MEANS FOR THE QUANTITATIVE DETERMINATION OF CATIONIC ELECTROLYTE CONCENTRATION AND CREATININE CONCENTRATION AND OF THEIR RATIOS

Abstract

The present invention relates to a single-use test strip for the quantitative determination of a concentration of a cationic electrolyte which is not sodium, and of creatinine concentration, and for the subsequent determination of their ratio, and to a non-invasive point-of-care (POC) device for detecting a disorder of electrolyte balance in patient's body. Furthermore, the present invention relates to a method for simultaneously and quantitatively determining a cationic electrolyte concentration and creatinine concentration in a patient's urine sample and to a method of detecting a disorder of electrolyte balance in a patient's body.

Claims

1. A single-use test-strip for the quantitative determination of a concentration of a cationic electrolyte which is not sodium, and of creatinine concentration in a patient's urine sample, said test-strip comprising: a substrate which either is electrically insulating or which has an electrically insulating layer applied thereon, an electrode assembly applied on said substrate or on said electrically insulating layer, if present, said electrode assembly comprising at least one working electrode that is selective for said cationic electrolyte; one creatinine-selective working electrode; either one joint reference electrode for both said cationic electrolyte-selective working electrode and said creatinine-selective working electrode, or a reference electrode for said cationic electrolyte-selective working electrode and a separate reference electrode for said creatinine-selective working electrode; optionally; one or two neutral electrodes for measuring and eliminating interferences, and an interface for electrically connecting said electrode assembly to a read out-meter device.

2. The single-use test-strip according to claim 1, wherein said working electrodes, said reference electrode(s) and said neutral electrode(s), if present, have been applied on said substrate or on said electrically insulating layer, if present, by a suitable deposition technique, thus forming an electrode assembly on said substrate or on said electrically insulating layer, and wherein said cationic electrolyte-selective working electrode comprises a cationic electrolyte-selective membrane, and said creatinine-selective working electrode comprises a creatinine-selective membrane, and wherein said neutral electrode(s) comprises(comprise) a membrane that is not selective for said cationic electrolyte and not creatinine-selective.

3. The single-use test-strip according to claim 1, wherein said cationic electrolyte which is not sodium is selected from the group consisting of, potassium, calcium, magnesium, zinc and copper.

4. The single-use test strip according to claim 1, wherein said substrate is made of a material selected from plastic, ceramic, alumina, paper, cardboard, rubber, textile, carbon-based polymers, fluoropolymers, silicon-based substrates, quartz, silicon nitride, silicon oxide, silicon based polymers, semiconducting materials, organic dielectric materials, and inorganic dielectric materials, and wherein said electrically insulating layer, if present, is made of a dielectric material, wherein, if said electrically insulating layer is present on said substrate, said electrode assembly is located on said electrically insulating layer.

5. The single-use test-strip according to claim 2, wherein said cationic electrolyte-selective working electrode comprises a cationic electrolyte-selective membrane that comprises a cationic electrolyte-selective carrier in a polymer matrix, and said creatinine-selective membrane comprises a creatinine-selective carrier in a polymer matrix.

6. The single-use test-strip according to claim 1, wherein said electrode assembly further comprises one or two neutral electrodes for measuring and eliminating interferences, wherein said neutral electrode(s) comprise a membrane comprising a polymeric matrix without any cationic electrolyte-selective carrier and without any creatinine-selective carrier.

7. The single-use test-strip according to claim 1, wherein each of said electrodes in said electrode assembly has an electrical lead, respectively, wherein said electrical lead connects said electrode with said interface for electrically connecting said electrode assembly to a readout-meter device.

8. The single-use test-strip according to claim 1, wherein said joint reference electrode has a surface larger than the surface of each of said working electrodes, or each of said separate reference electrodes has a surface larger than the surface of each of said working electrodes.

