WO2008009951A1

WO2008009951A1 - Electrochemical gas sensor comprising mesoporous layer between working and counter electrodes

Info

Publication number: WO2008009951A1
Application number: PCT/GB2007/002748
Authority: WO
Inventors: Mark Varney; Michael Garrett
Original assignee: Anaxsys Technology Limited
Priority date: 2006-07-21
Filing date: 2007-07-18
Publication date: 2008-01-24
Also published as: GB0614505D0; GB2440750A; GB2440750B

Abstract

A sensor for sensing a target substance in a gas stream is provided, the sensor comprising a sensing element disposed to be exposed to the gas stream, the sensing element comprising a working electrode; a counter electrode; and a layer of mesoporous material extending between the working electrode and the counter electrode; whereby contact of the mesoporous layer with the gas stream forms an electrical contact between the working and counter electrodes.

Description

ELECTROCHEMICAL GAS SENSOR COMPRISING MESOPOROUS LAYER BETWEEN WORKING AND COUNTER ELECTRODES

The present invention is related to a sensor for detecting gaseous substances, in particular a sensor for detecting the presence of substances in a gaseous phase or gas stream. The sensor is particularly suitable for, but not limited to, the detection of carbon dioxide. The sensor finds particular use as a capnographic sensor for detecting and measuring the concentration of gases, such as carbon dioxide, in the exhaled breath of a person or animal. The sensor may also be used to determine the moisture content or humidity of a gas stream, for example a stream of exhaled breath.

The analysis of the carbon dioxide content of the exhaled breath of a person or animal is a valuable tool in assessing the health of the subject. In particular, measurement of the carbon dioxide concentration allows the extent and/or progress of various pulmonary and/or respiratory diseases to be estimated, in particular asthma and chronic obstructive lung disease (COPD).

Carbon dioxide can be detected using a variety of analytical techniques and instruments. The most practical and widely used analysers use spectroscopic infra-red absorption as a method of detection, but the gas may also be detected using mass spectrometry, gas chromatography, thermal conductivity and others. Although most analytical instruments, techniques and sensors for carbon dioxide measurement are based on the physicochemical properties of the gas, new techniques are being developed which utilise electrochemistry, and an assortment of electrochemical methods have been proposed. However, it has not been possible to measure carbon dioxide (CO₂) gas directly using electrochemical techniques. Indirect methods have been devised, based on the dissolution of the gas into an electrolyte with a consequent change in the pH of the electrolyte. Other electrochemical methods use high temperature catalytic reduction of carbon dioxide. However, these methods are generally very expensive, cumbersome to employ and often display very low sensitivities and slow response times. These drawbacks render them inadequate for analyzing breath samples, in particular in the analysis of tidal breathing.

A more recently applied technique is to monitor a specific chemical reaction in an electrolyte that contains suitable organometallic ligands that chemically interact following the pH change induced by the dissolution of the carbon dioxide gas. The pH change then disturbs a series of reactions, and the carbon dioxide concentration in the atmosphere is then estimated indirectly according to the change in the acid-base chemistry.

Carbon dioxide is an acid gas, and interacts with water, and other (protic) solvents. For example, carbon dioxide dissolves in an aqueous solution according to the following reactions:

CO₂ + H₂O <r> H₂CO₃ (1)

H₂CO₃ «• HCO₃ ^" + H⁺ (2)

HCO₃- <=> CO₃ ^2- + H⁺ (³) f

It will be appreciated that, as more carbon dioxide dissolves, the concentration of hydrogen ions (H⁺) increases.

The use of this technique for sensing carbon dioxide has the disadvantage that when used for gas analysis in the gaseous phase the liquid electrolyte must be bounded by a semi-permeable membrane. The membrane is impermeable to water but permeable to various gases, including carbon dioxide. The membrane must reduce the evaporation of the internal electrolyte without seriously impeding the permeation of the carbon dioxide gas. The result of this construction is an electrode which works well for a short period of time, but has a long response time and in which the electrolyte needs to be frequently renewed. WO 04/001407 discloses a sensor comprising a liquid electrolyte retained by a permeable membrane, which overcomes some of these disadvantages. However, it would be very desirable to provide a sensor that does not rely on the presence and maintenance of a liquid electrolyte.

US 4,772,863 discloses a sensor for oxygen and carbon dioxide gases having a plurality of layers comprising an alumina substrate, a reference electrode source of anions, a lower electrical reference electrode of platinum coupled to the reference source of anions, a solid electrolyte containing tungsten and coupled to the lower reference electrode, a buffer layer for preventing the flow of platinum ions into the solid electrolyte and an upper electrode of catalytic platinum.

GB 2,287,543 A discloses a solid electrolyte carbon monoxide sensor having a first cavity formed in a substrate, communicating with a second cavity in which a carbon monoxide adsorbent is located. An electrode detects the partial pressure of oxygen in the carbon monoxide adsorbent. The sensor of GB 2,287,543 is very sensitive to the prevailing temperature and is only able to measure low concentrations of carbon monoxide at low temperatures with any sensitivity. High temperatures are necessary in order to measure carbon monoxide concentrations that are higher, if complete saturation of the sensor is to be avoided. This renders the sensor impractical for measuring gas compositions over a wide range of concentrations.

