WO2010094414A1

WO2010094414A1 - Method and device for performing analyses of breath gas samples

Info

Publication number: WO2010094414A1
Application number: PCT/EP2010/000798
Authority: WO
Inventors: Jürgen KAPPLER; Thomas Liedtke; Walter Fabinski; Uvo HÖLSCHER; Heinz Fischer; Josef Vogt
Original assignee: Abb Ag
Priority date: 2009-02-19
Filing date: 2010-02-10
Publication date: 2010-08-26
Also published as: DE102009009583A1

Abstract

The invention relates to a method and to a device for performing analyses of breath gas samples according to the preamble of claims 1 and 20. In order to further develop a method and a device such that the same function without the diluting method known from the prior art, and ensuring the precision requirements and rapid online measurement even in a broad range of oxygen concentrations, the invention proposes that calibration data are obtained across targeted variations of interference variables and used for forming a calibration function by means of statistical methods. A method is thereby proposed by means of which the interference variables can be modified independently of each other. Alternatively, the correction data for comparing the CO2 cross-sensitivity influence effects can be first determined in a calibration, wherein the limit concentrations for the working range for CO2 are simultaneously set. In a second step, the correction data and the working range for O2 are set, wherein the CO2 correction had been previously activated.

Description

Method and device for carrying out analyzes of respiratory gas samples

The invention relates to a method and a device according to the preamble of claims 1 and 19.

Measurement of the δ ¹³ C value in respiratory gas diagnosis with the NDIR method (non-dispersive infrared spectroscopy) is subject to various influence effects. These must be corrected to meet the accuracy requirements. The influence effects include:

- The CO2 concentration. Non-linear effects on the δ ¹³ C value can occur over the CO2 working range of the respiratory gas. These deviations are compensated according to the prior art by an automated method. For this purpose, a (deeper) breath is given to the device, which is diluted in a gas cycle successively with CO2-free air. The dependence on the CO2 concentration is determined, stored and used in the signal processing to correct the deviation (linearization).

Such methods are known from DE 195 38 431 A1 and EP 1111371 A2. EP 1111371 differs from DE19538431 and provides CO 2 correction breaths that are taken at different depths and placed on the device. The EP 1111371 A2 thus takes into account the corresponding 02 concentration in the case of the CO2 correction. Both of these documents refer to breathing air without increased oxygen content.

- The 02 concomitant concentration also influences the δ ¹³ C measurement. This influence is superimposed with the influence of CO 2. It is neglected when working in the air, because the O2 concentration in the exhalation with the comparative measurement only slightly differs. The situation is different in the case of ventilation with high 02 concentrations, as can occur in intensive care patients. Here, the dynamic range of about 90Vol% to about 15Vol% O2 (air). This influence effect is not based on the cross-sensitivity, but on the carrier gas dependence (impact broadening of the rotation lines) and generates a concentration-proportional influence effect. It is currently being corrected by the prior art with a dilution method, as known from WO 01/47416 A1. For this purpose, the exhaled air is diluted until the O2 concentration in the work area as in working with air.

On this basis, the invention has the object of developing a method and a device to the effect that this or this works without said dilution method and the accuracy requirements and the fast online measurement is ensured even in the wide range of oxygen concentration.

In a method of the generic type, the object is achieved by the characterizing features of claim 1.

Further advantageous embodiments of the method according to the invention are specified in the dependent claims 2 to 18.

With regard to a device of the generic type, the object is achieved by the characterizing features of claim 19.

With regard to a software program product, the stated object is achieved by the features of claim 20.

Even with the dilution method according to WO 01 / 47416A1 for the correction of the influence of oxygen with increased O2 ventilation, the accuracy requirements are achieved in the work area. However, this method has the disadvantage that the nitrogen to be provided for dilution in bottles disturbs in a confined spatial situation. Another negative effect is that the CO2 concentration in this method also diluted and the CO2 working range to small concentrations limited and the sensitivity is lowered. Furthermore, since the successive dilution steps are measured individually, the speed of the overall determination is reduced and thus the online measurement considerably narrows.

The present invention is intended to provide a correction method for the e.g. two in the

Operation simultaneously occurring, overlapping influencing variables produce CO2 and increased O2 content with simple process steps and for ongoing operation and their effectiveness at any time with simple means verifiable and adjustable.

