Optimization of ion-selective electrode measurements

Abstract

A fluid sample testing system uses an ion-selective electrode (ISE)-based flow cell, a bypass line, and a suction source configured to introduce a sample to the flow cell, measure activity or concentration of certain ions, and remove the sample. The flow cell includes a reference electrode and a plurality of measurement electrodes. The reference electrode has an internal fluid that can affect output of the measurement electrodes to an orderable degree, and the measurement electrodes are placed such that the measurement electrodes are positioned greater proximity to the reference electrode when the internal fluid has a lower effect on the measurement electrodes.

Description

Technical Field

[0001] This disclosure relates to the analysis of sample solutions using ion-selective electrode (ISE) technology. Background Technology

[0002] Ion-selective electrodes (ISEs) are used in a variety of applications to convert the activity of a specific ion dissolved in an aqueous solution into the potential difference between a measuring electrode and a reference electrode. The measured activity can be converted into the ion concentration using the Nernst equation. Summary of the Invention

[0003] This disclosure describes an improved ISE-based system and method for the chemical analysis of samples, which substantially simultaneously measures the activity / concentration of multiple ionic analytes with improved accuracy over a wider range of conditions than some prior systems and methods. Embodiments of the system and method of the invention use a reference electrode and multiple measurement electrodes, wherein the reference electrode has an internal liquid. While the internal liquid may diffuse toward the measurement electrodes, the measurement electrodes are positioned such that the measurement electrode expected to be least affected by internal liquid diffusion is closest to the reference electrode, while other measurement electrodes are arranged further away from the reference electrode in order of increasing sensitivity to internal liquid diffusion interference. Other features, benefits, advantages, and objectives of the various embodiments will be apparent to those skilled in the art in light of this disclosure. Attached Figure Description

[0004] Figure 1 This is a block diagram of an exemplary fluid sample testing system according to an embodiment of the present disclosure.

[0005] Figure 2 This is a schematic diagram of an exemplary fluid sample testing system according to an embodiment of the present disclosure.

[0006] Figure 3 This is a schematic diagram of an exemplary flow cell according to an embodiment of the present disclosure.

[0007] Figure 4 This illustrates an embodiment of the present disclosure for use with Figure 3 flow cell Figure 2 A flowchart of the steps in the method for testing fluid samples. Detailed Implementation

[0008] This disclosure relates to systems and methods for chemical analysis using ion-selective electrode (ISE) technology. Various ISE-based systems and methods have been used in chemical analysis; however, it has been observed that internal liquids in the reference electrode of some systems can diffuse into the measuring electrode and affect their measurements. Unfortunately, in many systems, the presence of other ions can affect the electrode response, thereby affecting the measurement of the analyte, thus requiring adjustments to the Nernst equation, and potentially introducing errors when using ISE in the presence of interfering ions.

[0009] Some systems use multiple measuring electrodes suitable for different analytes, along with a single reference electrode, within the same sample stream. One such system includes a chloride ion (Cl...) measurement electrode. - Sodium ions (Na) + ) and potassium ions (K + The system consists of a sensitive measuring electrode and a plastic reference electrode, all within a single flow sequence. The internal liquid of the plastic reference electrode is a high concentration of potassium chloride (KCl), and if the system is not operated for an extended period, this internal liquid may diffuse into the measuring electrode and affect its measurements upon system resumption.

[0010] Aspirating the analyte into the bypass line can also affect the diffusion rate in the plastic reference electrode. If diffusion is rapid, it may affect the measurement at the measuring electrode. If diffusion is slow, it may be impossible to aspirate all the simple liquid from the line, and residual liquid may affect subsequent measurements. Embodiments of the disclosed systems and methods mitigate these effects.

[0011] Figure 1 Components of a sample testing system 100 according to some embodiments are depicted. Typically, a sample 105 is optionally advanced to a flow cell 120 via a sample preparation device 110, and the flow cell 120 is specifically configured to expose the prepared sample to multiple ion-selective measurement electrodes, as will be discussed further below. The sample testing system 100 measures the response of the electrodes in the flow cell 120 and sends the measurement data to an analysis system 130. During measurement, the measured sample is discharged to a waste container 150, while the analysis system 130 calculates necessary information (such as the detection concentration of a specific ion in the prepared sample) and generates corresponding outputs, such as a report 140.

