GB2434647A

GB2434647A - Gas Concentration and Humidity Sensor

Info

Publication number: GB2434647A
Application number: GB0600629A
Authority: GB
Inventors: Mark Varney; Alexandra Lindsell
Original assignee: Anaxsys Technology Ltd; Asthma Alert Ltd
Current assignee: Anaxsys Technology Ltd; Asthma Alert Ltd
Priority date: 2006-01-13
Filing date: 2006-01-13
Publication date: 2007-08-01
Also published as: WO2007080381A1; GB0600629D0

Abstract

A sensor for detecting a target substance, in particular carbon dioxide or water, in a gas stream comprises a sensing element disposed to be exposed to the gas stream, the sensing element comprising a working electrode; and a counter electrode; whereby the gas stream may be caused to impinge directly upon at least a portion of both the working electrode and the counter electrode. A method of sensing a target substance in a gas stream comprises causing the gas stream comprising water vapour to impinge upon at least a portion of both a working electrode and a counter electrode; applying a 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. The sensor and method are particularly suitable for analyzing tidal carbon dioxide concentrations and humidity in the exhaled breath of a person, to diagnose and/or monitor a variety of respiratory conditions. The sensor design is particularly useful for applications requiring fast response times, e.g. personal respiratory monitoring of tidal breathing ("capnography").

Description

GAS SENSOR

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 fbr detecting and measuring the concentration of gases, such as carbon dioxide, in the exhaled breath of a person or animal. The sensor may also he 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 olthe carbon dioxide concentration allows the extent and/or progress of * .e. 15 various pulmonary and/or respiratory diseases to be estimated, in particular asthma and chronic obstructive lung disease (COPD).

S * *

Carbon dioxide can be detected using a variety of analytical techniques and instruments. The most practical and widely used analysers use spectroscopic infra-red *:*e 20 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 physicochernical properties of the gas, new techniques are being developed which utilise electrochemistry, and an assortment of electrochemical methods have been proposed. 1-lowever, it has not been possible to measure carbon dioxide (C02) gas directly using electrochemica! 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: * a. S...

CO2 H2OH2CO3 (1) FI2CO3HCO3+I-I (2) HC03 C032 + H (3) * , It will be appreciated that, as more carbon dioxide dissolves, the concentration of S.,.,.

hydrogen ions (I-J) 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 04/00 1407 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 o La 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.

: *s GB 2,287,543 A discloses a solid electrolyte carbon monoxide sensor having a S...

* *.. first cavity formed in a substrate, communicating with a second cavity in which a *S'.

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 S.....

* 20 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 2,3 16,178 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 arc 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. S... * * S...

1 5 A particularly effective sensor is disclosed in pending international application * : No. PCT/GB2005/003 196. 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 S.....

* 20 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.

In addition to the detection and measurement of specific species in a gas stream, there is a need to accurately measure the water vapour content or humidity of the stream. Humidity may be measured using hair hygrometers, wet bulb psychrometers, dew point mirrors, and capacitive humidity meters. Capacitive humidity sensors respond to the variation in electronic impedance, that is changes in resistance, resistivity, conductance, or conductivity (hereafter generally referred to as "impedance") from materials coated on the surface of electrodes, which are sensitive to water vapour (hereafter generally referred to as "humidity"). It is generally known that the electrical conductivity of these materials changes in proportion to relevant changes in humidity of the environment to which such materials are exposed.

Capacitive humidity meters have been regarded as unreliable and unstable.

Many of these meters require frequent re-calibration, are highly inaccurate, slow, expensive and not battery-operated. The main drawback of these sensors is that they are not very sensitive to the relevant humidity changes of the environment to which they are exposed, as a sudden change the environmental humidity does not elicit an equal change in electrical resistivity value due to slow response times.

