WO2023110492A1

WO2023110492A1 - Determining a concentration of a gas in a breath of a subject

Info

Publication number: WO2023110492A1
Application number: PCT/EP2022/084398
Authority: WO
Inventors: Zhi-Xing JANG
Original assignee: Koninklijke Philips N.V.
Priority date: 2021-12-15
Filing date: 2022-12-05
Publication date: 2023-06-22

Abstract

According to an aspect, there is provided a computer-implemented method (500) of determining a concentration of a gas in a breath of a subject comprising: receiving (502) data relating to a radiation intensity at each wavelength of a plurality of wavelengths in a defined wavelength range, the radiation intensity measured using a sensor of an absorption spectrometer; determining (504), based on the received data, a transmittance of the radiation at each wavelength of the plurality of wavelengths in the defined wavelength range through a cell of the absorption spectrometer; determining (506), based on the transmittance, a transmittance profile over the defined wavelength range; and determining (508), based on the transmittance profile, a concentration of carbon dioxide and a concentration of oxygen in the cell of the absorption spectrometer.

Description

DETERMINING A CONCENTRATION OF A GAS IN A BREATH OF A SUBJECT

FIELD OF THE INVENTION

The invention relates to a method, system and device for determining a concentration of a gas in a breath of a subject and, more specifically, to determining a concentration of oxygen and a concentration of carbon dioxide in the breath of the subject.

BACKGROUND OF THE INVENTION

Monitoring the health status of a person can be achieved in numerous ways including monitoring the gaseous composition of the person’s breath, such as oxygen and carbon dioxide. The ability to monitor and quantify respiratory gases is desirable to provide a better and more complete understanding of a person’s metabolic status and pulmonary function.

In some cases, monitoring the gaseous composition of a person’s breath can require multiple sensors each determining a different property of the breath. Also, the accuracy with which a concentration of a respiratory gas can be determined may be impacted by the presence of other gases, which has been overcome in prior art systems by the introduction of a known concentration of a particular gas.

It is therefore desirable to reduce the complexity of the system required to monitor respiratory gases, and to improve the accuracy with which a determination of the concentration of respiratory gases can be determined.

SUMMARY OF THE INVENTION

There is a desire for a device for measuring a property of a gas such that measurements enabling determination of the property of the gas are simplified and more accurate. For example, there is a desire for a device that is able to provide measurements from which a concentration of carbon dioxide and a concentration of oxygen can be determined using a single sensor, and which avoids the need to introduce a known concentration of another gas to counteract its effect on the determination of the concentration of carbon dioxide. Embodiments disclosed herein provide a solution to these problems, enabling the determination of a property (e.g. a concentration) of one or more gases (e.g. oxygen and/or carbon dioxide) using a single sensor, which does not require a known input of a first gas to enable accurate determination of a property of a second gas.

According to a first specific aspect, there is provided a computer-implemented method of determining a concentration of a gas in a breath of a subject, the method comprising: receiving data relating to a radiation intensity at each wavelength of a plurality of wavelengths in a defined wavelength range, the radiation intensity measured using a sensor of an absorption spectrometer; determining, based on the received data, a transmittance of the radiation at each wavelength of the plurality of wavelengths in the defined wavelength range through a cell of the absorption spectrometer; determining, based on the transmittance, a transmittance profile over the defined wavelength range; and determining, based on the transmittance profile, a concentration of carbon dioxide and a concentration of oxygen in the cell of the absorption spectrometer.

In some embodiments, determining a transmittance profile may comprise determining a line width associated with an absorption line of carbon dioxide.

The defined wavelength range may, in some embodiments, encompass at least one absorption line of carbon dioxide between trough absorption strength values located on either side of a maximum intensity value.

In some embodiments, the defined wavelength range may encompass a wavelength associated with a reference radiation intensity value falling within a waveband between two adjacent absorption lines of carbon dioxide; and the determination of the transmittance of the radiation at each wavelength of the plurality of wavelengths may comprise using the reference radiation intensity value as a baseline value.

The computer-implemented method may, in some embodiments, further comprise determining, based on the reference radiation intensity value, a stability of a radiation source used to generate radiation; and refining the determination of the concentration of carbon dioxide and the concentration of oxygen based on the stability of the radiation source.

In some embodiments, the defined wavelength range may be between 4.20 pm and 4.35 pm.

The received data may, in some embodiments, be obtained by determining a transmittance incrementally over a defined wavelength range while increasing and/or decreasing wavelength.

In some embodiments, determining a concentration of carbon dioxide may comprise inputting an absorption coefficient of carbon dioxide and a path length of radiation within the cell of the absorption spectrometer into the Beer-Lamb ert-Bouguer law.

Determining a concentration of oxygen may, in some embodiments, comprise comparing the determined transmittance profile to a reference transmittance profile in which the amount of oxygen present was below a defined threshold concentration.

In some embodiments, the computer-implemented method may further comprise refining the determination of a concentration of carbon dioxide based on the determination of a concentration of oxygen. According to a second specific aspect, there is provided a computer program product comprising a non-transitory computer readable medium, the computer readable medium having computer readable code embodied therein, the computer readable code being configured such that, on execution by a suitable computer or processor, the computer or processor is caused to perform steps of any of the methods disclosed herein.

According to a third specific aspect, there is provided a system comprising: an absorption spectrometer comprising: a radiation source configured to generate radiation at a plurality of wavelengths in a defined wavelength range; a cell configured to contain a sample of breath of a subject; and a radiation sensor configured to detect radiation over a range of wavelengths; and a processor configured to: receive data relating to a radiation intensity at each wavelength of the plurality of wavelengths measured using the radiation sensor; determine, based on the received data, a transmittance of the radiation at each of the plurality of wavelengths through the cell; determine, based on the transmittance, a transmittance profile over the defined wavelength range; and determine, based on the transmittance profile, a concentration of carbon dioxide and a concentration of oxygen in the cell.

