WO2009043795A1 - Dispositif de prélèvement d'échantillon pour l'analyse tamponnée d'air expiré - Google Patents

Dispositif de prélèvement d'échantillon pour l'analyse tamponnée d'air expiré Download PDF

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Publication number
WO2009043795A1
WO2009043795A1 PCT/EP2008/062844 EP2008062844W WO2009043795A1 WO 2009043795 A1 WO2009043795 A1 WO 2009043795A1 EP 2008062844 W EP2008062844 W EP 2008062844W WO 2009043795 A1 WO2009043795 A1 WO 2009043795A1
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WO
WIPO (PCT)
Prior art keywords
buffer tube
air
tube
respiratory
analysis
Prior art date
Application number
PCT/EP2008/062844
Other languages
German (de)
English (en)
Inventor
Ingrid Kohl
Jonathan Beauchamp
Thorsten Titzmann
Original Assignee
Ionimed Analytik Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from EP07117483A external-priority patent/EP2042866A1/fr
Application filed by Ionimed Analytik Gmbh filed Critical Ionimed Analytik Gmbh
Priority to EP08804740A priority Critical patent/EP2064543A1/fr
Publication of WO2009043795A1 publication Critical patent/WO2009043795A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/083—Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/08—Detecting, measuring or recording devices for evaluating the respiratory organs
    • A61B5/097—Devices for facilitating collection of breath or for directing breath into or through measuring devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/497—Physical analysis of biological material of gaseous biological material, e.g. breath