9. A non-invasive point-of-care (POC) device for detecting a disorder of electrolyte balance in a patient's body, said POC device comprising: a readout-meter-device for quantitative and selective measurement of cationic electrolyte concentration and creatinine concentration in a urine sample and for determining a ratio of cationic electrolyte-to-creatinine, said readout-meter-device comprising: a receiving module for receiving an interface of a single-use test-strip according to claim 1 and for establishing electrical contact between said readout-meter-device and an electrode assembly of said single-use test-strip, thus allowing the detection and transmission of electrical signal(s) from said single-use test-strip to said readout-meter-device, wherein said receiving module has electrical connectors for separately contacting each electrode via said interface of said test-strip a multichannel amplifier for amplifying electrical signal(s) transmitted from a single-use test-strip according to claim 1 a controller including an analog/digital converter and a storage memory, for converting electrical signals received from a single-use test-strip according to claim 1 into cationic electrolyte concentration measurement(s) and creatinine concentration measurement(s) and for subsequently determining a ratio of cationic electrolyte concentration to creatinine concentration based on said cationic electrolyte concentration measurements and creatinine concentration measurements an output device for indicating concentration measurements and/or said ratio to a user, preferably a display, and a power supply.

10. The non-invasive point-of-care (POC) device according to claim 9, further comprising: a single-use test-strip according to claim 1 inserted into said receiving module of said readout-meter-device by way of said interface of said single-use test-strip, thus establishing electrical contact between said electrode assembly of said test-strip and said readout-meter device.

11. The non-invasive point-of-care (POC) device according to claim 9, wherein said device further comprises a user-interface for operating said device, and/or a memory for storing a plurality of cationic electrolyte and creatinine concentration measurements and determined ratios of cationic electrolyte concentration to creatinine concentration, and/or a connection interface for transferring and/or exchanging data with an external computer or external network.

12. A method for quantitatively determining cationic electrolyte concentration and creatinine concentration in a patient's urine sample, comprising the steps: a) providing a patient's urine sample, b) contacting a single-use test-strip according to claim 1 with said urine sample and allowing the electrode assembly of said test-strip to be wetted by and come into contact with said urine sample, optionally withdrawing the urine-wetted test-strip from said urine sample, c) connecting said test-strip to a readout-meter-device of a point-of-care (POC) device, to assemble a point-of-care (POC) device, wherein said single-use test-strip is inserted into a receiving module of said readout-meter device, thus establishing electrical contact between said electrode assembly of said test-strip and said readout-meter-device, wherein said connecting of said test strip to said readout-meter device of said point of care in step c) occurs either before or after step b), d) measuring cationic electrolyte concentration and creatinine concentration in said urine sample, using said point-of-care (POC) device assembled in step c); wherein said POC device comprises: a readout-meter-device for quantitative and selective measurement of cationic electrolyte concentration and creatinine concentration in a urine sample and for determining a ratio of cationic electrolyte-to-creatinine, said readout-meter-device comprising: a receiving module for receiving an interface of a single-use test-strip according to claim 1 and for establishing electrical contact between said readout-meter-device and an electrode assembly of said single-use test-strip, thus allowing the detection and transmission of electrical signal(s) from said single-use test-strip to said readout-meter-device, wherein said receiving module has electrical connectors for separately contacting each electrode via said interface of said test-strip a multichannel amplifier for amplifying electrical signal(s) transmitted from a single-use test-strip according to claim 1 a controller including an analog/digital converter and a storage memory, for converting electrical signals received from a single-use test-strip according to claim 1 into cationic electrolyte concentration measurement(s) and creatinine concentration measurement(s) and for subsequently determining a ratio of cationic electrolyte concentration to creatinine concentration based on said cationic electrolyte concentration measurements and creatinine concentration measurements an output device for indicating concentration measurements and/or said ratio to a user, and a power supply.