In some embodiments, the radiation source may comprise a tuneable distributed feedback interband cascade laser diode; and wherein the radiation sensor comprises a photo detector.

Determining a transmittance profile may, in some embodiments, comprise determining a line width associated with an absorption line of carbon dioxide.

According to a fourth specific aspect, there is provided a capnography device comprising components of a system disclosed herein; and a breath receiving unit configured to receive breath from a subject; wherein the sample of breath contained in the cell is obtained from the breath receiving unit.

These and other aspects will be apparent from and elucidated with reference to the embodiment s) described hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments will now be described, by way of example only, with reference to the following drawings, in which:

Figs. 1 A and IB are schematic drawings of two examples of an apparatus for gas sensing;

Fig. 2 is an example of an absorption spectrum of carbon dioxide;

Fig. 3 is an example absorption spectrum of carbon dioxide both in the absence of oxygen and in the presence of oxygen;

Fig. 4 is an example of data representative of a sensed concentration of carbon dioxide during respiratory cycles; Fig. 5 is a flowchart of an example of a computer-implemented method of determining a concentration of a gas in a breath of a subject;

Fig. 6 is a flowchart of a further example of a computer-implemented method of determining a concentration of a gas in a breath of a subject;

Fig. 7 is a schematic illustration of a processor in communication with a non-transitory computer readable medium;

Fig. 8 is a schematic illustration of an example of a system for determining a concentration of a gas in a breath of a subject; and

Fig. 9 is a schematic illustration of a further example of a system for determining a concentration of a gas in a breath of a subject.

DETAILED DESCRIPTION OF EMBODIMENTS

Determining a concentration of a gas is important in a range of contexts, including, for example, determining a concentration of a gas in a person’s breath. Gaseous components of a person’s breath that may be of particular interest include carbon dioxide and/or oxygen, which can be important when assessing a person’s metabolic status and pulmonary function. For example, monitoring metabolic gases such as carbon dioxide and oxygen may be useful in a hospital setting (e.g. in emergency care), for sleep respiratory care, and/or for personal care. Determining a concentration of carbon dioxide and/or a concentration of oxygen can be performed in a number of ways, including, for example, via absorption spectroscopy (e.g. tuneable diode laser absorption spectroscopy (TDLAS), photoacoustic methods (e.g. photoacoustic spectroscopy), methods involving the use of a nondispersive infrared sensor (NDIR), or the like).

Fig. 1 shows an example of an apparatus 100 for gas sensing (e.g. an absorption spectrometer). The apparatus 100 may, for example, be configured to determine a concentration of a gas via tuneable diode laser absorption spectroscopy (TDLAS). The absorption spectrometer 100 shown in Fig. 1 comprises a radiation source 102 (e.g. a radiation source configured to generate radiation at a plurality of wavelengths in a defined wavelength range), a cell 104 configured to contain a sample of breath of a subject, and a radiation sensor 106 configured to detect radiation over a range of wavelengths. In some examples, the absorption spectrometer may optionally comprise optics 108 (e.g., one or more optical elements, such as lenses) for altering a light path through the system. In some examples, the absorption spectrometer may include optics that are configured, or operative, to increase the path length of radiation within the cell of the absorption spectrometer, thereby increasing the sensitivity of the absorption spectrometer. Improving the sensitivity of the absorption spectrometer may allow a more precise measurement and/or determination of a property of a species (e.g. a gas) within the cell of the absorption spectrometer, and may allow for relatively lower concentrations of a gas to be determined.

In some examples, the radiation source may comprise a tuneable, narrow bandwidth distributed feedback interband cascade laser diode. Using a radiation source of this type allows a property of a gas (e.g. the absorption coefficient) to be determined across a range of wavelengths with high precision. For example, a tuneable, narrow bandwidth distributed feedback interband cascade laser diode is able to generate radiation over a range of wavelengths sufficient to resolve individual absorption peaks of carbon dioxide, such as absorption peaks within the range of wavelengths falling between 2 pm (micrometres) to 5 pm, as will be described in more detail herein. The radiation source may be tuned via temperature tuning, current tuning, or the like.

Fig. 2 is a plot showing an example of an absorption spectrum of carbon dioxide over a wavelength range of 4.2 to 4.35 micrometres. The x-axis represents wavelength in micrometres and the y-axis represents absorption cross section in units of cm². The absorption cross section is one way of representing an absorption strength. Fig. 2 shows that there are a plurality of absorption peaks (e.g. fine absorption peaks), which, when taken together, form a broader absorption peak or cluster. Carbon dioxide has similar absorption peak clusters at approximately 2.0 pm and 2.7 pm, respectively (not shown).

