Potassium sensor film composition

Abstract

The present invention is + K for use with select sensors + The present invention provides a selective membrane composition comprising: + It contains the ionophore KI-II, the cation exchanger potassium tetrakis(4-chlorophenyl)borate, the base membrane polymer polyurethane, and the plasticizer dioctyl sebacate. + Ionophore (KI-II): present in an amount of 15 wt% (ionophore II), cation exchanger (CE): 2.25 wt% (potassium tetrakis(4-chlorophenyl)borate), plasticizer (DOS): 29.5 wt% (bis(2-ethylhexyl) sebacate), and polymer (PU): 58 wt% (polyurethane).

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to, and is a nonprovisional application of, U.S. Provisional Application No. 63 / 291,804, filed December 20, 2021. [Background technology]

[0002] Potassium (K + ) Selective membrane compositions are known in the art and include K + Components such as ionophores (Type I), cation exchangers (CE) such as potassium tetrakis(pentafluorophenyl)borate or potassium tetrakis(4-chlorophenyl)borate, plasticizers such as bis(2-ethylhexyl) sebacate, and polymers such as poly(vinyl chloride) may be included.

[0003] The problem with the film composition in the art is that the film composition is + The problem is that it does not provide sufficient selectivity for use in monitoring K + 50 mM Na, which results in a much larger concentration change (one order of magnitude) than + K of 1 mM for concentration change + Changes in concentration (e.g., 1 mM K in solution) + can be observed, for example, in blood or interstitial fluid), sodium ions (Na + ) concentration change is K + During testing, for example, 10 mM Na + A low concentration solution of sodium is typically used. Even under these conditions, a change in the sensor response with varying sodium concentration can be observed.

[0004] K + K for use with select sensors + Improved selective membrane compositions are desired to improve sensor response and performance. Summary of the Invention

[0005] The present invention provides a K sensor that exhibits excellent sensor response and performance. + K for use with select sensors + A selective membrane composition is provided. The invention also provides sensors comprising said compositions, and methods of using said compositions and sensors.

[0006] In a first aspect, the present invention provides a method for the preparation of a medicament for the treatment of a pulmonary artery disease comprising + First Functionality K for Use with a Specific Sensor + A sensor film composition is provided. The film composition comprises a K sensor comprising (KI-II). + The composition comprises, consists of, or consists essentially of a cation exchanger comprising an ionophore, (potassium tetrakis(4-chlorophenyl)borate), a base membrane polymer (polyurethane), and a plasticizer (dioctyl sebacate). The composition has a weight percent, mole percent ratio of KI-II / CE of 0-30.0.

[0007] In a second aspect, the present invention provides a method for the preparation of a medicament for the treatment of a pulmonary artery disease comprising + Alternative functionalities for use with specific sensors + A sensor film composition is provided. The film composition comprises a K sensor comprising (KI-II). + The composition comprises, consists of, or consists essentially of an ionophore, a cation exchanger including potassium tetrakis(4-chlorophenyl)borate, a base membrane polymer such as a polyurethane, and a plasticizer such as dioctyl sebacate. The composition has a weight percent ratio of base membrane polymer / plasticizer of 0 to 10 (e.g., 0 / 10 to 10 / 1 weight percent).

[0008] In a third aspect, the present invention provides a method for the preparation of a medicament for the treatment of cancer, comprising: + Functional K for use with specific sensors + A sensor film composition is provided. The composition comprises a K + The membrane comprises, consists of, or consists essentially of an ionophore, a cation exchanger comprising potassium tetrakis(4-chlorophenyl)borate, a base membrane polymer comprising polyurethane, and a plasticizer (dioctyl sebacate (DOS)). The components are present in the following amounts: +Ionophore (KI-II): present at 15 wt% (ionophore II), cation exchanger (CE): present at 2.25 wt% (potassium tetrakis(4-chlorophenyl)borate), plasticizer (DOS): present at 29.5 wt% (bis(2-ethylhexyl) sebacate), and polymer (PU): present at 58 wt% (polyurethane). [Brief description of the drawings]

