HK1154076B - Gas sensor with a microporous electrolyte layer - Google Patents

Description

Gas sensor with microporous electrolyte layer

The invention relates to an electrochemical sensor for determining gaseous analytes dissolved in an aqueous measuring medium, to a method for the production thereof, and to a method for determining gaseous analytes dissolved in an aqueous measuring medium using the electrochemical sensor. The invention relates in particular to a reaction space of an electrochemical sensor which is spatially separated from an aqueous measuring medium by a gas-permeable and ion-impermeable cover.

For analysis ofThe measurement system of body fluids is an important component of clinically relevant analytical methods. This particular focus is on rapid and accurate measurement of analytes, the so-called Point-of-care parameters (p.i.). Point-of-care tests (Point-of-care tests) have the advantage: the results are already obtained after a short time, since on the one hand it is not necessary to send the sample to a professional laboratory and on the other hand the timing of the laboratory does not have to be taken into account. The instant testing is mainly performed in intensive care units and in anesthesia rooms as well as in outpatient departments. These so-called "emergency parameters" include, in particular, the blood gas value (pCO)₂、pO₂) pH, electrolyte value (e.g. Na)⁺、K⁺、Ca²⁺、Cl^-) And certain metabolite values.

Such as test strips or other medical analyzers with multi-purpose sensors, may be used to perform such point-of-care tests, thereby minimizing labor costs for the implementation. Measuring devices for point-of-care applications are typically almost fully automated from sample preparation to test results, and require only a small and simple user intervention. They can include one-time as well as repeated measurements of the parameter to be determined.

Electrochemical sensors have proven to be particularly suitable for measuring gaseous analytes, such as oxygen or carbon dioxide dissolved in whole blood or other aqueous media. An electrochemical sensor allows an analyte to be measured by means of two or more electrodes, at least one of which is a working electrode on which the analyte to be determined is electrochemically altered (e.g. oxidised or reduced).

For example, it is possible to use a current sensor comprising at least one working electrode and at least one counter electrode for the measurement of oxygen or its partial pressure (pO) in an aqueous medium₂) The measurement of (2). In clark-type electrodes, a gas permeable and substantially ion and liquid impermeable membrane typically spatially separates the sample space from the internal electrolyte space. The internal electrolyte space is filled with an electrolyte solution that holds the working and counter electrodes.

For example, can use a composition comprising at least onePotentiometric sensors for measuring electrodes and at least one reference electrode for carbon dioxide or partial pressure thereof (pCO) in a liquid or gas₂) The measurement of (2). In a Severinghaus type electrode, CO is introduced₂The measurement of partial pressure translates into a pH measurement. This generally requires a reaction space which is spatially separated from the aqueous measurement medium by a gas-permeable and substantially ion-impermeable membrane. The pH is measured in the reaction space from the respective pCO of the sample to be tested₂A value is determined. At a predetermined temperature and concentration of the buffer in the reaction space (internal electrolyte), the pH of the reaction space depends only on the CO of the sample₂Partial pressure. The pH can be detected in a variety of ways, for example potential monitoring by means of an electrochemical measuring chain using ion-selective glass electrodes or ion-sensitive or ion-selective field effect transistors (ISFETs), pH-sensitive solid-state systems (e.g. noble metal/noble metal oxide systems), redox systems (quinone hydroquinone electrodes), etc.

An important criterion in the preparation of electrochemical sensors is their lifetime. In this respect it is necessary to achieve a long shelf life before the sensor is put into use and a long service life. To ensure a long shelf life, the electrodes located in the electrochemical sensor should be stored dry, i.e. essentially anhydrous, and not in contact with the liquid internal electrolyte until shortly before the sensor is put into use. In order to obtain at least 500 measurements or a lifetime of 3 to 4 weeks, the layers of the sensor must also be matched to each other. It is essential that they should not become detached from each other or form cracks, for example due to swelling.

An additional important criterion in the preparation of electrochemical sensors for point-of-care testing is their size. A small amount of sample (e.g., 100. mu.l or less) is typically provided for the purpose of determining emergency parameters. If a large number of parameters are to be determined with a small number of samples, the individual electrodes and their spacing from one another must be as small as possible.

EP 0805973B 1 discloses an apparatus and a method for measuring the concentration of a gas in a sample. The device used was an electrochemical sensor comprising a working electrode, a counter or reference electrode, an electrolyte layer consisting of photopatterned (fotogeformt) protein gelatin and a gas permeable membrane. In order to avoid premature contamination of the negatively polarized working electrode (cathode) made of gold by positively charged silver ions originating from the counter electrode (anode) made of silver, the distance between the two electrodes electrically contacted by the gelatin layer must be at least 1 mm.

US 5,387,329 describes a planar electrochemical oxygen sensor in which a swellable polymer having a swelling ratio of less than twice its dry volume is used as the hygroscopic electrolyte and in this case forms a hydrophilic electrolyte layer which is permeable to water and cations. Preferred swellable polymers in this document areI.e., a sulfonated tetrafluoroethylene polymer, the lithium-bearing sulfonate groups impart ionic properties to the polymer and result in the exchange of lithium ions by silver ions. In current oxygen sensors with silver counter electrodes, this reduces the effective migration rate of silver ions to the working electrode.

The electrolyte layers used in EP 0805973B 1 and US 5,387,329 have a number of disadvantages. Thus, for example, it is expensive to produce very thin layers (of about 1 μm) of swellable polymers (e.g. protein gelatin photopatterned in EP 0805973B 1).

Furthermore, in the case of very thin layers and very low electrolyte bodies, the silver ions released during operation of the oxygen sensor quickly lead to an interference signal. On the other hand, if thicker swelling layers (about 10-50 μm) are used in the multilayer structure, leakage is promoted in the layer construction. Which makes it difficult to obtain the desired long service life of the sensor.

