to those skilled in the art, and so on.

[0029] The modifier "about" should also be considered to disclose a range defined by the absolute values ​​of the two endpoints. For example, the expression "about 2 to about 4" also discloses the range "2 to 4". When used to modify a single number, the term "about" may refer to plus or minus 10% of the indicated number, and includes the indicated number. For example, "about 10%" may indicate a range of 9% to 11%, and "about 1" means 0.9 to 1.1.

[0030] Where a list is given, unless otherwise specified, each individual element of that list and every combination of that list shall be understood to be a separate embodiment. For example, a list of embodiments given as "A, B, or C" shall be understood to include embodiments "A", "B", "C", "A or B", "A or C", "B or C", or "A, B, or C".

[0031] For clarity, it should also be understood that certain features of the invention described herein in relation to separate embodiments may also be provided in combination in a single embodiment. That is, unless obviously incompatible or excluded, each individual embodiment is considered combinable with other embodiments, and such combination is considered a separate embodiment. Conversely, for brevity, various features of the invention described in relation to a single embodiment may also be provided separately or in any subcombination. Furthermore, it should be noted that the claims may be drafted to exclude any element. Thus, this statement is intended to serve as an antecedent for the use of exclusive terms such as "alone" or "only" in relation to the description of elements in the claims or the use of "negative" limitations. Finally, while embodiments may be described as part of a series of steps or as part of a more general structure, each of the steps described above may also be considered an independent embodiment in itself.

[0032] While this disclosure illustrates several embodiments by description and describes these embodiments in considerable detail, the applicant does not intend to limit or restrict the scope of the appended claims in any way to such detail. Additional advantages and modifications will be readily apparent to those skilled in the art. Furthermore, features from the individual lists can be combined, and features from the examples can be generalized to the entire disclosure. [Examples]

[0033] Example 1: Using a single conductivity detector to monitor the effluent from a desalination plant is not effective in indicating the composition of the effluent. Figure 5 shows a schematic diagram of the setup for monitoring the conductivity of the desalination effluent. After desalination, the eluents of sodium acetate (NaOAc) and sodium hydroxide (NaOH) are converted to a mixture of acetic acid (HOAc) and sodium acetate (NaOAc). Eluents of various concentrations were pumped through the system at 0.25 mL / min. After desalination of the eluents, the conductivity was measured with a conductivity detector (CD). In this experiment, a Dionex ERD 500 2-mm device was used as the desalination device. According to the manual, a properly operated Dionex ERD 500 replaces ≥99.5% (maximum 0.35M) of the present sodium ions.

[0034] To simplify calculations, the composition of the desalination effluent was derived using a 99% desalination efficiency. The corresponding conductivity of the effluent is given by the effluent concentration and the acetic acid dissociation constant (K). a The calculations were performed using the critical equivalent conductivity values ​​of sodium, hydrogen, and acetate ions. The results are shown in Table 1. Conductivity readings collected through conductivity detectors are shown for comparison. The measured values ​​are quite close to the calculated values. The conductivity values ​​appear to be related to the eluent concentration; i.e., higher conductivity corresponds to higher eluent concentration. [Table 1]

[0035] At a given NaOAc / NaOH eluent concentration, the composition of the HOAc / NaOAc mixture depends on the desalination efficiency. Lower desalination efficiency results in a higher concentration of sodium ions in the HOAc / NaOAc mixture. A series of HOAc / NaOAc solutions were prepared based on calculations of the eluent composition at a specific selected sodium concentration (assuming a 5 mM sodium concentration was chosen as a threshold to divert the flow from the MS). The series of HOAc / NaOAc solutions were pumped into the conductivity detector using the setup shown in the schematic diagram in Figure 6.

