WO2016165838A2 - Système de surveillance optique et capteur associé - Google Patents

Système de surveillance optique et capteur associé Download PDF

Info

Publication number
WO2016165838A2
WO2016165838A2 PCT/EP2016/025038 EP2016025038W WO2016165838A2 WO 2016165838 A2 WO2016165838 A2 WO 2016165838A2 EP 2016025038 W EP2016025038 W EP 2016025038W WO 2016165838 A2 WO2016165838 A2 WO 2016165838A2
Authority
WO
WIPO (PCT)
Prior art keywords
optical sensor
light
probe
wavelength
sensor according
Prior art date
Application number
PCT/EP2016/025038
Other languages
English (en)
Other versions
WO2016165838A3 (fr
Inventor
John Julian DAVENPORT
Panayiotis Anastasios Kyriacou
Justin Phillips
Michelle Hickey
Original Assignee
The City University
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
Application filed by The City University filed Critical The City University
Publication of WO2016165838A2 publication Critical patent/WO2016165838A2/fr
Publication of WO2016165838A3 publication Critical patent/WO2016165838A3/fr

Links

Classifications

    • 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
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • 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"
    • 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
    • A61B5/14551—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 for measuring blood gases
    • A61B5/14556—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 for measuring blood gases by fluorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G01J3/4406—Fluorescence spectrometry
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
    • 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
    • G01N33/0004—Gaseous mixtures, e.g. polluted air
    • G01N33/0009—General constructional details of gas analysers, e.g. portable test equipment
    • G01N33/0027—General constructional details of gas analysers, e.g. portable test equipment concerning the detector
    • G01N33/0036—Specially adapted to detect a particular component
    • G01N33/004—Specially adapted to detect a particular component for CO, 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
    • G01N21/62—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"
    • G01N2021/6434—Optrodes
    • 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
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N2021/6484—Optical fibres
    • 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
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N2021/7793—Sensor comprising plural indicators

