WO2015104531A1 - Bronchial gas analyser - Google Patents

Bronchial gas analyser Download PDF

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Publication number
WO2015104531A1
WO2015104531A1 PCT/GB2014/053827 GB2014053827W WO2015104531A1 WO 2015104531 A1 WO2015104531 A1 WO 2015104531A1 GB 2014053827 W GB2014053827 W GB 2014053827W WO 2015104531 A1 WO2015104531 A1 WO 2015104531A1
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WO
WIPO (PCT)
Prior art keywords
light
spectroscopic cell
bronchoscope
light path
elongate member
Prior art date
Application number
PCT/GB2014/053827
Other languages
French (fr)
Inventor
John Couper
Peter Robbins
Gus HANCOCK
Grant Ritchie
Luca CIAFFONI
Original Assignee
Isis Innovation Limited
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Publication date
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Publication of WO2015104531A1 publication Critical patent/WO2015104531A1/en

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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
    • A61B5/0836—Measuring rate of CO2 production
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/267—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor for the respiratory tract, e.g. laryngoscopes, bronchoscopes
    • A61B1/2676—Bronchoscopes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
    • G01N21/3504—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing gases, e.g. multi-gas analysis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/1459—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters invasive, e.g. introduced into the body by a catheter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M16/00—Devices for influencing the respiratory system of patients by gas treatment, e.g. mouth-to-mouth respiration; Tracheal tubes
    • A61M16/04—Tracheal tubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2230/00—Measuring parameters of the user
    • A61M2230/40—Respiratory characteristics
    • A61M2230/43—Composition of exhalation
    • A61M2230/432—Composition of exhalation partial CO2 pressure (P-CO2)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G01N2021/6432—Quenching
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
    • G01N21/39—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using tunable lasers

Definitions

  • the present invention relates to a bronchial gas analyser, in particular to a device for measuring the concentration of carbon dioxide in the bronchi of the lung.
  • FIG. 8 of the accompanying drawings schematically illustrates the airway and lungs of a human.
  • the trachea (windpipe) 81 extends downwards from the larynx 80 until it divides into two main (stem or primary) bronchi 82. These in turn divide into five secondary (or lobar) bronchi 83.
  • the secondary bronchi further subdivide into tertiary or segmental bronchi 84.
  • the tertiary bronchi divide into bronchioles and eventually terminate in alveolar sacs where respiratory gas exchange takes place.
  • Bronchoscopes are inserted through the nose or mouth of the patient, or sometimes via a tracheotomy and typically include lighting and a camera and an instrument or suction channel to allow the physician to advance instruments down the bronchoscope, for example to extract foreign bodies or collect specimens, or to apply suction to remove material from the lungs.
  • bronchoscopes There are typically two broad types of bronchoscope, flexible and rigid.
  • Figure 1 of the accompanying drawings schematically shows a flexible bronchoscope 1 which consists of an elongate section 3 for advancement into the lungs of the patient and a proximal section 5 which, in use, the physician holds.
  • the elongate section 3 is typically steerable by means of controls 7 provided on the proximal section 5 and includes an instrument channel 9, typically of 2 or 2.8 mm diameter (visible in the cross-section of Figure 2) and fibre optics which deliver illumination from light sources 11 and provide an image to a camera 13.
  • a controller 15 is provided, which may be integral with proximal section 5, to supply power and to receive the output from the camera 13.
  • the instrument channel 9 is connected to a port 17 allowing for the application of suction or for the advancement of an instrument down the bronchoscope.
  • FIG 3 schematically illustrates a rigid bronchoscope in which the elongate section 20 is a straight rigid tube, usually of metal.
  • the rigid bronchoscope is typically provided with a viewing port 23, an instrument/suction channel 21 and a controller 25 to provide corresponding functionality to the flexible bronchoscope mentioned above.
  • the instrument/suction channel 21 of a rigid bronchoscope is typically wider than that of the flexible bronchoscope and thus can offer better access for surgery or other therapeutic procedures.
  • capnography which is the monitoring of the concentration or partial pressure of carbon dioxide in the respiratory gases, has been used to monitor patients during anaesthesia and intensive care. Capnography can also be used to indicate the presence of lung disease because a lower than usual difference in carbon dioxide concentration in inhaled and exhaled breath indicates decreased lung performance.
  • US-A-5, 193,544 discloses the provision of an optical path in an endotrachial tube to analyse carbon dioxide in the trachea, but analysing gas in the trachea (windpipe) does not give information on which part of a lung may be diseased. Also, it proposes the use of a gas-permeable but water impermeable material to define a light chamber which can exclude water (which interferes with the analysis), but the carbon dioxide must diffuse through the material, which means that analysis is very slow.
  • WO- Al -2007/084189 discloses an endoscopic system with an integrated system for analysing expired air, but the provision of a light source and detector across the end of a sampling tube means that the system is impracticable for a bronchial gas analyser, and the use of a non-tunable light source means that it cannot distinguish between absorption from carbon dioxide and absorption from water - which is a problem for bronchial analysis.