In addition, a significant disadvantage of thin aqueous polymer layers is that, after application of an electric field between the two electrodes, interfering silver ions migrate in a direct path through the polymer and thus reach and contaminate the working electrode after a relatively short operating period.

It is an object of the present invention to provide an electrochemical sensor for the determination of a gaseous analyte, whereby the disadvantages of the prior art are at least partially eliminated. In particular, it will be possible to store the sensor for a long period of time without thereby losing activity, and in addition, the sensor should have a long life span after being put into use. Furthermore, it should be possible to manufacture the sensor simply and cost-effectively.

According to the invention, this object is achieved by means of an electrochemical sensor for determining a gaseous analyte dissolved in an aqueous measuring medium, comprising:

(a) a working electrode and a counter electrode,

(b) an electrolyte layer disposed between the working electrode and the counter electrode,

(c) a gas-permeable cover for spatially separating the working electrode, the counter electrode and the electrolyte layer from the aqueous measuring medium,

characterized in that the electrolyte layer comprises at least one particulate material and at least one binder, which together form a porous, non-swellable (nice-quellbar) skeleton structure, wherein the pores in the non-swellable skeleton structure are provided to absorb or contain a liquid electrolyte.

For example, as used herein, the expression "determining a gaseous analyte dissolved in an aqueous medium" includes determining the presence or concentration of a dissolved gaseous component in an aqueous medium, as well as determining the partial pressure of a gas of the dissolved gaseous component in the aqueous medium.

According to the invention, the pores of the non-swellable framework structure are arranged between the particles of the at least one particulate material. The tortuous path of the pores formed in this manner increases the distance that ions must travel between the electrodes compared to a pure polymer layer or gelatin or gel layer, thereby increasing the lifetime of the sensor.

The particulate material used in the electrochemical sensor of the invention may be inorganic or organic in nature and in particular comprises a dense inorganic material or a dense (plasticizer-free) organic polymer. Suitable inorganic particulate materials include Controlled Pore Glass (CPG), silica gel, silicates and aluminosilicates (Alumosilikate) in the group consisting essentially of framework silicates and phyllosilicates (also known as aluminosilicates). Organic polymers that may be used as particulate material according to the present invention include, for example, but are not limited to, particles of polystyrene, polyamides, polyvinyl chloride, polyvinylidene chloride, poly (meth) acrylates, polyacrylonitrile and copolymers thereof (Mikropartikel).

It has proven advantageous in the present invention to use naturally occurring or synthetic aluminosilicates, more preferably synthetic aluminosilicates, as particulate material. The term "synthetic aluminosilicate" as used in the present invention includes fully synthetic aluminosilicates as well as aluminosilicates obtained by artificially altering (e.g. chemically) naturally occurring aluminosilicates. Examples of naturally occurring or synthetic aluminosilicates include, but are not limited to, feldspar, mica, mullite, sillimanite, and zeolites.

In a preferred variant of the electrochemical sensor according to the invention, the particulate material has pores, in particular pores with a diameter of about 0.1nm to about 10nm, and optionally ion exchanger groups. In a more preferred embodiment, the particulate material is a corner-bonded [ (Al, Si) O) comprising a network of anion spaces formed across the pore channels₄]Tetrahedral polyhedrons, layers or chains of zeolites, such as faujasite (faujasite), chabazite (Chabasit), mordenite (Mordenit) or Natrolith (Natrolith). The channels have a diameter of from about 0.5nm to about 5.0nm, preferably from about 0.7nm to about 2.0nm, depending on the kind of zeolite, and contain ion exchanger groups, in particular cation exchanger groups, on their inner and outer surfaces. The use of zeolites having an internal pore structure and ion exchanger groups has proven particularly advantageous, particularly in clark-type current electrodes. In a particularly preferred embodiment, the sensor according to the invention comprises faujasite (most preferably faujasite-Na) as particulate material.

Due to their pore-containing structure, zeolites have large internal surfaces that can remain in contact with the liquid electrolyte. On the other hand, since ions of an appropriate size contained in the electrolyte liquid can migrate through the pores of the zeolite, the amount of undesired ions can be reduced. Thus, there is a particular problem in electrochemical sensors comprising a silver-containing counter electrode, when the sensor is put into use, silver ions are released from the counter electrode, migrate towards the working electrode and deposit thereon as elemental silver, passivating the working electrode. Similar processes also occur on other metals used as electrode materials, such as lead, which upon contact with an electrolyte liquid can release lead ions that can also act as interfering cations. The use according to the invention of an electrochemical sensor whose electrolyte layer preferably comprises at least one zeolite enables the effective distance between the counter electrode and the working electrode to be increased, thus reducing the risk of rapid passivation of the working electrode, which is reflected in an increased lifetime of the sensor.

On the other hand, the anionic framework structure of zeolites also allows them to function as ion exchangers. Thus, for example, silver ions released from the counter electrode and migrating towards the working electrode can be absorbed by the zeolite and exchanged for suitable, milder cations, such as sodium ions, with the result that the amount of free silver ions in the electrolyte is reduced to counter passivation of the working electrode; this also results in an increased lifetime of the sensor.

The particle size of the granular material can be varied as required in each case. In the present invention, the particles of the particulate material generally have an average particle size of from about 0.1 μm to about 10 μm, preferably from about 1.0 μm to about 5.0 μm. In any case, the particle size of the porous material should always be smaller than the layer thickness of the electrolyte layer, which is in the range from about 5 μm to about 30 μm, and preferably in the range from about 10 μm to about 20 μm.