[0009] [Figure 1] FIG. 13 shows sensor response results from an example section. [Diagram 2] FIG. 13 shows a sensor calibration plot from the Examples section. [Diagram 3] FIG. 13 shows sensor response results from an example section. [Figure 4] FIG. 13 shows sensor response results from an example section. [Diagram 5] FIG. 13 shows EMF curves from example terms. [Figure 6] FIG. 1 shows the electrodeposition of PPy using chronoamperometry as described in the Examples section. [Figure 7] FIG. 1 shows a preliminary optimization study described in the Examples section. [Figure 8] FIG. 1 shows preliminary cytotoxicity studies described in the Examples section. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention is + K for use with select sensors + The present inventors have unexpectedly found that the membrane composition has a selective K + Use with select sensors has been found to provide superior sensor response and performance.

[0011] In a first aspect, the present invention provides a method for the preparation of a medicament for the treatment of a pulmonary artery disease comprising + Functional K for use with specific sensors + A sensor film composition is provided. The film composition comprises K +The composition comprises, consists of, or consists essentially of an ionophore (K), a cation exchanger (CE), a base membrane polymer, and a plasticizer. The composition has a weight % or molar % ratio of K / CE of 0-30.0 wt.%, 0-20.6 mol.% (e.g., 0 / 10-30 / 1 wt.%), more preferably 0.6-10.0 wt.%, 0.97-14.5 mol.% (e.g., 2 / 3-30 / 3 wt.%), and most preferably 3.3-6.7 wt.%, 4.8-9.7 mol.% (e.g., 10 / 3-10 / 1.5 wt.%).

[0012] In a further aspect, the film composition, alone or in combination with any of the compositions described herein, comprises a K + It comprises an ionophore (K), a cation exchanger (CE), a base membrane polymer (BMP), and a plasticizer (P). In this embodiment, the composition has a weight percent ratio of BMP / P of 0-10 wt% (e.g., 0 / 10-10 / 1 wt%), more preferably 0.2-4 wt% (e.g., 1 / 5-4 / 1 wt%), and most preferably 0.3-2.5 wt% (e.g., 1 / 3-5 / 2 wt%).

[0013] In yet another preferred embodiment, the film composition, alone or in combination with any of the compositions described herein, comprises K + The components include an ionophore (K), a cation exchanger (CE), a base membrane polymer (BMP), and a plasticizer (P). In this embodiment, the components are present in the following amounts by weight: K-15%, CE-2.25%, P-29.5% (bis(2-ethylhexyl) sebacate), and BMP-58%.

[0014] Components K, CE, BMP, and P are not particularly limited herein. However, it should be noted that in particularly preferred embodiments, the components include any or all of the following:

[0015] K +Ionophores are not particularly limited herein. The word ionophore is derived from the Greek ("ion" and "phore", "ion carrier") and is a chemical species that can reversibly bind ions and transport them across membranes. Synthetic potassium ionophores include (I=valinomycin, II, III, IV), all of which can potentially be used in hydrophobic membranes. The most commonly used K + Ionophores are graded I>II>III, with type IV being the rarest.

[0016] Molecules derived from organisms that act as ionophores and encompass other biological functions such as antibacterial, anti-inflammatory, and antibiotic functions also exist and can be used. These ionophores derived from organisms can be produced using Streptomyces bacteria. Examples of such ionophores include 1) Na + , Ca 2+ and Mg 2+ In addition to other alkali metal ions such as K + 2) salinomycin, which has high preference for bafilomycin A1, and 3) K + and H + 4) Nigericin, which is reactive with both ions and + and NH4 + and 5) gramicidin, where type D is formed from types A, B, and C. Gramicidin is a type that binds K + and Na + Examples of suitable microbial proteins include gramicidin, which forms a transport channel through which microbial proteins can pass and can be derived from the genus Bacillus.

[0017] However, in a preferred embodiment, K +The ionophore preferably comprises, consists of, or consists essentially of potassium ionophore II ((KI-II) (CAS: 69271-98-3), also known as bis[(benzo-15-crown-5)-15-ylmethyl] pimelic acid or bis(2,5,8,11,14-pentaoxabicyclo[13.4.0]nonadeca-1(15),16,18-trien-17-ylmethyl) heptanedioate, having the structure: [ka] has.