Definitions

  • This invention relates to optical monitoring systems and sensors therefor, particularly but not exclusively to optical systems and sensors for use in diagnostic applications - such as, for example, in medical applications.
  • one presently preferred embodiment of the present invention provides an optical sensor comprising first and second photoresponsive components that are each configured to fluoresce, responsive to excitation by light of a first wavelength, and emit light including a second and a third wavelength respectively; wherein the fluorescence of said first component varies with oxygen concentration of a medium with which the sensor is in contact, and the fluorescence of said second component varies with carbon dioxide concentration of a medium with which the sensor is in contact.
  • such a sensor is advantageous as compared with gastric tonometry, as a system incorporating such a sensor can provide an immediate indication of both oxygen and carbon dioxide concentration, and as a consequence a medical team can more quickly intervene in situations where the onset of MODS appears to be occurring.
  • the first photoresponsive component comprises a chemical whose fluorescence quenches in response to oxygen exposure.
  • the first photoresponsive component may include a chemical selected from the group consisting of: pentrafluoropheny porphine (PtTFPP); platinum octaethylporphine (PtOEP); platinum octaethylporphyrin-polystyrene (PtOEP-PS); tris (4,7-diphenyl- 1 ,10-phenathroline) ruthenium(ll) dichloride ([Ru(dpp)3]CI2); and meso- tetraphenylporphyin (TPP).
  • PtTFPP pentrafluoropheny porphine
  • PtOEP platinum octaethylporphine
  • PtOEP-PS platinum octaethylporphyrin-polystyrene
  • TPP meso- tetrapheny
  • the second photoresponsive component may include a luminescent pH sensitive dye.
  • the luminescent pH sensitive dye may comprise a chemical selected from the group consisting of: 1 -hydroxypyrene-3,6,8-trisulfonate (HPTS); polym-H7 tm ; a-naphtholphthalein (NAF); naphthol blue black (NBB); and calmagite (CMG).
  • the second photoresponsive component may include a phase transfer agent, for example tetraoctylammonium hydroxide solution.
  • the second photoresponsive component may include a photo-bleaching reduction agent, for example 1 -ethyl-3-methylimidazolium tetrafluoroborate.
  • the first photoresponsive component includes platinum octaethylporphine and the second photoresponsive component includes 1 -hydroxypyrene-3,6,8-trisulfonate.
  • the first and second photoresponsive components may fluoresce in response to excitation by blue light.
  • the first wavelength may be in the region of 470 nm.
  • the second wavelength may comprise red light.
  • the second wavelength may be in the region of 650 nm.
  • the third wavelength may comprise green light.
  • the third wavelength may be in the region of 550 nm.
  • the first and second components may be bound together in a matrix, preferably a polymer matrix.
  • the polymer matrix may comprise ploy(ethyl methacrylate).
  • the senor may be formed as a layer having a thickness of 100 microns or less.
  • the sensor may further comprise an oxygen and carbon dioxide permeable protective coating, for example of silicone.
  • the senor is at least substantially transparent to red and infrared light, having wavelengths in the region of 660 and 860 nm respectively.
  • a probe for use in a MODS monitoring system comprising an optic fibre having a proximal end that is connectable to said MODS detection system, and a distal end for insertion into a patient, the probe further comprising an optical sensor as described herein, said optical sensor being optically coupled to said distal end of said optic fibre.
  • the sensor may comprise a coating on said distal end of said optic fibre.
  • the probe may comprise a ferrule having a first and a second surface, and a bore extending from said first surface through the ferrule to said second surface, wherein the optic fibre is retained within said bore so that said distal end of said fibre is in the vicinity of said first surface, and said sensor is formed as a coating on said first surface.
  • the probe may comprise a flexible tube having a distal end and a proximal end, said ferrule being mounted in said tube in the vicinity of said distal end.
  • said tube is of a biocompatible material, such as silicone.
  • a wall of said tube may be of such a thickness that an optic fibre within the tube cannot puncture the tube wall.
  • said tube wall may be in the region of 700 microns in thickness.
  • said tube is externally coated with a lubricious coating, for example of parylene.
  • said optic fibre has a radius of approximately 600 microns.
  • said ferrule further comprises second and third bores, a first optic fibre of a pulse oximetry system being located in said second bore and a second optic fibre of said pulse oximetry system being located in said third bore.
