WO1983003344A1 - Fiber optic p¿o2? probe - Google Patents
Fiber optic p¿o2? probe Download PDFInfo
- Publication number
- WO1983003344A1 WO1983003344A1 PCT/US1982/001418 US8201418W WO8303344A1 WO 1983003344 A1 WO1983003344 A1 WO 1983003344A1 US 8201418 W US8201418 W US 8201418W WO 8303344 A1 WO8303344 A1 WO 8303344A1
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- Prior art keywords
- dye
- porous
- probe according
- oxygen
- jacket
- Prior art date
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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
- G01N21/75—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
-
- 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
- G01N21/62—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"
-
- 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
- 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
- G01N2021/7706—Reagent provision
- G01N2021/772—Tip coated light guide
-
- 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
- G01N2021/7769—Measurement method of reaction-produced change in sensor
- G01N2021/7786—Fluorescence
Definitions
- the present invention relates to measurement of oxygen partial pressure, and more particularly to a fiber optic probe device for implantation to measure oxygen partial pressure in the blood or tissue.
- Physiologic oxygen measurement is important for many reasons, as follows: - -
- the corresponding protein change (globin) embedding the heme controls its adsorptive charac ⁇ teristics, and determines the shape of the transfer function, thus suiting the heme to the needs of a particular species.
- the globin chain also is part of a control loop to adjust the curve to biochemical signals, most significantly pH, 2,3-diphosphoglycerate and C0 2 -
- hemoglobin In people, approximately 200 genetic variants of hemoglobin are known; most are innocuous, some are pathologically severe because of alteration of the transfer function (sickle cell disease, etc.).
- tissue oxygenation is one of the most important short-range concerns in a variety of surgical and intensive care situations, requiring either quick response sampling or continuous monitoring of P Q levels.
- Clark electrode membrane-diffusion, amperometric
- the diffusion dependence is subject to calibration and drift problems.
- Haase USP 4,201,222 discloses an optical catheter, including a fiber-optic bundle, adapted to be inserted into a blood vessel of a living body for measuring the partial pressure of oxygen gas in the blood stream.
- the catheter comprises a semi-permeable wall member for excluding the entry therethrough of blood liquid while permitting passage of blood gases.
- the intensity of a reflected visible light beam entering the optical fiber bundle when compared to the intensity of the incident beam, is said to accurately correspond to the partial pressure of the oxygen gas in the bloodstream.
- Ostrowski et al USP 3,807,390 disclose a fiber optic catheter for monitoring blood oxygen saturation in a human blood stream, in vivo, by insertion of the catheter tip into the cardiovascular system of the living body.
- Willis et al USP 4,033,330 is of general interest in showing a transcutaneous optical pH measuring device for determining blood pH or carbon dioxide ⁇ oncentraton in the blood.
- 4,041,932 is likewise of general interest in teaching an apparatus used to measure and monitor the concentration and partial pressure of gases, such as oxygen and carbon dioxide in arterial blood vessels, and the pH of the blood during various time periods.
- the P electrode literature is enormous, °2 but there is still not a suitable electrode available.
- Oxygen measurement by luminescence quenching has also been suggested. The idea originated in the 1930's, but has had relatively little use, although oxygen quenching of fluorescence is widely recognized as a nuisance.
- Stevens USP 3,612,866 discloses an apparatus for measuring the oxygen content concentration of liquids or gases based on the molecular luminescence quenching effect of gaseous oxygen on aromatic molecules, derivatives of such aromatics and aliphatic ketones.
- Another object of the invention is to overcome the defects of the prior art, such as above described. Another object of the invention is to provide for improved P n in vivo measurement.
- a further object of the invention is to provide for an improved P Q measurement device, particularly one based on oxygen measurement using luminescence quenching and including a fiber optic probe.
- a still further object of the invention is to provide an improved P Q measurement device employing luminescence quenching as its operational principle and utilizing a fiber optic probe in combination with a relatively simple optical system in association with photomultiplier tubes and an electronic computing circuit driven by said photo ⁇ multiplier tubes and arranged to provide a direct analog computation of Q based on said luminescence quenching as detected by said optical system.
- a typical fiber optic probe for measuring oxygen partial pressure according to the present invention based on the principle of fluorescence quenching, comprises two 150-micrometer strands of plastic optical fiber ending in a section of porous polymer tubing about 5 mm long and 0.6 mm in diameter.
- the tubing is packed with a dye on an adsorptive particulate support.
- the general construction is similar to a physiological pH probe which has previously been described in the Peterson et al USP 4,200,110.
- a dye had to be found with the combined properties of suitable oxygen quench sensitivity (long activated state lifetime) , fluorescence excitation by visible light, and resistance to fading.