Moreover, the currently known sensors measure humidity and rate of change of humidity only in a narrow range of values and/or temperatures, therefore their : *s application is limited. * S

* SS a 1 5 While the sensor disclosed in PCT/GB2005/003 196 represents a significant improvement over the previously known sensor assemblies, it nevertheless relies upon the use of a solid electrolyte. While the sensor relies on the presence of water vapour * in the gaseous stream, it does not readily indicate the humidity of the gaseous stream.

It would be most useful if a sensor able to detect gaseous species, in particular carbon *5*SS* * 20 dioxide, could he found that has a simpler construction, preferably without needing to rely upon any form of electrolyte. It would be most advantageous if the same sensor could also be used to measure the water vapour content and humidity of the gaseous stream.

Most surprisingly, it has been found that a sensor comprising bare electrodes having their surfaces directly exposed to the gaseous stream being analysed provides a reliable indication of the concentration of the target species in the gaseous stream, when the gas stream comprises the target species and water vapour. Accordingly, in a first aspect, the present invention provides a sensor for sensing a target substance in a gas stream comprising water vapour, 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 whereby the gas stream may be caused to impinge directly upon at least a portion of the surfaces of both the working electrode and the counter electrode.

The target substance in the gas stream may he a 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.

: *** It has been found that the sensor of the present invention exhibits a very fast * ... and significant response to the presence of water vapour in a gas stream that contacts S...

1 5 both electrodes. Accordingly, the sensor is effective in indicating the moisture content or humidity of the gas stream. However, surprisingly, it has also been found that the response of the sensor is elevated when the gas stream contains an acidic gas, : * * in which case the sensor may be used to detect the present of both the acidic gas and S... . . . water vapour. Acidic gases that may be present in the gas stream and give rise to the I.....

* 20 elevated response include carbon dioxide, sulphur dioxide, hydrogen chloride and compounds, in particular oxides, of phosphorous.

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. In addition, the sensor indicates the water vapour content of the gas stream being analysed and can indicate changes in humidity. Of particular advantage, the sensor is able to respond to rapid changes in humidity over a broad range of humidity values, providing a very high speed of response and accuracy. 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. As the sensor does not employ or rely upon an electrolyte whether solid or liquid, providing the sensor with a long storage and operational lifespan. In addition, the absence of an electrolyte or electrolyte precursor allows the sensor to be used in a variety of positions, locations and orientations. Further, the absence of an electrolyte renders the sensor particularly robust.

The sensor prelerably 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 * S. S 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 *.**..

* 20 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, the sensor relies upon the presence of water vapour in the gaseous stream being analysed. If insufficient water vapour is present, 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.

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 he 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 S...

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. S...

S

* 20 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 surlace 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. fhe 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. As the sensor of the present invention does not rely on the presence of any form of electrolyte or electrolyte precursor, the substrate may be made of a flexible material, allowing the electrodes to be shaped to configure to any desired shape or pattern. It is important that the substrate is non-conducting, that is electrically insulating or of a sufficiently high dielectric coefficient. * *. * I I I...

To improve the electrical insulation of the electrodes, the portions of the I...

electrodes that are not disposed to be in direct 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. I... *

I.....

* 20 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. I)ual 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' 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 : *. 15 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 * 0S* a powder of one or more of the aforementioned metals used to form the electrode.

OS*S*s * * The binder holds the ink to the substrate and merges with the substrate during * * 20 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 are lost 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 -I 2Sum below the substrate surface.

: * This will allow a consistent print thickness to be achieved across the substrate whilst S...

simultaneously protecting the screen mesh from distortion and possible plastic 4I*S deformation due to excessive pressure. *SS.. * S

To determine the print thickness the following equation can be used: * * Tw(Tm x Ao)+Te * 20 Where Tw = Wet thickness (urn); Tm = mesh weave thickness (urn); Ao = % open area; Te = Emulsion thickness (urn).

After the printing process the sensor elernent 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 1 0 minutes.

Firing is typically accomplished in a belt furnace. Firing temperatures vary according to the ink chemistry. Most commercially available systems fire at 850 C 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 spinlsputter 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 he **** 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.