13. A method of detecting a disorder of electrolyte balance in a patient's body, said method comprising the steps: performing the method according to claim 12, determining a ratio of cationic electrolyte concentration to creatinine concentration using said point-of-care (POC) device, detecting a disorder of electrolyte balance, if said ratio of cationic electrolyte concentration to creatinine concentration in said urine sample, as determined in the previous step, is outside of a range of physiologically adequate ratio values for the respective patient.

14. The method according to claim 13, wherein said disorder of electrolyte balance is a cationic electrolyte depletion or cationic electrolyte overload selected from: a potassium depletion in the plasma of a patient, a potassium overload in the plasma of a patient, a calcium depletion in the body of a patient, a calcium overload in the body of a patient, a magnesium depletion or magnesium overload in the body of a patient, a zinc depletion in the body of a patient, a copper depletion in the body of a patient, and a copper overload in the body of a patient, due to hampered renal excretion of copper.

15. The method according to claim 13, wherein said range of physiologically adequate ratio values is or has been separately determined by reference to a healthy person.

16. The method, according to claim 2, wherein the deposition technique is screen printing or ink jet printing.

17. The method according to claim 4, wherein the organic dielectric material is selected from polyimide, polycarbonate, polyvinyl, chloride, polystyrene, polyethylene, polypropylene, polyester, polyethylene terephthalate, polyurethane, polyvinylidene fluoride and the inorganic dielectric material is silicium dioxide.

18. The method according to claim 11, wherein the connection interface is a USB and/or a wireless interface.

19. The method according to claim 14, wherein a potassium depletion in the plasma of a patient is due to an acquired or genetic kidney disease; diuretic intake; prolonged vomiting and/or diarrhea during an infection; or an inflammatory, malignant or genetic bowel disease, a potassium overload in the plasma of a patient is due to intake of drugs raising potassium level, or acute kidney injury, or cardiovascular disease or diabetes mellitus, a calcium depletion in the body of a patient is due to a metabolic disorder, Vitamin D deficiency or enhanced renal calcium loss, a calcium overload in the body of a patient is due to decreased renal calcium loss, a magnesium depletion or magnesium overload in the body of a patient is due to urolithiasis, migraine, Alzheimer's disease, coronary heart disease, hypertension, diabetes mellitus type 2, or pre-eclampsia or eclampsia disease, a zinc depletion in the body of a patient is due to Crohn's disease, Wilson's disease, diabetes, chronic liver or kidney disease, a copper depletion in the body of a patient is due to nephrotic syndrome, Menkes, disease or hypoproteinemias, and/or a copper overload in the body of a patient is due to hampered renal excretion of copper.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0175] The present invention is now further described by reference to the following figures, wherein

[0176] FIG. 1 shows a schematic representation of an embodiment of a point-of-care (POC) device for detecting depletion and/or overload of an electrolyte in a patient's body; EMF=electromotive force; uEl=concentration of a cationic electrolyte in a urine sample (El=K.sup.+, Ca.sup.2+, Mg.sup.2+, Zn.sup.2+, Cu.sup.2+); uCrea=creatinine concentration in a urine sample; uEl/uCrea=ratio cationic electrolyte:creatinine concentration. 1=POC device, 2=test-strip, 3=readout-meter device, 4=electrode assembly, 5=interface for electrical connection, 6=cationic electrolyte-selective electrode, 7=creatinine-selective electrode, 8=reference electrode, 9=electrical leads

[0177] FIG. 2 shows top views of exemplary test strips with exemplary possible patterns of an electrode array and electrical leads applied on an insulating layer [0178] A) exemplary round shape of working electrodes+round shape of reference electrode [0179] 5=interface for electrical connection [0180] 6=cationic electrolyte-selective electrode [0181] 7=creatinine-selective electrode [0182] 8=reference electrode [0183] 9=electrical leads [0184] B) exemplary round shape of working electrodes+oval reference electrode [0185] C) exemplary round shape of working electrodes+rectangular reference electrode [0186] D) exemplary square shape of working electrodes+rectangular reference electrode [0187] E) 9a)=exemplary contact paths at the end of electrical leads for contacting readout-meter device [0188] F) 10=neutral electrode for determining interferences