[0018] The cation exchanger (CE) is not particularly limited, and may be, for example, a lipophilic salt such as a tetraphenylborate-based lipophilic salt. In a preferred embodiment, the CE preferably has the following structure: [ka] The composition may comprise, consist of, or consist essentially of potassium tetrakis(4-chlorophenyl)borate having the formula:

[0019] The plasticizer is not particularly limited, but preferably comprises, consists of, or consists essentially of a compound(s) selected from the group consisting of succinic acid derived plasticizers and / or compounds having a long hydrocarbon chain with a nitrophenyl ether group (e.g., 2-nitrophenyl octyl ether, dodecyl 2-nitrophenyl ether), phthalate derivatives (e.g., dibutyl phthalate, dioctyl phthalate), and bis(1-butylpentyl)decane-1,10-diyl diglutarate. In the most preferred embodiment, the plasticizer comprises, consists of, or consists essentially of dioctyl sebacate (di(2-ethylhexyl) sebacate) (DOS). DOS is a colorless oily liquid and an organic compound that is a diester of sebacic acid and 2-ethylhexanol. DOS has the following structure: [ka] has.

[0020] The base membrane polymer preferably comprises, consists of, or consists essentially of a polymer selected from the group consisting of polyurethane (PU), polydimethylsiloxane (PDMS), polyvinyl chloride (PVC), polyetheretherketone (PEEK), cycloolefin copolymer (COC), polymethylmethacrylate (PMMA), polystyrene, acrylate, poly(vinyl butyral), polyamide, polyimide, and Teflon. In a most preferred embodiment, the polymer comprises, consists of, or consists essentially of PU. In a preferred embodiment, the PU has a molecular weight of 100 kg / mol and has the following structure: [ka] has.

[0021] In a most preferred embodiment, the inventors unexpectedly demonstrated that a membrane concentration recipe with a KI-II / CE weight percent ratio of 15 / 2.25 and a PU / DOS weight percent ratio of 2 / 1, particularly when tested in an artificial ISF solution with 2 mM LiCl, 2 mM MgCl2, 4 mM CaCl2, and 50 mM NaCl, exhibited a significant improvement in the K + It was found that this provides optimal selectivity for

[0022] The membrane composition may contain additional components, which are added in amounts such that the above ratio is maintained.These additional components can be added to perform functions known in the art.For example, the additional components can include materials such as conductive materials, including nanomaterials or pyrrole-type monomers, that do not significantly affect the performance and selectivity of the membrane but can increase sensitivity.

[0023] Additional components can also include redox markers that are incorporated into the membrane to enable voltammetric-based (e.g., DPV, SWV, and CV) ion detection. These redox markers are well known in the art and are described, among others, in https: / / analyticalsciencejournals.onlinelibrary.wiley.com / doi / 10.1002 / elan.201800080.

[0024] Other additives (e.g., additional components) may also be introduced to modify the mechanical or surface chemical properties of the membrane, such as to improve adhesion, modify hydrophobicity / hydrophilicity, adjust stiffness, or provide enhanced anti-biofouling properties.

[0025] The K described herein + The sensor film composition is particularly suitable for use in biological and biomedical applications (e.g., in conjunction with potassium sensors for determining potassium in biological fluids such as blood and / or interstitial fluid). This is due to the biocompatibility of all film components. As demonstrated in the Examples section, the preferred films did not show significant differences in cell viability after 24 hours of exposure by direct contact. The p-values ​​for the preferred films with and without PPy were 0.11 and 0.12, respectively, which are above the standard cut-off value of 0.05 for biocompatibility purposes. No significant morphological differences were observed between the negative control and both preferred film compositions. Thus, in another aspect, the present invention provides methods of using the film compositions described herein, alone or in combination with sensors, in in vivo and / or biomedical applications and / or biomedical devices. In another aspect, the film compositions of the present invention can be used in conjunction with potassium sensors in biological samples such as blood and / or interstitial fluid to detect very low and high as well as normal blood K. + Covering levels from 0.5 to 10 mM K + It is useful for determining potassium levels within the range (e.g., linear range) of blood K. + The levels may be correlated with interstitial fluid (ISF) levels.