The core of the method according to the invention is that the respiratory gas sample is taken as expiration gas directly at the sample and fluidized in a mixing chamber, and subsequently discharged there by a controllable valve and mixed with mixed gases or fed undiluted to a measuring cuvette of the NDIR spectrometer, and that the correction is performed using an equation of the form δ ¹³ C g _em = basal value + sensitivity * δ ¹³ C of the sample, basal value and sensitivity being functions of the disturbances (actual value of the sample). Basal value and sensitivity describe the dependence of the δ ¹³ C values on the current disturbance variables such as CO2 and 02 concentrations of a sample. To determine the basal value function, for a calibration sample that has not been enriched with 13C, the CO2 and O2 concentrations are varied by appropriate technical measures. The resulting δ ¹³ C values as well as the O 2 and CO 2 concentrations are measured and from this a mathematical correlation between the δ ¹³ C values and the O 2 and CO 2 content as a device-dependent variable is derived by regression methods. The range of 02 and CO2 concentrations is referred to as the working range of the device. This work area can be considered as a generalization of the EP 1111371 A2 defined calibration. In a second step, the sensitivity is estimated. For this purpose, 13C-enriched samples are examined to determine the sensitivity of the instrument to changes in the 13C content of a sample. The 02 and CO2 concentrations of these samples should be in the Working area of the device are. This dependence should also be described from the corresponding measured values via regressions. For the correction of disturbance influences they are measured online. Ideally, for example, the measurements of O2 and CO2 for a sample should yield concentrations of the current values of basal value and sensitivity. Thus, from the measured δ ¹³ C value of the corresponding δ ¹³ C value of the sample can be derived. Thus, from only one measurement of a sample, its δ ¹³ C value can be determined. This makes online operation possible. For quality control (verification of correction functions) 02 and CO2 concentrations of the sample can be easily modified with the mechanisms described below. A new measurement would have to give comparable values. Other Störgrößeneinflußeffekte such as the air pressure can be taken into account with appropriate procedures.

The second part of the application according to the invention is the acquisition of the measurement data by means of which the functions for basal value and sensitivity are obtained. The various options and details for the method steps are explained in more detail below in their details. The limit concentrations for the working range for CO2 are set at about 0.5% to 4% by volume. The working range for 02 is set at approx. 16 - 90% by volume. The influence effects of 02 and CO2 are superimposed. To capture this overlay, both disturbances should be varied independently. However, since these are based on different technical principles (cross sensitivity vs. carrier gas dependence), it should alternatively be possible to first eliminate the cross sensitivity (CO2) and then correct the carrier gas dependence of the oxygen. Both options are supported with the approaches described below.

For practical reasons, it should also be taken into account that the two independent influencing factors (CO 2 respiration depth and increased O 2 content) can be verified and corrected at any time, even on site, with simple, existing means. The CO2 production with the help of breathing air and the present CO2 analysis as well as the O2-analysis and the highly concentrated O2-gas (100Vol%) in intensive care units are to be resorted to here. The 02- Correction must take into account the concentration range between 90% by volume and approx. 16% by volume.

In the event that the CO2 cross-sensitivity is first characterized, it is indicated that for the O2 calibration, various changes in the O2 concentration are made in the expected O2 concentration range of the respiratory gas sample, and from the related or related measurements, the O2 correction values. Dependence of the δ ¹³ C values can be determined. The CO2 cross-sensitivity should have been corrected in a previously performed step with the resulting correction data. The at the

Changes in the CO2 concentrations with changing CO2 concentration thus have no effect on the δ ¹³ C values. Make sure that the dilution steps result in CO2 concentrations that are within the limits specified by the analyzer's operating range.

For independent variation of the disturbances it is stated that in order to obtain the calibration values a respiratory gas sample is taken with previous ventilation of the test subject with air and the respiratory gas sample is gradually concentrated with O 2, such that in as few steps as possible a further O 2 concentration range, preferably between 16 and 90 vol% is covered, with the

Concentration (admixture) made from 100% 02-filled gas containers.

Alternatively, it is suggested that a sample of respiratory gas be sampled with previous ventilation of the subject at 100 vol% O 2 to obtain the calibration data, and dilution of the oxygen by O 2 absorption in absorbers with the simultaneous addition of N 2 or CO2 free air performed in order to obtain the calibration data To compensate pressure drop.

With regard to a device, the invention consists in that a mixing chamber for collecting the respiratory gas samples with a plurality of downstream valves via a control device corresponds such that between the operating conditions - O2 correction with O2 dilution or concentration, - O2 correction with O2 absorption,

- O2 correction with CO2-free air dilution

- Direct introduction of the breathing gas sample into the measuring cuvette can be switched in each case in a closed circuit.

Furthermore, the software program product provides a solution in which the method is configured as a software program product, and thus can be read into the control device, which then controls the individual elements of the device in the manner according to the invention.

The invention is illustrated in an embodiment in the drawing and described in more detail below.

