WO1988006726A1 - In vivo blood testing - Google Patents
In vivo blood testing Download PDFInfo
- Publication number
- WO1988006726A1 WO1988006726A1 PCT/GB1988/000125 GB8800125W WO8806726A1 WO 1988006726 A1 WO1988006726 A1 WO 1988006726A1 GB 8800125 W GB8800125 W GB 8800125W WO 8806726 A1 WO8806726 A1 WO 8806726A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- light guide
- active surface
- light
- metal
- transmitting
- Prior art date
Links
Classifications
-
- 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
- G01N21/65—Raman scattering
- G01N21/658—Raman scattering enhancement Raman, e.g. surface plasmons
-
- 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
-
- 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
- G01N21/01—Arrangements or apparatus for facilitating the optical investigation
- G01N21/03—Cuvette constructions
- G01N2021/0385—Diffusing membrane; Semipermeable membrane
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2201/00—Features of devices classified in G01N21/00
- G01N2201/08—Optical fibres; light guides
Definitions
- This invention relates to iii vivo blood gas analysis using Raman spectroscopy.
- Vibrational spectroscopy has been employed for many years to study the structure and bonding of molecules. As each bond has its own, characteristic frequency, vibrational spectra and molecular structure are related. In this way, compositional analysis can be carried out by inspecting the vibrational spectrum of a 0 sample and comparing it with the spectra of known compounds.
- the two main techniques employed are infrared absorption and Raman spectroscopy.
- a wavelength tunable or broadband light source is used to 5 illuminate the specimen, and the wavelengths at which energy is absorbed are recorded.
- Raman spectroscopy a fixed wavelength source is employed, and the spectrum of emitted radiation recorded; the maxima in the emission spectrum represent the difference in energy ° between the incoming light quanta and the vibrational energy of the molecular bonds in the sample.
- vibrational energy levels lie in the infrared, and this represents a disadvantage for infrared absorption spectroscopy.
- Raman spectroscopy With Raman spectroscopy, however, one can ° illuminate the sample in the visible waveband, for example using a fixed frequency laser, and generate an emitted spectrum, shifted to the red, representative of the sample composition.
- the present invention is particularly concerned with a sensor head designed specifically for use in in vivo monitoring of blood gases.
- the sensor is capable of both identification of gases and continuous measurement of their concentration.
- ISFETS ion selective field effect transistors
- fibre optic sensors In addition to optical sensors based on absorption and fluorescence, fibre optic sensors, either extrinsic or intrinsic, can be developed for application in blood gas analysis. The problem with such intrinsic sensors is the identification of a transduction mechanism appropriate to the particular parameter which is to be sensed.
- the present invention utilises a single optical technique for the monitoring of a number of blood gases e.g. pO and pCO- j .
- the technique is also applicable to the detection and measurement of other blood gas analytes. Its simplicity compared with electrochemical sensors and versatility to monitor a plurality of analytes make it an attractive alternative sensor technology.
- the present invention provides a method of analysis which utilises enhancement of the efficiency of Raman spectrum generation in a configuration in which a surface plasmon resonance is generated in an appropriate surface layer and the Raman spectrum is generated (normally simultaneously with the plasmon excitation).
- apparatus for sensing blood gas concentration ijn vivo which comprises a probe adapted for emplacement in a vein or artery and including: (a) at .
- the light guide comprises a pair of parallel optical fibres, one acting as an afferent light guide and the other as an efferent light guide.
- the gas-permeable membrane will come into contact with a patient's blood and dissolved gases (0 and CO ) will cross the membrane and contact the active surface. This is then illuminated by radiation arriving via the afferent fibre and a plasmon resonance-enhanced Raman spectrum is collected by the efferent fibre and directed towards a remotely located spectral detection system.
- the active surface can be in the form of a metal-coated grating or prism surface.
- the surface may be constituted by a dispersion of small metal spheres, as will be described in more detail hereinafter.
- FIGURE 1 is a schematic illustration of the generation of a surface plasmon resonance enhanced Raman spectrum
- FIGURES 2a and 2b illustrate schematically two embodiments ot the active surface used in the invention
- FIGURE 2c illustrates schematically the production of a Raman spectrum
- FIGURES 3 and 4 are schematic illustrations of two arrangements in accordance with the invention.
