Optimization of ion-selective electrode measurement

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 the sample to the flow cell, measure the activity or concentration of certain ions, and remove the sample. The flow cell includes a reference electrode and a plurality of measuring electrodes. The reference electrode has an internal fluid that can affect the outputs of the measuring electrodes to an orderable degree, and the measuring electrodes are situated so that the measuring electrodes are positioned so their proximity to the reference electrode is greater when the effect on the measuring electrodes is lower.

Description

OPTIMIZATION OF ION-SELECTIVE ELECTRODE MEASUREMENTFIELD

[0001] The present disclosure relates to analysis of sample solutions using ion-selective electrode (ISE) techniques.BACKGROUND

[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 an electrical potential between a measuring electrode and a reference electrode. The measured activity may be converted to a concentration of the ion using the Nemst equation.BRIEF SUMMARY

[0003] The present disclosure describes improved ISE-based systems and methods for chemical analysis of samples, measuring activity / concentration of multiple ionic analytes substantially simultaneously with improved accuracy under a wider range of conditions than certain previous systems and methods. Embodiments of the present systems and methods use a reference electrode and multiple measuring electrodes, where the reference electrode has an internal liquid. Though the internal liquid may diffuse toward the measuring electrodes, the measuring electrodes are positioned so that the measuring electrode expected to be least affected by diffusion of the internal liquid is closest to the reference electrode, and the other measuring electrode(s) are farther from the reference electrode in order of increasing susceptibility to interference from diffusion of the internal liquid. Other features, benefits, advantages, and objectives of various embodiments will be apparent to those skilled in the art in view of the present disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

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

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

[0006] FIG. 3 is a schematic diagram of an exemplary flow cell according to embodiments of the present disclosure.

[0007] FIG. 4 is a flowchart showing steps in a method for using the fluid sample testing system of FIG. 2 with the flow cell of FIG. 3 according to embodiments of the present disclosure.DETAILED DESCRIPTION

[0008] The present disclosure relates to systems and methods for performing chemical analysis using ion-selective electrode (ISE) technology. A variety of ISE-based systems and methods have been used for chemical analysis, but it has been observed that the internal liquid of reference electrodes in some systems can diffuse toward the measuring electrodes and affect their measurements. Unfortunately, in many systems the presence of other ions can affect the response of the electrode and, hence, the measurement of the analyte, so adjustments need to be made to the Nemst equation, and error can be introduced, when an ISE is used in the presence of interfering ions.

[0009] Some systems use multiple measuring electrodes adapted for different analytes and a single reference electrode in the same sample flow. One such system includes measuring electrodes sensitive to chlorine ions (Cl"), sodium ions (Na+), and potassium ions (K+) and a plastic reference electrode, all in one flow sequence. The internal liquid of the plastic reference electrode in the system is highly concentrated potassium chloride (KC1), and if the system is not operated for an extended period of time, that internal liquid may diffuse toward the measuring electrodes and affect their measurements when use of the system resumes.

[0010] The suction of the analyte to the bypass line can also affect the speed of diffusion in the plastic reference electrode. If the diffusion is fast, it may affect the measurements by the measurement electrodes. If the diffusion is slow, it may not be possible to aspirate all of the simple liquid from the line, and residual liquid may affect subsequent measurements. Embodiments of the disclosed systems and methods mitigate those effects.

[0011] FIG. 1 depicts the components of sample testing system 100 according to some embodiments. Generally, sample 105 optionally proceeds through sample preparation 110 to flow cell 120, and flow cell 120 has a certain configuration and exposes the prepared sample to a plurality of ion-selective measurement electrodes as will be discussed further below. Sample testing system 100 measures the response of the electrodes in the flow cell 120, sending the measurement data to analysis system 130. When the measurement has been taken, the measured sample is expelled to waste receptacle 150, while analysis system 130 computes the desired information (such as detected concentrations of specific ions in the prepared sample) and produces corresponding output, such as a report 140.

[0012] FIG. 2 schematically depicts the functional components of and the fluid flow through sample testing system 100. In this depiction, sample 105 enters sample testing system 100 and is optionally combined with buffer (and / or diluting fluid) 1 15 by mixer 117.Valve 122 is opened, valve 124 is closed, and vacuum source (e.g., pump) 160 applies suction, drawing the sample from mixer 117 into flow cell 120. Valve 122 is closed, valve 124 is opened, and vacuum source 160 ceases to apply suction, and the sample remains in flow cell 120 for an amount of time adequate to achieve acceptably stable outputs from the electrodes in flow cell 120. The electrode outputs are converted, if needed, to desired units by analysis system 130 (see FIG. 1), and internal standard solution is drawn from mixer 117 into bypass line 125. Valve 122 is opened and valve 124 is closed so vacuum source 160 can remove the sample from flow cell 120 through bypass line 125 to waste receptacle 150 while internal standard solution is drawn into flow cell 120. The cycle may then be repeated with another sample 105.