In addition to the particulate material, the electrolyte layer comprises at least one binder as a further component. Preferably the binder is an organic binder, such as a crosslinked or uncrosslinked, linear or branched organic polymer. More preferably, the organic binder contained in the electrolyte layer comprises any desired crosslinked or uncrosslinked synthetic polymer, preferably selected from the group consisting of phenolic resins, epoxy resins, vinyl resins, PVC copolymers, two-component epoxy resins, polyurethane resin systems and UV curable polyacrylate monomer mixtures. Particularly preferably, the crosslinked or uncrosslinked synthetic polymers used are phenolic resins, in particular crosslinked phenolic resins.

The amount of non-swellable binder is preferably such that the binder connects the particles of inorganic or organic particulate material to form a porous, non-swellable skeletal structure. This means that the binder does not completely fill the interstitial spaces between the particles of the particulate material, thereby forming a non-swellable framework structure with pores having a diameter of from about 500nm to about 5 μm, preferably from about 1 μm to about 3 μm. In accordance with the present invention, the porous, non-swellable framework structure results in a relative liquid uptake of from about 20 to about 50 weight percent, preferably from about 26 to about 44 weight percent, based on the dry weight of the porous, non-swellable framework structure.

The amount of binder required may vary depending on the type and amount of particulate material used and the desired pore size, and one skilled in the art can adapt to the needs of any given situation. Fig. 1a and 1b each show an electron micrograph of an electrolyte layer of a sensor according to the invention in which particles of a particulate material are connected with a binder to form a porous, non-swellable framework structure. The porous, non-swellable backbone structure exhibits a uniform distribution of pores and is composed of units that are typically about 1 to 3 particles wide and linked in a chain-like fashion.

According to the invention, the electrolyte layer can additionally comprise one or more auxiliaries in addition to the at least one particulate material and the at least one binder. Auxiliaries which can be used for this purpose include in particular synthetic cellulose derivatives, for example alkylcelluloses, the term "alkyl" representing a straight-chain or branched hydrocarbon radical comprising from 1 to 6 carbon atoms. Preferably, the alkyl cellulose in the sense of the present invention is selected from the group consisting of methyl cellulose, ethyl cellulose, propyl cellulose, ethyl methyl cellulose and propyl methyl cellulose. The ability of the surface of the structure to be wetted by the liquid electrolyte can be improved by adding small amounts of these alkylcelluloses. Further suitable auxiliaries include, for example, defoamers.

The liquid electrolyte that ensures the electrically conductive electrolyte connection between the working electrode and the counter electrode in the electrochemical sensor according to the invention can be any desired electrolyte, for example an aqueous-based electrolyte that transports charge carriers due to the directional movement of ions when a voltage is applied. In the present invention, it is preferred that the liquid electrolyte comprises an alkali metal chloride and a pH buffer system.

In particular sodium chloride and/or potassium chloride can be used as alkali metal chloride, which in the electrochemical sensor according to the invention functions as a conductive salt component of the liquid electrolyte. The use of sodium chloride and/or potassium chloride as the main component of the electrolyte has the advantage that, due to the precipitation of silver chloride, the migration of silver ions released from the counter electrode in the direction of the working electrode is additionally prevented when using a silver-containing counter electrode, as a result of which the deposition of elemental silver on the working electrode can be reduced.

pH buffering systems that can be used in the liquid electrolyte solution include any desired buffering system known in the art and that functions to stabilize the pH in the liquid medium. Exemplary pH buffering systems include, but are not limited to, bicarbonate buffers, phosphate buffers, and the like.

In a preferred embodiment, the liquid electrolyte additionally comprises at least one water-soluble polymer in addition to the alkali metal chloride and the pH buffer system. The water-soluble polymer used may be any desired polymer which when introduced into the liquid electrolyte solution described above results in an increase in the viscosity of the liquid and thereby can also help to reduce the rate of migration of released ions, such as released silver ions. The water-soluble polymer that can be used in the present invention is, for example, polyethylene glycol, polyvinylpyrrolidone and alkyl polyglucoside, and the electrolyte liquid preferably contains polyethylene glycol and/or polyvinylpyrrolidone as the water-soluble polymer. Such electrolyte liquids can be used particularly advantageously in sensors for measuring oxygen.

In an alternative embodiment, the electrolyte liquid can additionally include, in addition to the alkali metal chloride and the pH buffering system, an enzyme that accelerates a desired reaction, such as hydration of a predetermined substrate. Particularly preferred enzymes in the present invention are carbonic anhydrases which catalyze the hydration of carbon dioxide to bicarbonate in the presence of water. Such electrolytes are particularly suitable for use in Severinghaus type electrodes for the determination of carbon dioxide based on pH measurement of the internal electrolyte.

In the present invention, it is further preferred that the electrolyte layer comprises a non-volatile component of the liquid electrolyte before the electrochemical sensor is put into use. For this purpose, it is possible to introduce the liquid, preferably liquid electrolyte, comprising these components, for example by dripping into the pores of the non-swellable framework structure, and, after removal of the electrolyte liquid supernatant, for example by wiping, to store it at a temperature of > 25 ℃, for example at a temperature of 65 ℃, for a period of several hours, for example for a period of 48 hours or more, in order to evaporate the volatile components of the liquid electrolyte. In this way it is possible to ensure that the electrolyte layer of the electrochemical sensor contains, after the drying step, nonvolatile components of the electrolyte, such as alkali metal chlorides, components of the pH buffer system and further substances including, in particular, water-soluble polymers or enzymes.