- FIGURE 5 illustrates an alternative embodiment of the active surface.
- FIGURES 6 to 9 illustrate four arrangements of a probe in accordance with the inventions each incorporating a different active surface/light collecting arrangement.
- a sensor head 1 supports an active surface 2 which, in this embodiment, is in the form of a grating.
- a source 3 of coherent radiation e.g. a laser operating in the visible or near infra-red, produces a collimated beam lambda 1, which is directed at the active surface 2 at an angle of incidence theta.
- Surface plasmon enhanced Raman emission occurs and the emitted rays lambda are detected by a detection system 4.
- the illumination source and detection systems do not form a part of the present invention.
- the enhanced Raman emission is affected in a specific and detectable manner? in this way, the detection and measurement of the Raman emission is used to give a qualitative and/or quantitative indication of the presence of the material.
- a material e.g. a specific gas
- the sensor itself comprises a metal coated substrate which may be part either of a prism (also known as Kretchmann or Otto geometry) or of a grating assembly. These arrangements are shown schematically in Figure 2.
- the metal grating has a dielectric constant EM w while the dielectric medium onto which the ⁇ i metal layer is deposited has a dielectric constant E..
- Surface plasmon generation can occur at the metal dielectric interface E. , E .
- the wavelength and angle of incidence of the illumination source, and the pitch, c - depth and groove shape of the grating (if used) are chosen to ensure efficient surface plasmon generation at the interface. This configuration, in which surface plasmon and Raman spectrum are generated simultaneously, provides enhancement of the efficiency of Raman spectrum
- the sensor head comprises a prism which carries a metal film 2 on one surface; the film 2 communicates directly with a conduit C through which the material undergoing analysis is passed.
- the illuminating light is transmitted to the sensor, e.g. via an optical fibre, with the generated
- a single fibre or two fibres, delivery and receiver may be used. This is shown in diagrammatic form in Figures 3 and 4.
- Fig. 3 there is a single optical fibre 5 which conveys light at 6 from the 0 illumination system (not shown) to the sensor assembly 1 and also conveys the Raman emission at 7 from the sensor assembly 1 to the detector system (not shown).
- Fig. 4 two separate optical fibres are located in a conduit 8 and serve to transmit the afferent illumination 6 and the efferent signal 7.
- the wavelength and angle of incidence of the illumination source and the grating pitch, depth and groove shape are chosen to ensure efficient surface plasmon generation at the interface. Illumination from the dielectric o side of the grating is possible if the metal coating is sufficiently thin ( ⁇ 10' nm) to allow penetration of the enhanced electric field into the material to be sensed, iii) It is known that under optimised conditions of physical parameters efficient surface plasmon generation can occur when a colloidal suspension of metalised spheres is illuminated. The dimensions of the spheres should be comparable with the wavelength of light.
- Figure 5 illustrates this arrangement, where the metal coated spheres 9 are located in a housing which constitutes the sensor head 1.
- a sub-miniature system allowing delivery of the complete sensor into the blood supply, remote from the illumination source and detection systems. Intregration of the light delivery and collection systems (fibres) and the interaction surface.
- the end of the fibre 5 may be metal coated as at 11.
- Dielectric cladding 10 surrounds the fibre 5.
- the sensor areas be surrounded by a membrane structure (indicated as either 12 or 14) permitting the flow of blood gases into the sensor volume but preventing the sensor from coming into direct contact with the blood.
- the total diameter of the sensor should not exceed 2 mm.
Abstract
Apparatus is disclosed for sensing blood gas concentration in vivo, which comprises a probe adapted for emplacement in a vein or artery and including: (a) at one end thereof, a gas-permeable membrane formed of a biologically acceptable material; (b) contiguous with said membrane, an active surface in the form of a surface capable of supporting a plasmon resonance; and (c) a light guide of a type capable of transmitting a light input to said active surface and of transmitting a light output away from said active surface, without mutual interference, wherein the light guide constitutes a support or substrate for said active surface and is in optical communication therewith.