[0189] FIG. 3 shows cross-sectional views of an exemplary analyte-selective electrode [0190] A) Without “inner contact layer” [0191] 11=substrate [0192] 12=insulating layer [0193] 13=conductive layer [0194] 14=analyte-selective membrane [0195] B) With “Inner contact layer” [0196] 15=optionally, “inner contact layer” (transducer) [0197] C) With “covering layer” and “ [0198] 16=optionally, “covering layer”

[0199] FIG. 4 shows an exemplary embodiment for the fabrication of an exemplary test-strip with an additional covering layer. In such exemplary fabrication method, the following steps are performed: [0200] Step 1) Provide substrate with insulating layer on top [0201] Step 2) Apply electrode assembly and electrical leads [0202] Step 3) Form analyte-selective electrodes [0203] Step 4) preferably, apply a suitable covering film, e.g. a plastic insulating material with openings for the electrodes [0204] 2a=test-strip with covering layer [0205] 4a=electrode assembly and electrical leads [0206] 5=interface for electrical connection [0207] 11a=substrate with insulating layer [0208] 15a=analyte-selective membrane solutions [0209] 16=covering layer with openings for electrodes

[0210] FIG. 5 shows the potentiometric response of fabricated test-strips (K1-K4) according to the present invention to different concentrations of potassium (K.sup.+) in aqueous solutions.

[0211] FIG. 6 shows a potentiometric response of exemplary fabricated test-strips in accordance with the present invention (Ca1-Ca4) to different calcium (Ca.sup.2+) concentrations in aqueous solutions.

[0212] FIG. 7 shows a potentiometric response of exemplary fabricated test-strips in accordance with the present invention (Crea1-Crea4) to different protonated creatinine concentrations in aqueous solutions.

[0213] FIG. 8 shows top view of an exemplary test strip with exemplary dimensions of the electrode array and substrate. WE1=a first working electrode; WE2=a second working electrode; RE=reference electrode.

[0214] FIG. 9 shows an exemplary embodiment of a point-of-care (POC) device for detecting electrolyte depletion and/or electrolyte overload in a patient's body consisting of [0215] A) a test-strip and readout-meter having a release button (17a) [0216] B) a test-strip and readout-meter equipped with a test-strip holder (18) and a release button (17a) [0217] C) a test-strip and readout-meter equipped with a test-strip holder (18) having a release button in form of a lever (17b)

[0218] FIG. 10 shows an exemplary point-of-care (POC) device for detecting electrolyte depletion and/or electrolyte overload in a patient's body consisting of a test-strip and readout-meter displaying exemplary analysis results.

[0219] FIG. 11 shows a prototype of a (POC) device in accordance with embodiments of the present invention.

Panel A shows a (POC) device comprising a single-use test-strip connected to a readout-meter device via a test-strip holder unit, prepared for measurement;
Panel B shows a (POC) device, where the test-strip is contacting the urine sample and after the measurement mechanism had been activated to initiate a measurement in a “time-controlled manner”;
Panel C shows a POC device after the measurement, where the result just after the measurement is displayed via the output unit, i.e. display, of the readout-meter to which a single-use test-strip is connected via a test-strip holder unit.

[0220] Furthermore, the present invention is now further described by reference to the following examples which are given to illustrate, not to limit the present invention.

EXAMPLES

Example 1

Structure of a Test-Strip

[0221] For proof of principle experiments, test-strips with electrode array exhibiting dimensions according to the present invention were fabricated. The system consists of a carbon working electrode (WE) with Ø=3 mm, a (Ag/AgCl) counter/reference electrode (RE), electrical leads that were screen printed onto a plastic substrate and interface for electrical connection to a readout meter.