Alternatively, a liquid containing nonvolatile electrolyte components can be added to the mixture comprising at least one particulate material, at least one binder and optionally further substances, for example in the form of a slurry, even before the porous, non-swellable framework structure is formed. The mixture thus obtained can subsequently be hardened, so that a porous, non-swellable framework structure is formed, the pores of which contain the non-volatile constituents of the liquid electrolyte. This procedure offers the following advantages over the above-described methods, i.e. over introducing the liquid electrolyte into the pores of the pre-existing framework structure: i.e. it is possible to introduce the various components of the liquid electrolyte more easily, more homogeneously and more reproducibly into the porous, non-swellable framework structure of the sensor according to the invention.

The gas-permeable cover allows (in the standard case) the analyte in the gaseous state to penetrate into the electrochemical sensor, but prevents ionic and/or nonvolatile constituents of the aqueous measuring medium from entering the electrochemical sensor. In a preferred embodiment, the breathable cover is therefore impermeable to ionic and non-volatile components of the aqueous measurement medium.

The breathable cover may be made of any desired material that can be considered for such purposes. Preferably, the breathable cover comprises at least one polymeric material, with silicone, polysulfone and/or polytetrafluoroethylene having proven particularly advantageous. The siloxane used in the present invention may be, for example, oxime-crosslinked silicone rubber, such as that marketed under the trademark TELESCHEXANESI480 (from DELO, Germany) is available. Suitable polysulfones include, inter alia, those having longer alkyl chains such as C₁₆An alkyl chain of a polysulfone. Such products are known under the trademark BIOBLAND (from ANATRACE, USA).

The breathable cover can be produced in different ways. The preferred method consists in using a prefabricated cover layer applied to the electrochemical sensor. The membrane can in this respect be fixed to the sensor by means of any desired process, wherein adhesive bonding or laser welding is considered to be preferred.

Alternatively, the gas permeable cover film may be produced in situ by applying a solution of a suitable gas permeable polymer or prepolymer to the electrochemical sensor and subsequently dried. The polymer is preferably applied to the electrochemical sensor by spraying, dipping, dispersing or screen printing a preferably diluted solution of the polymer or prepolymer, although application is not limited to these methods. The solvents used are preferably organic solvents, in particular organic solvents having a boiling point of 100 ℃ or less, wherein, in principle, a person skilled in the art is able to select suitable solvents depending on the nature of the polymers or prepolymers used and/or the application technique.

The gas-permeable cover obtained in this way and used in the electrochemical sensor according to the invention generally has a thickness of from about 5.0 μm to about 30 μm, preferably from about 8.0 μm to about 15 μm.

The working electrode and the counter electrode of the electrochemical sensor according to the invention can be made of any desired material suitable for the purpose of the invention. The working electrode is preferably made of gold or a ruthenium oxide-based composite, the gold-based composite being particularly suitable for sensors for amperometric determination of oxygen, and the ruthenium oxide-based composite being particularly suitable for sensors for determination of carbon dioxide by means of a pH electrode potential according to the Severinghaus principle. In contrast, the counter electrode of the sensor according to the invention is preferably made of silver or a silver/silver chloride based composite material. In this respect, it has been confirmed that the silver-based composite material is particularly advantageous for the counter electrode in the sensor for measuring oxygen, while the silver/silver chloride-based composite material can be preferably used for the counter electrode in the sensor for measuring carbon dioxide. The terms "working electrode" and "measuring electrode" or the terms "counter electrode" and "reference electrode" which are used in each case mainly for galvanic or potential electrodes, for example, as customary in the art, are used synonymously in the present application.

In the case of working or measuring electrodes and in the case of counter or reference electrodes, the electrically conductive electrode material which can be prepared, for example, in the form of a paste for producing the electrode base body comprises, in addition to a metal or metal oxide, preferably also an electrically non-conductive polymer binder, particularly preferably a vinyl resin.

Preferably, the electrochemical sensor according to the invention is designed for multiple measurements of the analyte to be detected. This is particularly desirable in applications where the sensor is to be used to measure a large number of samples or to continuously, i.e. intermittently or intermittently monitor the presence and/or amount of an analyte over a longer period of time, e.g. 1 day or more, in particular 1 week or more. In a preferred embodiment, the invention accordingly provides an electrochemical sensor as a measuring cell through which a sample liquid containing a gaseous analyte flows and which is, for example, part of an analyzer.

The electrochemical sensor according to the invention can be used for determining gaseous analytes dissolved in an aqueous measuring medium which may originate from any desired source. In a preferred embodiment, the electrochemical sensor functions to measure gaseous analytes dissolved in body fluids including, but not limited to, whole blood, plasma, serum, lymph, bile, cerebrospinal fluid, extracellular tissue fluid, urine, and glandular secretions such as saliva or sweat, with whole blood, plasma, and serum being considered particularly preferred. The gaseous analyte to be qualitatively and/or quantitatively measured is preferably selected from oxygen and carbon dioxide.

In a further aspect, the invention relates to a method for manufacturing an electrochemical sensor according to the invention, comprising the steps of:

(a) at least one type of particulate material is prepared,

(b) mixing the particulate material and at least one binder, and optionally further substances,

(c) processing the mixture obtained in step (b) into a slurry,

(d) applying the slurry obtained in step (c) to a support,

(e) hardening the slurry applied to the support, wherein a porous, non-swellable framework structure is formed, and

(f) preparing an electrochemical sensor comprising the porous, non-swellable framework structure obtained in step (e) as electrolyte layer and a working electrode, a counter electrode and a gas-permeable cover.

For the manufacture of the electrochemical sensor according to the invention, at least one inorganic or organic particulate material and at least one inorganic or organic binder, each as defined above, and optionally further substances are mixed and processed to form a slurry. After applying the slurry to the carrier and subsequently hardening the slurry, a porous, non-swellable framework structure is formed which can be used as an electrolyte layer in the electrochemical sensor according to the invention. In addition to the porous electrolyte layer, the electrochemical sensor comprises a working electrode, a counter electrode and a gas permeable cover.