Fig. 3 is a plot showing an example absorption spectrum of carbon dioxide, both in the absence of oxygen and in the presence of oxygen. The absorption spectrum of carbon dioxide shown in Fig. 3 is represented as a transmittance profile of radiation through an absorption spectrometer. The x-axis represents wavelength and the y-axis represents a normalized transmittance of radiation through a cell of an absorption spectrometer. The peaks (e.g. the values of higher transmittance) in this example occur at wavelengths in which carbon dioxide absorbs relatively less radiation when compared to the troughs, which occur at wavelengths at which carbon dioxide absorbs relatively strongly. In Fig. 3, line 300 shows the absorption spectrum of carbon dioxide in the absence of oxygen whereas line 302 shows the absorption spectrum of carbon dioxide in the presence of oxygen. Similarly, the line 300 may represent the absorption spectrum of carbon dioxide in the presence of a first concentration of oxygen and the line 302 may represent the absorption spectrum of carbon dioxide in the presence of a second concentration of oxygen, wherein the second concentration of oxygen is higher than the first concentration of oxygen. The effect of the presence of oxygen, or an increased concentration of oxygen, in a cell of an absorption spectrometer when determining an absorption spectrum of carbon dioxide is that the absorption peaks of carbon dioxide may become wider, as shown in Fig. 3. The line width change may be a fraction of a picometre (e.g. 0.05 picometres, 0.1 picometres), a few picometres, a few nanometres, or the like.

As will be explained in more detail herein, since the presence of oxygen has a broadening effect on absorption peaks in the absorption spectrum of carbon dioxide, it is not necessary to supply a known concentration of oxygen to a system (e.g. a capnography device) and/or to a subject’s breath which is being analysed to determine a concentration of carbon dioxide. Another advantage of the line broadening effect of oxygen on the absorption spectrum of carbon dioxide is that a concentration of oxygen may also be determined using the same data (e.g. from a carbon dioxide absorption profile). Thus, a second sensor configured to measure a concentration of oxygen specifically may not be needed. An oxygen concentration may be determined based on a determination of a width of an absorption peak of carbon dioxide when compared to an expected width, or reference width, of the absorption peak of carbon dioxide (e.g. in the absence of oxygen). The determination of a concentration of oxygen may be used to refine the determination of a concentration of carbon dioxide and, therefore, the broadening effect of oxygen on the absorption peaks in the absorption spectrum of carbon dioxide may allow for a more accurate determination of a concentration of carbon dioxide within a sample (e.g. a person’s breath). In some examples, the concentrations of carbon dioxide and oxygen can be made simultaneously (e.g. using the same data obtained from a single sensor).

Fig. 4 is an example of data representative of the sensed concentration of carbon dioxide during respiratory cycles of a subject. More specifically, Fig. 4 shows a capnogram representing the concentration of carbon dioxide in a breath of a subject over a plurality of respiratory cycles. The y-axis represents the partial pressure (in millimetres of mercury, mmHg) of carbon dioxide, and the x-axis represents time. The capnogram indicates the level of carbon dioxide in the breath of the subject during multiple exhalations. The profile of the capnogram may be indicative of the health status of the subject. For example, the profile of the capnogram may be indicative of certain health issues.

The examples disclosed herein may be suitable for fast (e.g. breath to breath) measurements. In some examples, measurements may be taken (e.g. the radiation source turned on/off) at any frequency, such as a frequency of at least 50 Hz, or the like. In some examples, the radiation detector may be configured to detect radiation at any frequency, such as a frequency of 50 Hz, 100 Hz, 1000 Hz, or the like. The frequency at which the radiation detector is configured to detect radiation may be at least as high as the frequency at which the radiation source is configured to operate (e.g., the frequency at which the radiation source is turned on/off). According to a first aspect of the disclosure, a method is provided. Fig. 5 shows a flowchart of an example of a method 500 (e.g. a computer-implemented method) of determining a concentration of a gas in a breath of a subject. The method comprises, at step 502, receiving data relating to a radiation intensity at each wavelength of a plurality of wavelengths in a defined wavelength range, the radiation intensity measured using a sensor of an absorption spectrometer. In some examples, the received data comprises radiation intensity data at two or more wavelengths. In some examples, the radiation intensity data may comprise measurements at 2, 5, 10, 50, 100, 500, 1000, 5000, 10000 wavelengths, or the like. In some examples, the received data may comprise radiation intensity data at a number of wavelengths sufficient to resolve an absorption peak of carbon dioxide. In some examples, the received data may comprise radiation intensity data at a number of wavelengths sufficient to resolve two or more absorption peaks of carbon dioxide. In some examples, the received data may comprise radiation intensity data corresponding to two absorption peaks of carbon dioxide that are adjacent to one another. In some examples, the received data may comprise radiation intensity data corresponding to two absorption peaks of carbon dioxide that are not adjacent to one another (e.g. are separated by at least one absorption peak). The resolution with which an absorption peak can be resolved improves as the number of data points (e.g. the number of radiation intensity values) increases and/or as the wavelength increments between adjacent radiation intensity values decreases. For example, to resolve two adjacent absorption peaks of carbon dioxide in the range 4.231 pm to 4.236 pm (as shown in Fig. 3) at a wavelength interval of 0.1 pm, then a total of 5000 radiation intensity values would be required.

In some examples, the radiation intensity data may be received from a radiation sensor. In other examples, the intensity data may be received from a storage device (e.g. a memory, a hard drive of a computer, or the like). A radiation intensity may be represented in terms of a power (e.g. in units of Watts), in terms of a number of photons incident on the radiation detector per unit area of the detector, or the like. The radiation intensity may be representative of a radiation intensity once the radiation has passed through a cell of an absorption spectrometer (e.g. one or multiple times) and is detected by a radiation sensor.

The method 500 further comprises, at step 504, determining, based on the received data, a transmittance of the radiation at each wavelength of the plurality of wavelengths in the defined wavelength range through a cell of the absorption spectrometer.