[0026] The inventors have discovered that the role and amount of certain components affect sensor response and performance in unexpected ways. Traditionally, plasticizers are added to the base membrane polymer (usually PVC) to reduce stiffness and impart flexibility, thereby reducing the fragility of the resulting sensor and membrane. However, the inventors have discovered that (especially when the base polymer is PU) lower amounts of plasticizers can be used in the formulations of the present invention. In these embodiments, the inventors have also unexpectedly discovered that the use of lower amounts of plasticizers allows for the creation of durable, robust, and flexible membranes and sensors (e.g., still resulting in crosslinking and plasticization of the polymer (e.g., PU)) while at the same time creating a lipophilic environment for the cation exchangers and ionophores that are essential for their functionality. The preferred ratios are described above, and the total amount of plasticizer (e.g., DOS) used is significantly less than that reported in the art (PU / DOS ratio less than 1 / 1) and does not supersaturate the membrane when used in these amounts (reducing the chance of DOS leakage).

[0027] The inventors further note that the ratio of KI / CE used in compositions in the art is typically 2 / 1 with compositions having up to 5 wt% KI-I reported. Without being bound to a particular mechanism of action, it is believed that this ratio is elevated due to the total loading of CE being important for ion transfer from the aqueous solution to the membrane. On the other hand, a total KI concentration of 5 wt% produces membranes that are not selective enough for use in biomedical applications, resulting in the major interfering sodium ion (Na + ) can reach concentrations up to 125 mM, while the analytes of interest (e.g., potassium (K + )) concentrations as low as 5 mM.

[0028] Without being bound to a particular mechanism of action, the inventors unexpectedly discovered that increasing the KI concentration results in higher sensitivity and selectivity. Similarly, it was unexpectedly found that when the total CE amount had 15 wt% KI-II, a concentration as low as 2.25 wt% was sufficient to provide good sensitivity and high selectivity. Furthermore, it was unexpectedly found that this ratio may be specific to the ionophore molecule that affects function and selectivity. KI-II is a KI + It is less widely used than KI-I (valinomycin) in the preparation of selective membranes. Without being bound to a particular mechanism of action, it is believed herein that increasing the ionophore concentration retards the sensor response and requires increasing the CE concentration, which impairs membrane selectivity due to the reactivity of CE with most monovalent cations, and that increasing the ionophore concentration also requires a decrease in the overall amount of polymer in the membrane, which can lead to a loss of structural integrity of the membrane.

[0029] Throughout this specification, references to "one embodiment," "another embodiment," "embodiment," "some embodiments," etc. mean that a particular element (e.g., a feature, structure, property, and / or characteristic) described in connection with an embodiment is included in at least one embodiment described herein and may or may not be present in other embodiments. In addition, it should be understood that the embodiments and / or described element(s) may be combined in any suitable manner.

[0030] Numerical values ​​in the specification and claims of this application refer to average values. Moreover, unless otherwise indicated, the numerical values ​​should be understood to encompass numerical values ​​that are the same when reduced to the same number of significant figures and numerical values ​​whose difference from the stated value is less than the experimental error of conventional measuring techniques of the type described in this application for determining the value.

[0031] example The invention will now be further described with reference to the following non-limiting examples.

[0032] Experimental conditions and materials: Dissolve all components in tetrahydrofuran (THF). Pipette the desired membrane solution volume onto a commercial gold rod electrode surface modified with polypyrrole (PPy) and evaporate the THF solvent (overnight at room temperature) to obtain K. + A molded body of the sensor membrane is obtained. All experiments are carried out in artificial interstitial fluid (ISF).

[0033] Preliminary results obtained with our recipe show exceptional selectivity when tested with high reproducibility against 50 mM NaCl. + Interference studies. EMF response to addition of 1 mM KCl and 50 mM NaCl) shows the response of the sensor to addition of 1 mM KCl and 50 mM NaCl. The decrease in KCl response is due to the logarithmic relationship between concentration and the electromagnetic field (EMF) signal.