Definitions

  • the invention relates to a device and a method for the direct analysis of respiratory gas and their use as a quantitative detection method for renal function parameters in the respiratory air.
  • Breathing air analysis has great potential as a non-invasive method for medical diagnostics, therapy monitoring and / or quantification of exposure to certain substances (environmental toxins, workloads, etc.).
  • breathing air always stands for the exhaled air.
  • a small portion of the breath consists of volatile inorganic and organic substances. More than 3400 such substances are known in the respiratory air of normal healthy people. These substances are either formed in the body by metabolic processes or taken from the environment and excreted again via the respiratory air. Of particular interest for medical diagnostics is the alveolar air, since these are in one Balance with the blood stands. Since alveolar air is not contained in the breath, it is the correct term for the last part of the expired air, and this end-expiratory part is the part of the air that correlates best with alveolar air.
  • the respiratory donation takes place in a storage container. This may be stored temporarily, brought to the analyzer and then analyzed after any preprocessing.
  • the respiratory gas sample is fed directly to an analyzer during delivery and analyzed immediately.
  • breath samples affects their composition by diffusion through the walls of the storage medium as well as interactions and chemical reactions in the gas phase and at the contact surfaces. Due to the low concentrations of trace gases, these effects can lead to high relative concentration changes within short periods of time.
  • the typical problems of storage do not exist in the direct measurement to such an extent, since the interaction time of the gas sample with contact surfaces is very short. Losses due to diffusion are not expected to be appreciable.
  • the direct measurement provides immediate results and is associated with a relatively small amount of time, but in this way today often only accessible substances that are present in sufficient concentration and are known, since only a small amount of gas is available.
  • Devices for direct breathing air analysis are known, for example, from US 2007/093725 A1 and US 2007/016092 A1. However, these are only suitable for the analysis of relatively high concentrations.
  • indicator substances are used, such as in WO 2004/006766 A and WO 03/041565 A, the detection methods for "Helicobacter pylori" on the basis a urea gab described.
  • Such indicator substances must be administered sufficiently long before the actual measurement that their associated metabolites will later be present in sufficient concentration in the breathing air to be accessible for direct analysis. In such cases, however, they are no longer non-invasive methods in the narrower sense.
  • the invention provides a sampling device for the qualitative and quantitative determination of trace gases in the respiratory air.
  • the sampling device according to the invention has a buffer tube open to both ends, the breathing air being blown into one of these ends. Air is sucked out of the buffer tube via a transport tube connected centrally to the buffer tube.
  • the transport tube is arranged both axially and radially centrally on the buffer tube.
  • the sampling device is designed such that in the respiratory air analysis, a specific, well-defined flow pattern is generated.
  • the device can be optimized for a measurement of the end-expiratory portion of a breath.
  • suction is constantly generated by means of a suction device from the buffer tube through the transport tube. This allows the sample air from the buffer tube in a meter or a sensor, preferably a
  • the sampling device is rinsed permanently and thus conditioned.
  • the contact surfaces of the sampling device are preferably made of an inert material.
  • the sampling device can be heated. The heating and the use of inert materials serve to minimize interactions of the gas components with the interior surfaces.
  • breathing air samples can be transported unadulterated to the measuring device and as accurate as possible measured values can be achieved.
  • surface effects such as condensation and interaction, can be minimized.
  • the breathing air can be blown through a gas-tight attached to one end of the buffer tube mouthpiece and then the contact with the mouthpiece to be separated. This process is repeated within a few minutes, the subject always has contact with the sampling device only during an exhalation.
  • the last end-expiratory portion of the breath sample that has the best correlation with alveolar air remains in the buffer tube and there is a large reduction in flow in the buffer tube. Due to the permanent, defined suction through the transport tube, this portion stored in the buffer tube is transported slowly into the measuring instrument in succession. The entire volume of the buffer tube is thus sucked through the transport tube while ambient air flows. Thus, the breathing air flow is delayed by the imperspieherung the last, so the end-expiratory portion of the breath by several seconds and more time is available for the measurement. As a result, the accuracy of the measurement can be increased and the detection limit can be lowered.
  • the measurement data shows a strong signal change in a rectangular course caused by the change of an alveolar gas concentration to an ambient air gas concentration. This significantly simplifies the distinction between different gas sample fractions and the processing of the measured data.
  • the buffer tube may have a length of 25 to 35 cm.
  • the inner diameter of the buffer tube should be larger than the inner diameter of the transport tube, for example, about ten times as large.
  • the buffer tube may have an inner diameter of about 10 to 14 mm.
  • the transport tube may have an inner diameter of about 0.5 to 2 mm.
  • the present invention combines the advantages of the two above-described methods of measurement after storage and a direct measurement, without including the disadvantages of storage in particular. It is used for direct measurement in conjunction with the achieved detection limits of a measurement after storage and cumulation of multiple breaths. Furthermore, the separation of the respiratory gas fractions is achieved without expensive technical equipment. As with any direct method, the respiratory donation is available as a continuous course from the beginning to the end of exhalation, whereby the end-expiratory part is made available much longer via a buffer and thus the detection limit drops significantly. In addition, specific flow patterns have been established that minimize surface effects as observed in direct processes.
  • Fig. 1 shows schematically a sampling device according to the invention
  • Fig. 3 is a diagram showing the course of a typical
  • FIG. 5 shows a diagram of respiratory air measurement points of the protonated molecular mass 115 u with the associated amount of daily urine and FIG. 5
  • Fig. 6 shows the chemical structural formulas of the renal function parameter creatinine (b) and the metabolic precursor creatine (a). Detailed description of the invention
  • the sampling device has a buffer tube which is open towards both ends and which is connected to an analyzer via a transport tube.
  • the inlet of the very thin transport tube is arranged both axially and radially centered on the buffer tube.
  • Both tubes are made of inert materials (Teflon or surface-treated steel) and surrounded by an insulated heating jacket. The temperature in the heating jacket is kept constant by temperature controllers.
  • the transport tube is connected to the measuring device at the end remote from the probes. Furthermore, a teflon mouthpiece is shown, which is provided as an accessory and is not heated. The mouthpiece is intended for single use.
  • Typical flow conditions such as occur in a sampling device according to the invention are shown schematically in Figs. 2 (a) and 2 (b).
  • Figs. 2 (a) and 2 (b) When blowing into the buffer tube turbulent flow conditions prevail, which leads to an effective mixing in the tube interior. This serves to establish an equilibrium between surface and gas phase. Thus, from the beginning of exhalation, surface coverage of substances to be investigated is formed (see FIG. 2 (a)).
  • FIG. 3 shows an example of the course of a typical respiratory donation
  • the sampling device ensures that
  • the breathing resistance during exhalation is not greater than with nasal exhalation
  • Buffer tube is short enough to minimize the mixing with nachgesaugter ambient air as a result of diffusion and
  • the residence time of the breathing air in the transport tube is short. This will ensure that
  • the buffer tube may have an inner diameter of about 10 to 14 mm.
  • the volume of the buffer tube may be about 30 to 50 mL.
  • the transport tube may have an inner diameter of about 0.5 to 2 mm.
  • Inner diameter of storage tube 12 mm temperature; 80 0 C
  • the analysis unit can be a proton exchange reaction mass spectrometer (PTR-MS) or another high-sensitivity gas sensor for organic and inorganic trace gases.
  • PTR-MS proton exchange reaction mass spectrometer
  • the flow in the transport tube through an additional suction device can be established.
  • hundreds of substances can be analyzed for 20 to 30 seconds, with normal exhalation taking only 2 to 3 seconds.
  • a hitherto unachieved quality is achieved in the high-resolution direct analysis of many substances in the trace concentration range in breathing air without preprocessing when setting the correct flow regime. It is a non-invasive, fast, direct method that nevertheless allows highly sensitive and accurate analysis of even the smallest concentrations of respiratory gas constituents.
  • the correct trace gas concentration on the measuring sensor is ensured by the flow pattern and the heated, inert surfaces. Thus, trace gases in very small concentrations are amenable to analysis.
  • test person gives only about 1 breath per minute with otherwise normal tidal breathing. This serves to restore the balance of the gas exchange surfaces of the lung, as the Respiratory physiology with continuous breathing through a mouthpiece often (unconsciously) changes.
  • test person does not have to decide on the selection of the end-expiratory part of the respiratory system, but only exhale as steadily and completely as possible. He does not have to stop the air for a certain amount of time, nor discard a certain part of the breath.
  • the subjects are given no indicator substances, so there can be no side effects here.
  • the total duration of the measurement remains very short, even when determining hundreds of substances. In particular, the times for changing the surface coverage are short.
  • One application of the present invention is the measurement of a renal function parameter in the respiratory air.
  • This can be used, for example, to determine renal function in intensive care patients, to determine renal function after renal transplantation or to determine the progress of dialysis, the individually ideal dialysis duration and dialysis frequency.
  • the advantages of this diagnostic method over the alternatives are that they are noninvasive is, and a result is available immediately. It is suitable for monitoring kidney function / blood purification.
  • Creatinine and urea are two of many substances / toxins that accumulate in the blood when kidney function is poor.
  • a central issue in dialysis is the question of optimal dosage and frequency.
  • the effectiveness of dialysis is determined by purifying the blood from urea.
  • the dialysis duration is calculated on the basis of a kinetic model of the concentration of urea in the blood before dialysis and hemodialysis parameters.
  • Urea is the only one of many toxins that accumulate during dialysis-free periods.
  • a minimally invasive method that records in real time during dialysis the concentrations of a variety of toxins.
  • the breath analysis can monitor a variety of markers in real time.
  • at least one renal function parameter can be quantified, which can be used for the continuous evaluation of the dialysis progress and for determining the individually necessary remaining dialysis time.
  • the substance with the molecular mass 115 u also correlates with the conventional renal function parameters and is most probably an isotope of the substance with the molecular mass 114 u.
  • the substance is protonated therefore the figures indicate the "mass + 1"
  • the PTR-MS measurement signal at the protonated mass 115 u may be caused by the creatine substance ( Figure 6a)
  • the mass number can be explained as follows: Creatine has a molecular mass of 131 u This molecule fragments upon ionization in the PTR MS with elimination of ammonia, so the substance is detected at 17 U lower mass.
  • the substances with masses 114 and 115 u do not correlate with the occurrence of a rejection reaction or an infection.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Medical Informatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Surgery (AREA)
  • Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Physiology (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • General Physics & Mathematics (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Emergency Medicine (AREA)
  • Obesity (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