  • a further aspect of the present invention relates to a monitoring system for MODS, the system comprising: a light source operable to emit light at said first wavelength, a first detector for detecting light at said second wavelength, and a second detector for detecting light at said third wavelength, and a processor for processing signals from said first and second detectors, said system being configured for coupling to the proximal end of the optic fibre of a probe as described herein so that light from said source can illuminate the proximal end of said fibre and light of said second and third wavelengths emanating from said fibre proximal end can pass to said first and second detectors respectively.
  • the system may further comprise a first band pass-filter configured to pass light of said second wavelength from the optic fibre to said first detector, and a second band-pass filter configured to pass light of said third wavelength from the optic fibre to said second detector.
  • the system comprises second and third light sources operable to emit red and infra-red light respectively, and a third detector for detecting red and infra-red light; wherein the second and third light sources are configured to illuminate a proximal end of said second optic fibre, and said third detector is configured to receive light from a proximal end of said third optic fibre.
  • said processor is configured to process signals from said third detector.
  • said processor is configured to generate, based on signals from said first and second detectors, an indication of oxygen and carbon dioxide concentration in the medium that the probe is in contact with.
  • the processor may additionally be configured to generate, based on signals from said third detector, an indication of haemoglobin oxygen saturation.
  • Another aspect of the invention relates to a method of fabricating a sensor as described herein, the method comprising: (i) mixing a measure of said first component with a measure of polymer matrix; (ii) adding a solvent (for example a mixture of dichloromethane and methanol) and allowing said first component and polymer matrix to dissolve; (iii) adding said second component; (iv) adding a photo-bleaching inhibitor; (v) adding a liquid phase transfer agent (for example tetraoctylammonium hydroxide solution) and allowing any solids to dissolve; and (vi) allowing said solvent to evaporate leaving said first and second components bound together in a polymer matrix.
  • a solvent for example a mixture of dichloromethane and methanol
  • Fig. 1 is a schematic representation of a sensor according to an embodiment of the present invention
  • Fig. 2 is a schematic representation of a probe according to another embodiment of the invention.
  • Fig. 3 is a schematic representation of a probe according to another embodiment of the present invention.
  • Fig. 4 is a schematic cross-sectional view through an end portion of the probe depicted in Fig. 3;
  • Fig. 5 is a schematic representation of a probe according to a further embodiment of the present invention
  • Fig. 6 is a schematic representation of a monitoring system according to another embodiment of the invention.
  • Fig. 7 is a schematic representation of a monitoring system according to a yet further embodiment of the invention.
  • Fig. 8 is a schematic spectrum of signals from a PO2/PCO 2 sensor according to an embodiment of the invention.
  • Fig. 9 is a schematic graphical representation of phase shifts between exciting illumination (upper line) and resultant fluorescence (lower line) for a chemical whose fluorescence quenches in response to oxygen exposure;
  • Fig. 10 is schematic graphical representation of data from a pulse oximetry sensor.
  • one aspect of the present invention provides a sensor that has first and second photoresponsive components that are each configured to fluoresce when excited by light of a first wavelength. In response to this excitation, these components fluoresce and emit light including a second and a third wavelength respectively and the fluorescence these components varies with oxygen concentration and carbon dioxide concentration, respectively, of a medium with which the sensor is in contact.
  • the sensor can be provided as part of a probe that is insertable into a patient, for example into the gullet of a patient so that it comes into contact with mucous and other fluids within the patient's body.
  • concentration of oxygen and carbon dioxide in these fluids is related to oesophageal blood gas concentrations, and by monitoring these concentrations (optionally in conjunction with monitoring of other factors) it is possible to be warned of the early onset of MODS.
  • teachings of the present invention are useful wherever it is desired to monitor oxygen and carbon dioxide concentration in a medium that the sensor is in contact with.
  • teachings of the invention could be embodied in a probe that is indwelling, or inserted into another orifice - for example into the mouth, rectum or colon on a patient.
  • teachings of the present invention could also have non-medical applications - for example monitoring oxygen and carbon dioxide concentration in the water of a fish tank.
  • the first photoresponsive component of the sensor includes a chemical whose fluorescence quenches in response to oxygen exposure