Description
1 IN VIVO BLOOD TESTING
This invention relates to iii vivo blood gas analysis using Raman spectroscopy.
Vibrational spectroscopy has been employed for many years to study the structure and bonding of molecules. As each bond has its own, characteristic frequency, vibrational spectra and molecular structure are related. In this way, compositional analysis can be carried out by inspecting the vibrational spectrum of a 0 sample and comparing it with the spectra of known compounds.
The two main techniques employed are infrared absorption and Raman spectroscopy. In the first case, a wavelength tunable or broadband light source is used to 5 illuminate the specimen, and the wavelengths at which energy is absorbed are recorded. In Raman spectroscopy, a fixed wavelength source is employed, and the spectrum of emitted radiation recorded; the maxima in the emission spectrum represent the difference in energy ° between the incoming light quanta and the vibrational energy of the molecular bonds in the sample.
In general, vibrational energy levels lie in the infrared, and this represents a disadvantage for infrared absorption spectroscopy. Ideally one requires a tunable 5 or broadband source of IR radiation. Although this is clearly possible using thermal radiation, in general power levels are low, and detectors with the required sensitivity are expensive.
With Raman spectroscopy, however, one can ° illuminate the sample in the visible waveband, for example using a fixed frequency laser, and generate an emitted spectrum, shifted to the red, representative of the sample composition.
The major disadvantage to Raman scattering is that it is a weak process, relying on a non-linear interaction between the source radiation and the sample. In the past this has meant that even for concentrated samples under
ideal conditions photon counting and photomultiplier tubes have to be employed to detect the emitted radiation. Remote detection, when the sample volume may be small, or dilute, has therefore been impractical. In the technique we propose, a method of compositional analysis utilises the enhancement of the efficiency of generation of the Raman spectrum by using a configuration in which a surface plasmon is excited in an appropriate surface layer and the Raman spectrum is simultaneously generated. It is known that when a surface plasmon is excited, the electric field associated with the electromagnetic wave is highly enhanced (by a factor of 10 3 to 104). This means that it will interact with high efficiency with molecules in close proximity to the surface; the excitation efficiency of the Raman spectrum is much higher than would be the case without the surface plasmon phenomenon. In addition, excited molecules in close proximity to a metal surface can radiate light by co-operating with the metal surface; the 'image' of the molecular dipoles acts with the molecules themselves to form a "phased array1 of emitters. This emission can interact with the surface plasmon resonances of the metal surface so that the light is emitted in known, calculable directions. Thus the collection^ efficiency of the Raman spectrum is enhanced.
The present invention is particularly concerned with a sensor head designed specifically for use in in vivo monitoring of blood gases. The sensor is capable of both identification of gases and continuous measurement of their concentration.
In blood gas analysis, one is usually concerned with the measurement of O and CO partial pressures in both arterial and veinous flow, although the technique of the present invention may also be applicable to the detection of other analytes. Current techniques are based on either electrochemical (potentiometric or amperometric) or optical sensors. For example, the
^ Cardiomet 4000 system manufactured by Biomedical Sensors Limited of High Wycombe, UK combines pO-, measurement using an electrochemical sensor based on a Clark electrode with pC02 and pH measurement based on the c- optical absorption properties of chemical dyes. Electrochemical sensors suffer from some problems associated with their complexity and fragility which makes for example miniaturisation of the sensors difficult. This is particularly relevant to iji vivo blood gas analysis.
There have been recent developments in electrochemical sensors, such as the use of ion selective field effect transistors (ISFETS). However the productionisation of such systems has not yet been fully addressed.
In addition to optical sensors based on absorption and fluorescence, fibre optic sensors, either extrinsic or intrinsic, can be developed for application in blood gas analysis. The problem with such intrinsic sensors is the identification of a transduction mechanism appropriate to the particular parameter which is to be sensed.
The present invention utilises a single optical technique for the monitoring of a number of blood gases e.g. pO and pCO-j. The technique is also applicable to the detection and measurement of other blood gas analytes. Its simplicity compared with electrochemical sensors and versatility to monitor a plurality of analytes make it an attractive alternative sensor technology.