In some embodiments, a radiation intensity (e.g. a radiation intensity value) measured at the radiation sensor of the absorption spectrometer at a given wavelength may be used a reference radiation intensity value from which a transmittance value through the cell of the absorption spectrometer can be determined. In some examples, a reference radiation intensity value may be a radiation intensity value at an input of an absorption spectrometer. In some examples, the reference radiation intensity value may be a radiation intensity value at an output of an absorption photometer (e.g. when the cell of the absorption photometer comprises a gas with low, or no, absorption, at the wavelengths at which measurements are being taken and/or when the cell comprises no, or a low concentration of, carbon dioxide).

In some examples, a reference transmittance value may be determined by dividing the radiation intensity value at the output of the absorption spectrometer by the radiation intensity value at the input of the absorption spectrometer. In this way, the reference transmittance value may comprise a value between 0 and 1, which may account for radiation losses between the input and output of the absorption photometer. In some examples, the reference transmittance value may be determined by dividing the radiation intensity value at the output of the absorption spectrometer by itself. The reference transmittance value may be set to the value 1 by default.

A transmittance value may be determined by dividing a measured radiation intensity value (e.g. at the output of an absorption spectrometer) by a reference radiation intensity value. A plurality of transmittance values may be determined by dividing each radiation intensity value (e.g. the radiation intensity value at each wavelength in the defined wavelength range) by the reference radiation intensity value, to determine transmittance values over the defined wavelength range corresponding to a gas sample of interest. In some embodiments, the determination of a transmittance of radiation through a cell of an absorption spectrometer at each wavelength of the plurality of wavelengths may comprise using a reference radiation intensity value as a baseline value. In other words, all radiation intensity values may be compared to the reference radiation intensity value, as described in more detail hereinafter. It is noted that a peak in the absorption spectrum of a gas would correspond to a trough in the corresponding transmittance profile.

In some examples, the defined wavelength range may encompass a wavelength associated with a reference radiation intensity value and/or a reference transmittance value falling within a waveband between two adjacent absorption lines of carbon dioxide. In other words, the reference radiation intensity value may comprise a single value corresponding to a wavelength associated with relatively low, or no, absorption by a gas, such as carbon dioxide. For example, the reference radiation intensity value may comprise a value at a wavelength corresponding to a trough (e.g., a minimum) region of an absorption spectrum of a gas (e.g. a region of relatively low, or no, absorption). In this case, the reference radiation intensity value would correspond to a peak (e.g., a maximum) in the corresponding transmittance profile, due to absorption and transmittance being inversely related. In some examples, the reference radiation intensity value may comprise a value at a wavelength falling at, or around, the midpoint between two absorption peaks. In some examples, a reference radiation intensity value is selected based on the lowest absorption value (or, equivalently, the highest transmittance value) within a range of wavelengths encompassing at least one absorption peak. Fig. 3 shows multiple trough regions in an absorption spectrum of carbon dioxide where there is relatively low absorption.

In some embodiments, a plurality of reference radiation intensity values (and/or reference transmittance values) may be determined. For example, an absorption spectrometer may be flushed with a gas (e.g. nitrogen) that is associated with low, or no, absorption in a wavelength range of interest. In this way, a reference radiation intensity value and/or a reference transmittance value may be determined at each wavelength of a plurality of wavelengths in a defined wavelength range. For example, each radiation intensity value may be divided by each reference radiation intensity value for each wavelength in the plurality of wavelengths in a defined wavelength range, respectively, to obtain a transmittance value at each wavelength in the defined wavelength range.

In some embodiments, a reference radiation intensity value may comprise an intensity value at a wavelength corresponding to a trough region of the absorption spectrum located on one of the sides of an absorption peak (e.g. a trough portion 304 located on one side of absorption peak 300, 302). In some examples, a reference radiation intensity value may comprise a radiation intensity value at a wavelength corresponding to a trough region of the absorption spectrum that is not on either side of the absorption peak of interest directly, but rather is located at a trough region located on one side of a neighbouring or subsequent absorption peak (e.g. a trough portion 306 located on one side of absorption peak 300, 302).

A reference radiation intensity value and/or a reference transmittance value may be updated depending on the number of absorption peaks measured. For example, while a single reference radiation intensity value, or a single reference transmittance value, may be used in some examples, in other examples, multiple reference radiation intensity values, or multiple reference transmittance values (e.g. updated reference transmittance values), may be used, respectively. For example, a reference transmittance value may be used that falls on either side of an absorption peak and, therefore, if multiple absorption peaks are measured, multiple reference transmittance values may be used corresponding to each absorption peak, respectively.

A peak in a transmittance profile associated with radiation passing through a cell of an absorption spectrometer may correspond to a trough in a corresponding absorption spectrum. Similarly, a trough in the transmittance profile associated with radiation passing through a cell of an absorption spectrometer may correspond to a peak in the corresponding absorption spectrum.

In some examples, a reference radiation intensity value and/or a reference transmittance value may be determined prior to, during and/or after determining radiation intensity values and/or transmittance values corresponding to a gas sample measurement. In some examples, two or more reference radiation intensity values and/or reference transmittance values are averaged prior to determining transmittance and/or reference radiation intensity values corresponding to a gas sample measurement. In some examples, an interpolation (e.g. a linear interpolation) is performed between the reference radiation intensity values and/or reference transmittance values, wherein the interpolated values are used in the determination of transmittance values corresponding to a gas sample. In some examples, the interpolated reference value corresponding to the time at which a radiation intensity measurement of a gas sample was made may be used in the determination of a transmittance value corresponding to the radiation intensity measurement of the gas sample at that time.