[0036] Table 2 shows the measured conductivity values, effluent concentration, and acetic acid dissociation constant (K). a), and the conductivity values ​​are compared based on the critical equivalent conductivity. The desalination efficiency based on calculations is also shown in Table 2. The deviation of the measured values ​​from the calculated values ​​can be explained by the fact that the calculations are based on the critical equivalent conductivity at infinite dilution when the eluent concentration exceeds 100 mM. The CD reading at 700-800 μS (corresponding to the conductivity of a fully suppressed 250 mM NaOAc / 100 mM NaOH as shown in Table 1, an eluent condition commonly used for column washing at the end of separation) is the threshold for bypassing the flow (any CD reading below this value is recognized by the system as indicating that the desalination unit is functioning properly), while 400-500 μS (approximately corresponding to 5 mM sodium ions from a 50 mM NaOAc / 100 mM NaOH or 100 mM NaOAc / 100 mM NaOH eluent under compromised suppression conditions as shown in Table 2) is not recognized by the system as indicating the onset of desalination unit failure. Because the desalination effluent contains acetic acid at various concentrations, the conductivity readings of the desalination effluent can vary significantly for a given sodium concentration (e.g., 5 mM), as shown in Table 2. In the separation of oligosaccharides using HPAE, various concentrations and gradients of NaOAc / NaOH eluent gradients are typically employed, making it impractical to directly use the conductivity of the desalination effluent to indicate the desalination status for switching the flow divider. No clear correlation was observed between ΔCD and solution composition. [Table 2]

[0037] Example 2: A potassium ion selective electrode (ISE) effectively detects potassium ions present in the effluent of a desalination system. Mixtures of potassium hydroxide (KOH) and potassium acetate (KOAc) of various concentrations were pumped through the system shown in Figure 7 to contain the potassium ISE in a flow cell, positioned at the outlet of the conductivity detector. The desalination unit was a Dionex ERD 500 2-mm. The potential output of the potassium ISE was recorded on a Dionex Chromeleon 7 via a Dionex UCI-100 interface. Calibration of the potassium ISE was performed in a sample cup, and the electrode output was recorded (Figure 8). All dips between two plateaus represent the interval between the two calibration solutions. In this example, an appropriate current was applied to the desalination unit, and eluents of known concentrations were pumped through the system. A graph of the relationship between ISE voltage and potassium concentration is shown in Figure 9. During operation with 10 mM KOH and 5 mM mM KOH / 5 mM KOAc, the desalination unit was turned off (current turned off) as shown in Figures 10 and 11, respectively. The desalination unit effluent was monitored using the conductivity detector and potassium ISE. The purpose of the conductivity detector in this experiment was to provide a reference for the response time of potassium ISE.

[0038] Example 3: The pH sensor effectively identifies changes in the desalination efficiency of the desalination unit. The concentration of the simulated desalination effluent, a mixture of HOAc / NaOAc solution, was calculated based on various desalination efficiencies of 200 mM NaOAc / 100 mM NaOH eluent. The solution was prepared in sample cups and measured with a pH electrode. The concentration and acetic acid dissociation constant (K) were also calculated. a The pH of the desalination effluent simulated from the data was also calculated. The calculated pH was compared with the measured pH in Table 3. [Table 3]

[0039] Example 4 The conductivity readings of the desalination effluent do not show a correlation with the amount of sodium ions present in the effluent. The response from the conductivity detector located after the cation suppressor shows a linear correlation with the sodium concentration in the desalination effluent.

[0040] A simulated desalination effluent (a mixture of HOAc / NaOAc) was prepared at a concentration of 200 mM NaOAc / 100 mM NaOH and pumped through a first conductivity detector (CD1), then a cation suppressor (Dionex CERS 4 mm), and a second conductivity detector (CD2), as shown in the schematic diagram in Figure 12. The Dionex CERS suppressor detected acetate ions (OAc). - ) is electrolytically generated hydroxide ions (OH - ) was replaced, and HOAc was converted to water (H2O) with a low conductivity background. This allows for the selective detection of sodium concentration in high-salt eluents.

[0041] As shown in Figure 13 and Table 4, the response from CD2 is linearly related to the sodium concentration in the mixture, while the response from CD1 does not show a clear correlation with the sodium concentration. Therefore, CD2 provides an effective indicator of the sodium concentration in the desalination effluent. [Table 4]