  • the second photoresponsive component of the sensor includes a luminescent pH sensitive dye.
  • these components are bound together in a matrix, for example a polymer matrix such as poly(ethyl methacrylate) (PEMA, CAS Number 9003-42-3) applied as a solution in dichloromethane (CH 2 CL 2 , CAS Number 75-09-2) and methanol.
  • PEMA poly(ethyl methacrylate)
  • the first photoresponsive component includes platinum octaethylporphyrin (PtOEP, CAS Number 31248-39-2).
  • oxygen molecules in the medium that the sensor is in contact with quench the PtOEP molecules from their excited state, thereby reducing the intensity of fluorescent light.
  • the fluorescent signals are relatively small and thus more difficult to measure accurately. For this reason it is preferred to monitor the concentration of oxygen in the medium by considering the decay time of the excited PtOEP molecules, in particular by considering the phase difference between the light from the exciting source and the fluorescent light.
  • Fig. 9 is a schematic representation of the phase difference between a signal attributable to an excitation source (in this instance, an LED) and a signal attributable to fluorescence of the first component of the sensor.
  • the partial pressure of oxygen in the medium can be calculated from the following equations:
  • ⁇ 1 + K SV [0 2 ]
  • ⁇ is the lifetime of the excited fluorophore in the absence of oxygen
  • ⁇ is the lifetime of the excited fluorophore in the presence of oxygen of concentration [02]
  • Ksv is the Stern-Volmer quenching constant.
  • the lifetime ⁇ is typically between 5 and 50 ⁇ and can be found by finding the phase difference between a modulated excitation source and the resultant fluorescence signal:
  • ⁇ is the phase difference in degrees and f is the modulation frequency of the source.
  • the second photoresponsive component of the sensor it is again the case that a variety of different luminescent pH sensitive dyes can be used (for example: polym-H7 tm ; a-naphtholphthalein (NAF); naphthol blue black (NBB); or calmagite (CMG)).
  • the second photoresponsive component includes HPTS (8-hydroxypyrene-1 ,3,6-trisulfonic acid trisodium salt, CAS Number: 6358-69-6).
  • the second component also preferably includes a phase transfer agent (preferably: tetraoctylammonium hydroxide solution (TONOH, CAS Number 17756-58-0) in -20% solution in methanol (CH 3 OH, CAS Number 67-56-1 )), and may also include a photo- bleaching reduction agent such as ionic liquid 1 -ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF ). HPTS fluoresces green (550) when excited by blue (470nm) light.
  • a phase transfer agent preferably: tetraoctylammonium hydroxide solution (TONOH, CAS Number 17756-58-0) in -20% solution in methanol (CH 3 OH, 67-56-1 )
  • EMIMBF photo- bleaching reduction agent
  • HPTS fluoresces green (550) when excited by blue (470nm) light.
  • the concentration of CO2 increases the fluorescent intensity decreases, due to the fact that CO2 undergoes an equilibrium reaction with the phase transfer agent (in the preferred embodiment: TONOH) and thereby reduces the quantity of fluorescent HPTS present.
  • the concentration of CO2 can then be determined by looking at this decrease in fluorescent intensity.
  • / is the fluorescence intensity in the presence of carbon dioxide of concentration [CO2]
  • b is the intensity in its absence
  • Ksv is the Stern-Volmer quenching constant. Since / and b are both directly proportional to the voltage output of a photodetector (for example a photodiode), the ratio can be measured directly and the concentration of CO2 calculated.
  • the first and second photoresponsive components may be bound within a polymer matrix of poly(ethyl methacrylate) (PEMA, CAS Number 9003-42-3), applied as a solution in dichloromethane (CH 2 CL 2 , CAS Number 75-09-2) and methanol, and in a particularly preferred implementation of the teachings of the invention a sensor embodying the teachings of the present invention can be prepared as follows (n.b.
  • a sensor 1 that embodies the teachings of the present invention.
  • the sensor 1 has, in this particular arrangement, been formed as a layer on a substrate 3 and includes first 5 and second 7 photoresponsive components bound within a polymer matrix 9.
  • the sensor is placed in contact with (for example, immersed in) a medium whose oxygen and carbon dioxide concentration is to be monitored and illuminated with blue light, including light having a wavelength of 470 nm, from a suitable source (not shown) such as a light emitting diode (LED).
  • a suitable source such as a light emitting diode (LED).
  • the photoresponsive components fluoresce, and a detector (such as a photodiode (not shown)) is employed to generate signals representative of that fluorescence.
  • Fig. 2 is a schematic representation of a probe 1 1 that embodies the teachings of the invention.
  • the probe 1 1 comprises an optic fibre 13 (one end of which is shown), and a sensor 1 optically coupled to the fibre 13.
  • the sensor 1 is formed as a coating on the end of the optic fibre 13.