The method 500 further comprises, at step 506, determining, based on the transmittance, a transmittance profile over the defined wavelength range. In some examples, determining a transmittance profile may comprise plotting transmittance as a function of wavelength on a graph and/or determining parameters associated with the transmittance data. In some embodiments, determining parameters associated with the transmittance data may be based on the transmittance profile (e.g. a plot of transmittance as a function of wavelength). Parameters associated with the transmittance data include, for example, the maximum radiation intensity value and the associated wavelength, the maximum transmittance value and the associated wavelength, the minimum transmittance value and the associated wavelength, or the like. In some embodiments, determining a transmittance profile may comprise determining a line width (e.g. the full width half maximum) associated with an absorption line of a gas sample (e.g. carbon dioxide). The transmittance profile and the associated absorption line of a gas sample may be inversely correlated. Determining a transmittance profile may comprise, for example, determining a parameter of the transmittance profile, such as a line width of the transmittance profile, or the like.

The method 500 further comprises, at step 508, determining, based on the transmittance profile, a concentration of carbon dioxide and a concentration of oxygen in the cell of the absorption spectrometer. In some embodiments, a concentration of carbon dioxide may be determined using the Beer-Lambert-Bouguer law, by inputting an absorption value of the sampled gas (e.g. an absorption cross section, absorption coefficient, or the like) and a path length of radiation within the cell of the absorption spectrometer. The Beer-Lambert-Bouguer law can be represented as:

T = e~^anl, where c represents the absorption cross section of an attenuating species, n represents the number density of the attenuating species and I represents the path length of radiation through the attenuating species (e.g. the path length of radiation through a cell of an absorption spectrometer).

Determining a concentration of oxygen may comprise comparing the determined transmittance profile to a reference transmittance profile in which the amount of oxygen present was below a defined threshold concentration. In some examples, the defined threshold concentration of oxygen may comprise an oxygen concentration below 1% (or 10000 parts per million), or any other value. In some examples, the defined threshold concentration of oxygen may be defined in terms of an absorption value or a transmittance value (e.g. the defined threshold concentration of oxygen corresponding to an oxygen concentration that leads to a minimum transmittance value of 0.95, an maximum absorption value of 1 inverse megametre (Mm⁴), or the like). A concentration of oxygen may be determined based on a parameter of the transmittance profile determined at step 506. For example, a line width (e.g. a full width half maximum) associated with an absorption peak of a gas (e.g. carbon dioxide) may be determined. The determined line width may be compared to an expected line width for the absorption peak associated with a particular wavelength and associated with a particular oxygen concentration. For example, in the absence of oxygen, the determined line width should match the expected line width. The expected line width may comprise a tolerance, which may account for slight variations between measurements (e.g. due to temperature differences, pressure differences, random variations in the radiation source stability, uncertainties in the radiation sensor, and the like). A lookup table may be used to compare the determined line width of an absorption peak of carbon dioxide (or other gas) at a given wavelength to a line width associated with an absorption peak of carbon dioxide for varying concentrations of oxygen, until a closest value is found. In some examples, a lookup table, or calibration table, may comprise absorption peak line broadening and/or transmission profile broadening information relating to known mixtures of carbon dioxide and oxygen. If a line width falls between two reference line width values, then an average oxygen concentration corresponding to each of the two reference line widths may be calculated. The line broadening effect, which may be used to determine an oxygen concentration from an absorption peak of carbon dioxide, can be seen in Fig. 3. In some examples, a determined absorption peak of carbon dioxide can be compared to a pre-calibrated absorption line (e.g. in the absence of oxygen) to quantify the extent of broadening of the absorption line, which may be used to calculate the oxygen concentration.

In some examples, determining a concentration of oxygen from absorption measurements of carbon dioxide may be referred to as monitoring oxygen in situ of capnography.

In some examples, a concentration of a gas (e.g. carbon dioxide) can be determined by comparing the transmittance profile and/or absorption profile (e.g. one or more transmittance and/or one or more absorption peaks) to a reference profile. For example, one or more parameters of the transmittance profile (e.g. maximum intensity, full width half maximum, or the like) may be compared to a parameters of a plurality of transmittance profiles corresponding to varying levels of carbon dioxide (e.g. collected during a calibration phase).

In some embodiments, the defined wavelength range may comprise wavelengths in the infrared region of the electromagnetic spectrum. In other examples, the defined wavelength range may comprise wavelengths in other parts of the electromagnetic spectrum, such as the ultraviolet region, visible light region, microwave region, radio wave region, or the like. The defined range of wavelengths may comprise, for example, the wavelength range 2 pm to 5 pm, 4.20 pm to 4.35 pm, 10 pm to 12 pm, 10 pm to 20 pm, 2 pm to 20 pm or the like. The wavelengths in the defined wavelength range may be separated by intervals of 0.1 pm, 0.5 pm, 1 pm, 0.1 nm, 1 nm, less than 1 pm, or the like. In some examples, wavelengths in the defined wavelength range may be separated in a non-linear way (e.g. separated by different size intervals). In some examples, the defined wavelength range may comprise a minimum range of 6 nm (e.g. to cover two absorption lines of carbon dioxide), or the like.

In some embodiments, the defined wavelength range may encompass at least one absorption line of carbon dioxide between trough absorption strength values located on either side of a maximum intensity value. For example, the defined wavelength range may comprise the range 4.231 pm to 4.233 pm as shown in Fig. 3, which may thereby include wavelengths corresponding to an absorption peak and trough portions located on either side of the absorption peak. In some examples, the defined wavelength range may encompass two or more absorption lines (e.g. absorption peaks) of carbon dioxide (e.g. the defined wavelength range may comprise the range 4.231 pm to 4.236 pm as shown in Fig. 3). In some examples, the defined wavelength range may encompass two absorption lines that are adjacent to one another. In some examples, the defined wavelength range may encompass two absorption lines that are not adjacent to one another (e.g. are separated by at least one absorption line).