To carry out the above-described method, the paste can be applied to the support, for example, by means of screen printing or knife coating techniques (Rakeltec nik). Thus, in one embodiment of the invention, the carrier can, for example, comprise a working electrode and a counter electrode even before the slurry is applied. Alternatively, but also possible, the working electrode and the counter electrode are applied to the carrier after the paste has been applied and hardened. In this respect, the production method according to the invention has proven to be advantageous because the paste and the electrodes can be applied to the carrier by means of screen printing, so that a thin and defined layer thickness is possible.

Preferably the method according to the invention additionally comprises introducing a liquid, e.g. a liquid electrolyte, containing non-volatile electrolyte components into the porous, non-swellable backbone structure and subsequently evaporating the volatile components thereof. From these non-volatile components, a liquid electrolyte can be formed which ensures an electrically conductive connection between the working electrode and the counter electrode in the sensor according to the invention. In this case, the liquid can be introduced into the pores of the non-swellable framework structure using, for example, the techniques already described in the explanation of the electrochemical sensor.

Alternatively, it is possible to introduce a liquid comprising a non-volatile electrolyte component into a mixture comprising at least one particulate material and at least one binder and optionally further substances even before the formation of the porous, non-swellable backbone structure, as a result of which a homogeneous distribution of the solid components of the electrolyte in the porous, non-swellable backbone structure obtained after hardening of the mixture can be obtained in a simple manner. In a preferred embodiment of the invention, the method according to the invention comprises introducing a liquid into the slurry, which liquid may in particular be added to the slurry before applying the slurry to a suitable carrier. In this embodiment a liquid is added comprising a non-volatile electrolyte component, preferably in a solvent miscible with the binder. The solvent may for example be a glycol, such as ethylene glycol, propylene glycol or mixtures thereof, optionally may contain up to 20% (v/v) water.

In a preferred embodiment, putting into use the electrochemical sensor according to the invention additionally comprises pre-activating it using suitable measures. Activation can be caused, for example, by contacting the sensor with a suitable liquid, in particular an aqueous liquid. During this time, the liquid, in particular water, which acts as an activation sensor, for example as a result of isothermal distillation, passes through the gas-permeable cover of the electrochemical sensor and condenses in the pores of the non-swellable framework structure, dissolving the solid components of the previously introduced electrolyte liquid.

Preferably, the fluid used to activate the sensor has an osmolarity comparable or similar to the osmolarity of the electrolyte fluid absorbed in the porous, non-swellable framework structure of the sensor and includes, in particular, aqueous calibration and control fluids, such as buffer systems or salt solutions having a salt concentration of from about 100 to about 200mmol/l or an osmolarity of from about 200mosmol/l to about 500 mosmol/l. If the analyte to be determined is contained in the aqueous liquid, the sensor can also be activated, if appropriate, by means of an aqueous measuring medium.

The method can ensure long-term storage life and long-term service life of the electrochemical sensor. Alternatively, however, the invention also envisages that the electrolyte layer contains the electrolyte already in the liquid state before the electrochemical sensor is put into use.

In a further aspect, the invention relates to a method for determining a gaseous analyte dissolved in an aqueous measurement medium, comprising the following steps:

(a) bringing an aqueous measuring medium into contact with an electrochemical sensor according to the invention, and

(b) the determination of the gaseous analyte dissolved in the aqueous measuring medium is carried out by measuring the signal generated by the electrochemical sensor.

For the determination of gaseous analytes, the electrochemical sensor according to the invention can be arranged in any manner that allows contact between the electrochemical sensor and the aqueous measuring medium. Thus, the sensor can be designed, for example, as a measuring cell through which an aqueous measuring medium containing a gaseous analyte is guided. Furthermore, the sensor according to the invention and further sensors, for example, for determining different instantaneous parameters, can be embodied in exchangeable measuring chambers (sensor cassettes).

Depending on the presence and/or amount of the analyte, the sensor generates a measurable signal. Preferably the signal is an electrical signal, such as current, voltage, resistance, etc., which is evaluated or read using a suitable device. Preferably, the electrochemical sensor is a current sensor, for example in the case of an oxygen sensor, or a potential sensor, for example in the case of a carbon dioxide sensor.

The invention will be described in more detail by the following figures and examples.

Description of the invention

Fig. 1a and 1b are electron micrographs of a porous electrolyte layer in an electrochemical sensor according to the present invention.

FIG. 2 is a graph of electrochemical pO according to the invention₂A cross-section through the tunnel region in the sensor. The support (1) used is a polycarbonate-thin-film-coated plate made of an Al/Mg alloy, to which a gas barrier layer (2a) is applied which serves to reduce or completely prevent the diffusion of gases into or out of the polycarbonate layer. An insulating layer (2b) is applied to the gas barrier layer (2a) to prevent disturbing potentials/currents upon liquid contact. A window closed by a gas-permeable cover (7) is left free in the measuring region. Electrochemical pO₂The sensor itself consists of a working electrode (3), a counter electrode (5), a porous electrolyte layer (6) and a gas-permeable cover layer (7), the porous electrolyte layer (6) extending along the measuring channel and completely covering the active surfaces of the working electrode (3) and the counter electrode (5), the gas-permeable cover layer (7) in turn completely covering the porous electrolyte layer (6).