[0012] Figure 2The functional components of the sample testing system 100 and the fluid flow through the system are schematically depicted. In this depiction, sample 105 enters the sample testing system 100 and is optionally combined with buffer (and / or dilution fluid) 115 via mixer 117. Valve 122 is opened, valve 124 is closed, and a vacuum source (e.g., a pump) 160 applies suction, drawing the sample from mixer 117 into flow cell 120. Valve 122 is closed, valve 124 is opened, the vacuum source 160 stops applying suction, and the sample remains in flow cell 120 for a sufficient amount of time for the electrodes in flow cell 120 to achieve an acceptable stable output. If desired, the sample can be transferred via analysis system 130 (see [link to analysis system]). Figure 1 The electrode output is converted to the desired unit, and the internal standard solution is drawn from mixer 117 into bypass line 125. Valve 122 is opened and valve 124 is closed, so that vacuum source 160 can remove the sample from flow cell 120 to waste container 150 through bypass line 125, while the internal standard solution is drawn into flow cell 120. This cycle can then be repeated for another sample 105.

[0013] The path through which the sample travels can be periodically cleaned by pump 114, thereby moving the internal standard solution 112 through an optional mixer 117, across flow cell 120 and bypass line 125, and into waste container 150 as needed by controlling pump 114, mixer 117 and valves 122, 124. Cleaning can be automatically initiated by a control system associated with sample testing system 100 after a certain number of operation or downtime cycles, after a certain number of uses, after a trigger determined by the instrument operator, or after testing multiple samples (e.g., 100-200, 500, 1000-1250, 1100-1200, 3000 or 5000). For example, cleaning can be automatically initiated after a certain operation interval (e.g., every 25 minutes, every 35-40 minutes, every hour, every day or every 4-8 days), after a certain downtime interval (e.g., eight hours, one day, one week or one month), and at other times that a person skilled in the art would conceive of in light of this disclosure.

[0014] Figure 3Flow cell 200 is illustrated, which is a possible embodiment of flow cell 120. In this embodiment, the sample is introduced via flow cell line 205, which passes approximately through the center of each of the reference electrode 210 and measuring electrodes 220, 230, and 240. The reference electrode 210 has an internal liquid such as potassium chloride (KCl) to facilitate its function. Each of the measuring electrodes 220, 230, and 240 is selective for a specific target ion and produces an output signal that may be more or less affected by the proximity of the measuring electrode 220, 230, or 240 to the internal liquid of the reference electrode 210. The degree of this effect can be quantifiable, or it can simply be “rankable” (i.e., the measuring electrodes can be ranked by the degree of influence, regardless of whether the precise amount of influence is known).

[0015] Electrodes 210, 220, 230, and 240 are arranged along flow cell line 205 such that measuring electrodes 220, 230, and 240, which are more significantly affected by their proximity to the reference electrode 210, are placed further away from the reference electrode 210. In other words, if the measuring electrode 220 is less affected by its proximity to the reference electrode 210 than the measuring electrode 230 is, they are positioned such that the distance between the measuring electrode 220 and the reference electrode 210 is less than the distance between the measuring electrode 230 and the reference electrode 210. Similarly, if the measuring electrode 230 is less affected by its proximity to the reference electrode 210 than the measuring electrode 240 is, they are positioned such that the distance between the measuring electrode 230 and the reference electrode 210 is less than the distance between the measuring electrode 240 and the reference electrode 210. In this way, the diffusion of the internal liquid of the reference electrode 210 to the measuring electrodes 220, 230, and 240 has less impact on the output of the measuring electrodes 220, 230, and 240 than if the measuring electrodes 220, 230, and 240 were placed in a different order. In some embodiments, measuring electrodes 220 and 230 are adjacent to each other, and measuring electrodes 230 and 240 are adjacent to each other. In other embodiments, two or more adjacent measuring electrodes are spaced apart.

[0016] For example, if sample testing system 100 needs to determine K + Cl - and Na + The activity (or concentration) of the reference electrode is determined by using KCl as its internal liquid, and K is known to be... + Selective ISE is most affected by the proximity of the KCl-based reference electrode, and Na + Selective ISE is least affected by the proximity of the KCl-based reference electrode, therefore the reference... Figure 3 Various electrodes were arranged as reference electrodes 210 and Na. +Selective measurement electrode 220, Cl - Selective measurement electrodes 230 and K + Selective measurement electrode 240. Of course, measurement electrodes 220, 230, and 240 (or any other two or more or three or more measurement electrodes) will be present in different embodiments of the systems and methods presented in this disclosure.