[0042] Example 5: A cation suppressor coupled to a conductivity sensor effectively detects sodium ions present in the effluent of the desalination plant. In this example, a desalination failure is simulated. NaOAc / NaOH eluents of various concentrations were pumped through an HPAE system, the current to the desalination unit (Dionex ERD 500 2-mm) was turned off, and an appropriate suppressor current was applied to the cation suppressor (Dionex CERS 500 1-mm prototype). The flow rate through the desalination unit (Dionex ERD500 2-mm) was 0.25 mL / min. The flow rate through the cation suppressor (Dionex CERS 500 1-mm prototype) was 0.05 to 0.063 mL / min. The regeneration fluid flow rate through the cation suppressor was 0.1 to 0.13 mL / min. The current applied to the Dionex CERS 500 1-mm prototype was 15 mA. Since the desalination unit was not powered on, the concentrations of sodium ions passing through the desalination unit and cation suppressor were known. The dotted rectangles in the schematic diagram of the setup (Figure 14) indicate the placement of the flow divider and mass spectrometer in the current experimental setup. Conductivity detector 1 (CD1) was placed in the system to demonstrate that the conductivity of the desalination effluent is not effective in indicating the sodium concentration in the effluent. The CD2 response was plotted against sodium concentration to show a linear correlation.

[0043] In this example, the sodium concentrations of both sodium hydroxide (NaOH) eluents and sodium acetate (NaOAc) / NaOH eluents are investigated. The conductivity of NaOH solutions with sodium concentrations of 5–50 mM was calculated and plotted in Figures 15 and 16 as theoretical values ​​for reference. The conductivity of the eluents measured for both CD1 and CD2 is reported in Table 4. The conductivity from CD2 measured at various eluent concentrations is plotted in Figures 15 and 16. As shown in Figures 15 and 16, the curve of the experimental data for CD2 is linear, and as the sodium concentration increases, the curve deviates from the theoretical curve. This deviation can be explained by the fact that the theoretical conductivity is based on the sum of critical equivalent conductivity ions, which is the equivalent conductivity of the electrolyte at infinite dilution of the solution (Kohlrausch's law). This deviation is caused by high sodium concentrations. With regard to setting a threshold for sodium concentration, the deviation does not affect the validity of the method, as the concentration falls within the linear range of the curve. This experiment demonstrates the effective measurement of sodium concentration in the desalination effluent when a cation suppressor coupled to a conductivity detector is used. This can be used to monitor the status of the desalination system. Figures 15 and 16 show the conductivity plotted against sodium concentration in (A) NaOH eluent and (B) NaOAc / NaOH eluent, showing a linear relationship. The dotted circles represent theoretical values ​​calculated based on the equivalent conductivity of 5–10 mM NaOH. To confirm the results, two flow rates of 0.05 and 0.063 mL / min were tested on different days. Table 5 shows the data used to construct the plots in Figures 15 and 16, illustrating the daily consistency of the measurements and the minimal influence of the flow rate (0.5 mL / min vs. 0.063 mL / min) on the conductivity signal. To set a 5 mM sodium concentration as the threshold, approximately 1200 μS can be used to trigger the switching of the diversion valve.

[0044] Figure 17 is a plot of the response time of a conductivity detector sensing sodium concentration. Eluent concentrations: (A) 100mM NaOAc / 100mM NaOH (B) 200mM NaOAc / 100mM NaOH. Flow rate of eluent through the desalination unit (Dionex ERD 500 2-mm): 0.25 mL / min, flow rate through the cation suppressor (prototype Dionex CERS 1-mm): 0.05 mL / min, Dionex ERD 500 2-mm current: 150 mA, prototype Dionex CERS 1-mm current: 18 mA, regeneration flow rate of Dionex ERD 500 2-mm: 1.5 mL / min, regeneration flow rate of prototype Dionex CERS 1-mm: 0.1 mL / min, solid line trace: CD2, dotted line trace: CD1.

[0045] To evaluate the response time of conductivity sensing (CD2) to changes in sodium concentration, the CD1 and CD2 signals are superimposed and shown in Figure 17. In this example, two eluent concentration conditions were tested: (A) 100 mM NaOAc / 100 mM NaOH and (B) 200 mM NaOAc / 100 mM NaOH. They were first operated with appropriate desalination and cation suppressor currents. Then, as shown in Figure 17, the desalination current was turned off at 0 minutes of operation. As a result of no self-regeneration (zero current applied), the conductive eluent increased as the hydronium ions were eliminated. The change in conductivity before (CD1) and after (CD2) the cation suppressor was recorded. The CD1 signal was used as a reference to evaluate the response time of CD2, despite the physical distance between the two detectors. The difference in rise times between CD1 and CD2 was approximately 0.4 minutes under both conditions, indicating effective and actual sensing of sodium concentration. [Table 5]