FIG. 3a is a graph of electrochemical pO according to the invention₂A longitudinal section through the working electrode in the sensor. The working electrode (3) is preferably made of a gold-based composite material additionally comprising a polymer component. The working electrode lead (4) can be extended, for example, from a thin oneAn elongate silver-based composite material, one end of which is held in planar contact with the working electrode (3), and the second end of which forms an open contact for electrical plug-in connection. The remaining reference numerals each have the meaning as indicated in fig. 2.

FIG. 3b is a graph of electrochemical pO according to the invention₂A longitudinal section through a working electrode with alternating silver bridging layers and silver/silver chloride conductors in the sensor. In this case, the only change to fig. 3a is to transfer the measurement area out to the bridging layer (2a) in the silver/silver chloride lead (4 b). The leads (4b) can be produced, for example, from a corresponding screen printing paste by means of screen printing. The remaining reference numerals each have the meaning as indicated in fig. 2.

FIG. 4 is a graph of electrochemical oxygen in accordance with the present invention₂A longitudinal section through the counter electrode in the sensor. The counter electrode (5), which can be produced, for example, by means of screen printing, is preferably made of a silver-based composite material additionally comprising a polymer component. The remaining reference numerals each have the meaning as indicated in fig. 2.

FIG. 5 is an electrochemical CO according to the invention₂A cross-section through the tunnel region in the sensor. Electrochemical CO₂The sensor itself consists of a working electrode (8) (pH sensitive measuring electrode), a bridging layer (8a), a counter electrode (reference electrode) (10), a porous electrolyte layer (11) and a gas permeable cover (7). The working or pH electrode (8) which can be produced, for example, by means of screen printing, is preferably made of a ruthenium oxide-based composite material which additionally comprises a polymer component. This layer is electrically connected out of the direct measuring region by means of a bridging layer (8a) produced, for example, from a graphite slurry. The counter electrode (10) which is designed in a layered manner is produced in particular by means of screen printing and is preferably made of a silver/silver chloride-based composite material. The remaining reference numerals each have the meaning as indicated in fig. 2.

Examples

Example 1: production of screen-printable pastes

12.0g of ethylcellulose powder N50 and 192.0g of terpineol were weighed into a closable glass and the mixture was stirred at room temperature for 2 weeks until the ethylcellulose was completely dissolved. To produce a quantity of 100g of ready-to-use screen-printable paste, 25.6g of the resulting ethylcellulose solution, 32.3g of phenolic resin PR 373, 1.0g of defoamer Byk 051 (from Byk Chemie), 5.0g of benzyl alcohol and 2.9g of butyl diglycol (Butyldigiykol) are subsequently weighed into a glass beaker and the mixture is stirred vigorously. To this mixture was added 43.2g of zeolite LZ-Y52 (from Sigma-Aldrich, product number 334448) and the batch was vigorously stirred until the filler was uniformly dispersed to obtain a screen-printable slurry.

Example 2: determination of the relative liquid absorption of the slurries produced and hardened according to example 1

To determine the relative liquid absorption of the slurries produced according to example 1, a plurality of slides (76X 26mm, ISO Standard 8038/I from Roth) (m) were weighed out on an analytical balance_{Slide glass}). The slurry produced according to example 1 was then applied to a slide by using an 80 μm spiral stripping blade (Spiralabziehrakel) to apply a test layer to the slide. The applied slurry covered a rectangular area of about 60 x 18 mm. Because the area is variable, it is accurately determined when the slurry has hardened. 10-15 minutes after the slurry is applied, the test piece is hardened in a drying oven for 4 hours at 110 ℃. Subsequently, the test pieces were stored in a desiccator (on CaO) until measurement. The slide (m) containing the hardened paste was reweighed_{Dry matter}) And thereafter in each case immediately immersed in approximately 40ml of liquid placed in a rotatable plastic tank having a volume of 100 ml. The tank containing the immersed test piece is kept closed during the measurement. At a determined point in time, the test piece is removed from the tank, gently wiped off and weighed in order to determine the amount of liquid absorbed. When the amount of absorbed liquid and thus the mass (m)_Wet) The measurement is terminated while remaining unchanged. The measurement was carried out at room temperature and atmospheric pressure. From the collected measured values, averaging the respective measured values of at least 3 test pieces with a standard deviation of at most 1%The relative liquid absorption of each test piece was calculated.

The respective relative absorption of the liquids in each case is related to the dry weight of the hardened paste (in each case the weight of the slide subtracted) determined previously in each case: (relative liquid absorption [% ])]＝[(m_Wet-m_{Slide glass})/(m_{Dry matter}-m_{Slide glass})-1]*100). The relative liquid absorption value varies according to the porosity of the hardened paste. Hardened slurries with undesirably high porosity have a relative liquid absorption in the range of 50-70%; hardened slurries with undesirably low porosity have a relative liquid absorption of less than 20%. The hardened pastes used in the present invention have a porosity that results in a relative liquid absorption of between 20% and 50% by weight, preferably between 26% and 44% by weight.

Example 3: production of sensor semifinished products with porous electrolyte layer

In order to produce a sensor semifinished product which can be used as a component of an electrochemical sensor according to the invention, the paste produced according to example 1 is applied to a screen, applied by means of screen printing to a suitable carrier comprising a working electrode and a counter electrode, and hardened at elevated temperature. The thickness of the hardened layer is 10 to 20 μm.