Example 2

Fabrication of a Potassium-Selective Test-Strip

[0222] To realize a potassium-selective electrode (K-ISE), a solution of poly(3-octylthiophene) in tetrahydrofuran (0.5 mg/1 mL) was casted (2.5 μL) on the area of the carbon WE of test-strip of Example 1. Then the substrate was dried to remove solvent forming a thin transducer layer. Subsequently, a solution of a potassium-selective membrane (K-ISM) solution (3.5 μL) was casted on the top of that transducer layer. Then, the substrate was dried to remove solvent forming a potassium-selective membrane on the WE. The K-ISM solution consisted of a mixture of 2.0 mg potassium ionophore valinomycin, 0.5 mg potassium tetrakis(4-chlorophenyl) borate, 32.8 mg PVC (high molecular weight polyvinylchloride) and 64.7 mg bis(2-ethylhexyl) sebacate in 1 mL tetrahydrofuran.

Example 3

[0223] Potentiometric Measurements with the Potassium-Selective Test-Strip

[0224] The potassium-selective test-strip was dipped into the sample solution until all electrodes were covered and the potential difference (EMF) between modified WE(s) and RE was measured with a high input impedance voltmeter that was integrated in a prototype of a readout meter having receiving module for receiving the interface of the test-strip and a display, where result was immediately displayed.

Example 4

[0225] Sensor calibration by measuring a standard potassium solution series Standard solutions with potassium concentrations of 1M, 10.sup.−1M, 10.sup.−2M, 10.sup.−3M respectively, were prepared by dissolving potassium chloride (KCl) in water. The EMF values were recorded and a calibration curve was set up by plotting the EMF values as a function of the minus logarithm of potassium concentrations. Four different test strips (K1-K4) were fabricated and tested. The results are summarized in Table 1.

TABLE-US-00001 TABLE 1 EMF values for four different potassium concentrations (1.0-0.001M) obtained by measurements with four different test strips (K1-K4) EMF Concentration K1 K2 K3 K4 KCl [mM] −log[K.sup.+] [mV] [mV] [mV] [mV] 1.0 3 −116 −111 −109 −107 10.0 2 −5 −3 0 3 100.0 1 100 100 105 106 1000.0 0 200 203 208 209

[0226] The data clearly show good reproducibility and—as shown in FIG. 5—a linear (dynamic) range between 0.001M and 1M potassium solution. Thus, the linear range of the test strips covers medically relevant concentrations in physiological fluids as in human urine, where the range for potassium concentrations typically lies between 0.025-0.125M.

[0227] Out of these data for each test strip a regression equation of type

EMF=slope×(−log[K.sup.+])+intercept,

their average and deviation values were calculated (Table 2).

TABLE-US-00002 TABLE 2 Overview of linear regression equations and correlation coefficients obtained for EMF measurements with four different sodium sensors (K1-K4); slope in [mV/(−log[K.sup.+])], intercept in [mV], R.sup.2 = coefficient of determination Test-strip Slope Intercept R.sup.2 K1 −105.3 202.7 0.9995 K2 −104.5 204.0 0.9999 K3 −105.6 208.0 0.9998 K4 −105.1 210.4 0.9997 Average −105.1 206.3 0.9997 Deviation 0.4 3.1 0.0002

[0228] Using these regression equations, the concentration of potassium in a sample can be determined from the measured EMF as illustrated by following example:

EMF of a sample measured: 2.0 mV
Regression equation (averaged): EMF=−105.1 (−log[K])+206.3
than