  • the present invention provides a bronchial gas analyser device for measuring the concentration of carbon dioxide in the bronchi of the lung, the device comprising an elongate member having a proximal end and a distal end, and a
  • the spectroscopic cell disposed on the elongate member distally from the proximal end for positioning in the bronchi, the elongate member and spectroscopic cell being advancable through an instrument channel of 3mm diameter or less, the spectroscopic cell comprising a light path which is open to the outside of the device via openings which allow lung gases to flow into and out of the spectroscopic cell, the device further comprising a tunable light source for generating light which travels along the light path, a light detector to receive light that has travelled along the light path and a controller connected to control the tunable light source and light detector to detect absorption of the light by carbon dioxide in the light path.
  • the elongate member and spectroscopic cell are preferably advancable through the instrument channel of a bronchoscope, preferably a flexible bronchoscope.
  • they are advancable through an instrument channel of 3 mm diameter or less, more preferably 2.8 mm diameter or less, yet more preferably 2 mm diameter or less.
  • the distal parts of the device namely the spectroscopic cell and the part of the elongate member which extends from the spectroscopic cell back towards the proximal end, have an external diameter of no greater than 3 mm, more preferably no greater than 2.8 mm, more preferably no greater than 2 mm, at any point along their length.
  • the device of the invention allows the device of the invention to sample gases in the bronchi, namely the primary bronchi, preferably the secondary bronchi, and more preferably the tertiary bronchi too.
  • at least one of the light source and light detector are optically connected to the light path in the spectroscopic cell by one or more optical fibres extending along the elongate member.
  • separate fibres for delivery of light to and from the spectroscopic cell can be used, or a single optical fibre can be used with an optical isolator to avoid the light source being flooded with stray reflections (or the free running operation of the light source to be modified/perturbed by optical feedback arising from stray reflections).
  • one end of the light path in the cell is defined by a mirror, which can be a circular metal mirror of 1-3 mm, more preferably 2 mm diameter with a plane or spherical surface.
  • the spectroscopic cell consists of a light path extending from the end of the optical fibre delivering light from the light source, to the mirror, and back to the end of the optical fibre delivering light to detector.
  • the spectroscopic cell may be up to 10 mm long, giving a light path of 20mm, buttypically the spectroscopic cell is no more than 5 mm long, giving a light path of approximately 10 mm, though shorter light paths are possible.
  • the spectroscopic cell can be from 1-5 mm long giving a light path from 2-10 mm.
  • the light source and light detector are disposed at the proximal end of the device, preferably with the controller.
  • the light source is tunable, i.e. the wavelength of its output can be varied by the controller.
  • a diode laser is preferred for this.
  • the tunability of the light source means that spectroscopic features of the analyte which are clear of interfering species can be probed. For example, spectroscopic features of water can be avoided.
  • the light source can have its injection current (and hence output frequency) rapidly modulated while it is being scanned in frequency over the transition of interest, such as in wavelength modulation spectroscopy, to increase the sensitivity of the detection method
  • the light source is tunable over a range of about l.Onm, more preferably 0.5nm. (sufficiently far to discern an (atmospheric) pressure broadened rovibrational transition of carbon dioxide). Tuning of the wavelength may be achieved by controlling the supplied current or the temperature of the device.
  • the light source is typically a laser diode emitting light of approximately 2 ⁇ wavelength and the light detector is a near-IR gallium arsenide detector though other light sources and detectors can be used for probing whichever absorption line of carbon dioxide is selected.
  • the spectroscopic cell forms the distal tip of the device.
  • the optical fibre or fibres preferably terminate and are sealed using a sealant such as a potting material, for example EPO-TEK 301.
  • a sealant such as a potting material, for example EPO-TEK 301.
  • the emitting optical fibre is terminated with a gradient index (GRIN) lens to collimate the emitted light beam.
  • GRIN gradient index
  • the openings which allow lung gases to flow into and out of the light path are large enough to allow flow of gas rather than diffusion or permeation (as with a membrane or permeable wall) which is slower and , thus providing for quicker exchange and equilibration of gas in the spectroscopic cell with the gas in the bronchi.
  • the openings preferably provide equilibration of gas inside and outside the spectroscopic cell within one breath cycle. That is to say they are large enough to allow equilibration within 5 seconds, preferably within one second.
  • the openings are preferably perforations? in the walls of the distal portion of the device.
  • the spectroscopic cell preferably comprises one or more support members which surround the light path and form an open structure defining the openings for providing gas communication between the light path and the outside of the device so that lung gases can quickly pass into the light path as the device is advanced into the lungs.
  • the support member may support the mirror defining the distal end of the light path and the distal tip of the device may be provided with a soft or shaped tip to prevent it damaging the airway.