In some embodiments, the received data may be obtained by determining a transmittance incrementally over a defined wavelength range while increasing and/or decreasing wavelength. For example, a transmittance (e.g. a transmittance value) may be determined by dividing the radiation intensity at an output of an absorption spectrometer by the radiation intensity at an input of the absorption spectrometer. Transmittance values may be determined in this way for each wavelength in the defined wavelength range, respectively (e.g. by dividing the radiation intensity at an output of an absorption spectrometer at each wavelength in the defined wavelength range by the radiation intensity at an input of the absorption spectrometer at each wavelength in the defined wavelength range, respectively). In some examples, transmittance values may be determined using a radiation intensity value at an input of the absorption spectrometer at a single (e.g. fixed) wavelength (e.g. by dividing the radiation intensity at an output of an absorption spectrometer at each wavelength in the defined wavelength range by the reference radiation intensity at an input of the absorption spectrometer at a particular, fixed wavelength from within the defined wavelength range). In some examples, the radiation source is configured to emit radiation at a first wavelength (e.g. 1 pm) and, subsequently, to emit radiation at a second, longer wavelength (e.g. 1.1 pm). This process of emitting radiation at increasing wavelength may iterate up to a defined wavelength (e.g. 2 pm). In some examples, the radiation source may be configured to emit radiation at a first wavelength and decrease wavelength at an interval (e.g. 0.1 pm).

In some examples, multiple absorption peaks may be used to determine a concentration of a gas, such as carbon dioxide. For example, parameters associated with two or more absorption peaks may be compared to parameters of absorption peaks determined during a calibration phase. In some examples, a transmittance value is determined for each wavelength in a plurality of defined wavelengths, which, in combination with absorption cross section data, path length data, and the Beer-Lambert-Bouguer law, may be used to determine a concentration of carbon dioxide. A concentration of carbon dioxide may be made at each wavelength in the plurality of defined wavelengths. In some examples, an average concentration value may be determined. In other examples, a concentration of carbon dioxide may be determined based on a combination of these methods (e.g. based on parameters associated with an absorption peak of carbon dioxide and based on the Beer-Lambert-Bouguer law).

In some examples, determining the properties (e.g. absorption peak width and the like) of two or more absorption peaks may allow for a more accurate determination of a concentration of carbon dioxide and/or a concentration of oxygen. For example, two absorption peaks may change differently with respect to one another in response to a change in a concentration of oxygen (e.g. in the presence of oxygen compared to the absence of oxygen).

Fig. 6 is a flowchart of a further example of a computer-implemented method 600 of determining a concentration of a gas in a breath of a subject. The method 600 comprises, at step 602, determining, based on the reference radiation intensity value, a stability of a radiation source used to generate radiation. In some examples, the stability of the radiation source may be determined based on a calibration (e.g. pre-calibration) of the radiation source. In some examples, the radiation source may be calibrated so that the output of the radiation source is known at each wavelength in the defined wavelength range. In some examples, the stability of the radiation source may be determined by determining a reference radiation intensity value at one or more points in time, and comparing the reference radiation intensity value(s) to a reference radiation intensity value measured during a calibration period (e.g. measured during a calibration period prior to measuring radiation intensity data of a gas sample of interest). In some examples, the reference radiation intensity value measured during a calibration period prior to measuring radiation intensity data of a sample of interest may be referred to as a precalibration, a first calibration, an initial calibration, or the like. Subsequent reference radiation intensity values may be determined during a second calibration period, a third calibration period, or the like, which may occur at a time after the first calibration period. In some examples, a reference radiation intensity value may be determined for each wavelength in the defined wavelength range.

The radiation source may be controlled using a radiation source control. The radiation source control may adjust a temperature and/or a current associated with the radiation source (e.g. the current provided to the radiation source) to achieve stability of the radiation source. In some examples, the laser diode (e.g. the lasing medium and/or its cavity) may be temperature stabilized. In this way, the laser diode may be controlled to produce radiation sweeping a desired wavelength range (e.g. the defined wavelength range). In some examples, the radiation source control may adjust the temperature and/or current associated with the radiation source such that the reference radiation intensity value(s) are brought into line with (e.g. matches or is similar to) the reference radiation intensity value(s) measured during a pre-calibration. In other words, the radiation source control may recalibrate the radiation source based on a comparison of the reference radiation intensity value(s) (e.g. second, or subsequent, radiation intensity values) and radiation intensity values measured during a pre-calibration by varying the temperature and/or current associated with the radiation source.

Calibration of the radiation source may be part of a re-zeroing process for the radiation detector where a starting wavelength is identified relative to the calibration gas and/or gas absorption profile, and/or between the spans between the absorption lines/profiles. The starting wavelength may be a wavelength corresponding to a trough absorption strength value (e.g. 4.232 pm, a wavelength between 4.230 and 4.232 pm, a wavelength in the trough portion shown by 306 in Fig. 3, or the like).

The method 600 comprises, at step 604, refining the determination of the concentration of carbon dioxide and the concentration of oxygen based on the stability of the radiation source. As explained previously, the stability of the radiation source may be determined by comparing a reference radiation intensity value to a reference radiation intensity value measured during a calibration period (e.g. a pre-calibration period).