[0034] Figure 2 (Calibration plot. EMF response of the sensor to the addition of KCl (left) and K + The respective calibration plots of log concentration vs. EMF change (right) show the calibration plots obtained using 10 wt% KI-II, 1.5 wt% CE, 29.5 wt% DOS, and 59 wt% PU. log(K + ) vs. EMF linear range was obtained within the range of 0.5 to 10 mM KCl.

[0035] Figures 3 and 4 show + The results of the optimal CE and KI-II wt.% study are shown, taking into account the selectivity of the sensor for Li. The sensor was incubated with 2 mM Li in artificial ISF. + , 2 mM Mg ++ , 4 mM Ca ++ , and 50 mM Na + The best response was observed when using 15 wt% KI-II and 3 wt% CE, i.e., a KI-II to CE ratio of 5 to 1. Figure 5 shows the EMF curves obtained when using a membrane with this ratio. No significant overall EMF changes were observed after addition of any of the tested interfering ions at the concentration of their ISF counterparts.

[0036] Figure 3 - Optimization of the cation exchanger concentration. Comparison of the potentiometric response of the sensor to selected interfering ions with respect to the response obtained for the addition of 1 mM KCl. Error bars represent the standard deviation of three independent experiments. The best results were obtained with 1.5 wt. % CE and a KI-II / CE ratio of 10 / 1.5.

[0037] Figure 4-K + Optimization of the ionophore concentration. Comparison of the potentiometric response of the sensor to selected interfering ions relative to the response obtained on addition of 1 mM KCl. Error bars represent the standard deviation of three independent experiments. The best results were obtained with 15 wt% KI-II and a KI-II / CE ratio of 15 / 3.

[0038] Figure 5: Selectivity study. EMF response of the sensor to the addition of selected interfering ions. The membrane recipe contains 15 wt% KI-II, 3 wt% CE, 27.3 wt% DOS, and 54.6 wt% PU.

[0039] Throughout the experiments, PPy was used as an exemplary transducer layer, although others may be used with similar results expected. The electrodeposition of PPy using chronoamperometry with continuous application of a potential of +1 V is shown in Figure 6. The increase in conductivity caused by PPy was analyzed by CV in a ferrocyanide / ferricyanide redox probe and can be seen in the inset of Figure 6. This recipe of PPy resulted in desirable conductivity and stability when the film was dissolved and deposited on a PPy-coated electrode using the organic solvent tetrahydrofuran (THF). Conversely, the CV-based PPy film lifted off after the film deposition step due to the THF solvent.

[0040] Figure 6: Electropolymerization of polypyrrole. A potential of 1 V was applied for 1 min and polypyrrole deposition was monitored by chronoamperometry. The inset shows a comparison of the CV plot of the bare electrode with that of the PPy-deposited electrode in a 5 mM potassium ferrocyanide / ferricyanide redox couple solution.

[0041] Figure 7: Preliminary PU / DOS (wt%) optimization study. EMF signals obtained from sensor films with different PU / DOS wt% ratios and 10 wt% KI-II and 3 wt% CE.

[0042] Preliminary cytotoxicity studies of membranes with and without PPy are shown in Figure 8. Cell viability assays were performed using mouse fibroblast GPE86 cell line seeded at approximately 5000 cells / well in 96-well plates. Polydimethylsiloxane (PDMS) samples, known to be non-cytotoxic, were used as negative controls, and dimethylsulfoxide (DMSO), known to be cytotoxic, was used as positive control. Sample specimens were placed directly on top of the cells after 24 h of incubation in the plates (n=5) and cultured for 24 h at 37°C with 5% CO2. The specimens were removed before adding the cell viability assay reagent. A colorimetric assay (Cell Counting Kit 8, CCK-8) was used to quantify the metabolic activity of live cells. After 3 h of incubation of the cells with the colorimetric assay reagent, the morphology of the cells was observed using light microscopy after exposure to the membrane specimens to compare the cell confluency. The cell confluency observed in both the membrane and PPy-containing membrane samples was not significantly different from that of the negative control group, indicating that the tested membrane samples did not induce cytotoxicity in the tested cells.