−log[K.sup.+]=(2−206.3)/(−105.1)=1.9439

[K.sup.+]=10.sup.−1.9439=0.0114 M=11.4 mM

Example 5

Fabrication of a Calcium-Selective Test-Strip

[0229] To realize a calcium-selective electrode (Ca-ISE), a solution of poly(3-octylthiophene) in tetrahydrofuran (0.5 mg/1 mL) was casted (2.5 μL) on the area of the carbon WE. Then the substrate was dried to remove solvent forming a thin transducer layer. Subsequently, a solution of a calcium-selective membrane (Ca-ISM) solution (3.5 μL) was casted on the top of that transducer layer. Then, the substrate was dried to remove solvent and to form a calcium-selective membrane on the WE. The Ca-ISM solution consisted of a mixture of 2.0 mg calcium ionophore II (N,N,N′,N′-tetra[cyclohexyl]diglycolic acid diamide), 0.5 mg potassium tetrakis(4-chlorophenyl) borate, 32.8 mg PVC (high molecular weight polyvinylchloride) and 64.7 mg 2-Nitrophenyl octyl ether in 1 mL tetrahydrofuran.

Example 6

[0230] Potentiometric Measurements with the Calcium-Selective Test-Strip

[0231] The calcium-selective test-strip was dipped into the sample solution until all electrodes were covered and the potential difference (EMF) between modified WE(s) and RE was measured with a high input impedance voltmeter that was integrated in a prototype of a readout meter having receiving module for receiving the interface of the test-strip and a display, where result was immediately displayed.

Example 7

Sensor Calibration by Measuring a Standard Calcium Solution Series

[0232] Standard solutions with calcium concentrations of 10.sup.−1M, 5×10.sup.−2M, 10.sup.−2M, 5×10.sup.−3M respectively, were prepared by dissolving calcium chloride (CaCl.sub.2) in water. The EMF values were recorded and a calibration curve was set up by plotting the EMF values as a function of the minus logarithm of calcium concentrations. Four different test strips (Ca1-Ca4) were fabricated and tested. The results are summarized in Table 3.

TABLE-US-00003 TABLE 3 EMF values for four different calcium concentrations (0.1-0.005M) obtained by measurements with four different test strips (Ca1-Ca4) EMF Concentration Ca1 Ca2 Ca3 Ca4 CaCl.sub.2 [mM] −log(c) [mV] [mV] [mV] [mV] 5.0 2.3 159 157 158 155 10.0 2 171 168 170 167 50.0 1.3 211 212 212 210 100.0 0 229 228 228 224

[0233] The data clearly show good reproducibility and—as shown in FIG. 6—a linear (dynamic) range between 0.005 M and 0.1 M calcium solution. Thus, the linear range of the test strips covers medically relevant concentrations in physiological fluids as in human urine, where the calcium concentrations typically lies around 10 mM range.

[0234] Out of these data for each test strip a regression equation of type

EMF=slope×(−log[Ca.sup.2+])+intercept,

their average and deviation values were calculated (Table 4).

TABLE-US-00004 TABLE 4 Overview of linear regression equations and correlation coefficients obtained for EMF measurements with four different sodium sensors (Ca1-Ca4); slope in [mV/(−log[Ca.sup.2+])], intercept in [mV], R.sup.2 = coefficient of determination Test-strip Slope Intercept R.sup.2 Ca1 −54.6 282.6 0.9966 Ca2 −56.5 284.4 0.9945 Ca3 −55.2 283.1 0.9966 Ca4 −55.0 279.7 0.9957 Average −55.3 282.4 0.9959 Deviation 0.7 1.7 0.0009

[0235] Using these regression equations, the concentration of potassium in a sample can be determined from the measured EMF as illustrated by following example:

EMF of a sample measured: 155.0 mV
Regression equation (averaged): EMF=−55.3 (−log[Ca.sup.2+])+282.4
than

−log[Ca.sup.2+]=(155−282.4)/(−55.3)=2.3038

[Ca.sup.2+]=10.sup.−2.3038=0.00498 M=4.98 mM

Example 8

Fabrication of a Creatinine-Selective Test-Strip

[0236] To realize a creatinine-selective electrode (Crea-ISE), a solution of poly(3-octylthiophene) in tetrahydrofuran (0.5 mg/1 mL) was casted (2.5 μL) on the area of the carbon WE. Then the substrate was dried to remove solvent forming a thin transducer layer on the surface. Subsequently, a solution of a creatinine-selective membrane (Crea-ISM) solution (3.5 μL) was casted on the top of that transducer layer. Then, the substrate was dried to remove solvent and to form a creatinine-selective membrane on the WE. The Crea-ISM solution consisted of a mixture of 4.0 mg creatinine molybdophosphate, 63 mg PVC (high molecular weight polyvinylchloride) and 125 mg o-Nitrophenyl octyl ether in a mixture of 2 mL tetrahydrofuran and 0.5 mL acetone.