[0017] Figure 4 Flowcharts describing certain methods of using the system described herein are provided. Test method 300 begins by introducing sample 105 (310) into sample test system 100. Test system 100 prepares (320) the sample for subsequent steps, for example, by diluting the sample or mixing it with reagents. Other preparation steps may also be used for test system 100 and test method 300, as will be appreciated by those skilled in the art.

[0018] The prepared sample is then introduced (330) into the flow cell line of flow cell 120, thereby exposing the prepared sample to the ordered electrodes of flow cell 120. After a sufficient amount of time to allow the electrodes to measure the activity (and thus the concentration) of the analyte of interest, the prepared sample is removed (340) from the flow cell line of flow cell 120 and placed into waste reservoir 150. The analytical system processes (350) the electrical and / or digital data signals from flow cell 120 and generates a report 140. Optionally, if a system flushing is indicated (a "Y" result at decision box 360), a cleaning solution is run (370) through the line. Then, or if no flushing is indicated (an "N" result at decision box 360), the system returns to the beginning of test method 300 and another sample 105 is introduced.

[0019] In some variations of these embodiments, the sample testing system 100 accepts a sample 105 that does not require dilution or reagent mixing, thus the sample preparation element 110 can be omitted (see [link to relevant documentation]). Figure 1 ), buffer supply device 115 and mixer 117 (see Figure 2 ).

[0020] In some variations of these implementations, the cleaning process described above is achieved using external reservoirs, pumps, etc., thus omitting the internal standard solution 112 reservoir and pump 114 in such systems.

[0021] In some variations of these implementations, the preparation and introduction operations are performed by automated sample processing equipment known in the art.

[0022] In various implementations, the ISE will use any of a variety of types of ion-selective membranes, such as glass, insoluble salt particles, plastics, crystals, polymers, or other materials that a person skilled in the art would think of.

[0023] Example

[0024] In a first embodiment, a fluid sample testing system includes: a flow cell based on an ion-selective electrode (ISE), further comprising a flow cell line having a first end and a second end; a reference electrode adjacent to the first end of the flow cell line, the reference electrode having an internal liquid; and a plurality of measuring electrodes, each measuring electrode being selective for a specific target ion, and its output being influenced by the orderability resulting from the proximity of the internal liquid; wherein the reference electrode and the plurality of measuring electrodes are arranged along the flow cell line to measure the concentration of each target ion in a target sample in the flow cell line. The fluid sample testing system also includes a bypass line in fluid communication with the flow cell line and a suction source configured to aspirate the target sample through the flow cell line and into the bypass line, wherein the measuring electrodes are arranged such that the decreasing order of their proximity to the reference electrode matches the degree to which their output is influenced by the proximity of the internal liquid to the measuring electrode.

[0025] The second embodiment is a fluid sample testing system as described in Embodiment 1, wherein the first electrode of the plurality of measuring electrodes is for Na + The ions are selective; the second electrode of the plurality of measuring electrodes is selective for Cl. - The ions are selective; and the third electrode of the plurality of measuring electrodes is for K + Ions are selective.

[0026] The third embodiment is a fluid sample testing system as described in Embodiment 2, wherein the internal liquid is KCl; the first electrode is a first distance away from the reference electrode; the second electrode is a second distance away from the reference electrode; the third electrode is a third distance away from the reference electrode; the first distance is less than the second distance; the second distance is less than the third distance; the first electrode and the second electrode are adjacent; and the second electrode and the third electrode are adjacent.

[0027] The fourth embodiment is a fluid sample testing system as described in Embodiment 2, wherein the internal liquid is KCl; the first electrode is a first distance away from the reference electrode; the second electrode is a second distance away from the reference electrode; the third electrode is a third distance away from the reference electrode; the first distance is less than the second distance, and the second distance is less than the third distance.

[0028] The fifth embodiment is a fluid sample testing system as described in any one of Embodiments 1 to 4, wherein the reference electrode comprises a plastic membrane.

[0029] The sixth embodiment is a fluid sample testing system as described in any one of embodiments 1 to 5, the fluid sample testing system further comprising a pump in communication with the flow cell line, wherein the pump is configured to periodically introduce an internal standard solution to flush the reference electrode and the plurality of measuring electrodes.

[0030] The seventh embodiment is a fluid sample testing system as described in any one of embodiments 1 to 6, the fluid sample testing system further comprising a control system configured to initiate automated cleaning of the flow cell pipeline.

[0031] The eighth embodiment is a fluid sample testing system as described in Embodiment 7, wherein automated cleaning is initiated after a certain operating cycle.