The present invention provides a method of analysis which utilises enhancement of the efficiency of Raman spectrum generation in a configuration in which a surface plasmon resonance is generated in an appropriate surface layer and the Raman spectrum is generated (normally simultaneously with the plasmon excitation).
According to one aspect of the present invention, there is provided apparatus for sensing blood gas concentration ijn vivo, which comprises a probe adapted for emplacement in a vein or artery and including: (a) at. one end thereof, a gas-permeable membrane formed of a biologically acceptable material; (b) contiguous with said membrane, an active surface in the form of a surface capable of supporting a plasmon resonance; and (c) a light guide of a type capable of transmitting a light input to said active surface and of transmitting a light output away from said active surface, without mutual interference, wherein the light guide constitutes a support .or substrate for said active surface and is in optical communication therewith. Conveniently, the light guide comprises a pair of parallel optical fibres, one acting as an afferent light guide and the other as an efferent light guide.
In practice, the gas-permeable membrane will come into contact with a patient's blood and dissolved gases (0 and CO ) will cross the membrane and contact the active surface. This is then illuminated by radiation arriving via the afferent fibre and a plasmon resonance-enhanced Raman spectrum is collected by the efferent fibre and directed towards a remotely located spectral detection system.
The active surface can be in the form of a metal-coated grating or prism surface. Alternatively the surface may be constituted by a dispersion of small metal spheres, as will be described in more detail hereinafter. The invention will now be described in more detail by way of example,, with reference to the accompanying drawings, in which:
FIGURE 1 is a schematic illustration of the generation of a surface plasmon resonance enhanced Raman spectrum;
FIGURES 2a and 2b illustrate schematically two embodiments ot the active surface used in the invention;
FIGURE 2c illustrates schematically the production of a Raman spectrum;
FIGURES 3 and 4 are schematic illustrations of two arrangements in accordance with the invention; FIGURE 5 illustrates an alternative embodiment of the active surface; and
FIGURES 6 to 9 illustrate four arrangements of a probe in accordance with the inventions each incorporating a different active surface/light collecting arrangement.
Referring now to the drawings, the general layout is as shown in Figure 1. It will be appreciated that components shown in the drawings are not drawn to scale; the enlargement of certain items whose dimensions are of the order of the wavelength of light is necessary for clarity. A sensor head 1 supports an active surface 2 which, in this embodiment, is in the form of a grating. A source 3 of coherent radiation, e.g. a laser operating in the visible or near infra-red, produces a collimated beam lambda 1, which is directed at the active surface 2 at an angle of incidence theta.. Surface plasmon enhanced Raman emission occurs and the emitted rays lambda are detected by a detection system 4. The illumination source and detection systems do not form a part of the present invention. In the presence of a material, e.g. a specific gas, whose presence is to be • detected, the enhanced Raman emission is affected in a specific and detectable manner? in this way, the detection and measurement of the Raman emission is used to give a qualitative and/or quantitative indication of the presence of the material.
The sensor itself comprises a metal coated substrate which may be part either of a prism (also known as Kretchmann or Otto geometry) or of a grating assembly. These arrangements are shown schematically in Figure 2.
AS shown in Figure 2c, the metal grating has a dielectric constant EMw while the dielectric medium onto which the
■i metal layer is deposited has a dielectric constant E.. Surface plasmon generation can occur at the metal dielectric interface E. , E . The wavelength and angle of incidence of the illumination source, and the pitch, c- depth and groove shape of the grating (if used) are chosen to ensure efficient surface plasmon generation at the interface. This configuration, in which surface plasmon and Raman spectrum are generated simultaneously, provides enhancement of the efficiency of Raman spectrum
•, Q generation.
In Figure 2a, the sensor head comprises a prism which carries a metal film 2 on one surface; the film 2 communicates directly with a conduit C through which the material undergoing analysis is passed. The arrangement
-,5 of Figure 2b is different in that the active metal film 2 is spaced from the prism by a narrow gap (e.g. of 1 micrometre or less) which forms part of the conduit C.