GB 2,316,178 A discloses a solid electrolyte gas sensor, in which a reference electrode is mounted within a cavity in the electrolyte. A gas sensitive electrode is provided on the outside of the solid electrolyte. The sensor is said to be useful in the detection of carbon dioxide and sulphur dioxide. However, operation of the sensor requires heating to a temperature of at least 200°C, more preferably from 300 to 400°C. This represents a major drawback in the practical applications of the sensor. Sensors for use in monitoring gas compositions in heat treatment processes are disclosed in GB 2,184,549 A. However, as with the sensors of GB 2,316,178, operation at high temperatures (up to 600°C) is disclosed and appears to be required.

Accordingly, there is a need for a sensor that does not rely on the presence of an electrolyte in the liquid phase or high temperature catalytic method, that is of simple construction and may be readily applied to monitor gas compositions at ambient conditions.

EP 0 293 230 discloses a sensor for detecting acidic gases, for example carbon dioxide. The sensor comprises a sensing electrode and a counter electrode in a body of electrolyte. The electrolyte is a solid complex having ligands that may be displaced by the acidic gas. A similar sensor arrangement is disclosed in US 6,454,923.

A particularly effective sensor is disclosed in pending international application

No. PCT/GB2005/003196. The sensor comprises a sensing element disposed to be exposed to the gas stream, the sensing element comprising a working electrode; a counter electrode; and a solid electrolyte precursor extending between and in contact with the working electrode and the counter electrode; whereby the gas stream may be caused to impinge upon the solid electrolyte precursor such that water vapour in the gas stream at least partially hydrates the precursor to form an electrolyte in electrical contact with the working electrode and the counter electrode.

It has been found that, while the sensor of PCT/GB2005/003196 is an efficient sensor, its performance can be improved by the appropriate selection of the material used to provide the coating extending between the electrodes. In particular, is has been found that an improved performance and response of the sensor may be obtained by having a layer of mesoporous material extending between the electrodes, such that when the sensor is exposed to a gas stream containing water vapour an electrical contact is established by the mesoporous material between the electrodes. Such a sensor can provide an improved indication of the lung function of a patient or subject and assist in the ready examination of a patient and diagnosis of abnormalities in the operation and performance of the lungs and respiratory system.

According to the present invention there is provided a sensor for sensing a target substance in a gas stream, the sensor comprising: a sensing element disposed to be exposed to the gas stream, the sensing element comprising: a working electrode; a counter electrode; and a layer of mesoporous material extending between the working electrode and the counter electrode; whereby contact of the mesoporous layer with the gas stream forms an electrical contact between the working and counter electrodes..

In the present specification, references to a mesoporous material are to a material having pores in the range of from 1 to 75 nm, more particularly in the range of from 2 to 50 nm. The mesoporous material acts as the support medium for electrical conduction to occur, as it allows a temporary hydrated ionic layer to form across the electrodes. The layer of mesoporous material provides a medium that is highly controllable and hydrates uniformly to provide a suitable medium for conduction to occur.

Suitable mesporous materials for use in the sensor of the present invention include metal oxides, in particular oxides of metals from Group IV of the Periodic Table of the Elements, in particular oxides of titanium or zirconium. A particularly preferred metal oxide is titanium oxide, including the titanates, Alternative mesoporous materials of use are synthetic clays, of particular preference due to the inherent layered nature of the clays. Laponite is a synthetic layered silicate with a structure resembling that of the natural clay mineral, hectonite. When added to water with stirring it will disperse rapidly into nanoparticles. It is cost effective, heat stable, thixotropic and can retain levels of hydration. Laponite is of special interest because of its single ion conducting character, where concentration polarization can be minimised. Hydrotalcite-like compounds are known also as layered double hydroxides or anionic clays. These compounds have a layered crystal structure composed of positively charged hydroxide layers and interlayers containing anions and water molecules. These compounds exhibit anion-exchange properties and can recover the layered crystal structure during rehydration.

The mesoporous material may be present in the sensor in the dry state, in which case the material will require the addition of water, for example as water vapour present in the gas stream. Alternatively, the mesoporous material may be present with water in a saturated or partially-saturated state, in which case a dry gas stream may be analysed. In such a case, the output of the sensor will change in response to a change in the conductance of the mesoporous material, due to the dissolution of ions in the water present.

The thickness of the mesoporous material will determine the response of the sensor to changes in the composition of the gas stream in contact with the mesoporous layer. To minimize internal resistance within the sensor, it is preferred to use an ultra thin mesoporous layer.