- Plastic optical fibers which transmit light sufficiently at wavelengths shorter than 450 nm are not available. Ultraviolet transmitting inorganic fibers are not desirable for this application because of their brittleness.
- the traditional silica dye support is not suitable for use in an aqueous medium.
- the probe device of the present invention is intended to provide a small-size, low-cost probe suitable for tissue and blood vessel implantation through a hypodermic needle.
- Fiber optic probes have substantial advantages, including the following: a. Very small size is possible, such as less than 0.5 mm ⁇ . b. They are flexible, so that they can be threaded through small blood vessels or can be located in a variety of tissues. c. They are low in cost, disposable, and easy to fabricate. d. They introduce no electrical hazard. e. They are suitable for equilibrium measurement, rather than dynamic. The s ⁇ Iectionof luminescence quenching as the mechanism for oxygen measurement was based on the following factors:
- a reversible indicator is needed for a
- Aromatic molecules form charge-transfer complexes with oxygen upon activation by light absorption. This provides a mechanism for deactivation of the fluorescent state which is specific for oxygen. A high energy of activation of the molecule, sufficient to achieve formation of activated oxygen by collision transfer, is not needed, i.e., the quenching phenomenon can be observed with visible light activation of luminescence.
- Fluorescence (and phosphorescence) quenching is the result of a non-luminescent decay mode competing with the luminescent decay of an activated molecule, thereby decreasing the mean lifetime of the activated state and decreasing the luminous intensity (see Figure 2) .
- the rate of decay of the excited state is the sum of the rates of the various decay modes ?
- the collision decay rate is proportional to the activated state mean lifetime (approximately, the fluorescence lifetime) and the collision rate, which is in turn proportional to the pressure of the quench gas.
- Phosphorescence with a very long lifetime (seconds) , is very sensitive to quenching, but is weakin intensity. Fluorescence is less sensitive to quenching, but has a high brightness (high quantum efficiency). P 1 should be of the order of the pressure to be measured to best compromise brightness and sensitivity (see Figure 3) .
- Figure 1 is a graph showing the classic concentration vs. pressure relationship of oxygen in human blood.
- Figure 2 is a schematic representation of competing modes of deactivation of an optically excited molecule.
- Figure 3 is a schematic representation showing the relationship between P' and P Q .
- Figure 4 is a diagrammatic view of an embodiment of a P n probe in accordance with the ⁇ 2 present invention.
- Figure 5 is a graph comparing theoretical Stern-Volmer data with typically observed data according to the invention.
- Figures 6 and 7 respectively show schematically the optical system and the electronic c-mputing system of a simple analog instrument employing testing probes according to the present invention.
- a P 0 probe according to the present invention is generally designated at 8.
- the P Q probe 8 is modelled after the pH probe previously developed by use (see Peterson et al, USP 4,200,110).
- the dye 15 on an adsorbent support 16 is contained inside a section of tubing 10 of porous polyethylene, providing rapid equilibration with the surrounding oxygen and isolating the dye packing 16 from contamination.
- the tubing 10 is closed at one end, providing an axial tapered closure tip 9.
- a pair of flexible plastic optical fibers 12 and 14, for example, 150-micrometer strands of plastic optical fiber, are suitably secured in the other end of the tubing 10, with their ends optically exposed to the dye 15 in the packing 16.
- the tubing 10 may comprise a section of porous polymer tubing about 5 mm long and 0.6 mm in diameter.
- Blue light illumination passes down one optical fiber 12 to excite the dye 15 to fluorescence.
- the green fluorescent light along with scattered blue light, enters the other fiber 14 and passes to a measuring instrument (see Figures 6 and 7) .
- the blue light intensity I 0 is used as the reference for optical compensation, and the green light intensity I is a measure of the oxygen quenching.
- the Stern-Volmer relation provides a linear quantitative basis for measuring P Q by quenching (see Figure ' 5) .
- a curved relation is commonly observed (the literature with Stern-Volmer plotted data is large) and an exponent is often attached to the oxygen pressure to fit the data to the equation.
- a suitable dye 15 has the following characteristics: a. It must be capable of excitation by and generation of visible wavelengths which can be transmitted by plastic optical fibers of a type which is unbreakable when subjected to sharp bends, is highly flexible, and which can be formed to provide easy optical coupling, such as with flared ends. b. It must be stable to light and have adequate resistance to aging. c. It must be non-toxic. d. It must have sufficient oxygen quenching sensitivity (long mean lifetime of the excited state) as needed to attain measurement to the nearest 1 mm ⁇ t g
- a suitable dye is perylene dibutyrate.
- Another suitable dye is Pylam Products LX7878. Less suitable; but usable dyes are Terasil Brilliant Flavine 8GFF; Nylosan Brilliant Flavine; Acridine Yellow; Brilliant Sulfaflavine; 2,7-dichloro- fluorescein; Acridine Orange; Cou arin 34; Coumarin 6; sodium fluorescein (Auranine) , and some rhodamines. Others have appeared in the literature references given herein.