It is a feature of the _in vivo blood gas sensor to which this invention relates that the sensor head is
2o positioned remote from the illumination source, for example at the end of a catheter assembly which can be inserted into the patient's blood flow in a vein or artery. The illuminating light is transmitted to the sensor, e.g. via an optical fibre, with the generated
25 Raman spectrum returning to the main instrument via the same route. A single fibre or two fibres, delivery and receiver, may be used. This is shown in diagrammatic form in Figures 3 and 4. In Fig. 3, there is a single optical fibre 5 which conveys light at 6 from the 0 illumination system (not shown) to the sensor assembly 1 and also conveys the Raman emission at 7 from the sensor assembly 1 to the detector system (not shown). In Fig. 4, two separate optical fibres are located in a conduit 8 and serve to transmit the afferent illumination 6 and the efferent signal 7.
Particular features of the _in vivo sensor head are described below. Highly efficient surface plasmon
•j_ generation can occur at a metal-dielectric interface when the momentum of the incident radiation and the surface plasmon are matched. This does not occur under normal circumstances, since the surface plasmon momentum is always less than that of light. However momentum matching can be achieved by a number of techniques: i) Metal coated Prism ATR (attenuated total internal reflection), also known as Otto or Kretchmann geometry configuration as shown in Figures 2a and 0 2b. At a particular angle of incidence, the momentum of the evanescent wave matches the surface plasmon mode ensuring efficient surface plasmon generation, ii) Use of a metal coated grating to ensure momentum matching (Figure 2c). The wavelength and angle of incidence of the illumination source and the grating pitch, depth and groove shape are chosen to ensure efficient surface plasmon generation at the interface. Illumination from the dielectric o side of the grating is possible if the metal coating is sufficiently thin (< 10' nm) to allow penetration of the enhanced electric field into the material to be sensed, iii) It is known that under optimised conditions of physical parameters efficient surface plasmon generation can occur when a colloidal suspension of metalised spheres is illuminated. The dimensions of the spheres should be comparable with the wavelength of light. Figure 5 illustrates this arrangement, where the metal coated spheres 9 are located in a housing which constitutes the sensor head 1. iv) Surface plasmon generation can also occur at a statistically rough metal-dielectric interface. We now describe ways in which some of these geometries could be integrated with a catheter based delivery system for _in vivo blood gas analysis.
unique features of this sensor are as follows.
A sub-miniature system allowing delivery of the complete sensor into the blood supply, remote from the illumination source and detection systems. Intregration of the light delivery and collection systems (fibres) and the interaction surface. For example: i) AS shown in Fig. 6, the end of the fibre 5 may be metal coated as at 11. Dielectric cladding 10 surrounds the fibre 5. A gas-permeable membrane
12 overlies the metal layer 11. Surface plasmon generation can then occur in a similar way to the
Kretchmann geometry of Figure 2a. Here "free space" propagation of the conventional Kretchmann arrangement is replaced by a coupling of a propagation mode of the fibre to the surface plasmon mode. Raman scattered light can be collected by the same fibre. ii) Minaturised and integrated fibre grating assemblies are shown in Figure 7. A spherical collimating lens 13 is attached to the end of the fibre 5 which provides illumination and a combined membrane/grating support 14 is provided between the lens 13 and a grating 15. Alternatively, a fibre structure could be moulded into the fibre tip and metallised, as at 15 in Figure 8. iii) An arrangement utilising a colloidal suspension of metal spheres is shown in Figure 9.
In all the described configurations, it is essential that the sensor areas be surrounded by a membrane structure (indicated as either 12 or 14) permitting the flow of blood gases into the sensor volume but preventing the sensor from coming into direct contact with the blood. The total diameter of the sensor should not exceed 2 mm.
Claims
1. Apparatus for sensing blood gas concentration in vivo, which comprises a probe adapted for emplacement in a vein or artery and including: (a) at one end thereof, a gas-permeable membrane formed of a biologically acceptable material; (b) contiguous with said membrane, an active surface in the form of a surface capable of supporting a plasmon resonance; and (c) a light guide of a type capable of transmitting a light input to said active surface and of transmitting a light output away from said active surface, without mutual interference, wherein the light guide constitutes a support or substrate for said active surface and is in optical communication therewith.