The mesoporous material may comprise a binder, in particular a conductive

(ion exchanger type) binder. Suitable conductive binders include ionomers, a class of synthetic polymers with ionic properties. A particularly preferred group of ionomers are the sulphonated tetrafluoroethylene copolymers. An especially preferred ionomer from this class is Nafion ®, available commercially from Du Pont. The sulphonated tetrafluroethylene copolymers have superior conductive properties due to their proton conducting capabilities. The pores in the mesoporous material allow movement of cations but the membranes do not conduct anions or electrons. The sulphonated tetrafluroethylene copolymers can be manufactured with various cationic conductivities. They also exhibit excellent thermal and mechanical stability and are biocompatible, thus making them suitable materials for use in the controlled electrode coating. The sensor is particularly suitable for the detection of carbon dioxide, in particular carbon dioxide present in the exhaled breath of a person or animal. The sensor is also particularly suitable for the detection of water vapour in the exhaled breath of a person or animal, which may in turn be used to reliably determine the concentration of carbon dioxide in the exhaled breath. In this case, the water vapour present in the gas stream being analysed, in particular exhaled breath, is caused to condense on the mesoporous coating, in turn changing the conductivity of the coating, thereby allowing an accurate measurement of the concentration of water vapour to be obtained.

In addition, the sensor provides a fast and accurate response to changes in the composition of the gas stream being analysed. These features make the sensor of the present invention particularly suitable for use as a capnographic sensor in the analysis of exhaled breath of a subject.

The present invention provides a sensor that is particularly compact and of very simple construction. In addition, the sensor may be used at ambient temperature conditions, without the need for any heating or cooling, while at the same time producing an accurate measurement of the target substance concentration in the gas being analysed.

The sensor preferably comprises a housing or other protective body to enclose and protect the electrodes. The sensor may comprise a passage or conduit to direct the stream of gas directly onto the electrodes. In a very simple arrangement, the sensor comprises a conduit or tube into which the two electrodes extend, so as to be contacted directly by the gaseous stream passing through the conduit or tube. When the sensor is intended for use in the analysis of the breath of a patient, the conduit may comprise a mouthpiece, into which the patient may exhale. Alternatively, the sensor may be formed to have the electrodes in an exposed position on or in the housing, for direct measurement of a bulk gas stream. The precise form of the housing, passage or conduit is not critical to the operation or performance of the sensor and may take any desired form. It is preferred that the body or housing of the sensor is prepared from a non-conductive material, such as a suitable plastic.

As noted above, in one embodiment, the sensor relies upon the presence of water vapour in the gaseous stream being analysed to hydrate the mesoporous layer. If insufficient water vapour is present in the gaseous stream, the sensor may be provided with a means for increasing the water vapour content of the gas stream. Such means may include a reservoir of water and a dispenser, such as a spray, nebuliser or aerosol. When analyzing the exhaled breath of a human or animal, water vapour will be present in the gas stream, which is caused to condense onto the mesoporous layer, as described hereinbefore.

The electrodes may have any suitable shape and configuration. Suitable forms of electrode include points, lines, rings and flat planar surfaces. The effectiveness of the sensor can depend upon the particular arrangement of the electrodes and may be enhanced in certain embodiments by having a very small path length between the adjacent electrodes. This may be achieved, for example, by having each of the working and counter electrodes comprise a plurality of electrode portions arranged in an alternating, interlocking pattern, that is in the form of an array of interdigitated electrode portions, in particular arranged in a concentric pattern.

The electrodes are preferably oriented as close as possible to each other, to within the resolution of the manufacturing technology. The working and counter electrode can be between 10 to 1000 microns in width, preferably from 50 to 500 microns. The gap between the working and counter electrodes can be between 20 and 1000 microns, more preferably from 50 to 500 microns. The optimum track-gap distances are found by routine experiment for the particular electrode material, geometry, configuration, and substrate under consideration. In a preferred embodiment the optimum working electrode track widths are from 50 to 250 microns, preferably about 100 microns, and the counter electrode track widths are from 50 to 750 microns, preferably about 500 microns. The gaps between the working and counter electrodes are preferably about 100 microns.

The counter electrode and working electrode may be of equal size. However, in one preferred embodiment, the surface area of the counter electrode is greater than that of the working electrode to avoid restriction of the current transfer. Preferably, the counter electrode has a surface area at least twice that of the working electrode. Higher ratios of the surface area of the counter electrode and working electrode, such as at least 3:1, preferably at least 5 : 1 and up to 10:1 may also be employed. The thickness of the electrodes is determined by the manufacturing technology, but has no direct influence on the electrochemistry. The magnitude of the resultant electrochemical signal is determined principally by exposed surface area, that is the surface area of the electrodes directly exposed to and in contact with the gaseous stream. Generally, an increase in the surface area of the electrodes will result in a higher signal, but may also result in increased susceptibility to noise and electrical interference. However, the signals from smaller electrodes may be more difficult to detect.

The electrodes may be supported on a substrate. Suitable materials for the support substrate are any inert, non-conducting material, for example ceramic, plastic, or glass. The substrate provides support for the electrodes and serves to keep them in their proper orientation. Accordingly, the substrate may be any suitable supporting medium. It is important that the substrate is non-conducting, that is electrically insulating or of a sufficiently high dielectric coefficient.