The method 600 comprises, at step 606, refining the determination of a concentration of carbon dioxide based on the determination of a concentration of oxygen. In some examples, the line broadening effect of oxygen on the absorption peaks of carbon dioxide may be used to detect the presence of oxygen. In some examples, a reduced and/or a broadened transmittance profile associated with a measurement of a measurement of a gas sample (e.g. a gas sample included an amount of carbon dioxide) may be indicative of the presence of oxygen, and/or may be used to monitor and/or quantify the presence of oxygen. For example, an absorption line associated with carbon dioxide may be broadened and/or the absorption strength associated with the absorption peak reduced, due to the presence of oxygen. In some examples, refining the determination of a concentration of carbon dioxide based on the line broadening effect of oxygen on carbon dioxide absorption peaks may be referred to as in-situ compensation of carbon dioxide measurements. For example, the presence of oxygen may lead to a broader absorption line of carbon dioxide and/or may lead to a lower absorption strength. This information may therefore be used to refine the determination of a concentration of carbon dioxide (e.g. by comparing an absorption and/or transmittance profile associated with carbon dioxide in the absence of oxygen with absorption and/or transmittance profiles associated with various mixtures of carbon dioxide and oxygen). A lookup table, or calibration table, may be used to refine the determination of a concentration of carbon dioxide by comparing the absorption spectrum, or transmittance profile, to absorption spectrums, or transmittance profiles, corresponding to known mixtures of carbon dioxide and oxygen, respectively.

In some examples, refining the determination of a concentration of carbon dioxide may comprise using a calibration (e.g. a pre-calibration) and/or the relative spectral transmittance of two adjacent absorption/transmittance lines (e.g. the relative intensity may be related to the gas concentration and the midpoint between the absorption lines). In some examples, the midpoint between two absorption lines may be where the absorption strength of carbon dioxide is at a minimum. The absorption strength at the midpoint between two absorption lines may be used as a reference value to determine the absorption strength to calculate a concentration of carbon dioxide.

According to a second aspect of the disclosure, a computer program product is provided. Fig. 7 is a schematic illustration of an example of a processor 702 in communication with a computer-readable medium 704. According to various embodiments, a computer program product comprises a non-transitory computer-readable medium 704, the computer-readable medium having computer-readable code 706 embodied therein, the computer-readable code being configured such that, on execution by a suitable computer or processor 702, the computer or processor is caused to perform steps of the methods 500, 600 discussed herein.

According to a third aspect of the disclosure, a system is provided. Fig. 8 is a schematic illustration of an example of a system 800 for determining a concentration of a gas in a breath of a subject. The system 800 comprises an absorption spectrometer 804 comprising a radiation source 806 configured to generate radiation at a plurality of wavelengths in a defined wavelength range, a cell 808 configured to contain a sample of breath of a subject, and a radiation sensor 810 configured to detect radiation over a range of wavelengths. The system 800 further comprises a processor 802 configured to perform the steps of method 500 and/or method 600 disclosed herein. While, in some embodiments, the system 800 may comprise a processor configured to perform steps of the method 500 and/or the method 600, the processor may, in other embodiments, be a separate component. The processor 802 may communicate with components of the system 800 (e.g. the radiation source 806 and/or the radiation sensor 810) via a wired or wireless communication protocol.

In some embodiments, the radiation source 806 may be a laser diode (e.g. a tuneable, narrow bandwidth distributed feedback interband cascade laser diode, a tuneable distributed feedback interband cascade laser diode, a quantum cascade laser, or the like). The radiation source 806 may be tuned to emit various wavelengths within the wavelength ranges disclosed herein (e.g. 4.20 pm to 4.35 pm). In some examples, the output of the radiation source 806 may be pre-calibrated. In some examples, the radiation source 806 is directed towards a gas cell with a known path length.

In some examples, the radiation sensor 810 may comprise a PbSe detector, an InAsSb detector, a thermal detector (e.g. a pyroelectric sensor or a thermopile sensor), or the like.

Fig. 9 is a schematic illustration of a further example of a system for determining a concentration of a gas in a breath of a subject. Fig. 9 shows an example of a capnography device 900 comprising a system as shown in Fig. 8 and a breath receiving unit 902 configured to receive breath from a subject (e.g. from a wearer of a wearable mask), wherein the sample of breath contained in the cell 808 is obtained from the breath receiving unit 902. Capnography may be used to measure a carbon dioxide concentration profile in a breath of a subject (e.g. the gaseous component of a person’s breath), and may be used to provide useful information on the metabolic status of patients. In some examples, oxygen may be considered to be the raw material for metabolism whereas carbon dioxide may be considered to be a waste product of metabolism. The ability to monitor and quantify oxygen and carbon dioxide in the respiratory gases of a subject is desirable to provide better and more complete understandings of their metabolic status.

The processor 702, 802 can comprise one or more processors, processing units, multicore processors or modules that are configured or programmed to control components of the system 900 in the manner described herein. In particular implementations, the processor 702, 802 can comprise a plurality of software and/or hardware modules that are each configured to perform, or are for performing, individual or multiple steps of the method described herein.

The term “module”, as used herein is intended to include a hardware component, such as a processor or a component of a processor configured to perform a particular function, or a software component, such as a set of instruction data that has a particular function when executed by a processor.