  • a precision dip coater may be employed to coat the end of the fibre, and as the fibre is withdrawn from the solution resulting from the preparation method outlined above, the solvents evaporate and allow the polymer to form a coating matrix on the tip of the optic fibre.
  • the thickness of the layer is typically in the region of less than 100 microns in thickness, and can be varied by controlling the rate at which the fibre is withdrawn from the solution or by dipping the fibre into the solution on multiple occasions.
  • the sensor coating 1 on the end of the fibre 13 may be protected by a cover layer (not shown) applied over the sensor coating 1 .
  • the cover layer is permeable to both oxygen and carbon dioxide, and may comprise silicone.
  • Fig. 3 shows a probe according to another embodiment of the invention.
  • the probe 15 comprises a flexible tube 17 that has a proximal end and a distal end 19 (the distal end being depicted).
  • the tube is preferably of a biocompatible material (for example, silicone), and the outside of the tube may include a lubricious coating (for example of parylene) to facilitate insertion of the probe into a patient.
  • a ferrule 21 is fitted into the open distal end
  • the outer surface of the ferrule 21 (and hence the optic fibre tip) has been, at least partially, covered with a sensor 1 of the type described above, and that sensor has been covered by a protective outer cover 27 (again, preferably of silicone) that is permeable to both oxygen and carbon dioxide.
  • the fibre tip may be coated with a sensor and then secured within the ferrule before the outer protective cover is applied.
  • the cover may cover just the sensor or may cover the entire external surface of the ferrule (and potentially some or all of the external surface of the tube 17).
  • blue light (for example from an LED) illuminates one end of the optical fibre and propagates along the fibre until it reaches the sensor 1 , whereupon the blue light excites the first and second photoresponsive components.
  • These components fluoresce (at different frequencies) and that fluorescent illumination propagates back up the optic fibre to a monitoring system (more details of which will later be provided) coupled to the other end of the fibre.
  • FIG. 5 depicts another probe 29 that is similar to that depicted in Figs. 3 and 4, apart from the fact that the ferrule 21 includes two additional through-holes (bores) one to either side of the aforementioned first through-hole 23.
  • An optic fibre 31 , 33 is secured in each of these additional through holes, and these fibres are coupled to a conventional optical pulse oximetry system.
  • red and infra-red light is transmitted down one of the two optic fibres, through tissue of interest, and returns back up the other of the two optic fibres.
  • oxygen saturation (SPO 2 ) of the tissue can be found from the difference in intensity of the two wavelengths.
  • oxygen saturation can be calculated from the normalised ratio of red and infra-red light as follows:
  • Fig. 10 is a data plot showing (in the upper plot) the DC and AC components of the absorbtion spectra for red light, and (in the lower plot) the DC and AC components of the absorbtion spectra for infra-red light.
  • An advantage of the sensor herein disclosed is that it is, at least substantially, transparent to red (c. 660 nm) and infra-red (c. 680 nm) light, and thus does not interfere (at least to an appreciably significant degree) with the light that is used for the pulse oximetry monitoring.
  • the sensor is at least substantially transparent to light of 600 to 940 nm.
  • the tube 17 of the probes (15, 21 ) is of such a thickness that if one of the optic fibres within the tube should be broken, the broken end of the fibre cannot puncture the tube (and potentially injure a patient).
  • the wall of the tube is at least 700 microns in thickness.
  • the monitoring system 34 includes an excitation and sensing component 35 and a signal processing component 37 (for example a laptop computer) coupled to the excitation and sensing component - although it will be appreciated that these two components could readily be combined into one unit.
  • a signal processing component 37 for example a laptop computer
  • the excitation and sensing component comprises a constant current driver 41 controllable by a microcontroller 43 to drive an excitation source 45 (for example an LED, preferably a surface mounted LED) configured to generate blue light including a wavelength of 470 nm.
  • an excitation source 45 for example an LED, preferably a surface mounted LED
  • the microcontroller is configured to pulse the source 45 at 4 kHz for two cycles.
  • a first branch of an optic fibre 13, 25 is coupled to the excitation and sensing component 37 to receive light from the excitation source and extends to a probe 1 1 , 15.
  • Light returning from the probe 1 1 , 15 passes into two branches of the optic fibre, a first of which directs light to a red filter 47 that passes light including a wavelength of 650 nm to a first photodiode 49, and the second of which directs light to a green filter 51 that passes light including a wavelength of 550 nm to a second photodiode 53.