The electrodes may be disposed on the surface of the substrate, with the layer of mesoporous material extending over the electrodes and substrate surface. Alternatively, the mesoporous material may be applied directly to the substrate, with the electrodes being disposed on the surface of the mesoporous layer. This would have the advantage of providing mechanical strength and a thin layer of base giving greater control of path length.

The mesoporous material is conveniently applied to the surface of the substrate by evaporation from a suspension or solution in water or other solvent.

To improve the electrical insulation of the electrodes, the portions of the electrodes that are not disposed to be in contact with the gaseous stream (that is the non-operational portions of the electrodes) may be coated with a dielectric material, patterned in such a way as to leave exposed the active portions of the electrodes.

While the sensor operates well with two electrodes, as hereinbefore described, arrangements with more than two electrodes, for example including a third or reference electrode, as is well known in the art. The use of a reference electrode provides for better potentiostatic control of the applied voltage, or the galvanostatic control of current, when the "iR drop" between the counter and working electrodes is substantial. Dual 2-electrode and 3 -electrode cells may also be employed.

A further electrode, disposed between the counter and working electrodes, may also be employed. The temperature of the gas stream may be calculated by measuring the end-to-end resistance of the electrode. Such techniques are known in the art.

The electrodes may comprise any suitable metal or alloy of metals, with the proviso that the electrode does not react with the electrolyte or any of the substances present in the gas stream. Preference is given to metals in Group VIII of the Periodic Table of the Elements (as provided in the Handbook of Chemistry and Physics, 62^nd edition, 1981 to 1982, Chemical Rubber Company). Preferred Group VIII metals are rhenium, palladium and platinum. Other suitable metals include silver and gold. Preferably, each electrode is prepared from gold or platinum. Carbon or carbon- containing materials may also be used to form the electrodes. The electrodes of the sensor of the present invention may be formed by printing the electrode material in the form of a thick film screen printing ink onto the substrate. The ink consists of four components, namely the functional component, a binder, a vehicle and one or more modifiers. In the case of the present invention, the functional component forms the conductive component of the electrode and comprises a powder of one or more of the aforementioned metals used to form the electrode.

The binder holds the ink to the substrate and merges with the substrate during high temperature firing. The vehicle acts as the carrier for the powders and comprises both volatile components, such as solvents and non- volatile components, such as polymers. These materials evaporate during the early stages of drying and firing respectively. The modifiers comprise small amounts of additives, which are active in controlling the behaviour of the inks before and after processing.

Screen printing requires the ink viscosity to be controlled within limits determined by rheological properties, such as the amount of vehicle components and powders in the ink, as well as aspects of the environment, such as ambient temperature.

The printing screen may be prepared by stretching stainless steel wire mesh cloth across the screen frame, while maintaining high tension. An emulsion is then spread over the entire mesh, filling all open areas of the mesh. A common practice is to add an excess of the emulsion to the mesh. The area to be screen printed is then patterned on the screen using the desired electrode design template.

The squeegee is used to spread the ink over the screen. The shearing action of the squeegee results in a reduction in the viscosity of the ink, allowing the ink to pass through the patterned areas onto the substrate. The screen peels away as the squeegee passes. The ink viscosity recovers to its original state and results in a well defined print. The screen mesh is critical when determining the desired thick film print thickness, and hence the thickness of the completed electrodes.

The mechanical limit to downward travel of the squeegee (downstop) should be set to allow the limit of print stroke to be 75 - 125um below the substrate surface. This will allow a consistent print thickness to be achieved across the substrate whilst simultaneously protecting the screen mesh from distortion and possible plastic deformation due to excessive pressure.

To determine the print thickness the following equation can be used:

Tw = (Tm x Ao) + Te

Where Tw = Wet thickness (um); Tm = mesh weave thickness (um);

Ao = % open area; Te = Emulsion thickness (um).

After the printing process the sensor element needs to be levelled before firing. The levelling permits mesh marks to fill and some of the more volatile solvents to evaporate slowly at room temperature. If all of the solvent is not removed in this drying process, the remaining amount may cause problems in the firing process by polluting the atmosphere surrounding the sensor element. Most of the solvents used in thick film technology can be completely removed in an oven at 150 °C when held there for 10 minutes.

Firing is typically accomplished in a belt furnace. Firing temperatures vary according to the ink chemistry. Most commercially available systems fire at 850 ⁰C peak for 10 minutes. Total furnace time is 30 to 45 minutes, including the time taken to heat the furnace and cool to room temperature. Purity of the firing atmosphere is critical to successful processing. The air should be clean of particulates, hydrocarbons, halogen-containing vapours and water vapour.