It will be appreciated that the embodiments of the invention also apply to computer programs, particularly computer programs on or in a carrier, adapted to put the invention into practice. The program may be in the form of a source code, an object code, a code intermediate source and an object code such as in a partially compiled form, or in any other form suitable for use in the implementation of the method according to embodiments of the invention. It will also be appreciated that such a program may have many different architectural designs. For example, a program code implementing the functionality of the method or system according to the invention may be sub-divided into one or more sub-routines. Many different ways of distributing the functionality among these sub-routines will be apparent to the skilled person. The sub-routines may be stored together in one executable file to form a self-contained program. Such an executable file may comprise computer-executable instructions, for example, processor instructions and/or interpreter instructions (e.g. Java interpreter instructions). Alternatively, one or more or all of the sub-routines may be stored in at least one external library file and linked with a main program either statically or dynamically, e.g. at run-time. The main program contains at least one call to at least one of the sub-routines. The sub-routines may also comprise function calls to each other. An embodiment relating to a computer program product comprises computer-executable instructions corresponding to each processing stage of at least one of the methods set forth herein. These instructions may be sub-divided into sub-routines and/or stored in one or more files that may be linked statically or dynamically. Another embodiment relating to a computer program product comprises computer-executable instructions corresponding to each means of at least one of the systems and/or products set forth herein. These instructions may be sub-divided into sub-routines and/or stored in one or more files that may be linked statically or dynamically.

The carrier of a computer program may be any entity or device capable of carrying the program. For example, the carrier may include a data storage, such as a ROM, for example, a CD ROM or a semiconductor ROM, or a magnetic recording medium, for example, a hard disk. Furthermore, the carrier may be a transmissible carrier such as an electric or optical signal, which may be conveyed via electric or optical cable or by radio or other means. When the program is embodied in such a signal, the carrier may be constituted by such a cable or other device or means. Alternatively, the carrier may be an integrated circuit in which the program is embedded, the integrated circuit being adapted to perform, or used in the performance of, the relevant method.

Variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the principles and techniques described herein, from a study of the drawings, the disclosure and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. A single processor or other unit may fulfil the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. A computer program may be stored or distributed on a suitable medium, such as an optical storage medium or a solid- state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.

Claims

1. A computer-implemented method (500) of determining a concentration of a gas in a breath of a subject, the method comprising: receiving (502) data relating to a radiation intensity at each wavelength of a plurality of wavelengths in a defined wavelength range, the radiation intensity measured using a sensor of an absorption spectrometer; determining (504), based on the received data, a transmittance of the radiation at each wavelength of the plurality of wavelengths in the defined wavelength range through a cell of the absorption spectrometer; determining (506), based on the transmittance, a transmittance profile over the defined wavelength range; and determining (508), based on the transmittance profile, a concentration of carbon dioxide and a concentration of oxygen in the cell of the absorption spectrometer.

2. A computer-implemented method (500) according to claim 1, wherein determining a transmittance profile comprises determining a line width associated with an absorption line of carbon dioxide.

3. A computer-implemented method (500) according to any preceding claim, wherein the defined wavelength range encompasses at least one absorption line of carbon dioxide between trough absorption strength values located on either side of a maximum intensity value.

4. A computer-implemented method (500) according to claim 3, wherein the defined wavelength range encompasses a wavelength associated with a reference radiation intensity value falling within a waveband between two adjacent absorption lines of carbon dioxide; and wherein the determination of the transmittance of the radiation at each wavelength of the plurality of wavelengths comprises using the reference radiation intensity value as a baseline value.

5. A computer-implemented method (500, 600) according to claim 4, further comprising: determining (602), based on the reference radiation intensity value, a stability of a radiation source used to generate radiation; and refining (604) the determination of the concentration of carbon dioxide and the concentration of oxygen based on the stability of the radiation source.

6. A computer-implemented method (500, 600) according to any preceding claim, wherein the defined wavelength range is between 4.20 pm and 4.35 pm.

7. A computer-implemented method (500, 600) according to any preceding claim, wherein the received data is obtained by determining a transmittance incrementally over a defined wavelength range while increasing and/or decreasing wavelength.

8. A computer-implemented method (500, 600) according to any preceding claim, wherein determining a concentration of carbon dioxide comprises inputting an absorption coefficient of carbon dioxide and a path length of radiation within the cell of the absorption spectrometer into the Beer-Lamb ert-Bouguer law.

9. A computer-implemented method (500, 600) according to any preceding claim, wherein determining a concentration of oxygen comprises comparing the determined transmittance profile to a reference transmittance profile in which the amount of oxygen present was below a defined threshold concentration.

10. A computer-implemented method (500, 600) according to any preceding claim, further comprising: refining (606) the determination of a concentration of carbon dioxide based on the determination of a concentration of oxygen.

11. A computer program product comprising a non-transitory computer readable medium (704), the computer readable medium having computer readable code (706) embodied therein, the computer readable code being configured such that, on execution by a suitable computer or processor (702), the computer or processor is caused to perform the method of any of the preceding claims.

12. A system (800) comprising: an absorption spectrometer (804) comprising: a radiation source (806) configured to generate radiation at a plurality of wavelengths in a defined wavelength range; a cell (808) configured to contain a sample of breath of a subject; and a radiation sensor (810) configured to detect radiation over a range of wavelengths; and a processor (802) configured to: receive data relating to a radiation intensity at each wavelength of the plurality of wavelengths measured using the radiation sensor; determine, based on the received data, a transmittance of the radiation at each of the plurality of wavelengths through the cell; determine, based on the transmittance, a transmittance profile over the defined wavelength range; and determine, based on the transmittance profile, a concentration of carbon dioxide and a concentration of oxygen in the cell.

13. A system (800) according to claim 12, wherein the radiation source comprises a tuneable distributed feedback interband cascade laser diode; and wherein the radiation sensor comprises a photo detector.

14. A system (800) according to claim 12, wherein determining a transmittance profile comprises determining a line width associated with an absorption line of carbon dioxide.

15. A capnography device (900) comprising: a system (800) according to claim 12 or claim 13; and a breath receiving unit (902) configured to receive breath from a subject; wherein the sample of breath contained in the cell is obtained from the breath receiving unit.