  • the one or more support members may be a cylindrical support member which is provided with openings, such as drilled holes, typically of at least 50 ⁇ diameter, more preferably at least 100 ⁇ diameter.
  • the support members may comprise a plurality, for example, 3, elongate elements which support the mirror at the distal end of the light path and define between them gaps through which lung gases can pass.
  • the support member can be integral with or separate from the elongate member.
  • the spectroscopic cell may be coated, sheathed or otherwise surrounded with a polymeric material which will allow carbon dioxide to penetrate, and prevent excess mucus from interfering with or reducing the optical signal.
  • the openings allow gas equilibration between the inside of the spectroscopic cell and the lungs well within a single breath cycle, for example within a second or so.
  • the device is preferably capable of measuring gas concentrations of the order of at least 1% (by volume).
  • the controller preferably controls the light source and detector to measure the carbon dioxide concentration by means of absorption spectroscopy, for example wavelength modulation spectroscopy or direct absorption spectroscopy.
  • the device may further be provided with the capability of measuring oxygen concentration, for example by oxygen fluorescence quenching.
  • a fluorescent substance is coated onto the distal part of an optical fibre extending down the elongate member and the temporal change in light emitted from the fluorescent substance is measured at the proximal end - e.g. by the same light detector as used for carbon dioxide analysis, this temporal change being dependent upon the oxygen concentration in the vicinity of the fluorescent coating.
  • the same optical fibre may be used as for delivery or receiving the light for carbon dioxide detection, or a dedicated optical fibre may be used. .
  • the invention also provides a device as described above in combination with a bronchoscope.
  • the device may be integrated with the bronchoscope or may be advanced down the instrument channel of the bronchoscope.
  • the spectroscopic cell is positioned to expose the light path to lung gases at the distal end of the bronchoscope, for example by projecting from the distal end of the bronchoscope.
  • FIG 1 schematically illustrates a prior art flexible bronchoscope
  • FIG 2 is a schematic cross-section along line II-II of FIG 1;
  • FIG 3 is a schematic diagram of a rigid prior art bronchoscope
  • FIG 4 is a schematic diagram of one embodiment of a device for measuring carbon dioxide concentration in accordance with the invention.
  • FIG 5 schematically illustrates a support member usable with the embodiment of FIG 4;
  • FIG 6 illustrates an alternative arrangement of support members usable with the embodiment of FIG 4
  • FIG 7 schematically illustrates a polymeric coating or sheath which may be used with the spectroscopic cell.
  • FIG 4 illustrates a device in accordance with an embodiment of the invention. It consists generally of an elongate member 40 which is terminated at its distal end by a tip portion 41 containing a spectroscopic cell for positioning in the lung of a patient, for example in the bronchi, and having a proximal portion 42 which remains outside the patient and contains the light source, light detector and associated power supplies and signal analysis functionality.
  • the elongate member 40 is of the order of 600 mm long so that it can access deep within the lung.
  • diode laser radiation of wavelength 2.0035 ⁇ from a VCSEL or DFB laser diode (such as provided by Vertilas or Eblana) 50 is passed into a first optical fibre 51 which delivers light from the light source 50 to a distal end of the optical fibre terminated with a GRIN lens 52 which delivers it into the spectroscopic cell 53.
  • the light travels along light path 54 through the free space inside the spectroscopic cell and is reflected by a plane or spherical metal mirror 55 back towards the receiving end of a second optical fibre 56.
  • the second optical fibre delivers the received light to a near IR semiconductor detector such as an InGaAs PIN photodiode (Hamamatsu model G5852- 01).
  • the device includes a controller 58, which can be integral with the light source and detector housing or separate therefrom and which contains a driver for the light source 50 and an analyser to analyse the output from the detector 57 to calculate the absorption by carbon dioxide over light path 54 and thus the concentration of carbon dioxide in the gas in the spectroscopic cell.
  • the light source 50 is tuned to a desired spectral feature of carbon dioxide, for example a transition within the 2vi+v 3 combination band of carbon dioxide, typically the isolated R(18) line at 2.0035 ⁇ .
  • the light source 50 is scanned in frequency over the transition of interest by ramping the current supply to it.
  • Wavelength modulation spectroscopy can be used to increase the sensitivity of the detection method.
  • the signal produced by the detector 57 is related to the local C0 2 concentration in the spectroscopic cell 53 through the well-known Beer-Lambert law.
  • the operation of the light source 50 and detector 57 by controller 58 to conduct absorption spectroscopy to detect the carbon dioxide concentration is entirely conventional and is explained, for example, in Cummings et al., J.Appl. Physiol. Ill, 303-307 (2011).
  • the first and second optical fibres 51 and 56 are contained within the elongate member 40 by a flexible polymer sleeve 60 such as a fluoropolymer (Unasco Inc.) of less than 2 mm in diameter so that it can pass through the 2 mm diameter access tube of a conventional flexible bronchoscope.