2. Apparatus as claimed in claim 1, wherein said light guide comprises a pair of optical fibres, one functioning as an afferent light guide and the other functioning as an efferent light guide.
3. Apparatus as claimed in claim 1 or 2, wherein said surface is a grating.
4. Apparatus as claimed in claim 1 or 2, wherein said surface is a metal coated fibre.
5. Apparatus as claimed in claim 1 or 2, wherein said surface is a suspension of metal particles whose dimensions are of the order of the wavelength of light.
6. Apparatus as claimed in claim 1 or 2, wherein said surface is a statistically rough surface.
7. Apparatus as claimed in claim 1 or 2, wherein said surface is a prism one surface of which is coated with a thin film of a metal.
8. Apparatus as claimed in any preceding claim, wherein said active surface, said gas-permeable membrane and said light guide are housed in a catheter.
9. Apparatus as claimed in claim 8, which further comprises a source of coherent light located remote from said active surface but optically in communication therewith via said light guide.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB878704423A GB8704423D0 (en) | 1987-02-25 | 1987-02-25 | Compositional analysis |
GB8704423 | 1987-02-25 | ||
GB878722449A GB8722449D0 (en) | 1987-02-25 | 1987-09-24 | In vitro blood testing |
GB8722449 | 1987-09-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1988006726A1 true WO1988006726A1 (en) | 1988-09-07 |
Family
ID=26291943
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB1988/000125 WO1988006726A1 (en) | 1987-02-25 | 1988-02-24 | In vivo blood testing |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0305428A1 (en) |
AU (1) | AU1349388A (en) |
WO (1) | WO1988006726A1 (en) |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5359681A (en) * | 1993-01-11 | 1994-10-25 | University Of Washington | Fiber optic sensor and methods and apparatus relating thereto |
WO1996029925A2 (en) * | 1995-03-27 | 1996-10-03 | Massachusetts Institute Of Technology | Apparatus and methods of raman spectroscopy for analysis of blood gases and analytes |
DE19630538A1 (en) * | 1996-07-29 | 1998-02-05 | Rossendorf Forschzent | Composite material for resonance amplification of optical signals and method for its production |
US6044285A (en) * | 1997-11-12 | 2000-03-28 | Lightouch Medical, Inc. | Method for non-invasive measurement of an analyte |
US6289230B1 (en) | 1998-07-07 | 2001-09-11 | Lightouch Medical, Inc. | Tissue modulation process for quantitative noninvasive in vivo spectroscopic analysis of tissues |
WO2004008120A1 (en) * | 2002-07-10 | 2004-01-22 | E2V Technologies (Uk) Limited | Molecular detector arrangement |
US6726881B2 (en) | 2001-09-03 | 2004-04-27 | Fuji Photo Film Co., Ltd. | Measurement chip for surface plasmon resonance biosensor |
GB2403796B (en) * | 2002-07-10 | 2006-02-22 | E2V Tech Uk Ltd | Molecular detector arrangement |
US7254429B2 (en) | 2004-08-11 | 2007-08-07 | Glucolight Corporation | Method and apparatus for monitoring glucose levels in a biological tissue |
US7356365B2 (en) | 2003-07-09 | 2008-04-08 | Glucolight Corporation | Method and apparatus for tissue oximetry |
US7510849B2 (en) | 2004-01-29 | 2009-03-31 | Glucolight Corporation | OCT based method for diagnosis and therapy |
GB2470757A (en) * | 2009-06-04 | 2010-12-08 | Haemair Ltd | A sensing device for measuring the presence of gas in a substance. |
US9060721B2 (en) | 2008-03-04 | 2015-06-23 | Glt Acquisition Corp. | Flowometry in optical coherence tomography for analyte level estimation |
US9078560B2 (en) | 2004-08-11 | 2015-07-14 | Glt Acquisition Corp. | Method for data reduction and calibration of an OCT-based physiological monitor |
US9554737B2 (en) | 2004-08-11 | 2017-01-31 | Masimo Corporation | Noninvasively measuring analyte levels in a subject |