Alternative techniques for preparing the electrodes and applying them to the substrate, if present, include spin/sputter coating and visible/ultraviolet/laser photolithography. In order to avoid impurities being present in the electrodes, which may alter the electrochemical performance of the sensor, the electrodes may be prepared by electrochemical plating. In particular, each electrode may be comprised of a plurality of layers applied by different techniques, with the lower layers be prepared using one of the aforementioned techniques, such as printing, and the uppermost or outer layer or layers being applied by electrochemical plating using a pure electrode material, such as a pure metal.

In use, the sensor is able to operate over a wide range of temperatures. However, the need for water vapour to be present in the gaseous stream be analysed requires the sensor to be at a temperature above the freezing point of water and above the dew point. The sensor may be provided with a heating means in order to raise the temperature of the gas stream, if required.

In a further aspect, the present invention provides a method of sensing a target substance in a gas stream comprising water vapour, the method comprising: causing the gas stream to impinge on a layer of mesoporous material extending between a working electrode and a counter electrode; applying an electric potential across the working electrode and counter electrode; measuring the current flowing between the working electrode and counter electrode as a result of the applied potential; and determining from the measured current flow an indication of the concentration of the target substance in the gas stream. The target substance in the gas stream may be a component, such as an acidic component, present in addition to water vapour. Alternatively, the target substance may be water vapour itself, in which case the sensor is used to determine the moisture content or humidity of the gas stream.

As noted above, the method of the present invention is particularly suitable for use in the detection of carbon dioxide in a gas stream, in particular in the exhaled breath of a human or animal subject.

During operation, the impedance between the counter and working electrodes indicates the relative humidity and, if being measured, the target substance content of the gaseous stream, which may be electronically measured by a variety of techniques.

The method of the present invention may be carried out using a sensor as hereinbefore described.

Should the gas stream contain too little water vapour for operation, additional water may be added to the gas before contact with the electrodes takes place.

The method requires that an electric potential is applied across the electrodes.

In one simple configuration, a voltage is applied to the counter electrode, while the working electrode is connected to earth (grounded). In its simplest form, the method applies a single, constant potential difference across the working and counter electrodes. Alternatively, the potential difference may be varied against time, for example being pulsed or swept between a series of potentials. In one embodiment, the electric potential is pulsed between a so-called 'rest' potential, at which no reaction occurs, and a reaction potential.

In operation, a linear potential scan, multiple voltage steps or one discrete potential pulse are applied to the working electrode, and the resultant Faradaic reduction current is monitored as a direct function of the dissolution of target molecules in the water bridging the electrodes.

The measured current in the sensor element is usually small. The current is converted to a voltage using a resistor, R. As a result of the small current flow, careful attention to electronic design and detail may be necessary. In particular, special "guarding" techniques may be employed. Ground loops need to be avoided in the system. This can be achieved using techniques known in the art.

The current that passes between the counter and working electrodes is converted to a voltage and recorded as a function of the carbon dioxide concentration in the gaseous stream. The sensor responds faster by pulsing the potential between two voltages, a technique known in the art as 'Square Wave Voltammetry¹. Measuring the response several times during a pulse may be used to assess the impedance of the sensor.

The shape of the transient response can be simply related to the electrical characteristics (impedance) of the sensor in terms of simple electronic resistance and capacitance elements. By careful analysis of the shape, the individual contributions of resistance and capacitance may be calculated. Such mathematical techniques are well known in the art. Capacitance is an unwanted noisy component resulting from electronic artifacts, such as charging, etc. The capacitive signal can be reduced by selection of the design and layout of the electrodes in the sensor. Increasing the surface area of the electrodes and increasing the distance between the electrodes are two major parameters that affect the resultant capacitance. The desired Faradaic signal resulting from the passage of current due to reaction between the electrodes may be optimized, by experiment. Measurement of the response at increasing periods within the pulse is one technique that can preferentially select between the capacitive and Faradaic components, for instance. Such practical techniques are well known in the art. The potential difference applied to the electrodes of the sensor element may be alternately or be periodically pulsed between a rest potential and a reaction potential, as noted above. Figure 1 shows examples of voltage waveforms that may be applied. Figure Ia is a representation of a pulsed voltage signal, alternating between a rest potential, V₀, and a reaction potential V_R. The voltage may be pulsed at a range of frequencies, typically from sub-Hertz frequencies, that is from 0.1 Hz, up to 1OkHz. A preferred pulse frequency is in the range of from 1 to 500 Hz. Alternatively, the potential waveform applied to the counter electrode may consist of a "swept" series of frequencies, represented in Figure Ib. A further alternative waveform shown in Figure Ic is a so-called "white noise" set of frequencies. The complex frequency response obtained from such a waveform will have to be deconvoluted after signal acquisition using techniques such as Fourier Transform analysis. Again, such techniques are known in the art.

One preferred voltage regime is OV ("rest" potential), 25OmV ("reaction" potential), and 20Hz pulse frequency.

It is an advantage of the present invention that the electrochemical reaction potential is approximately +0.2 volts, which avoids many if not all of the possible competing reactions that would interfere with the measurements, such as the reduction of metal ions and the dissolution of oxygen.