  • a flexible polymer sleeve 60 such as a fluoropolymer (Unasco Inc.) of less than 2 mm in diameter so that it can pass through the 2 mm diameter access tube of a conventional flexible bronchoscope.
  • a potting material 61 which is optically transmitting at around 2 ⁇ , for example EPO-TEK 301.
  • the mirror 55 is supported in position by a perforated section 62 of the flexible polymer sleeve 60.
  • the perforated section 62 may be 1 cm long, to provide a path length of about 2 cm, or may be shorter, for example as short as 1 mm.
  • Figure 5 schematically illustrates the perforated section which includes multiple laser drilled holes of 100 ⁇ diameter or less which provide openings for respiratory gases in the lung to pass freely into the spectroscopic cell 53.
  • the perforated section 62 can be provided as a separate component which is permanently or removably attached to the elongate member 40.
  • the perforated section 62 is replaced by a section including or constituted by a cylinder of gas-permeable material which allows respiratory gases into the spectroscopic cell.
  • FIG 6 shows a further alternative tip portion 41 in which the mirror 55 is supported opposite the end of the optical fibres 51 and 56 by three elongate elements 65, for example of thin metal, leaving large gaps 67 between them for respiratory gases to enter the spectroscopic cell.
  • the extreme end of the tip portion 41 is provided with a soft rounded termination 70 to prevent the end of the device damaging the lung tissues.
  • any of the spectroscopic cells may be coated or sheathed by a polymeric material which allows carbon dioxide to pass through but blocks mucus.
  • a sheath 72 is schematically illustrated in Fig. 7.
  • the mirror 55 can be provided by a 2 mm diameter disc of metal, such as gold, silver or aluminium which is either planar or convex. Alternatively a plastic, metal-coated mirror can be used.
  • the tip portion 41 may be made removable by means of a suitable releasable fixing to the end of the elongate member 40 in which case the tip portion 41 can be single- use to avoid the need for it to be sterilisable. Alternatively, it can be permanently connected to the elongate member and sterilised with the rest of the instrument. In another alternative embodiment the entire elongate member 40 and tip portion 41 can be removable from the proximal portion 42 and thus be disposable with the controller 58 and light source and detector 50, 57 being retained for subsequent use with a new elongate member 40 and tip portion 41.
  • the instrument as illustrated in FIG 4 is advanced by the physician down the instrument channel 9 of a conventional bronchoscope such as that illustrated in FIG 1 or FIG 3 either after the bronchoscope has been positioned, or beforehand, the two then being advanced together into the patient's airway.
  • a conventional bronchoscope such as that illustrated in FIG 1 or FIG 3 either after the bronchoscope has been positioned, or beforehand, the two then being advanced together into the patient's airway.
  • a single optical fibre can be used for both purposes by using an optical isolator between the light source and optical fibre.
  • an optical isolator prevents optical feedback from stray reflections being transmitted to the laser source 50.
  • a distal tip portion 41 including a spectroscopic cell can be positioned near the distal end of a bronchoscope with light being delivered to and collected from the cell by one or two optical fibres which extend along the elongate part 3, 20 of the
  • the light source, detector and detection and control electronics can then be disposed in the proximal portion and controller of the bronchoscope.
  • the invention allows the direct measurement of the local concentration of C0 2 in the bronchi deep within the lung. It therefore allows the physician to measure the performance of different parts of the lung. Such measurements can also be made while blocking-off parts of the lung to see how the carbon dioxide level changes. This may allow a physician to determine whether blocking-off part of the lung permanently is worthwhile.
  • the device may also be used in combination with imaging of the lung either via the bronchoscope or via external X-ray or MRI scanning. The device can also be used to check whether a tracheotomy tube has been correctly positioned into the airway.

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Abstract

A device for measuring the concentration of carbon dioxide in the lung comprises an elongate member which includes one or more optical fibres to deliver light to and from a spectroscopic cell which can be advanced down the instrument channel of a bronchoscope deep into the bronchi of the lung. The spectroscopic cell is open to lung gases and terminated by a mirror which reflects light back up the optical fibre. The proximal portion of the device is provided with a light source and light detector together with driving and control circuitry for them.

Description

BRONCHIAL GAS ANALYSER
The present invention relates to a bronchial gas analyser, in particular to a device for measuring the concentration of carbon dioxide in the bronchi of the lung.