Example 4: will be applied to O ₂ Electrolyte introduction of sensor the sensor produced according to example 3 In the hole of the semi-finished product

For producing an electrochemical O for use in accordance with the invention₂100g of internal electrolyte of the sensor, 0.098g of Na₂HPO₄(p.a.)、0.094g KH₂PO₄(p.a.), 0.257g NaCl (p.a.), 0.060g polyethylene glycol 6000 (for synthesis), and 0.744g glycerol (p.a.) were dissolved in 98.75g deionized water to obtain a pH buffered electrolyte solution. The salt is introduced into the porous electrolyte layer by means of an excess process. For this purpose, before the introduction of the electrolyte solution,the sensor semifinished product produced according to example 3 was first stored in a container at 100% air relative humidity on deionized water for 1 h. Subsequently, an excess electrolyte solution was distributed on the porous layer of the sensor, which was opened upward, and the remainder was removed with filter paper. The sensor semifinished product treated in this way is then stored in water at 100% relative humidity of air in a closed container for such a long time that the pores of the porous layer are filled with electrolyte solution (approximately 2 h). After removing the electrolyte solution supernatant with filter paper, the sensor half-product was stored at 65 ℃ for 72h in order to evaporate the volatile components.

Example 5: will be suitable for CO ₂ Electrolyte introduction of sensor sensing produced according to example 3 In the holes of semi-finished products

For the production of electrochemical CO for use in accordance with the invention₂100g of internal electrolyte solution for the sensor, 0.252g of NaHCO₃(p.a.) and 0.559g KCl (p.a.) were dissolved in 99.04g deionized water with 0.15g carbonic anhydrase (from Serva, product number 15880). As in example 4, the electrolyte solution was introduced into the porous layer produced according to example 3 by means of an excess method.

Example 6: production is suitable for O ₂ Sensor semi-finished product with porous electrolyte layer

An alternative embodiment to examples 3 and 4 includes that the non-volatile electrolyte component in a suitable solvent has been introduced into the screen printable slurry.

To produce an electrochemical O which can be used as a catalyst according to the invention₂Sensor semi-finished product of a component of a sensor, 0.120g Na₂HPO₄(p.a.)、0.110g KH₂PO₄(p.a.), 0.310g NaCl (p.a.), and 0.066g polyethylene glycol 6000 (for use in the synthesis ofTo) was dissolved in 1.6g of deionized water. The solution obtained in this way was subsequently mixed with a solution of 0.900g of glycerol (p.a.) in 23.15g of ethylene glycol and stirred until a clear solution was obtained.

To produce a sensor semifinished product, 4.2g of an aqueous ethylene glycol solution are stirred into 100g of the paste produced according to example 1, whereupon the paste containing the liquid electrolyte is applied to a suitable carrier by means of screen printing and hardened at elevated temperature. No subsequent dispersing step is required.

Example 7: production is suitable for CO ₂ Sensor and sensor half-finished product with porous electrolyte layer Article (A)

An alternative embodiment to examples 3 and 5 includes that the non-volatile electrolyte component in a suitable solvent has been introduced into the screen printable slurry.

To produce electrochemical CO which can be used as per the invention₂Sensor semi-finished product of a component of a sensor, 0.150g Na₂CO₃(p.a.) and 0.250g KCl (p.a.) were dissolved in 1.6g deionized water. The solution was then mixed with 8g of ethylene glycol and stirred until a clear solution was obtained.

To produce a sensor semifinished product, 2.69g of an aqueous ethylene glycol solution are stirred into 100g of the paste produced according to example 1, whereupon the paste containing the liquid electrolyte is applied to a suitable carrier by means of screen printing and hardened at elevated temperature. No subsequent dispersing step is required.

Example 8: application of a gas-permeable coating to a sensor semi-finished product produced in accordance with one of embodiments 4 to 7 Cover sheet and sensor board for packaging the same

A cover layer was applied to the sensor semifinished product produced according to one of embodiments 4 to 7 by means of screen printing. For this purpose, the oxime-decomposing silicone is applied to the sensor semifinished product by means of screen printing and hardened at elevated temperature. The thickness of the hardened layer was about 10 μm. The sensor plate obtained in this way is then packaged in a suitable container in an airtight manner for storage until use.

Claims (44)

1. Electrochemical sensor for determining a gaseous analyte dissolved in an aqueous measuring medium, comprising:

(a) a working electrode and a counter electrode,

(b) an electrolyte layer disposed between the working electrode and the counter electrode,

(c) a gas-permeable cover for spatially separating the working electrode, the counter electrode and the electrolyte layer from an aqueous measurement medium,

characterized in that the electrolyte layer comprises at least one particulate material and at least one binder, which together form a porous, non-swellable framework structure, wherein the pores in the non-swellable framework structure are provided to absorb or contain a liquid electrolyte.

2. Electrochemical sensor according to claim 1, characterized in that the particulate material is an inorganic particulate material selected from the group consisting of Controlled Pore Glass (CPG), silica gel, silicates and aluminosilicates.

3. An electrochemical sensor according to claim 1 or claim 2, characterized in that the particulate material is a naturally occurring or synthetic aluminosilicate.

4. Electrochemical sensor according to claim 1 or 2, characterized in that the particulate material has pores, and optionally ion exchanger groups.

5. Electrochemical sensor according to claim 1 or 2, characterized in that the particulate material is a zeolite.

6. Electrochemical sensor according to claim 1 or 2, characterized in that the particles of the particulate material have an average particle size of from about 0.1 μm to about 10 μm.

7. Electrochemical sensor according to claim 1 or 2, characterized in that the binder is an organic binder.

8. Electrochemical sensor according to claim 7, characterized in that the organic binder comprises a crosslinked or uncrosslinked synthetic polymer.

9. Electrochemical sensor according to claim 8, characterized in that the crosslinked or uncrosslinked synthetic polymer is a compound selected from the group consisting of phenolic resins, epoxy resins, vinyl resins, PVC copolymers, two-component epoxy resins, polyurethane resin systems and UV curable polyacrylate monomer mixtures.

10. Electrochemical sensor according to claim 1 or 2, characterized in that the pores of the non-swellable backbone structure have a diameter of from about 500nm to about 5 μm.