The method of the present invention is particularly suitable for use in the analysis of the exhaled breath of a person or animal. From the results of this analysis, an indication of the respiratory condition of the patient may be obtained.

Accordingly, in a further aspect, the present invention provides a method of measuring the concentration of a target substance in the exhaled breath of a subject, such as a human or animal, the method comprising: causing the exhaled breath to impinge on a layer of mesoporous material extending between a working electrode and a counter electrode; applying an electric potential across the working electrode and counter electrode; measuring the current flowing between the working electrode and counter electrode as a result of the applied potential; and determining from the measured current flow an indication of the concentration of a target substance in the exhaled breath stream.

The gas exhaled by a person or animal is often saturated in water vapour, as a result of the action of the gas exchange mechanisms taking place in the lungs of the subject. The sensor may be used to measure and monitor the water-content of the exhaled breath of a subject human or animal.

The sensor and method of the present invention are of use in monitoring and determining the lung function of a patient or subject. The method and sensor are particularly suitable for analyzing tidal concentrations of substances, such as carbon dioxide, in the exhaled breath of a person or animal, to diagnose or monitor a variety of respiratory conditions. The sensor is particularly useful for applications requiring fast response times, for example personal respiratory monitoring of tidal breathing (capnography). Capno graphic measurements can be applied generally in the field of respiratory medicine, airway diseases, both restrictive and obstructive, airway tract disease management, and airway inflammation. The present invention finds particular application in the field of capnography and asthma diagnosis, monitoring and management, where the shape of the capnogram changes as a function of the extent of the disease. In particular, due to the high rate of response that may be achieved using the sensor and method of the present invention, the results may be used to provide an early alert to the onset of an asthma attack in an asthmatic patient.

Measuring the percentage saturation and variation of water vapour in the exhaled breath of a subject or animal may also be used in the diagnosis of Adult Respiratory Distress Syndrome (ARDS), an end-stage life-threatening lung disease. ARDS is characterized by pulmonary intersititial oedema. In a subject in good health, there is normally a steady state distribution of water between blood and tissues in the lung. The outward filtration of water (due to positive transcapillary hydrostatic pressure) is balanced by re-absorption from the insterstitium (by lymphatic drainage). ARDS upsets this balance. There are a number of phases to the disease, but increased capillary permeability commonly causes accumulation of water in the lungs.

Therefore, monitoring the amount and variation in the water exhaled by a patient may be useful in the diagnosis and management of ARDS.

Embodiments of the present invention will now be described, by way of example only, having reference to the accompanying drawings, in which:

Figures Ia, Ib and Ic are voltage versus time representations of possible voltage waveforms that may be applied to the electrodes in the method of the present invention, as discussed hereinbefore;

Figure 2 is a cross-sectional representation of one embodiment of the sensor of the present invention;

Figure 3 is an isometric schematic view of a face of one embodiment of the sensor element according to the present invention;

Figure 4 is an isometric schematic view of an alternative embodiment of the sensor element of the sensor of the present invention;

Figure 5 is a schematic view of a potentiostat electronic circuit that may be used to excite the electrodes of the sensor element;

Figure 6 is a schematic view of a galvanostat electronic circuit that may be used to excite the electrodes; Figure 7 is a schematic representation of a breathing tube adaptor for use in the sensor of the present invention; and

Figure 8 is a flow-diagram providing an overview of the inter-connection of sensor elements and their connection into a suitable measuring instrument of an embodiment of the present invention;

Referring to Figure 2, there is shown a sensor according to the present invention. The sensor is for analyzing the carbon dioxide content and humidity of exhaled breath. The sensor, generally indicated as 2, comprises a conduit 4, through which a stream of exhaled breath may be passed. The conduit 4 comprises a mouthpiece 6, into which the patient may breathe.

A sensing element, generally indicated as 8, is located within the conduit 4, such that a stream of gas passing through the conduit from the mouthpiece 6 is caused to impinge upon the sensing element 8. The sensing element 8 comprises a support substrate 10 of an inert material, onto which is mounted a working electrode 12 and a reference electrode 14. The working electrode 12 and reference electrode 14 each comprise a plurality of electrode portions, 12a and 14a, arranged in concentric circles, so as to provide an interwoven pattern minimizing the distance between adjacent portions of the working electrode 12 and reference electrode 14. In this way, the current path between the two electrodes is kept to a minimum.

A layer 16 of insulating or dielectric material extends over a portion of both the working and counter electrodes 12 and 14, leaving the portions 12a and 14a of each electrode exposed to be in direct contact with a stream of gas passing through the conduit 4. The arrangement of the support, electrodes 12 and 14, and the solid electrolyte precursor is shown in more detail in Figures 3 and 4.

Referring to Figure 3, there is shown an exploded view of a sensor element, generally indicated as 40, comprising a substrate layer 42. A working electrode 44 is mounted on the substrate layer 42 from which extend a series of elongated electrode portions 44a. Similarly, a reference electrode 46 is mounted on the substrate layer 42 from which extends a series of electrode portions 46a. As will be seen in Figure 3, the working electrode portions 44a and the reference electrode portions 46a extend one between the other in an intimate, interdigitated array, providing a large surface area of exposed electrode with minimum separation between adjacent portions of the working and reference electrodes. A layer of mesoporous material 48 overlies the working and reference electrodes 44, 46.