L'invention concerne un dispositif de prélèvement d'échantillon pour l'analyse de gaz à l'état de traces dans l'air expiré. Le dispositif de prélèvement d'échantillon selon l'invention comprend un tube tampon ouvert aux deux extrémités, de l'air expiré pouvant être insufflé par l'une des extrémités ouvertes. Un tube de transport est raccordé au milieu du tube tampon. Le dispositif selon l'invention comprend également un dispositif d'aspiration servant à générer un courant d'aspiration défini continu, du tube tampon à travers le tube de transport. Le dispositif de prélèvement d'échantillon selon l'invention est conçu de sorte qu'on a dans le tube tampon des écoulements se situant dans la zone de transition entre écoulement turbulent et écoulement laminaire avec des nombres de Reynolds supérieurs à 2000 au début de l'expiration d'air et des écoulements purement laminaires avec des nombres de Reynolds inférieurs à 1000 une fois l'expiration achevée. On dispose ainsi de la partie d'air de fin d'expiration pour l'analyse pendant un certain temps après l'expiration d'air grâce à la mise en tampon dans le tube tampon. L'invention concerne également un système de prélèvement d'échantillon d'air expiré en temps réel et un procédé pour l'analyse en temps réel de l'air expiré qui utilise ce système.
PCT/EP2008/062844 2007-09-28 2008-09-25 Dispositif de prélèvement d'échantillon pour l'analyse tamponnée d'air expiré WO2009043795A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP08804740A EP2064543A1 (fr) 2007-09-28 2008-09-25 Dispositif de prélèvement d'échantillon pour l'analyse tamponnée d'air expiré