Figure 1 shows the method and operation of the invention for a gas flow and control system employing a known calibrated NDIR gas analyzer (e.g., Uras). All measuring and calibration tasks described in detail can be carried out with this device. For the measuring task described here, first the operating points or working ranges for the CO2 and oxygen concentration are determined during the calibration.

To obtain the calibration data, the concentration variations are made in individual steps in the circulatory system. Optionally, the following options are available: Successive dilution of the respiratory burst by CO2-free air or oxygen. With the increase of the O2 concentration the CO2 dilutes at the same time. At higher dilution or mixing levels, the resulting CO2 concentration may become so low that it may be below the defined operating range of the analyzer.

To avoid this, alternatively or in addition, the O 2 concentration can be gradually reduced by selective absorption of oxygen. The oxygen concentration is according to the invention via a selective

Oxygen absorber in a gas circulation suksessive reduced, wherein the extracted oxygen is replaced by CO2-free air. The CO2 content remains in a first approximation. The steps for dilution or concentration are expediently arranged eg in a bypass in the circuit in which the meter and the oxygen sensor is located.

All of the process steps are automatically controlled by programmed algorithms, which in the The corresponding device consists of gas circuits with pumps, filters, valves and the integrated analyzer as they emerge from Figure 1.

As a result, incremental correction data can be obtained with the mentioned device. In particular, the following limitations of the previous

Dilution procedure abolished: increased space requirement, the restriction that the oxygen dependence of the measurements must be determined individually for each sample; that at high oxygen concentrations and relatively low CO2 concentration, the CO2 concentration, after the necessary dilution, is below the working range of the analyzer; The measurement is slow and not online.

The elements used for this purpose are the following in detail.

The expiration air of the patient is supplied to a mixing chamber M. Of the

Downstream of the mixing chamber is a first valve 8, which is controlled via the central control unit 1. This also contains the algorithms used. From there, the respiratory gas sample then passes to a distribution point 12 with several parallel outlets or inputs.

The algorithms implemented in the control unit then either direct the respiratory gas sample directly into the measuring cuvette of the NDIR photometer or make appropriate admixtures by appropriate valve admission.

On the one hand opens at the distribution point 12 there the admixture line from a 02- container and a container with CO2-free air. The mixture and the supply via a valve 6, which is also controlled via the central control unit. At the distribution point 12 is a parallel outlet to the pump 23, the one

Pressure sensor 11 is connected upstream. From there, the gas sample then flows via the valve 10, likewise controlled via the central control unit 1, optionally to a CO 2 Absorber 22 or directly to another valve 9, also controlled by the central control unit.

From there, the gas sample thus prepared then flows into the measuring cuvette 20 of an NDIR spectrometer. The gas sample flows through the measuring cuvette 20 up to the outlet at the opposite end, where it is either vented to the outside via an oxygen sensor 13 via a valve 7, or returned to the distribution point 12 for further conditioning and / or recylation. Also, the valve 7 is controlled as all valves via the central control unit. The detector 21 of the NDIR spectrometer supplies the determined output value to the signal processing 2, which corresponds to the one with the central control unit 1, as well as with the value output 3, for example in the form of a measured value display or storage.

Reference numerals:

1 central control unit

2 signal processing

3 measured value output

4 CO ₂ absorbers

5 O ₂ containers

6,7,8, 9,10 control valves

11 differential pressure sensor

12 feed point / mixing point

13 O ₂ sensor

20 NDIR cuvette

21 NDIR detector

22 O ₂ absorbers

23 pump

M mixing chamber

Claims

claims:

1. A method for operating an NDIR spectrometer in a measuring system for the analysis of respiratory gas with the aid of stable isotope-labeled substrates, with a correction of the δ ¹³ C values overlying disturbances such as

CO2 and 02 for online diagnosis, characterized in that the breathing gas sample is taken as expiration gas directly at the sample and in a mixing chamber is equalized in terms of flow, and subsequently discharged there by a controllable valve and with

Mixed or undiluted mixed gases is supplied to a measuring cuvette of the NDIR spectrometer, and that the correction is performed using an equation of the form δ ¹³ C g _em = basal value + sensitivity ^* δ ¹³ C of the sample, wherein basal value and sensitivity are functions of the disturbances.

2. The method according to claim 1, characterized in that the correction data for the basal value and the sensitivity by targeted changes of the disturbance variables such. CO2 and 02 are won.

3. The method according to claim 2, characterized in that determined from the correction data via suitable statistical methods, the functional relationship between measured value and disturbance and used according to claim 1. For basal value and / or sensitivity, the effects of CO2 (cross-sensitivity) and 02 (carrier gas dependence) can be described by means of possible formally separated functions.