The mesoporous material consists of a mixture of titanium dioxide (titanate) and Nafion ®, a commercially available sulphonated tetrafluoroethylene copolymer.

The mesoporous material 48 is applied by the repeated immersion in a suspension or slurry of the mesoporous material in a suitable solvent, in particular water. The sensor element is dried to evaporate the solvent after each immersion and before the subsequent immersion. Other materials may be incorporated into the mesoporous layer by subsequent immersion in additional solutions or suspensions, in particular a solution of Nafion ® in methanol. The pH will determine the ion exchanger characteristics of the Nafion ®. It is possible to manufacture a Nafion ® coating with principally H⁺, K⁺, Na⁺ and Ca²⁺ as the cationic exchanger. The number of immersions is determined by the required thickness of the mesoporous layer, and the chemical composition is determined by the number and variety of additional solutions that the sensor is dipped into.

It will be obvious that there are a number of other means whereby the thickeness and composition of the coating may be similarly achieved, such as: pad, spray, screen and other mechanical methods of printing. Such techniques are well known in the field.

An alternative electrode arrangement is shown in Figure 4, in which components common to the sensor element of Figure 3 are identified with the same reference numerals. It will be noted that the working electrode portions 44a and the reference electrode portions 46a are arranged in an intimate circular array. The electrodes and substrate are coated in a layer of mesoporous material, as described above in relation to Figure 3.

Referring to Figure 5, there is shown a potentiostat electronic circuit that may be employed to provide the voltage applied across the working and reference electrodes of the sensor of the present invention. The circuit, generally indicated as 100, comprises an amplifier 102, identified as 'OpAmpl', acting as a control amplifier to accept an externally applied voltage signal Vj_n. The output from

OpAmpl is applied to the control (counter) electrode 104. A second amplifier 106, identified as 'OpAmp2' converts the passage of current from the counter electrode 104 to the working electrode 108 into a measurable voltage (V_out)- Resistors Rl, R2 and R3 are selected according to the input voltage, and measured current.

An alternative galvanostat circuit for exciting the electrodes of the sensor is shown in Figure 6. The control and working electrodes 104 and 108 are connected between the input and output of a single amplifier 112, indicated as 'OpAmpl'. Again, resistor Rl is selected according to the desired current.

Turning to Figure 7, an adaptor for monitoring the breath of a patient is shown. A sensor element is mounted within the adaptor and oriented directly into the air stream flowing through the adaptor, in a similar manner to that shown in Figure 2 and described hereinbefore. The preferred embodiment illustrated in Figure 7 comprises and adaptor, generally indicated as 200, having a cylindrical housing 202 having a male-shaped (push-fit) cone coupling 204 at one end and a female-shaped (push-fit) cone coupling 206 at the other. A side inlet 208 is provided in the form of an orifice in the cylindrical housing 202, allowing for the adaptor to be used in the monitoring of the tidal breathing of a patient, as described in more detail in Example 2 below. The side inlet 208 directs gas onto the sensor element during inhalation by a patient through the device. The monitoring of tidal breathing may be improved by the provision of a one-way valve on the outlet of the housing 202.

With reference to Figure 8 there is shown in schematic form the general layout of a sensor system according to the present invention. The system, generally indicated as 400, comprises a sensor element having a counter electrode 402 and a working electrode 404. The counter electrode 402 is supplied with a voltage by a control potentiostat 406, for example of the form shown in Figure 5 and described hereinbefore. The input signal for the control potentiostat 406 is provided by a digital-to-analog converter (D/ A) 408, itself being provided with a digital input signal from a microcontroller 410. The output signal generated by the sensing element is in the form of a current at the working electrode 404, which is fed to a current-to-voltage converter 412, the output of which is in turn fed to an analog-to-digital converter (A/D) 414. The microcontroller 410 receives the output of the A/D converter 414, which it employs to generate a display indicating the concentration of the target substance in the gas stream being monitored. The display (not shown in Figure 8 for reasons of clarity) may be any suitable form of display, for example an audio display or visual display. In one preferred embodiment, the microcontroller 410 generates a continuous display of the concentration of the target substance, this arrangement being particularly useful in the monitoring of the tidal breathing of a patient.

The sensors of the present invention may be employed individually, or as a series of sensor elements connected sequentially together in-line to measure a series of gases from a single gas stream. For example, a series of sensors may be employed to analyse the exhaled breath of a patient. In addition, two or more sensors may be used to compare the composition of the inhaled and exhaled breath of a patient.

Claims

1. A sensor for sensing a target substance in a gas stream, the sensor comprising: a sensing element disposed to be exposed to the gas stream, the sensing element comprising: a working electrode; a counter electrode; and a layer of mesoporous material extending between the working electrode and the counter electrode; whereby contact of the mesoporous layer with the gas stream forms an electrical contact between the working and counter electrodes.