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP07117483.3 2007-09-28
EP07117483A EP2042866A1 (fr) 2007-09-28 2007-09-28 Analyse d'air inhalé
EP08162885 2008-08-25
EP08162885.1 2008-08-25

Publications (1)

Publication Number Publication Date
WO2009043795A1 true WO2009043795A1 (fr) 2009-04-09

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PCT/EP2008/062844 WO2009043795A1 (fr) 2007-09-28 2008-09-25 Dispositif de prélèvement d'échantillon pour l'analyse tamponnée d'air expiré

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EP (1) EP2064543A1 (fr)
WO (1) WO2009043795A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0573060A2 (fr) * 1992-06-03 1993-12-08 Hideo Ueda Appareil et méthode pour examiner de l'air expicée à des fins cliniques
WO2003041565A2 (fr) * 2001-11-13 2003-05-22 Photonic Biosystems Methode de diagnostic de l'infection a helicobacter pylori
WO2004006766A2 (fr) * 2002-07-12 2004-01-22 Baxter International Inc. Procede et appareil permettant de deceler la presence d'une bacterie dans le tractus gastro-intestinal d'un sujet
WO2004090534A1 (fr) * 2003-04-01 2004-10-21 The Charles Stark Draper Laboratory, Inc. Analyse respiratoire non invasive au moyen de la spectrometrie de mobilite ionique a champ asymetrique
US20070016092A1 (en) * 2005-07-15 2007-01-18 David Shaw Self-purging, air-stabilizing, illuminated collection system for breath analysis
US20070093725A1 (en) * 2005-10-06 2007-04-26 Shaw David I Dual entry collection device for breath analysis

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0573060A2 (fr) * 1992-06-03 1993-12-08 Hideo Ueda Appareil et méthode pour examiner de l'air expicée à des fins cliniques
WO2003041565A2 (fr) * 2001-11-13 2003-05-22 Photonic Biosystems Methode de diagnostic de l'infection a helicobacter pylori
WO2004006766A2 (fr) * 2002-07-12 2004-01-22 Baxter International Inc. Procede et appareil permettant de deceler la presence d'une bacterie dans le tractus gastro-intestinal d'un sujet
WO2004090534A1 (fr) * 2003-04-01 2004-10-21 The Charles Stark Draper Laboratory, Inc. Analyse respiratoire non invasive au moyen de la spectrometrie de mobilite ionique a champ asymetrique
US20070016092A1 (en) * 2005-07-15 2007-01-18 David Shaw Self-purging, air-stabilizing, illuminated collection system for breath analysis
US20070093725A1 (en) * 2005-10-06 2007-04-26 Shaw David I Dual entry collection device for breath analysis

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HERBIG J ET AL: "Buffered end-tidal (BET) sampling - A novel method for real-time breath-gas analysis", JOURNAL OF BREATH RESEARCH 20080901 GB, vol. 2, no. 3, 1 September 2008 (2008-09-01), pages 1 - 9, XP002510726, ISSN: 1752-7155 1752-7163 *

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