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GB2173895A (en) * | 1985-04-12 | 1986-10-22 | Plessey Co Plc | Optical assay |
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1988
- 1988-02-24 WO PCT/GB1988/000125 patent/WO1988006726A1/en not_active Application Discontinuation
- 1988-02-24 AU AU13493/88A patent/AU1349388A/en not_active Withdrawn
- 1988-02-24 EP EP19880901883 patent/EP0305428A1/en not_active Withdrawn
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GB2173895A (en) * | 1985-04-12 | 1986-10-22 | Plessey Co Plc | Optical assay |
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Analytical Chemistry, volume 54, no. 9, August 1982, American Chemical Society, (US), I. Chabay: "Optical waveguides", pages 1071 A - 1080 A * |
IBM Technical Disclosure Bulletin, volume 23, no. 11, April 1981, (New York, US), J.G. Gordon et al.: "Use of gratings to detect small quantities of materials by raman spectroscopy", page 5099 * |
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Cited By (32)
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US5647030A (en) * | 1993-01-11 | 1997-07-08 | University Of Washington | Fiber optic sensor and methods and apparatus relating thereto |
US5835645A (en) * | 1993-01-11 | 1998-11-10 | University Of Washington | Fiber optic sensor and methods and apparatus relating thereto |
US5359681A (en) * | 1993-01-11 | 1994-10-25 | University Of Washington | Fiber optic sensor and methods and apparatus relating thereto |
WO1996029925A2 (en) * | 1995-03-27 | 1996-10-03 | Massachusetts Institute Of Technology | Apparatus and methods of raman spectroscopy for analysis of blood gases and analytes |
WO1996029925A3 (en) * | 1995-03-27 | 1996-12-05 | Massachusetts Inst Technology | Apparatus and methods of raman spectroscopy for analysis of blood gases and analytes |
US5615673A (en) * | 1995-03-27 | 1997-04-01 | Massachusetts Institute Of Technology | Apparatus and methods of raman spectroscopy for analysis of blood gases and analytes |
DE19630538A1 (en) * | 1996-07-29 | 1998-02-05 | Rossendorf Forschzent | Composite material for resonance amplification of optical signals and method for its production |
US6044285A (en) * | 1997-11-12 | 2000-03-28 | Lightouch Medical, Inc. | Method for non-invasive measurement of an analyte |
US6377828B1 (en) | 1997-11-12 | 2002-04-23 | Lightouch Medical, Inc. | Method for non-invasive measurement of an analyte |
US6289230B1 (en) | 1998-07-07 | 2001-09-11 | Lightouch Medical, Inc. | Tissue modulation process for quantitative noninvasive in vivo spectroscopic analysis of tissues |
US6726881B2 (en) | 2001-09-03 | 2004-04-27 | Fuji Photo Film Co., Ltd. | Measurement chip for surface plasmon resonance biosensor |
AU2003260677C1 (en) * | 2002-07-10 | 2009-03-26 | E2V Biosensors Limited | Molecular detector arrangement |
GB2403796B (en) * | 2002-07-10 | 2006-02-22 | E2V Tech Uk Ltd | Molecular detector arrangement |
AU2003260677B2 (en) * | 2002-07-10 | 2008-11-06 | E2V Biosensors Limited | Molecular detector arrangement |
WO2004008120A1 (en) * | 2002-07-10 | 2004-01-22 | E2V Technologies (Uk) Limited | Molecular detector arrangement |
US7356365B2 (en) | 2003-07-09 | 2008-04-08 | Glucolight Corporation | Method and apparatus for tissue oximetry |
US7510849B2 (en) | 2004-01-29 | 2009-03-31 | Glucolight Corporation | OCT based method for diagnosis and therapy |
US9554737B2 (en) | 2004-08-11 | 2017-01-31 | Masimo Corporation | Noninvasively measuring analyte levels in a subject |
US10791971B2 (en) | 2004-08-11 | 2020-10-06 | Masimo Corporation | Method for data reduction and calibration of an OCT-based physiological monitor |
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Also Published As
Publication number | Publication date |
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AU1349388A (en) | 1988-09-26 |
EP0305428A1 (en) | 1989-03-08 |
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