2. The sensor according to claim 1, wherein the mesoporous material has a pore size in the range of from 2 to 50 nm.

3. The sensor according to claim 1 or 2, wherein the mesoporous layer comprises a binder, in particular an ionomer, especially a sulphonated tetrafluoroethylene copolymer.

4. The sensor according to any preceding claim, wherein the mesoporous material comprises an oxide of a metal from Group IV of the Periodic Table, in particular an oxide of titanium or zirconium, or a synthetic clay, in particular laponite, hydrotalcite or hydrotalcite-like compounds, silicalites, zeolites.

5. The sensor according to any preceding claim, wherein the mesoporous material comprises water, or condensed water vapour.

6. The sensor according to any preceding claim, wherein the target substance is an acidic substance, in particular carbon dioxide, or water.

7. The sensor according to any preceding claim, further comprising a conduit through which the gas stream is channeled to impinge upon the sensing element.

8. The sensor according to claim 7, wherein the conduit comprises a mouthpiece into which a patient may exhale.

9. The sensor according to any preceding claim, wherein the working electrode and counter electrode are in a form selected from a point, a line, rings and flat planar surfaces.

10. The sensor according to any preceding claim, wherein one or both of the working electrode and the counter electrode comprises a plurality of electrode portions.

11. The sensor according to claim 10, wherein both the working electrode and the counter electrode comprise a plurality of electrode portions arranged in an interlocking pattern.

12. The sensor according to claim 10, wherein the electrode portions are arranged in a concentric pattern.

13. The sensor according to any preceding claim, wherein the surface area of the counter electrode is greater than the surface area of the working electrode.

14. The sensor according to claim 13, wherein the ratio of the surface area of the counter electrode to the working electrode is at least 2:1, more preferably at least 5:1.

15. The sensor according to any preceding claim, wherein the electrodes are supported on an inert substrate.

16. The sensor according to any preceding claim, wherein each electrode comprises a metal selected from Group VIII of the Periodic Table of the Elements, copper, silver and gold, preferably gold or platinum.

17. The sensor according to any preceding claim, further comprising a layer of insulating material disposed over a portion of each electrode, the insulating layer being so shaped as to leave a portion of each electrode exposed for direct contact with a gas stream.

18. The sensor according to any preceding claim further comprising a reference electrode.

19. The sensor according to any preceding claim, wherein the electrodes are mounted on a substrate, the electrodes being applied to the substrate by thick film screen printing, spin/sputter coating or visible/ultraviolet/laser photolithography.

20. The sensor according to any preceding claim, wherein one or more electrodes is comprised of a plurality of layers, the outer layer being a layer of pure metal applied by electrochemical plating.

21. The sensor according to any preceding claim, further comprising a heater to heat the gas stream directly impinging upon the electrodes.

22. A method of sensing a target substance in a gas stream, the gas stream comprising water vapour, the method comprising: causing the gas stream to impinge on a layer of mesoporous material extending between a working electrode and a counter electrode; applying an electric potential across the working electrode and counter electrode; measuring the current flowing between the working electrode and counter electrode as a result of the applied potential; and determining from the measured current flow an indication of the concentration of the target substance in the gas stream.

23. The method of claim 22, wherein the target substance is an acidic substance, such as carbon dioxide, water vapour or a combination thereof.

24. The method of claim 22 or 23, wherein a constant voltage is applied across the working electrode and the counter electrode.

25. The method of claim 22 or 23 , wherein a variable voltage is applied across the working electrode and the counter electrode.

26. The method of claim 25, wherein the variable voltage alternates between a rest potential and a potential above the reaction threshold potential.

27. The method of claim 26, wherein the voltage is pulsed at a frequency of from 0.1Hz to 20 kHz.

28. A method of measuring the concentration of a target substance in the exhaled breath of a patient, the method comprising: causing the exhaled breath to impinge on a layer of mesoporous material extending between a working electrode and a counter electrode; applying an electric potential across the working electrode and counter electrode; measuring the current flowing between the working electrode and counter electrode as a result of the applied potential; and determining from the measured current flow an indication of the concentration of a target substance in the exhaled breath stream.

29. The method of claim 28, wherein the target substance is water and/or carbon dioxide.

30. The method of claim 28 or 29, wherein the method is applied to determine the lung function of a patient, in particular a patient suffering from asthma, COPD or ARDS.

31. The method of any of claims 28 to 30, wherein the tidal breathing of a patient is monitored.

32. A system for monitoring the composition of a gas stream comprising: a sensor according to any of claims 1 to 21 ; a microcontroller for receiving an output from the sensor; and a display; wherein the microcontroller is programmed to generate a continuous image of the concentration of a target substance in a gas stream being analysed on the display.

33. The system of claim 32, wherein the sensor is adapted to be exposed to the breath of a patient.

34. The system of claim 32 or 33, wherein the target substance is water and/or carbon dioxide.