[0013] The path through which the samples travel may be periodically cleaned by pump 114 moving internal standard solution 112 through optional mixer 117, the paths through flow cell 120 and bypass line 125, and into waste receptacle 150 by controlling pump 114, mixer 117, and valves 122, 124 as needed. Cleaning may be automatically initiated by a control system associated with sample testing system 100 after a certain period of operation or nonuse, after a certain number of uses, upon occurrence of a trigger determined by an instrument operator, or after testing a number of (for example, 100-200, 500, 1000-1250, 1100-1200, 3000, or 5000) samples. For example, cleaning may be automatically initiated after a certain interval (for example, every 25 minutes, every 35-40 minutes, every hour, every day, or every 4-8 days) of operation, after a certain interval (for example, eight hours, one day, one week, or one month) of nonuse, and at other times as will occur to those skilled in the art in view of this disclosure.

[0014] FIG. 3 illustrates flow cell 200, which is one possible embodiment of flow cell 120. In this embodiment, a sample is introduced through flow cell line 205, which passes approximately through the center of each of reference electrode 210 and measurement electrodes 220, 230, and 240. Reference electrode 210 has an internal liquid such as potassium chloride (KC1) to facilitate its function. Each of the measurement electrodes 220, 230, and 240 is selective to a particular subject ion and produces an output signal, which may be affected more or less by the proximity of the measurement electrode 220, 230, or 240 to the internal liquid of the reference electrode 210. The degree of that effect may be quantifiable, or it may merely be “orderable” (that is, one can sort the measurement electrodes by degree of effect, whether the precise quantity of the effect is known).

[0015] Electrodes 210, 220, 230, and 240 are arranged along the flow cell line 205 so that the measurement electrodes 220, 230, and 240 that are affected more by their proximityto the reference electrode 210 are placed farther away from reference electrode 210. Put another way, if measurement electrode 220 is affected less by proximity of reference electrode 210 than measurement electrode 230 is, they are situated so the distance between measurement electrode 220 and reference electrode 210 is less than the distance between measurement electrode 230 and reference electrode 210. Likewise, if measurement electrode 230 is affected less by proximity of reference electrode 210 than measurement electrode 240 is, they are situated so the distance between measurement electrode 230 and reference electrode 210 is less than the distance between measurement electrode 240 and reference electrode 210. In this way, diffusion of the internal liquid of reference electrode 210 toward the measurement electrodes 220, 230, and 240 affects the output of the measurement electrodes 220, 230, and 240 less than it would if the measurement electrodes 220, 230, and 240 were placed in a different order. In some embodiments, measurement electrodes 220 and 230 are adjacent, and measurement electrodes 230 and 240 are adjacent. In other embodiments, two or more neighboring measurement electrodes are spaced apart.

[0016] For example, if a sample testing system 100 is to determine activity (or concentration) of K+, CL, and Na+, the reference electrode uses KC1 as its internal liquid, and it is known that the K+-selective ISE is most affected by proximity of the KCl-based reference electrode and that the Na+-selective ISE is least affected by proximity of the KCl- based reference electrode, then with reference to FIG. 3, the various electrodes are arranged as reference electrode 210, Na+-selective measurement electrode 220, Cl‘-selective measurement electrode 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] FIG. 4 provides a flowchart describing certain methods of using the systems described herein. Testing method 300 begins by introducing (310) a sample 105 to a sample testing system 100. Testing system 100 prepares (320) the sample for subsequent steps, for example, by diluting the sample or mixing it with a reagent. Other preparation steps can be used with testing system 100 and testing method 300 as will occur to those skilled in the art.

[0018] The prepared sample is then introduced (330) to the flow cell line of flow cell 120, exposing the prepared sample to the ordered electrodes of the flow cell 120. After an amount of time sufficient to allow the electrodes to measure the activity (and, therefore, concentration) of the analyte(s) of interest, the prepared sample is then removed (340) from the flow cell line of flow cell 120 and into waste repository 150. The analysis systemprocesses (350) the electrical and / or digital data signals from the flow cell 120 and produces report 140. Optionally, if a rinse of the system is indicated (“Y” result at decision block 360), cleaning solution is run (370) through the lines. Then, or if no rinse is indicated (“N” result at decision block 360), the system returns to the beginning of testing method 300 with the introduction of another sample 105.

[0019] In some variations on these embodiments, the sample testing system 100 accepts samples 105 that have no need for dilution or reagent mixing, so sample preparation element 1 10 (see FIG. 1), buffer supply 1 15, and mixer 1 17 (see FIG. 2) can be omitted.

[0020] In some variations on these embodiments, the cleaning process described above is achieved using external reservoirs, pumps, and the like, so such systems omit internal standard solution 112 reservoir and pump 114.

[0021] In some variations of these embodiments, preparing and introducing operations are performed by automated sample handling equipment as is known in the art.