S..... * 20

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 impinge directly upon at least a portion of the surfaces of both a working electrode and a counter electrode; applying a 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.

: i''. As noted above, the method of the present invention is particularly suitable for *0*I use in the detection of carbon dioxide in a gas stream, in particular in the exhaled a.., 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 * a:, the gaseous stream, which may be electronically measured by a variety of techniques.

SI &. S * ! 20 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 with the metal ions 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 concentration of free metal ions present in or released by 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, I,'.

special "guarding" techniques may be employed. Ground loops need to be avoided in I..

the system. This can he achieved using techniques known in the art. * I

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 III in the gaseous stream. The sensor responds faster by pulsing the potential between I... )I two voltages, a technique known in the art as Square Wave Voltammetry'. 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 theshape, 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 1 a is a representation of a pulsed voltage signal, alternating between a rest potential, V0, and a reaction potential VR. The voltage may be pulsed at a range of * ** frequencies, typically from sub-Hertz frequencies, that is from 0.1 Hz, up to 10kHz.

A prefened pulse frequency is in the range of from 1 to 500 1-Iz. Alternatively, the S... . . . " ,, potential waveform applied to the counter electrode may consist of a swept series of * : * * frequencies, represented in Figure lb. 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 * 20 techniques are known in the art.

One preferred voltage regime is OV ("rest" potential), 250mV ("reaction" potential), and 20Hz pulse frequency.

It is an advantage of the present invention that the electrochernical 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 directly upon at least a portion of the surfaces of both a working electrode and a counter electrode; applying a 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 exhaled breath stream.

S

S..... * S

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 * 20 exhaled breath of a subject human or animal.

The sensor and method of the present invention 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).

Capnographic 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 he described, by way of : example only, having reference to the accompanying drawings, in which

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S.....

* 20 Figures Ia, lb and lc 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; 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; *s.. I...

* 15 Figure 9 is a typical output (capnogram) recorded by a sensor according to the present invention * * , : Figure 10 is the output of Figure 9 marked up to calculate the Q-angle; and **** :: 20 Figure 11 is a graph of Q-angles determined using a sensor according to the present invention plotted against the FEV1 values obtained using conventional spirometric techniques.

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 Is..

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.

I

Is.... * .

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 S..... . . * * 20 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 dielectric material 48 overlies the working and reference electrodes 44, 46, so as to leave the portions 44a and 46a of the working and counter electrode exposed.

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 dielectric layer 48 extends only over the portions of the working and counter electrodes 44 and 46 extending from the array of electrode portions 44a and 46a. In this way, the entire array of electrode portions 44a and 46a is left exposed and free to be directly contacted by the gas stream.

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 OpAmpi', acting as a control amplifier to accept an externally applied voltage signal V1). The output from OpAmpi 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 (V0). Resistors Ri, 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 OpAmpi'.

****** * 20 Again, resistor Ri 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 *.S.

* *, (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 * : e.. 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 * : 20 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.

EXAMPLES

The sensor and method of the present invention are further illustrated by the following working examples.

Example 1

A sensor element was prepared comprising gold working and reference electrodes supported on an alumina substrate. The electrodes were applied to the substrate using the screen printing method detailed hereinbefore. The electrodes were arranged as shown in Figure 4. Both electrodes had a track width of 100 microns.

The electrodes were separated by a gap of 100 microns. Each electrode was 15 mm in length.

: * The sensor element was housed in a T-piece adaptor, of the type shown in * Figure 7, so as to be positioned directly in the air stream passing from the inlet to the outlet of the T-piece. The adaptor was modified as follows to allow the tidal * : . . * breathing of a patient to be analysed. The adaptor was fitted with a one-way valve at its outlet. A side inlet in the form of a 2mm diameter hole was formed in the housing : adjacent the sensor element, so as to direct inhaled gases over the electrode. S.