4. The method of claim 1 and 2, or 3, characterized in that for measuring a single sample simultaneously δ ¹³ C values and the disturbance variables such as 02 and CO2 values are recorded from which current values for the basal value and the sensitivity and the actual δ ¹³ C

Sample value can be determined.

5. The method according to claim 1 and 2, characterized in that the working ranges for CO2 with about 0.4 to 4Vol% and for 02 with approx.

16 - 90Vol% are set.

6. The method according to claim 2, characterized in that to collect the correction data for CO2 a deep breath with

Ambient air is added to the measuring technique, which is successively diluted with room air or nitrogen in the given operating range for CO2.

7. The method according to claim 6 or 7, characterized in that for collecting the correction data for 02 a breathing gas sample is taken under previous ventilation of the test subject with air and the respiratory gas sample is gradually concentrated with 02, such that in as few steps as possible a further O2 Concentration range, preferably between 16 and 90 vol% is covered, wherein the concentration (admixing) takes place with 100% 02-filled gas containers wherein either the CO2 content is kept constant or the CO2 influence effect was previously corrected according to claim 6 or 7.

8. The method according to claim 6 or 7, characterized in that for determining the correction data, a breathing gas sample is taken with previous ventilation of the sample with 100Vol% 02, and a selective dilution of the oxygen by O2 absorption in absorbers with the simultaneous addition of N2 or C02 -free air is provided to compensate for the pressure drop and that either the CO2 content is kept constant or corrected beforehand according to claim 6 or 7.

9. The method according to any one of the preceding claims, characterized in that for determining the corrections, the disturbances 02 and CO2 are changed together in successive dilution steps, starting from a high CO2 concentration and a dilution by admixing a high O2 concentration, or starting from a sample with high O2 concentration and admixed with a gas with Ca4 volume% CO2 in air.

10. The method according to any one of the preceding claims, characterized in that the δ ¹³ C values on the density and location of the dilution or concentration steps are controlled and optimized by comparison with predetermined limits of the stored calibration curve.

11. The method according to claim 6 or 7, characterized in that the method measures are carried out by means of a measuring system integrated in the evaluation and control device.

12. The method according to claim 1, characterized in that the regression parameters and correction values are stored.

13. The method of claim 1 to 4, characterized in that the cross sensitivity and carrier gas dependence are determined separately and corrected, and that for the component, which is subject to greater fluctuations, more frequent correction data are collected.

Alternatively, if the basal value and / or sensitivity function relates to both disturbances, suitable statistical methods can be used to determine which combination of coefficients in the equations changes over time, and correction data is collected only to determine these variable components.

14. The method according to any one of the preceding claims, characterized in that for securing, plausibility and verification of the correction data in the measurement of a single sample with the given technical

Equipment 02 and / or CO2 content of a sample is changed, with a subsequent measurement of the sample should expect the same δ ¹³ C value and thus serves to plausibility of the measurement result

15. The method according to claim 8, characterized in that a by 02 absorption entering negative pressure with a differential pressure sensor is measurable, and that said sensor controls a valve which compensates the negative pressure with C02-free air.

16. The method according to any one of the preceding claims, characterized in that for the dilution or concentration of a pump, filters / absorbers and valves existing gas circuit is provided, in which an oxygen sensor is turned on with a measuring range of 16-100Vol%.

17. The method according to claim 16, characterized in that the 12 CO 2 value determined with the NDIR spectrometer serves simultaneously to determine the CO 2 correction parameter.

18. The method according to any one of the preceding claims, characterized in that dilution and concentration approaches can be implemented separately from each other.

19. The method according to claim any one of claims 1 to 15, characterized in that in addition to the concentration values further factors such. the air pressure are taken into account and integrated into the measuring system.

20. Measuring system with an NDIR spectrometer for the analysis of respiratory gas with the aid of stable isotope-labeled substrates, with a correction of the δ ¹³ C values overlying disturbances such as CO2 and 02 for online diagnosis, characterized in that a mixing chamber for collecting the respiratory gas samples with a plurality of downstream valves via a control device corresponds such that between the operating conditions - O2 correction with O2 dilution or concentration,

- O2 correction with O2 absorption,

- O2 correction with CO2-free air dilution can always be switched in a closed circuit.

21. Software control program for carrying out the method according to one of claims 1 to 19, characterized in that the control parameters via the sensor value determination via a exchangeable program software can be determined, and appropriate drivers for controlling the pumps and valves are provided, and that the respective algorithm for this purpose can be implemented via dialing options within the software program product as expandable functions in the device.