Bronchoscopes have been used for many years to allow physicians to visualise the inside of the airways for diagnostic and therapeutic purposes. Figure 8 of the accompanying drawings schematically illustrates the airway and lungs of a human. The trachea (windpipe) 81 extends downwards from the larynx 80 until it divides into two main (stem or primary) bronchi 82. These in turn divide into five secondary (or lobar) bronchi 83. The secondary bronchi further subdivide into tertiary or segmental bronchi 84. The tertiary bronchi divide into bronchioles and eventually terminate in alveolar sacs where respiratory gas exchange takes place. Bronchoscopes are inserted through the nose or mouth of the patient, or sometimes via a tracheotomy and typically include lighting and a camera and an instrument or suction channel to allow the physician to advance instruments down the bronchoscope, for example to extract foreign bodies or collect specimens, or to apply suction to remove material from the lungs. There are typically two broad types of bronchoscope, flexible and rigid. Figure 1 of the accompanying drawings schematically shows a flexible bronchoscope 1 which consists of an elongate section 3 for advancement into the lungs of the patient and a proximal section 5 which, in use, the physician holds. The elongate section 3 is typically steerable by means of controls 7 provided on the proximal section 5 and includes an instrument channel 9, typically of 2 or 2.8 mm diameter (visible in the cross-section of Figure 2) and fibre optics which deliver illumination from light sources 11 and provide an image to a camera 13. A controller 15 is provided, which may be integral with proximal section 5, to supply power and to receive the output from the camera 13. The instrument channel 9 is connected to a port 17 allowing for the application of suction or for the advancement of an instrument down the bronchoscope.
Figure 3 schematically illustrates a rigid bronchoscope in which the elongate section 20 is a straight rigid tube, usually of metal. The rigid bronchoscope is typically provided with a viewing port 23, an instrument/suction channel 21 and a controller 25 to provide corresponding functionality to the flexible bronchoscope mentioned above. The instrument/suction channel 21 of a rigid bronchoscope is typically wider than that of the flexible bronchoscope and thus can offer better access for surgery or other therapeutic procedures.
As well as the visual examination of the lungs allowed by a bronchoscope, there is also interest in measuring the function of the lungs, that is to say how well the lungs are allowing gas exchange between the blood and respiratory gases. For example, capnography, which is the monitoring of the concentration or partial pressure of carbon dioxide in the respiratory gases, has been used to monitor patients during anaesthesia and intensive care. Capnography can also be used to indicate the presence of lung disease because a lower than usual difference in carbon dioxide concentration in inhaled and exhaled breath indicates decreased lung performance.
US-A-5, 193,544 discloses the provision of an optical path in an endotrachial tube to analyse carbon dioxide in the trachea, but analysing gas in the trachea (windpipe) does not give information on which part of a lung may be diseased. Also, it proposes the use of a gas-permeable but water impermeable material to define a light chamber which can exclude water (which interferes with the analysis), but the carbon dioxide must diffuse through the material, which means that analysis is very slow. WO- Al -2007/084189 discloses an endoscopic system with an integrated system for analysing expired air, but the provision of a light source and detector across the end of a sampling tube means that the system is impracticable for a bronchial gas analyser, and the use of a non-tunable light source means that it cannot distinguish between absorption from carbon dioxide and absorption from water - which is a problem for bronchial analysis.
While measurement of carbon dioxide concentration in inhaled and exhaled breath sampled high in the patient's airways, or from the breathing tube outside the patient, as in the proposals above, can given an indication of overall lung function, commonly lung disease only affects certain parts of the lung and there is a need to identify which parts of the lung are diseased and which are normal. Diseased parts can then be treated, for example blocked-off, which can improve the function of the healthy parts of the lung and thus overall lung function as described in US- Al -2008/0200797. Although diseased parts of the lung are sometimes visually distinguishable from normal lung tissue, this is not always the case and thus it would be useful to be able to assess the ability of the lung to produce carbon dioxide in a more detailed way, in particular as a function of spatial position within the lung. The paper "Evaluation of Lung Ventilation and Perfusion by Intra-bronchial Capnography" by Hiroki Nishine et al published in Chest, 2011, discloses the
measurement of C02 concentration in the lung by advancing a C02 sampling tube through the working channel of a rigid bronchoscope into each main stem bronchus of a lung and collecting inspired and expired gas continuously through the tube. The samples of gas were analysed using a C02 monitor external of the patient. However this does not present physicians in general with a straightforward way of assessing lung function in a variety of bronchoscope procedures. Accordingly the present invention provides a bronchial gas analyser device for measuring the concentration of carbon dioxide in the bronchi of the lung, the device comprising an elongate member having a proximal end and a distal end, and a
spectroscopic cell disposed on the elongate member distally from the proximal end for positioning in the bronchi, the elongate member and spectroscopic cell being advancable through an instrument channel of 3mm diameter or less, the spectroscopic cell comprising a light path which is open to the outside of the device via openings which allow lung gases to flow into and out of the spectroscopic cell, the device further comprising a tunable light source for generating light which travels along the light path, a light detector to receive light that has travelled along the light path and a controller connected to control the tunable light source and light detector to detect absorption of the light by carbon dioxide in the light path.