:: 20 A D/A converter was used to apply successive voltages of OV and 250mV at a frequency of 0.055 seconds per pulse (18 Hz square wave cycle) across the working and counter electrodes of the sensor. The current response was converted to a measurable voltage by an AID converter, controlled by a microcontroller.

A human patient was requested to breath normally through the T-piece adaptor of the sensor. The response of the sensor element was recorded and is shown graphically in Figure 9, in which the measured current (microAmps) is plotted against time. The very high speed of response of the sensor will be noted from the data set out in Figure 9.

Exhaled breath is, by its' nature, 100% saturated with water vapour.

Condensing water vapour is itself saturated with C02 in proportion to the partial pressure in the breath at that time. The measurement of electrochemical impedance against time yields a graph, referred to in the art as a "capnogram".

Figure 9 shows the response of the sensor of the present invention to a patient breathing normally (tidally) across the face of the sensor. The shape of the response is divided into five regions: the onset of expiration, P; the mixing of dead space and alveolar gases, PQ; a plateau phase representing alveolar gas expiration, QR; the end of expiration, R; the beginning of inspiration, ST.

One standard method of interpreting the shape of a capnogram such as that of : . , Figure 9 is to calculate the ratio of the slopes PQ and QR, generally referred to as the e.

"Q Angle", as shown in Figure 10. The Q-angle determined from Figure 10 is 1.85, a value typically classified as normal'. * S

Example 2

Conventional techniques for taking spirometry measurements include forced 20 expiratory volume in 1 second (FEV1), forced vital capacity (FVC). These techniques are time consuming techniques, requiring professional supervision and expertise. As a result, these techniques are best undertaken within a clinical primary care environmental.

FEVI is an established clinical measurement to clinically assess the severity of respiratory disease, such as asthma, and is used extensively within primary and secondary care, and the population in general for personal respiratory management programmes. in order to further test the sensor of the present invention, a clinical trial was conducted using 110 patients suffering from varying degrees of asthma. In the clinical trial, each patient was provided with a sensor according to the present invention, as described in Example 1. The sensor of the present invention was used to calculate the Q-angle of each patient during tidal breathing, as described in Example I. In order to provide a direct comparison of the sensor of the present invention with the known techniques, the measurement of the Q-angle of each patient using the sensor of the present invention was undertaken at the same time as the measurement ofFEV1 and FVC, in order to avoid any change in the condition of the patient between the two sets of measurements, and thereby a consequent skew in results.

Figure 11 shows the overall results for 110 patients whereby the measurements of Q Angle are plotted against FEV I for each patient. The results show there is a clear relationship between the two measurements. in particular, the data in Figure 11 demonstrates that the Q angle increases with a decrease in FEY 1. Although there is scatter in the data, the relationship is generally linear. As a result, the Q angle can therefore be used to predict the asthmatic condition of a patient, as otherwise measured by FEV1.

* * The study also demonstrated positive correlations of the sensor of the present invention with other spirometric indices, including peak flow, determined using a * peak flow meter. The peak flow meter is another common device used by clinicians in * : the art to determine the respiratory status of a patient. The determination of Q-angle * 20 using the sensor of the present invention has proven in clinical trials to correlate directly with the results achieved using known peak flow meter devices and thus to be a reliable and repeatable indicator of patient respiratory condition.

The measurement of the electronic impedance of exhaled breath condensate using the sensor of the present invention, can be applied generally in the field of respiratory medicine, airway diseases (restrictive and obstructive), airway tract disease management, and airway inflammation, particularly in the field of capnography and asthma diagnosis, monitoring and management and more generally in various other fields of respiratory medicine, such as COPD, ARDS and other diseases, infections and tumours within the lungs.

Example 3

The sensor described in Example I was exposed to a stream of nitrogen gas saturated to 100% with water vapour. The gas stream was contacted with the sensor at a flowrate of 200 mi/mm. A steady state was reached after approximately 2 minutes, at which time a current across the electrodes of about 475 micro amps was recorded.