11. Electrochemical sensor according to claim 1 or 2, characterized in that the porous, non-swellable backbone structure results in a relative liquid uptake of from about 20 to about 50 wt. -%, based on the dry weight of the porous, non-swellable backbone structure.

12. Electrochemical sensor according to claim 1 or 2, characterized in that the electrolyte layer has a thickness of from about 5 μm to about 30 μm.

13. Electrochemical sensor according to claim 1 or 2, characterized in that the liquid electrolyte comprises an alkali chloride and a pH buffer system.

14. Electrochemical sensor according to claim 13, characterized in that the liquid electrolyte additionally comprises a water-soluble polymer.

15. Electrochemical sensor according to claim 13, characterized in that the liquid electrolyte additionally comprises an enzyme.

16. An electrochemical sensor according to claim 1 or 2, characterized in that the electrolyte layer comprises the non-volatile components of the liquid electrolyte before the sensor is put into use.

17. An electrochemical sensor according to claim 1 or 2, characterized in that the gas-permeable cover is impermeable to ionic and non-volatile components of the aqueous measuring medium.

18. Electrochemical sensor according to claim 1 or 2, characterized in that the gas-permeable cover comprises silicone, polysulfone and/or polytetrafluoroethylene.

19. Electrochemical sensor according to claim 1 or 2, characterized in that the gas-permeable cover has a thickness of from about 5.0 μm to about 30 μm.

20. Electrochemical sensor according to claim 1 or 2, characterized in that the working electrode is made of gold or ruthenium oxide based composite.

21. Electrochemical sensor according to claim 1 or 2, characterized in that the counter electrode is made of silver or a silver/silver chloride based composite.

22. Electrochemical sensor according to claim 1 or 2, characterized in that it is designed for multiple determination of a gaseous analyte dissolved in an aqueous measuring medium.

23. An electrochemical sensor according to claim 1 or 2 for the determination of a gaseous analyte in a body fluid.

24. An electrochemical sensor according to claim 1 or 2 for measuring oxygen.

25. An electrochemical sensor according to claim 1 or 2, for the determination of carbon dioxide.

26. An electrochemical sensor according to claim 1 or claim 2, characterized in that the particulate material is a synthetic aluminosilicate.

27. Electrochemical sensor according to claim 1 or 2, characterized in that the particulate material has pores with a diameter of about 0.1nm to about 10nm, and optionally ion exchanger groups.

28. Electrochemical sensor according to claim 1 or 2, characterized in that the particulate material is faujasite.

29. Electrochemical sensor according to claim 1 or 2, characterized in that the particles of the particulate material have an average particle size of from about 1.0 μm to about 5.0 μm.

30. Electrochemical sensor according to claim 8, characterized in that the crosslinked or uncrosslinked synthetic polymer is a phenolic resin.

31. Electrochemical sensor according to claim 1 or 2, characterized in that the pores of the non-swellable backbone structure have a diameter of from about 1 μm to about 3 μm.

32. Electrochemical sensor according to claim 1 or 2, characterized in that the porous, non-swellable backbone structure results in a relative liquid uptake of from about 26 to about 44 wt. -%, based on the dry weight of the porous, non-swellable backbone structure.

33. Electrochemical sensor according to claim 1 or 2, characterized in that the electrolyte layer has a thickness of from about 10 μm to about 20 μm.

34. Electrochemical sensor according to claim 13, characterized in that the liquid electrolyte additionally comprises polyethylene glycol and/or polyvinylpyrrolidone.

35. Electrochemical sensor according to claim 13, characterized in that the liquid electrolyte additionally comprises carbonic anhydrase.

36. Electrochemical sensor according to claim 1 or 2, characterized in that the gas-permeable cover has a thickness of from about 8.0 μm to about 15 μm.

37. An electrochemical sensor according to claim 1 or 2 for the determination of gaseous analytes in whole blood, plasma or serum.

38. A method for manufacturing an electrochemical sensor according to any one of claims 1 to 37, comprising the steps of:

(a) at least one type of particulate material is prepared,

(b) mixing the particulate material and at least one binder and optionally further substances,

(c) processing the mixture obtained in step (b) into a slurry,

(d) applying the slurry obtained in step (c) to a support,

(e) hardening the slurry applied to the support to form a porous, non-swellable skeletal structure, and

(f) preparing an electrochemical sensor comprising the porous, non-swellable framework structure obtained in step (e) as electrolyte layer and a working electrode, a counter electrode and a gas-permeable cover.

39. Method according to claim 38, characterized in that it additionally comprises introducing a liquid containing non-volatile electrolyte components into the porous, non-swellable backbone structure and subsequently evaporating the volatile components of the liquid.

40. The method according to claim 38, characterized in that it additionally comprises introducing a liquid containing non-volatile electrolyte components into the slurry obtained in step (c).

41. A method according to claim 39 or claim 40, characterized in that it additionally comprises activating the electrochemical sensor, wherein activation is caused by contacting the electrochemical sensor with a liquid.

42. A method according to claim 41, characterized in that the liquid has an osmotic pressure comparable to the osmotic pressure of the absorbed liquid electrolyte in the porous, non-swellable skeletal structure.

43. A method according to claim 39 or claim 40, characterised in that it additionally comprises activating the electrochemical sensor, wherein activation is caused by contacting the electrochemical sensor with an aqueous liquid.

44. Method for determining a gas analyte dissolved in an aqueous measuring medium, comprising the following steps:

(a) contacting an aqueous measurement medium with an electrochemical sensor according to any one of claims 1 to 37, and

(b) the determination of the gaseous analyte dissolved in the aqueous measuring medium is carried out by measuring the signal generated by the electrochemical sensor.