The elongate member and spectroscopic cell are preferably advancable through the instrument channel of a bronchoscope, preferably a flexible bronchoscope. Thus they are advancable through an instrument channel of 3 mm diameter or less, more preferably 2.8 mm diameter or less, yet more preferably 2 mm diameter or less. This means that the distal parts of the device, namely the spectroscopic cell and the part of the elongate member which extends from the spectroscopic cell back towards the proximal end, have an external diameter of no greater than 3 mm, more preferably no greater than 2.8 mm, more preferably no greater than 2 mm, at any point along their length. This allows the device of the invention to sample gases in the bronchi, namely the primary bronchi, preferably the secondary bronchi, and more preferably the tertiary bronchi too. Preferably at least one of the light source and light detector are optically connected to the light path in the spectroscopic cell by one or more optical fibres extending along the elongate member. Thus separate fibres for delivery of light to and from the spectroscopic cell can be used, or a single optical fibre can be used with an optical isolator to avoid the light source being flooded with stray reflections (or the free running operation of the light source to be modified/perturbed by optical feedback arising from stray reflections).
Preferably one end of the light path in the cell is defined by a mirror, which can be a circular metal mirror of 1-3 mm, more preferably 2 mm diameter with a plane or spherical surface. Thus the spectroscopic cell consists of a light path extending from the end of the optical fibre delivering light from the light source, to the mirror, and back to the end of the optical fibre delivering light to detector. The spectroscopic cell may be up to 10 mm long, giving a light path of 20mm, buttypically the spectroscopic cell is no more than 5 mm long, giving a light path of approximately 10 mm, though shorter light paths are possible. For example the spectroscopic cell can be from 1-5 mm long giving a light path from 2-10 mm.
Preferably the light source and light detector are disposed at the proximal end of the device, preferably with the controller. The light source is tunable, i.e. the wavelength of its output can be varied by the controller. A diode laser is preferred for this. The tunability of the light source means that spectroscopic features of the analyte which are clear of interfering species can be probed. For example, spectroscopic features of water can be avoided. Also, the light source can have its injection current (and hence output frequency) rapidly modulated while it is being scanned in frequency over the transition of interest, such as in wavelength modulation spectroscopy, to increase the sensitivity of the detection method Preferably the light source is tunable over a range of about l.Onm, more preferably 0.5nm. (sufficiently far to discern an (atmospheric) pressure broadened rovibrational transition of carbon dioxide). Tuning of the wavelength may be achieved by controlling the supplied current or the temperature of the device. The light source is typically a laser diode emitting light of approximately 2 μπι wavelength and the light detector is a near-IR gallium arsenide detector though other light sources and detectors can be used for probing whichever absorption line of carbon dioxide is selected. Preferably the spectroscopic cell forms the distal tip of the device. The optical fibre or fibres preferably terminate and are sealed using a sealant such as a potting material, for example EPO-TEK 301. Preferably the emitting optical fibre is terminated with a gradient index (GRIN) lens to collimate the emitted light beam.
The openings which allow lung gases to flow into and out of the light path are large enough to allow flow of gas rather than diffusion or permeation (as with a membrane or permeable wall) which is slower and , thus providing for quicker exchange and equilibration of gas in the spectroscopic cell with the gas in the bronchi. The openings preferably provide equilibration of gas inside and outside the spectroscopic cell within one breath cycle. That is to say they are large enough to allow equilibration within 5 seconds, preferably within one second. The openings are preferably perforations? in the walls of the distal portion of the device. The spectroscopic cell preferably comprises one or more support members which surround the light path and form an open structure defining the openings for providing gas communication between the light path and the outside of the device so that lung gases can quickly pass into the light path as the device is advanced into the lungs.
The support member may support the mirror defining the distal end of the light path and the distal tip of the device may be provided with a soft or shaped tip to prevent it damaging the airway.
The one or more support members may be a cylindrical support member which is provided with openings, such as drilled holes, typically of at least 50 μπι diameter, more preferably at least 100 μπι diameter. Alternatively the support members may comprise a plurality, for example, 3, elongate elements which support the mirror at the distal end of the light path and define between them gaps through which lung gases can pass. The support member can be integral with or separate from the elongate member. Alternatively the spectroscopic cell may be coated, sheathed or otherwise surrounded with a polymeric material which will allow carbon dioxide to penetrate, and prevent excess mucus from interfering with or reducing the optical signal.
Preferably the openings allow gas equilibration between the inside of the spectroscopic cell and the lungs well within a single breath cycle, for example within a second or so. The device is preferably capable of measuring gas concentrations of the order of at least 1% (by volume).
The controller preferably controls the light source and detector to measure the carbon dioxide concentration by means of absorption spectroscopy, for example wavelength modulation spectroscopy or direct absorption spectroscopy.
The device may further be provided with the capability of measuring oxygen concentration, for example by oxygen fluorescence quenching. In this case a fluorescent substance is coated onto the distal part of an optical fibre extending down the elongate member and the temporal change in light emitted from the fluorescent substance is measured at the proximal end - e.g. by the same light detector as used for carbon dioxide analysis, this temporal change being dependent upon the oxygen concentration in the vicinity of the fluorescent coating. The same optical fibre may be used as for delivery or receiving the light for carbon dioxide detection, or a dedicated optical fibre may be used. .