Example 9

[0237] Potentiometric Measurements with the Creatinine-Selective Test-Strip

[0238] The creatinine-selective test-strip was dipped into the sample solution until all electrodes were covered and the potential difference (EMF) between modified WE(s) and RE was measured with a high input impedance voltmeter that was integrated in a prototype of a readout meter having receiving module for receiving the interface of the test-strip and a display, where result was immediately displayed.

Example 10

Sensor Calibration by Measuring a Standard Creatinine Solution Series

[0239] Standard solutions with creatinine concentrations of 1M, 316.2×10.sup.−1M, 17.8×10.sup.−1M, 10.sup.−1M, 3.16×10.sup.−2M, 10.sup.−2M, 10.sup.−3M respectively, were prepared by dissolving creatinine hydrochloride in water. The EMF values were recorded and a calibration curve was set up by plotting the EMF values as a function of the minus logarithm of potassium concentrations. Four different test strips (Crea1-Crea2) were fabricated and tested. The results are summarized in Table 5.

TABLE-US-00005 TABLE 5 EMF values for seven different creatinine concentrations (1.0-0.001M) obtained by measurements with four different test strips (Crea1-Crea4) EMF Concentration Crea1 Crea2 Crea3 Crea4 [mM] log(Crea) [mV] [mV] [mV] [mV] 1.0 3 34 23 22 33 10.0 2 147 137 136 147 31.6 1.5 204 193 191 204 100.0 1 259 247 245 258 177.8 0.75 284 274 270 281 316.2 0.5 312 302 298 311 1000.0 0 362 354 349 357

[0240] The data clearly show good reproducibility and—as shown in FIG. 7—a linear (dynamic) range between 0.001M and 1M creatinine solution. Thus, the linear range of the test strips covers medically relevant concentrations in physiological fluids as in human urine, where the range for creatinine concentrations typically lies around 1-32 mM.

[0241] Out of these data for each test strip a regression equation of type

EMF=slope×(−log[Crea])+intercept,

their average and deviation values were calculated (Table 6).

TABLE-US-00006 TABLE 6 Overview of linear regression equations and correlation coefficients obtained for EMF measurements with four different sodium sensors (Crea1-Crea4); slope in [mV/(−log[Crea])], intercept in [mV], R.sup.2 = coefficient of determination Test-strip Slope Intercept R.sup.2 Crea1 −109.8 366.1 0.9995 Crea2 −110.4 356.6 0.9997 Crea3 −109.0 352.1 0.9996 Crea4 −108.7 363.1 0.9988 Average −109.8 358.3 0.9996 Deviation 0.6 5.8 0.0001

[0242] Using these regression equations, the concentration of potassium in a sample can be determined from the measured EMF as illustrated by following example:

EMF of a sample measured: 140.0 mV
Regression equation (averaged): EMF=−109.8 (−log[Crea])+358.3
than

