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US-20260126420-A1 - Desalting System For Chromatography

US20260126420A1US 20260126420 A1US20260126420 A1US 20260126420A1US-20260126420-A1

Abstract

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 the 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 an 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 the pump when the signal is greater than a predetermined threshold.

Inventors

  • Yongjing CHEN
  • Yan Liu

Assignees

  • DIONEX CORPORATION

Dates

Publication Date
20260507
Application Date
20260106

Claims (10)

  1. 1 . A method of analyzing a sample with a mass spectrometer and a chromatography system, the method comprising: injecting a sample into a chromatography column of the chromatography system; flowing a mobile phase into the chromatography column to separate the sample into one or more analytes that elute off the chromatography column at different times; flowing the mobile phase from the chromatography column into an ion removal device; removing at least ions of one charge from the mobile phase in the ion removal device; after the removing the ions in the ion removal device, splitting the mobile phase into a first portion and second portion; flowing the first portion to an ion selective sensor; measuring a signal with the ion selective sensor; and flowing the second portion to a mass spectrometer where the signal from the ion selective electrode is below a predetermined threshold.
  2. 2 . The method of claim 1 further comprising: flowing the second portion to a diverter valve; and flowing the second portion from the diverter valve to a mass spectrometer where the signal from the ion selective electrode is below a predetermined threshold.
  3. 3 . The method of claim 2 further comprising: determining that the signal from the ion selective sensor is above the predetermined threshold and then stopping the flow of the second portion from the diverter valve to the mass spectrometer; and switching the diverter valve so that the second portion flows from the diverter valve to a waste reservoir.
  4. 4 . The method of claim 2 further comprising: determining that the signal from the ion selective sensor is above the predetermined threshold and then stopping the flow of the second portion from passing to the mass spectrometer.
  5. 5 . The method of claim 1 further comprising: after the flowing the mobile phase into the chromatography column and before the removing at least ions of one charge in the ion removal device, splitting the mobile phase into a third portion and a fourth portion; flowing the third portion into an electrochemical detector and then measuring the one or more analytes in the electrochemical detector; and flowing the fourth portion into the ion removal device.
  6. 6 . The method of claim 1 , wherein the ion selective sensor comprises a solid state electrode and the ion selective sensor does not leach an ion exchange reagent.
  7. 7 . The method of claim 1 , further comprising an ion selective flow cell, ion selective flow cell having a flow cell inlet and a flow cell outlet, the ion selective flow cell containing the ion selective sensor, the flow cell inlet fluidly coupled to the outlet of the ion removal device.
  8. 8 . The method of claim 1 , wherein the ion selective sensor is a hydronium electrode and the signal corresponds to a pH value, wherein the predetermined threshold is selected from a pH value between the range of 2-4.
  9. 9 . The method of claim 1 , wherein the ion selective sensor is a potassium electrode and the signal corresponds to a potassium activity value, wherein the predetermined threshold corresponds to the potassium activity value of 1.75 mM.
  10. 10 . The method of claim 1 , wherein the ion selective sensor comprises a cation suppressor and a conductivity sensor, wherein the output of the cation suppressor is fluidly coupled with the input of the conductivity sensor.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional of U.S. patent application Ser. No. 17/553,956, filed Dec. 17, 2021, the entirety of which is incorporated by reference herein. BACKGROUND High-performance anion exchange chromatography coupled with pulsed amperometric detection (HPAE-PAD) permits direct quantification of non-derivatized carbohydrates with high sensitivity and minimal sample preparation. It has been shown that HPAE offers superior resolution of oligosaccharides compared to other chromatographic techniques, such as hydrophilic interaction chromatography (HILIC). When HPAE is coupled to a mass spectrometer (MS), it provides faster and more reliable identification and peak confirmation. More importantly, it can be used to elucidate complex oligosaccharide structures. One area of particular interest is glycan analysis, which has grown rapidly as a result of increasing use of biopharmaceutical products. Another area of importance is characterization of prebiotics and other oligosaccharides and polysaccharides in food and nutrition research, where HPAE-PAD has already been an established technique in profiling the oligosaccharides and polysaccharides, and HPAE-MS can offer a more in-depth characterization. Interfacing HPAE and MS is a technological challenge. Typical alkali acetate and hydroxide eluents used in separation of oligosaccharides are not compatible with electrospray ionization (ESI) used in a mass spectrometer, due to their non-volatility and high conductance, therefore, a desalting device is required between the column and the ESI-MS. The desalter (suppressor) employs a sandwich structure where two cation exchange membranes separating three channels. The central channel is the eluent channel while the flanking side channels are regenerate channels. Electrolysis of water occurs in the regenerate channels to generate hydronium ions passing the cation exchange membranes to continuously exchange the alkali cations in the eluent, converting the alkali hydroxide and acetate into water and acetic acid, which is volatile and compatible with ESI-MS. The performance of the desalter can be affected by a number of factors. The cation exchange membranes can be contaminated with sample matrix or contaminant precipitation causing ineffective ion exchange with lower desalting efficiency. The regenerant channels can be depleted of liquid due to regenerant bottle runout, causing regeneration to fail. The desalter can leak and fail due to high backpressure caused by clogging downstream. When the desalter is not functioning properly, the nonvolatile alkali acetate and hydroxide eluents can break through and result in instability of ESI, causing ionization suppression, extensive peak tailing, and complicated mass spectra. When continuous flow of the nonvolatile salts reaches the ESI probe, it can cause a buildup of salt deposits in the ESI source, which requires maintenance therefore extended system downtime. BRIEF SUMMARY An analytical system comprises a pump configured to pump a mobile phase; an injection valve configured to input a sample into the mobile phase, the injection valve is fluidly coupled to an output of the pump; a chromatography column configured to separate the sample into one or more analytes, the chromatography column fluidly coupled to an output of the injection valve; an ion removal device configured to remove at least ions of one charge from the 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 an 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 the pump when the signal is greater than a predetermined threshold. These and other objects and advantages shall be made apparent from the accompanying drawings and the description thereof. BRIEF DESCRIPTION OF THE FIGURES The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments, and together with the general description given above, and the detailed description of the embodiments given below, serve to explain the principles of the present disclosure. FIG. 1 is a schematic diagram of a typical HPAE-PAD/MS system. FIG. 2 is a schematic diagram of an embodiment. FIG. 3 is a schematic diagram of an embodiment. FIG. 4 is a schematic diagram of an embodiment. FIG. 5 is a schematic diagram of the system of Example 1. FIG. 6 is a schematic diagram of the system of Example 1 for testing conductivity readings. FIG. 7 is a schematic diagram of the system of Example 2. FIG. 8 is the calibration of the potassiu