  • the output from the first photodiode 49 (attributable to fluorescence of the first component of the sensor) is passed to an amplifier 55 and thence to a phase detection circuit 57 consisting of comparators, XOR gates, filters and sample and hold circuits.
  • the phase detection circuit 57 generates a voltage signal proportional to the phase shift, and this signal is then passed through anti- aliasing filters 59 before being digitised by a commercial DAQ card 61 .
  • the digital output signal of the card 61 is then passed to the signal processor 39 for subsequent processing.
  • the output from the second photodiode 53 (attributable to fluorescence of the second component of the sensor) is passed to an amplifier 63 and thence to a demultiplexer/sample and hold circuit 65 to separate pCO2 intensity from the background interference.
  • the signals are then passed through anti-aliasing filters 67 before being digitised by a commercial DAQ card 69.
  • the digital output signal of the card 69 is then passed to the signal processor 37 for subsequent processing.
  • the signal processor 37 is operable to execute software to determine, on the basis of the equations mentioned above, the concentration of oxygen and carbon dioxide in the medium that the probe is in contact with.
  • the software is configured to notify an operator (for example by sounding an alarm and/or displaying message) if the oxygen concentration and/or carbon dioxide concentration should deviate from a predetermined acceptable level for a patient in whom the probe is installed.
  • a monitoring system 73 for use with the probe of Figs. 5 (which probe provides for O2/CO2 monitoring as well as pulse oximetry).
  • the monitoring system 73 includes an excitation and sensing component 75 and a signal processing component 77 (for example a laptop computer) coupled to the excitation and sensing component - although it will be appreciated that these two components could readily be combined into one unit.
  • the excitation and sensing component 75 includes many of the components described above in connection with Fig. 6, and for brevity components common between the two systems (chiefly those components necessary for 02 and CO2 concentration monitoring) will not be described again.
  • the excitation and sensing component 75 includes a constant current driver 41 controllable by a microcontroller/multiplexer 79 to drive the aforementioned blue excitation source 45, a red excitation source 81 and an infra-red excitation source 83 (each of which may be LEDs, for example surface mounted LEDs).
  • the red excitation source is configured to direct light including a wavelength of 660 nm to a first branch of a first optic fibre 31 and thence to the probe 29 and into a tissue of interest.
  • the infra-red excitation source is configured to direct light including a wavelength of 860 nm to a second branch of the first optic fibre 31 and thence to the probe 29 and into a tissue of interest.
  • infra-red light is more strongly absorbed than red light.
  • the oxygen saturation of the tissue can therefore be found from the difference in intensity of the two wavelengths.
  • the microcontroller/multiplexer 79 is configured so that none of the LEDs are on at the same time, and so that the blue source has a different pulse width compared to those of the red and infra- red excitation sources.
  • the red source is turned on for 416 s, and then turned off.
  • the infra-red source is then turned on for 416 s, following which the infra-red source is turned off, and the blue source is pulsed at 4kHz for two cycles. Next, all the sources are turned off for a dark period of 416 s, following which the cycle is repeated. Whilst this is preferred it will be appreciated that other timing pulse width and modulation frequencies may instead be employed.
  • Red and infra-red light permeates through the tissue of interest, and any light that is not absorbed is picked up by the second optic fibre 31 and directed to a photodiode 85.
  • the output from photodiode 85 is passed to an amplifier 87 and thence to a demultiplexer 89 where the red and infrared signals from the amplified photodiode output are separated.
  • the signals from the demultiplexer 89 are passed through a sample and hold circuit 91 and an anti-aliasing filter 93 before being digitised by a commercial DAQ card 95.
  • the digital output signal of the card 69 is then passed to the signal processor 77 for subsequent processing.
  • the signal processor 77 is operable to execute software to determine, on the basis of the equations mentioned above, the concentration of oxygen and carbon dioxide in the medium that the probe is in contact with, and in addition to determine the saturation of haemoglobin with oxygen in a tissue of interest.
  • the software is configured to notify an operator (for example by sounding an alarm and/or displaying message) if the oxygen concentration and/or carbon dioxide concentration and/or oxygen saturation should deviate from a predetermined acceptable level for a patient in whom the probe is installed.