[0032] The ninth embodiment is a fluid sample testing system as described in Embodiment 7, wherein automated cleaning is initiated after a certain downtime period.

[0033] The tenth embodiment is a fluid sample testing system as described in Embodiment 7, wherein automatic cleaning is initiated after a certain number of samples have been tested.

[0034] The eleventh embodiment is a fluid sample testing system as described in Embodiment 7, wherein cleaning is initiated after a trigger determined by the instrument operator occurs.

[0035] The twelfth embodiment is a fluid sample testing method, which includes the following steps: preparing an input fluid to generate a test sample; and introducing the test sample into a fluid sample testing system as described in any one of Embodiments 1 to 11.

[0036] The thirteenth embodiment is a fluid sample testing method as described in Embodiment 12, wherein the preparation and introduction steps are performed by an automated sample processing device.

[0037] The fourteenth embodiment is a fluid sample testing method as described in any one of Embodiments 12 to 13, wherein preparing the input fluid includes diluting the input fluid.

[0038] The fifteenth embodiment is a fluid sample testing method as described in any one of Embodiments 12 to 14, wherein preparing the input fluid includes mixing the input fluid with a reagent.

Claims

1. A fluid sample testing system, the fluid sample testing system comprising: a. A flow cell based on an ion-selective electrode (ISE), comprising: A flow cell pipeline having a first end and a second end; A reference electrode, located near the first end of the flow cell line, having an internal liquid, and... Multiple measuring electrodes, each selective for a specific target ion, and their output is affected by the orderability of the proximity of the internal liquid; The reference electrode and the plurality of measuring electrodes are arranged along the flow cell line to measure the concentration of each target ion in the target sample in the flow cell line; b. A bypass line, said bypass line being in fluid communication with the flow cell line; and c. A suction source configured to aspirate the target sample through the flow cell line and into the bypass line; The measuring electrodes are arranged such that the order in which their proximity to the reference electrode decreases matches the degree to which their output is affected by the proximity of the internal liquid to the measuring electrodes.

2. The fluid sample testing system as described in claim 1, wherein: The first electrode among the plurality of measuring electrodes is selective for sodium ions; The second electrode among the plurality of measuring electrodes is selective for chloride ions; and The third electrode among the plurality of measuring electrodes is selective for potassium ions.

3. The fluid sample testing system as described in claim 2, wherein: The first electrode is separated from the reference electrode by a first distance; The second electrode is a second distance away from the reference electrode; The third electrode is a third distance away from the reference electrode; The first distance is less than the second distance; The second distance is less than the third distance; The first electrode and the second electrode are adjacent; and The second electrode and the third electrode are adjacent to each other.

4. The fluid sample testing system as described in claim 2, wherein: The internal liquid is potassium chloride; The first electrode is separated from the reference electrode by a first distance; The second electrode is a second distance away from the reference electrode; The third electrode is a third distance away from the reference electrode; The first distance is less than the second distance, and The second distance is less than the third distance.

5. The fluid sample testing system according to any one of claims 1 to 4, wherein the reference electrode comprises a plastic membrane.

6. The fluid sample testing system of any one of claims 1 to 5, further comprising a pump in communication with the flow cell line, wherein the pump is configured to periodically introduce a cleaning solution to flush the reference electrode and the plurality of measuring electrodes.

7. The fluid sample testing system according to any one of claims 1 to 6, the fluid sample testing system further comprising a control system configured to initiate automated cleaning of the flow cell pipeline.

8. The fluid sample testing system of claim 7, wherein automatic cleaning is initiated after a certain operating cycle.

9. The fluid sample testing system of claim 7, wherein automatic cleaning is initiated after a certain downtime period.

10. The fluid sample testing system of claim 7, wherein automatic cleaning is initiated after a certain number of samples have been tested.

11. The fluid sample testing system of claim 7, wherein automatic cleaning is initiated upon the occurrence of a trigger determined by the instrument operator.

12. A method for testing fluid samples, the method comprising the following steps: Prepare the input fluid to generate the test sample; as well as The test sample is introduced into the fluid sample testing system according to any one of claims 1 to 11.

13. The fluid sample testing method of claim 12, wherein the preparation and introduction steps are performed by an automated sample processing device.

14. The fluid sample testing method according to any one of claims 12 to 13, wherein preparing the input fluid includes diluting the input fluid.

15. The fluid sample testing method according to any one of claims 12 to 14, wherein preparing the input fluid comprises mixing the input fluid with a reagent.

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