The invention also provides a device as described above in combination with a bronchoscope. The device may be integrated with the bronchoscope or may be advanced down the instrument channel of the bronchoscope. In either case the spectroscopic cell is positioned to expose the light path to lung gases at the distal end of the bronchoscope, for example by projecting from the distal end of the bronchoscope.
The invention will be further described by way of examples with reference to accompanying drawings in which:
FIG 1 schematically illustrates a prior art flexible bronchoscope;
FIG 2 is a schematic cross-section along line II-II of FIG 1;
FIG 3 is a schematic diagram of a rigid prior art bronchoscope;
FIG 4 is a schematic diagram of one embodiment of a device for measuring carbon dioxide concentration in accordance with the invention;
FIG 5 schematically illustrates a support member usable with the embodiment of FIG 4;
FIG 6 illustrates an alternative arrangement of support members usable with the embodiment of FIG 4;
FIG 7 schematically illustrates a polymeric coating or sheath which may be used with the spectroscopic cell. FIG 4 illustrates a device in accordance with an embodiment of the invention. It consists generally of an elongate member 40 which is terminated at its distal end by a tip portion 41 containing a spectroscopic cell for positioning in the lung of a patient, for example in the bronchi, and having a proximal portion 42 which remains outside the patient and contains the light source, light detector and associated power supplies and signal analysis functionality. Typically the elongate member 40 is of the order of 600 mm long so that it can access deep within the lung.
In this embodiment diode laser radiation of wavelength 2.0035 μιη from a VCSEL or DFB laser diode (such as provided by Vertilas or Eblana) 50 is passed into a first optical fibre 51 which delivers light from the light source 50 to a distal end of the optical fibre terminated with a GRIN lens 52 which delivers it into the spectroscopic cell 53. The light travels along light path 54 through the free space inside the spectroscopic cell and is reflected by a plane or spherical metal mirror 55 back towards the receiving end of a second optical fibre 56. The second optical fibre delivers the received light to a near IR semiconductor detector such as an InGaAs PIN photodiode (Hamamatsu model G5852- 01). The device includes a controller 58, which can be integral with the light source and detector housing or separate therefrom and which contains a driver for the light source 50 and an analyser to analyse the output from the detector 57 to calculate the absorption by carbon dioxide over light path 54 and thus the concentration of carbon dioxide in the gas in the spectroscopic cell. In use the light source 50 is tuned to a desired spectral feature of carbon dioxide, for example a transition within the 2vi+v3 combination band of carbon dioxide, typically the isolated R(18) line at 2.0035 μπι. The light source 50 is scanned in frequency over the transition of interest by ramping the current supply to it. Wavelength modulation spectroscopy (WMS) can be used to increase the sensitivity of the detection method. In direct absorption the signal produced by the detector 57 is related to the local C02 concentration in the spectroscopic cell 53 through the well-known Beer-Lambert law. The operation of the light source 50 and detector 57 by controller 58 to conduct absorption spectroscopy to detect the carbon dioxide concentration is entirely conventional and is explained, for example, in Cummings et al., J.Appl. Physiol. Ill, 303-307 (2011).
The first and second optical fibres 51 and 56 are contained within the elongate member 40 by a flexible polymer sleeve 60 such as a fluoropolymer (Unasco Inc.) of less than 2 mm in diameter so that it can pass through the 2 mm diameter access tube of a conventional flexible bronchoscope. At the distal end of the flexible polymer sleeve 60 the optical fibres and GRIN lens are sealed in position using a potting material 61 which is optically transmitting at around 2 μπι, for example EPO-TEK 301.
The mirror 55 is supported in position by a perforated section 62 of the flexible polymer sleeve 60. The perforated section 62 may be 1 cm long, to provide a path length of about 2 cm, or may be shorter, for example as short as 1 mm. Figure 5 schematically illustrates the perforated section which includes multiple laser drilled holes of 100 μπι diameter or less which provide openings for respiratory gases in the lung to pass freely into the spectroscopic cell 53. Alternatively the perforated section 62 can be provided as a separate component which is permanently or removably attached to the elongate member 40.
In an alternative, un-illustrated, embodiment the perforated section 62 is replaced by a section including or constituted by a cylinder of gas-permeable material which allows respiratory gases into the spectroscopic cell.
FIG 6 shows a further alternative tip portion 41 in which the mirror 55 is supported opposite the end of the optical fibres 51 and 56 by three elongate elements 65, for example of thin metal, leaving large gaps 67 between them for respiratory gases to enter the spectroscopic cell.
Preferably in all embodiments the extreme end of the tip portion 41 is provided with a soft rounded termination 70 to prevent the end of the device damaging the lung tissues.
Any of the spectroscopic cells may be coated or sheathed by a polymeric material which allows carbon dioxide to pass through but blocks mucus. Such a sheath 72 is schematically illustrated in Fig. 7.