Abstract

La présente invention concerne un capteur optique comprenant des premier et second composants photosensibles qui sont chacun configurés de manière à être fluorescents, en réponse à une excitation par la lumière d'une première longueur d'onde, et à émettre de la lumière comprenant une deuxième et une troisième longueur d'onde respectivement ; la fluorescence dudit premier composant variant avec la concentration d'oxygène d'un milieu avec lequel le capteur est en contact, et la fluorescence dudit second composant variant avec la concentration de dioxyde de carbone d'un milieu avec lequel le capteur est en contact.
PCT/EP2016/025038 2015-04-14 2016-04-14 Système de surveillance optique et capteur associé WO2016165838A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB1506332.4A GB201506332D0 (en) 2015-04-14 2015-04-14 Optical sensing system & sensor therefor
GB1506332.4 2015-04-14

Publications (2)

Publication Number Publication Date
WO2016165838A2 true WO2016165838A2 (fr) 2016-10-20
WO2016165838A3 WO2016165838A3 (fr) 2016-11-24

Family

ID=53333772

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2016/025038 WO2016165838A2 (fr) 2015-04-14 2016-04-14 Système de surveillance optique et capteur associé

Country Status (2)

Country Link
GB (2) GB201506332D0 (fr)
WO (1) WO2016165838A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107084967A (zh) * 2017-06-15 2017-08-22 福州普贝斯智能科技有限公司 一种水中溶解氧测量仪

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5330718A (en) * 1989-08-16 1994-07-19 Puritan-Bennett Corporation Sensor element and method for making the same
US5152287A (en) * 1990-08-15 1992-10-06 Cordis Corporation Cross-linked fluorinated polymers for use in gas sensors
US5747349A (en) * 1996-03-20 1998-05-05 University Of Washington Fluorescent reporter beads for fluid analysis
US20010034479A1 (en) * 2000-04-19 2001-10-25 Ring Lawrence S. Optically based transcutaneous blood gas sensor
US20110105869A1 (en) * 2006-01-04 2011-05-05 The Trustees Of The University Of Pennsylvania Sensor for Internal Monitoring of Tissue O2 and/or pH/CO2 In Vivo
EP2150176B1 (fr) * 2007-04-27 2016-04-27 St. Jude Medical AB Détecteur de concentration implantable et dispositif
EP2337495A4 (fr) * 2008-09-19 2013-10-16 Sensors For Med & Science Inc Ensemble détecteur optique
CN202005754U (zh) * 2011-03-25 2011-10-12 复旦大学附属中山医院 可监测血液中溶氧分压和二氧化碳分压的荧光光纤传感器

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107084967A (zh) * 2017-06-15 2017-08-22 福州普贝斯智能科技有限公司 一种水中溶解氧测量仪

Also Published As

Publication number Publication date
GB201506332D0 (en) 2015-05-27
WO2016165838A3 (fr) 2016-11-24
GB2537504A (en) 2016-10-19

Similar Documents

Publication Publication Date Title
US9044179B2 (en) Oxygen sensor for internal monitoring of tissue oxygen in vivo
AU711444B2 (en) A method and apparatus to perform trans-cutaneous analyte monitoring
US4861727A (en) Luminescent oxygen sensor based on a lanthanide complex
JP3764482B2 (ja) ｐＨおよびｐＣＯ▲下２▼についての同時二重励起／一重発光蛍光感知方法
DK170510B1 (da) Sensorsystem og metode til bestemmelse af pH-værdien i en væske ved hjælp af sensorsystemet
US5190729A (en) Luminescent oxygen sensor based on a lanthanide complex
CA1187386A (fr) Sonde a fibre optique pour la mesure de la p ino2 xx
US20110105869A1 (en) Sensor for Internal Monitoring of Tissue O2 and/or pH/CO2 In Vivo
US11193916B2 (en) Calibration of a gas sensor
Mahutte On-line arterial blood gas analysis with optodes: current status
JP6074070B2 (ja) 化学−光学センサスポットにおける浸透圧変動の補正
EP2150176B1 (fr) Détecteur de concentration implantable et dispositif
Davenport et al. Dual p O 2/p CO 2 fibre optic sensing film
WO2016165838A2 (fr) Système de surveillance optique et capteur associé
Wolfbeis et al. Recent progress in optical oxygen sensing
US11313799B2 (en) Calibration of a sensor
Davenport et al. A fiberoptic sensor for tissue carbon dioxide monitoring
Schlain et al. Continuous arterial blood gas monitoring with transmitted light sensors and light emitting diode light sources
Schlain et al. Continuous arterial blood gas monitoring with transmitted light sensors and light emitting diode light sources
Bronzino Optical Sensors
Baldini Recent developments of optical fiber chemical sensors at IROE
Wahr et al. EMERGING TECHNOLOGIES
Bronzino J. Willard Marriott Library University of Utah

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16732227

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16732227

Country of ref document: EP

Kind code of ref document: A2