[0043] Figure 8: Preliminary cytotoxicity studies. Cell viability assays of membrane components with and without pyrrole. Direct contact of membrane preparations was tested using the GPE86 mouse fibroblast cell line. Error bars represent standard deviation of five replicates.

[0044] Consider an example: Without being bound to a particular mechanism of action, a discussion of preferred membrane compositions follows. The above examples of preferred membrane compositions exhibit excellent sensor response and calibration curves, with linear ranges covering the physiologically relevant range of K in blood and interstitial fluids, including the clinically relevant regions of hypokalemia, normokalemia, and hyperkalemia. +This membrane covers physiologically relevant concentrations of K in blood and interstitial fluid. + They show unprecedented selectivity for the detection of other ions at comparable relevant concentrations present in these human body fluids, most notably Na + (Figure 1) + , Mg ++ , and Ca + (Figure 5). The selectivity is proportional to the KI-II / CE weight percent ratio. However, the sensitivity, another important parameter of the sensor, is exactly the opposite, defined as the maximum sensitivity with the minimum interference, at 15 / 2.25 weight percent KI-II / CE (Figures 3 and 4).

[0045] The sensitivity was found to be inversely proportional to the PU / DOS weight % ratio and can therefore be adjusted by changing the PU / DOS weight % ratio. However, the membrane integrity is also proportional to the PU / DOS weight % ratio (Figure 7). DOS is the rate at which the ISF passes through the membrane. + Although important for transport, increasing the weight % can cause leakage and therefore reduce signal reproducibility, membrane integrity, and adhesion to the membrane substrate. Similarly, as seen in Figure 7, the selectivity of the sensor to 50 mM NaCl (which is the largest interfering substance as seen in Figure 5) is directly proportional to the PU / DOS weight % ratio due to the increase in EMF signal (relative to the EMF signal obtained for 1 mM KCl). A PU / DOS weight % below 1 / 2 results in poor membrane integrity and adhesion to the electrode, and therefore a lower ratio leads to a decrease in the EMF signal.

[0046] In the present specification, the KI-II / CE weight % ratio and the PU / DOS weight % ratio described above are the K + It has been discovered that this produces robust sensor films of extremely high reliability (low interference from other potential analytes), sensitivity, and resolution with excellent response and performance for applications such as direct detection and determination of changes in concentration.

[0047] Additionally, no cytotoxic responses were observed with the membrane compositions described herein when directly exposed to cells over a period of at least 24 hours ( FIG. 8 ), thereby demonstrating suitability for use in biomedical applications where direct contact of the membrane with patient tissues may result in irritation, discomfort and other potential adverse reactions.

Claims

1. Including the following: ＋ Functionality for use with specific sensors ＋ Sensor film composition: K including (KI-II) ＋ A cation exchanger (CE) containing an ionophore, (potassium tetrakis(4-chlorophenyl)borate), a base membrane polymer (polyurethane (PU)), and a plasticizer (dioctyl sebacate (DOS)); However, the composition has a weight percent and mole percent ratio of KI-II / CE of 0 to 30.0 weight percent.

2. 2. The composition of claim 1, having a weight percent, mole percent ratio of KI-II / CE of 0.6 to 10.0 wt.%, 0.97 to 14.5 mol.%, (e.g., 2 / 3 to 30 / 3 wt.%), or 3.3 to 6.7 wt.%, 4.8 to 9.7 mol.%, (e.g., 10 / 3 to 10 / 1.5 wt.%).

3. The composition of claim 1 having a weight percent ratio of PU / DOS of 0 to 10 weight percent (eg, 0 / 10 to 10 / 1 weight percent).

4. 5. The composition of claim 4 having a weight percent ratio of PU / DOS of 0.2 to 4 wt. % (e.g., 1 / 5 to 4 / 1 wt. %) or 0.3 to 2.5 wt. % (e.g., 1 / 3 to 5 / 2 wt. %).

5. Functionality K ＋ Specific membrane-containing K ＋ A specific sensor, ＋ The specific membrane is a functional K ＋ The sensor is formed from a specific membrane composition.