The composition of the gas stream was changed to one comprising 10% vol carbon dioxide and 90% vol nitrogen, again saturated to 100% with waler vapour.

The sensor was again left to reach a steady state for approximately 2 minutes, at which time the measured current was about 500 micro amps. * **

::::: In repeats of this experiment, the response of the sensor to the presence of 10% vol carbon dioxide and water vapour in the stream was repeatedly about 5% * : * * higher than the response of the sensor to the gas stream containing water vapour alone.

* :: This experiment served to confirm the response of the sensor to water vapour a...., . in an otherwise inert gas stream, such that the sensor can be used to measure the moisture content or humidity of a gas stream. In addition, the change in response arising from the presence of carbon dioxide in the gas stream demonstrates the heightened response of the sensor to the presence of carbon dioxide, an acidic gas.

Claims

CLAIMS

1. A sensor for sensing a target substance in a gas stream comprising water vapour, the sensor comprising: a sensing element disposed to be exposed to the gas stream, the sensing element comprising: a working electrode; and a counter electrode; whereby the gas stream may be caused to impinge directly upon at least a portion of both the working electrode and the counter electrode.

2. The sensor according to claim 1, wherein the target susbstance is water. * ** * I S I... S...

 15 3. The sensor according to claim 1, wherein the target substance is an acidic substance, in particular carbon dioxide.

* SSSIS * I 4. The sensor according to any preceding claim, further comprising a conduit * through which the gas stream is channeled to impinge upon the sensing element.

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5. The sensor according to claim 4, wherein the conduit comprises a mouthpiece into which a patient may exhale.

6. 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.

7. 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.

8. The sensor according to claim 7, wherein both the working electrode and the counter electrode comprise a plurality of electrode portions arranged in an interlocking pattern.

9. The sensor according to claim 8, wherein the electrode portions are arranged in a concentric pattern.

10. 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.

11. The sensor according to claim 10, 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.

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

*SSSSS * 13. 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.

14. 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.

15. The sensor according to any preceding claim further comprising a re1rence electrode.

16. 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.

17. 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.

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

19. 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 directly upon at least a portion of the surfaces of both a working electrode and a counter electrode; * applying an electric potential across the working electrode and counter electrode; s** 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. * S * S *

20. The method of claim 19, wherein the target substance is an acidic substance, such as carbon dioxide, water vapour or a combination thereof 21. The method of claim 19 or 20, wherein a constant voltage is applied across the working electrode and the counter electrode.

22. I'he method of claim 19 or 20, wherein a variable voltage is applied across the working electrode and the counter electrode.

23. The method of claim 22, wherein the variable voltage alternates between a rest potential and a potential above the reaction threshold potential.

24. The method of claim 23, wherein the voltage is pulsed at a frequency of from 0.1Hz to 20 kHz.

25. 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 directly upon at least a portion of the surfaces of both 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. *s..

.... 15 26. The method of claim 25, wherein the target substance is water and/or carbon dioxide. s.. * *

27. The method of claim 25 or 26, wherein the method is applied to a patient :.. suffering from asthma, COPD or ARDS.

28. The method of any of claims 25 to 27, wherein the tidal breathing of a patient is monitored.

29. A system for monitoring the composition of a gas stream comprising: a sensor according to any of claims Ito 18; 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.

30. The system of claim 29, wherein the sensor is adapted to be exposed to the breath of a patient.

31. The system of claim 29 or 30, wherein the target substance is water and/or carbon dioxide.

32. A sensor substantially as hereinbefore described having reference to any one of Figures Ito 8.

33. A method of detecting a target substance in a gaseous stream substantially as hereinbefore described having reference to the accompanying figures.

* 34. A method of measuring the composition of the exhaled gas of a subject *:.. substantially as hereinbefore described having reference to the accompanying figures. * *

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