The mirror 55 can be provided by a 2 mm diameter disc of metal, such as gold, silver or aluminium which is either planar or convex. Alternatively a plastic, metal-coated mirror can be used.
The tip portion 41 may be made removable by means of a suitable releasable fixing to the end of the elongate member 40 in which case the tip portion 41 can be single- use to avoid the need for it to be sterilisable. Alternatively, it can be permanently connected to the elongate member and sterilised with the rest of the instrument. In another alternative embodiment the entire elongate member 40 and tip portion 41 can be removable from the proximal portion 42 and thus be disposable with the controller 58 and light source and detector 50, 57 being retained for subsequent use with a new elongate member 40 and tip portion 41.
In use the instrument as illustrated in FIG 4 is advanced by the physician down the instrument channel 9 of a conventional bronchoscope such as that illustrated in FIG 1 or FIG 3 either after the bronchoscope has been positioned, or beforehand, the two then being advanced together into the patient's airway.
Although the illustrated embodiment uses separate optical fibres 51 and 60 for delivery and receiving light to and from the spectroscopic cell, a single optical fibre can be used for both purposes by using an optical isolator between the light source and optical fibre. Such an isolator prevents optical feedback from stray reflections being transmitted to the laser source 50.
Although the embodiments of the invention above provide a device for deployment through the instrument channel of a bronchoscope, it is of course possible to integrate the device into a flexible or rigid bronchoscope without utilising the instrument channel. Thus a distal tip portion 41 including a spectroscopic cell can be positioned near the distal end of a bronchoscope with light being delivered to and collected from the cell by one or two optical fibres which extend along the elongate part 3, 20 of the
bronchoscope. The light source, detector and detection and control electronics can then be disposed in the proximal portion and controller of the bronchoscope.
The invention allows the direct measurement of the local concentration of C02 in the bronchi deep within the lung. It therefore allows the physician to measure the performance of different parts of the lung. Such measurements can also be made while blocking-off parts of the lung to see how the carbon dioxide level changes. This may allow a physician to determine whether blocking-off part of the lung permanently is worthwhile. The device may also be used in combination with imaging of the lung either via the bronchoscope or via external X-ray or MRI scanning. The device can also be used to check whether a tracheotomy tube has been correctly positioned into the airway.

Claims

1. A bronchial gas analyser device for measuring the concentration of carbon dioxide in the bronchi of the lung, the device comprising an elongate member having a proximal end and a distal end, and a spectroscopic cell disposed on the elongate member distally from the proximal end for positioning in the bronchi, the elongate member and
spectroscopic cell being advancable through an instrument channel of 3mm diameter or less, the spectroscopic cell comprising a light path which is open to the outside of the device via openings which allow lung gases to flow into and out of the spectroscopic cell, the device further comprising a tunable light source for generating light which travels along the light path, a light detector to receive light that has travelled along the light path and a controller connected to control the tunable light source and light detector to detect absorption of the light by carbon dioxide in the light path.
2. A device according to claim 1 wherein the openings provide equilibration of gas inside and outside the spectroscopic cell within one breath cycle.
3. A device according to claim 1 or 2 wherein the elongate member and spectroscopic cell are advancable through the instrument channel of a bronchoscope.
4. A device according to claim 3 wherein the bronchoscope is a flexible
bronchoscope.
5. A device according to any one of the preceding claims wherein at least one of the light source and light detector are optically connected to the light path by one or more optical fibres extending along the elongate member.
6. A device according to any one of the preceding claims wherein one end of the light path is defined by a mirror.
7. A device according to claim 6 wherein the mirror is disposed at the distal end of the device.
8. A device according to any one of the preceding claims wherein at least one of the light source and light detector are disposed at the proximal end of the elongate member.
9. A device according to any one of the preceding claims wherein the controller is disposed at the proximal end of the elongate member.
10. A device according to any one of the preceding claims wherein the spectroscopic cell comprises one or more support members surrounding the light path and defining the openings for providing gas flow between the light path and the outside of the device.
11. A device according to claim 10 wherein the one or more support members are constituted by a cylindrical member with apertures of at least 100 micron diameter forming the openings.
12. A device according to claim 10 wherein the one or more support members comprise a plurality of elongate elements spaced around the light path, gaps between the elements forming the openings.
13. A device according to any one of the preceding claims wherein the spectroscopic cell is surrounded by a carbon dioxide-permeable polymeric material.
14. A device according to any one of the preceding claims in combination with bronchoscope.
15. A device according to claim 14 wherein the spectroscopic cell is positioned to expose the light path to lung gases at the distal end of the bronchoscope.
16. A device according to claim 15 wherein the spectroscopic cell projects from the distal end of the bronchoscope.
PCT/GB2014/053827 2014-01-10 2014-12-22 Bronchial gas analyser WO2015104531A1 (en)

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