6. Suitable for use in biological and biomedical applications relating to potassium sensors for determining potassium in biological fluids, such as blood and / or interstitial fluid, for example, in biological samples such as blood and / or interstitial fluid, and for use in biological samples ranging from 0.5 to 10 mM K ＋ 6. The sensor of claim 5, suitable for determining potassium levels within a linear range of 100 .mu.m.

7. K ＋ Functionality for use with specific sensors ＋ 1. A sensor film composition comprising, consisting of, or consisting essentially of: K including (KI-II) ＋ A cation exchanger (CE) comprising an ionophore, (potassium tetrakis(4-chlorophenyl)borate), a base membrane polymer (polyurethane), and a plasticizer (dioctyl sebacate); The composition has a weight percent ratio of PU / DOS of 0 to 10 weight percent (eg, 0 / 10 to 10 / 1 weight percent).

8. 8. The composition of claim 7 having a weight percent ratio of PU / DOS of 0.2 to 4 wt. % (e.g., 1 / 5 to 4 / 1 wt. %) or 0.3 to 2.5 wt. % (e.g., 1 / 3 to 5 / 2 wt. %).

9. Functionality K ＋ Specific membrane-containing K ＋ A specific sensor, ＋ The specific membrane is a functional K according to claim 7. ＋ The sensor is formed from a specific membrane composition.

10. For example, the sensor is suitable for use in biological and biomedical applications relating to a potassium sensor for determining potassium in biological fluids such as blood and / or interstitial fluid, e.g., the sensor is suitable for use in biological samples such as blood and / or interstitial fluid, and ... ＋ 10. The sensor of claim 9, suitable for determining potassium levels within a linear range of 100 .mu.m.

11. K ＋ Functionality for use with specific sensors ＋ 1. A sensor film composition comprising, consisting of, or consisting essentially of: K including (KI-II) ＋ a cation exchanger comprising an ionophore, (potassium tetrakis(4-chlorophenyl)borate), a base membrane polymer (polyurethane), and a plasticizer (dioctyl sebacate); The components are present in the following amounts: ＋ Ionophore (KI-II): 15 wt% (Ionophore II), cation exchanger (CE): 2.25 wt% (potassium tetrakis(4-chlorophenyl)borate), plasticizer (DOS): 29.5 wt% (bis(2-ethylhexyl) sebacate), and polymer (PU): 58 wt% (polyurethane).

12. Functionality K ＋ Specific membrane-containing K ＋ A specific sensor, ＋ The specific membrane is a functional K according to claim 11. ＋ The sensor is formed from a specific membrane composition.

13. The sensor is suitable for use in biological and biomedical applications, e.g. relating to potassium sensors for determining potassium in biological fluids, such as blood and / or interstitial fluid, e.g. the sensor is suitable for use in biological samples, such as blood and / or interstitial fluid, and for determining potassium in biological fluids, e.g. between 0.5 and 10 mM K ＋ 13. The sensor of claim 12, suitable for determining potassium levels within a linear range of 100 .mu.m.

14. Functionality K ＋ K with specific membrane ＋ A method for forming a specific sensor comprising the steps of: (1) K containing (KI-II) ＋ A cation exchanger (CE) containing an ionophore, potassium tetrakis(4-chlorophenyl)borate, a base membrane polymer, polyurethane (PU), and a plasticizer, dioctyl sebacate (DOS), were dissolved in a solvent to form a functionalized cation exchanger (CE). ＋ forming a sensor membrane composition, said composition having a weight percent, molar percent ratio of KI-II / CE of 0-30.0 wt.%, and / or said composition having a weight percent ratio of PU / DOS of 0-10 wt.%, e.g., 0 / 10-10 / 1 wt.%; and (2) The composition is applied to the surface of an electrode, and then the solvent is evaporated to form a functional K ＋ K with specific membrane ＋ Forming a specific sensor.

15. The method of claim 14 , wherein the electrode comprises gold (Au).

16. The method according to claim 15, wherein the surface of the electrode is modified with polypyrrole (PPy).

Images