[0022] In various embodiments, the ISEs will use ion-selective membranes of any of a variety of types, such as glass, pellets of insoluble salts, plastics, crystals, polymers, or other materials as will occur to those skilled in the art.EXAMPLES

[0023] In a first example, a fluid sample testing system comprises an ion-selective electrode (ISE)-based flow cell that, in turn, comprises a flow cell line having a first end and a second end; a reference electrode proximal 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 to a particular subject ion and having an output affected to an orderable degree by 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 subject ion in a subject sample in the flow cell line. The fluid sample testing system also comprises a bypass line in fluid communication with the flow cell line and a suction source configured to draw the subject sample through the flow cell line and into the bypass line, wherein the measuring electrodes are arranged such that the order of their decreasing proximity to the reference electrode matches the degree to which their outputs are affected by proximity of the internal liquid to said measuring electrode.

[0024] A second example is the fluid sample testing system of example 1 , wherein a first electrode of the plurality of measuring electrodes is selective to Na+ions; a secondelectrode of the plurality of measuring electrodes is selective to Cl" ions; and a third electrode of the plurality of measuring electrodes is selective to K+ions.

[0025] A third example is the fluid sample testing system of example 2, wherein the internal liquid is KC1; the first electrode is a first distance from the reference electrode; the second electrode is a second distance from the reference electrode; the third electrode is a third distance 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.

[0026] A fourth example is the fluid sample testing system of example 2, wherein the internal liquid is KC1; the first electrode is a first distance from the reference electrode; the second electrode is a second distance from the reference electrode; the third electrode is a third distance from the reference electrode; the first distance is less than the second distance, and the second distance is less than the third distance.

[0027] A fifth example is the fluid sample testing system of any of examples 1—4, wherein the reference electrode comprises a plastic membrane.

[0028] A sixth example is the fluid sample testing system of any of examples 1-5, further comprising a pump in communication with the flow cell line, where the pump is configured to periodically introduce internal standard solution to rinse the reference electrode and plurality of measurement electrodes.

[0029] A seventh example is a fluid sample testing system of any of examples 1-6, further comprising a control system configured to initiate automated cleaning of the flow cell line.

[0030] An eighth example is a fluid sample testing system of example 7, wherein automated cleaning is initiated after a certain period of operation.

[0031] A ninth example is a fluid sample testing system of example 7, wherein automated cleaning is initiated after a certain period of nonuse.

[0032] A tenth example is a fluid sample testing system of example 7, wherein automatic cleaning is initiated after testing a certain number of samples.

[0033] An eleventh example is a fluid sample testing system of example 7, wherein cleaning is initiated upon occurrence of a trigger determined by an instrument operator.

[0034] A twelfth example is a fluid sample testing method, comprising the steps of preparing an input fluid to produce a test sample; and introducing the test sample to a fluid sample testing system according to any of examples 1-11.

[0035] A thirteenth example is the fluid sample testing method of example 12, wherein the preparing and introducing steps are performed by automated sample handling equipment.

[0036] A fourteenth example is the fluid sample testing method of either of examples 12-13, wherein preparing the input fluid comprises diluting the input fluid.

[0037] A fifteenth example is the fluid sample testing method of either of examples 12-14, wherein preparing the input fluid comprises mixing the input fluid with a reagent.

Claims

I / We claim:

1. A fluid sample testing system, comprising: a. an ion-selective electrode (ISE)-based flow cell, comprising: a flow cell line having a first end and a second end; a reference electrode proximal 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 to a particular subject ion and having an output affected to an orderable degree by 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 subject ion in a subject sample in the flow cell line; b. a bypass line in fluid communication with the flow cell line; and c. a suction source configured to draw the subject sample through the flow cell line and into the bypass line; wherein the measuring electrodes are arranged such that the order of their decreasing proximity to the reference electrode matches the degree to which their outputs are affected by proximity of the internal liquid to said measuring electrode.

2. The fluid sample testing system of claim 1, wherein: a first electrode of the plurality of measuring electrodes is selective to sodium ions; a second electrode of the plurality of measuring electrodes is selective to chlorine ions; and a third electrode of the plurality of measuring electrodes is selective to potassium ions.

3. The fluid sample testing system of claim 2, wherein: the first electrode has a first distance from the reference electrode; the second electrode has a second distance from the reference electrode; the third electrode has a third distance 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.

4. The fluid sample testing system of claim 2, wherein: the internal liquid is potassium chloride; the first electrode has a first distance from the reference electrode; the second electrode has a second distance from the reference electrode; the third electrode has a third distance 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 of any of claims 1-4, wherein the reference electrode comprises a plastic membrane.

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

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

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

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

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

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

12. A fluid sample testing method, comprising the steps of: preparing an input fluid to produce a test sample; and introducing the test sample to a fluid sample testing system according to any of claims 1-11.

13. The fluid sample testing method of claim 12, wherein the preparing and introducing steps are performed by automated sample handling equipment.

14. The fluid sample testing method of any of claims 12-13, wherein preparing the input fluid comprises diluting the input fluid.

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

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