Claims

1. An analytical system, comprising: a) a pump configured to pump a mobile phase; b) an injection valve configured to input a sample into the mobile phase, the injection valve being fluidly coupled to the output of the pump; c) a chromatography column configured to separate the sample into one or more analytes, the chromatography column being fluidly coupled to the output of the injection valve; d) an ion removal device configured to remove ions of at least one charge from the mobile phase, the ion removal device being fluidly coupled to the output of the chromatography column; e) an ion selective sensor configured to measure a signal corresponding to the activity of the ions of at least one charge in the mobile phase, the ion selective sensor being fluidly coupled to the output of the ion removal device; f) a microprocessor configured to monitor the signal of the ion selective sensor and, when the signal is greater than a predetermined threshold, switch a shunt valve to interrupt the flow of the mobile phase, or a microprocessor configured to monitor the signal of the ion selective sensor and, when the signal is greater than a predetermined threshold, turn off the pump, an analytical system.

2. The analytical system further comprises g) a first splitting device having a first inlet, a first outlet, and a second outlet, the first inlet being fluidly coupled to each of the first outlet and the second outlet, the first inlet being also fluidly coupled to the ion removal device such that the mobile phase flows from the ion removal device to the first inlet, the first outlet being fluidly coupled to the input of the ion selective sensor such that the mobile phase flows from the first outlet to the input of the ion selective sensor, The analytical system according to claim 1, wherein the first splitting device is configured to split the mobile phase introduced into the first inlet from the ion removal device such that a first portion of the mobile phase flows to the first outlet and a second portion of the mobile phase flows to the second outlet.

3. The analysis system includes a flow divider valve capable of interrupting the flow of the mobile phase, the flow divider valve having a first valve inlet, a first valve outlet, and a second valve outlet, and the flow divider valve having a first state and a second state. In the first state, the first valve inlet is fluid-coupled to the first valve outlet, and not to the second valve outlet. The analysis system according to claim 2, wherein in the second state, the first valve inlet is fluid-coupled to the second valve outlet, and the first valve outlet is not fluid-coupled.

4. The analysis system according to claim 3, wherein the second outlet of the first splitting device is fluidly connected to the first valve inlet of the flow divider valve.

5. The analytical system according to claim 4, wherein either the first or second valve outlet of the flow divider valve is fluidly connected to a mass spectrometer.

6. The analytical system according to claim 1, wherein the ion of at least one charge is selected from the group consisting of lithium, sodium, potassium, cesium, and rubidium.

7. The analytical system according to claim 1, wherein the ion-selective sensor comprises a solid electrode, and the ion-selective sensor does not cause leaching of the ion-exchange reagent.

8. The analytical system according to claim 1, further comprising an ion-selective flow cell having a flow cell inlet and a flow cell outlet, wherein the ion-selective flow cell includes the ion-selective sensor, and the flow cell inlet is fluidly coupled to the output of the ion removal device.

9. The analytical system according to claim 2, wherein the ion-selective sensor is a hydronium electrode, the signal corresponds to a pH value, and the predetermined threshold is selected from pH values ​​in the range of 2 to 4.

10. The analytical system according to claim 2, wherein the ion-selective sensor is a potassium electrode, the signal corresponds to a potassium activity value, and the predetermined threshold corresponds to a potassium activity value of 1.75 mM.

11. The analytical system according to claim 1, wherein the ion selection sensor comprises a cation suppressor and a conductivity sensor, the cation suppressor having an output, the conductivity sensor having an input, and the output of the cation suppressor being fluidly coupled to the input of the conductivity sensor.

12. i) further comprising a second dividing device having a second inlet, a third outlet, and a fourth outlet, The second inlet is fluid-coupled to the third outlet and the fourth outlet, respectively; the second inlet is also fluid-coupled to the output of the chromatography column; the third outlet is fluid-coupled to the ion removal device; and the fourth outlet is fluid-coupled to the electrochemical detector. The analysis system according to claim 1, wherein the second splitting device is configured to split the mobile phase introduced into the second inlet such that a third portion of the mobile phase flows to the third outlet and a fourth portion of the mobile phase flows to the fourth outlet.

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