−log[Crea]=(140.0−358.3)/(−109.8)=1.9882

[Crea]=10.sup.−1.9882=0.01027 M=10.3 mM

REFERENCES

[0243] [1] Fluids, Electrolytes and Acid-Base Disorders Handbook, Editors: Canada T W, Tajchman S K, Tucker A M, Ybarra J V. ASPEN (2015); eBook edition: ISBN-13: 978-1-889622-18-7 [0244] [2] McDonough A A, Youn J H. Potassium homeostasis: the knowns, the unknowns and the health benefits. Physiology 32:100-11(2017) [0245] [3] Unwin R J, Luft F C, Shirley D G. Pathophysiology and management of hypokalemia: a clinical perspective. Nat Rev Nephrol 7:75-84(2011) [0246] [4] Glassock R J, Goldstein D A, Goldstone R, Hsueh W A. Diabetes mellitus, moderate renal insufficiency and hyperkalemia. Am J Nephrol 3:233-40(1983) [0247] [5] Barstow C. Calcium disorders. FP Essent 459:29-34(2017) [0248] [6] Gallagher J C, Smith L M, Yalamanchili V. Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women. Menopause 21:1173-80(2014) [0249] [7] Taufield P A, Ales K L, Resnick L M, Drusin M L, Gertner J M, Laragh J H. Hypocalciuria in preeclampsia. N Engl J Med 316:715-8(1987) [0250] [8] Volpe S L. Magnesium in disease prevention and overall health. Adv Nutr 4:378S-83S(2013) [0251] [9] Menditto V G, Lucci M, Polonara S. The role of hypomagnesuria in urolithiasis and renal colic: results from a prospective study of a metabolic protocol. Minaerva Med 103:377-82(2012) [0252] [10] Gordon A, Magee L A, Payne B, Firoz T, Sawtchuk D, Tu D, Vidler M, de Silva D, Dadelszen P. Magnesium sulphate for the management of preeclampsia and eclampsia in middle and low-income countries: a systematic review of dosing regimens. J Obstet Gynecol Can 36:154-63(2014) [0253] [11] Ackland M L, Michalczyk A. Zinc deficiency and its inherited disorders—a review. Genes Nutr 1(1); 41-50(2006) [0254] [12] Romana D L, Olivares M, Uauy R, Araya M. Risks and benefits of copper in light of new insights of copper homeostasis. J Trace Elem Med Biol 25; 3-13(2011) [0255] [13] Vashist S K, Luppa P B, Yeo L Y, Ozcan A, Luong J H T, Emerging Technologies for Next-Generation Point-of-Care Testing. Trends in Biotechnology, 33, 11; 692-705(2015) [0256] [14] Gubala et al. Point of Care Diagnostics: Status and Future. Anal. Chem. 84, 487-515(2012) [0257] [15] Koo H, Lee S G, Kim J H. Evaluation of random urine sodium and potassium compensated by creatinine as possible alternative for 24-hour urinary sodium and potassium excretion. Ann Lab Med 35:238-241(2015) [0258] [16] Tang N L S, Chan Y K, Hui E., Woo J. Application of Urine Magnesium/Creatinine Ratio as an Indicator for Insufficient Magnesium Intake. Clin. Biochemi. 33, 8, 675-678 (2000) [0259] [17] Newman D J, Price C P. Renal function and nitrogen metabolites. In Tietz Textbook of Clinical Chemistry. Third Edition. Edited by Burtis C A, Ashwood E R. pp 1204-1270(1990) [0260] [18] Newman J D, Turner A P F, Home blood glucose biosensors: a commercial perspective. Biosensors and Bioelectronics 20; 2435-2453(2005) [0261] [19] Thomas L. Labor and Diagnose. T H Books (2012) [0262] [20] Syal K., Banerjee D., Srinivasan A. Creatinine estimation and interference. Ind J Clin

[0263] Biochem 28(2); 210-211(2013) [0264] [21] C. S. Pundir C S. Sandeep Yadav S. Kumar A. Creatinine sensors, TRAC 50; 2-52 (2013) [0265] [22] http://www.novabio.us/uk/statstrip-creatinine/[23] Shephard M D S, Point-of-Care Testing and Creatinine Measurement, Clin Biochem Rev, 32; 109-114 (2011)

[0266] The features of the present invention disclosed in the specification, the claims, and/or in the accompanying figures may, both separately and in any combination thereof, be material for realizing the invention in various forms thereof.