- the problem with inorganic adsorbents is that the quenching is humidity-sensitive; quenching and/or fluorescence is destroyed at 100% humidity, the condition of physiologic measurement.
- Organic adsorbents such as porous polymers, avoid the humidity problem, with a sacrifice of quench sensitivity and these polymers determinable by routine testing in view of this disclosure, are desirably selected.
- a porous polymer Rohm & Haas "Amberlite XAD4", a non-ionic hydrophobic polymer, is the preferred support 16. Examples of others are Gas Chrom Q, Amberlite XAD2, XAD8; Dow XFS4022; Johns-Manville Chromosorb, Nos. 101, 102, 103, 104, 105, 106, 107, 108; Waters Porapak Nos. N, P, PS, Q, R, S, QS, T; Hamilton Co. PRP-1. In the illustrated embodiment of the ?
- the described embodiment works in aqueous media as well as in a gaseous system, and behaves- satisfactorily in test animals.
- the combination of the use of luminescence quenching for oxygen determination, together with fiber optics is believed to be novel and highly advantageous.
- the important features of the invention include the use of a porous polymer support, proper selection of dye, and the use of a porous jacket or envelope.
- the use of a porous polymer as the dye support 16 is essential for the best performance.
- a suitable jacket 10 may be formed of Celgard, although other porous materials can be used.
- the optical output of fiber 14 is transmitted through a collimating lens 13 to a 45°-inclined dichroic filter 19.
- the transmitted light component passes through a blue filter 20 to a first photomultiplier tube 21.
- the reflected light component passes through a green filter 22 to a second photomultiplier tube 23.
- the output currents from the photomultiplier tubes 21 and 23 are fed to respective current-to-voltage converter circuits 24, 25, and the resultant voltage signals are passed through respective active filters 26, 27 to the inputs of divider circuit 23 provided with means to apply an exponent m to the quotient (Ifc>iue divided by Igrpen' as given above) .
- the P Q analog value is then computed by feeding the output of circuit 28 to a final computing circuit 29 which subtracts the quantity 1 from its input signal and applies the coefficient P', as indicated in Figure 6.
Abstract
A fiber optic probe to be implanted in human body tissue for physiologic studies involving measurement and monitoring of the partial pressure of gaseous oxygen in the blood stream, which is coursing through a particular blood vessel in the body. The use of theprobe is based on the principle of dye florescence oxygen quenching. Structurally the probe comprises two 150/micrometer strands (12, 14) of plastic optical fiber ending in a section of porous polymer tubing (10) serving as a jacket or envelope for the fibers. The tubing is packed with a suitable fluorescent light-excitable dye placed on a porous adsorptive particulate polymeric support. The tubing or jacket is usually made of a hydrophobic, gas-permeable commercial material, known as Celgard, but other suitable hydrophobic gas-permeable material could be used for such structure. The fiber optic probe of the invention is of very small size and flexible so that it can easily be threaded through small blood vessels which are located in a variety of tissues of the body.
Description
FIBER OPTIC Pn PROBE
This application is a continuation-in-part of our previously filed United States application S.N. 363,425, filed March 30, 1982, entitled "Fiber Optic PQ Probe" , the contents of which are incor¬ porated by reference.
FIELD OF THE INVENTION
The present invention relates to measurement of oxygen partial pressure, and more particularly to a fiber optic probe device for implantation to measure oxygen partial pressure in the blood or tissue.
BACKGROUND OF THE INVENTION
Physiologic oxygen measurement is important for many reasons, as follows:
- -
- The transfer function (Figure 1) is the fundamental determinant of oxygen transport and distribution.
- Adsorption of O2 by heme is the most widely used mechanism of oxygen storage and transport throughout the animal kingdom.
- The corresponding protein change (globin) embedding the heme controls its adsorptive charac¬ teristics, and determines the shape of the transfer function, thus suiting the heme to the needs of a particular species.
- The globin chain also is part of a control loop to adjust the curve to biochemical signals, most significantly pH, 2,3-diphosphoglycerate and C02-
- In people, approximately 200 genetic variants of hemoglobin are known; most are innocuous, some are pathologically severe because of alteration of the transfer function (sickle cell disease, etc.).
- Direct measurement of Pπ is therefore u2 necessary to observe the oxygen transport behavior in an individual in any physiologic investigation.
Moreover, adequate tissue oxygenation is one of the most important short-range concerns in a variety of surgical and intensive care situations, requiring either quick response sampling or continuous monitoring of PQ levels.
A number of techniques and systems are known, but none of these is entirely suitable. For example:
- The Clark electrode (membrane-diffusion, amperometric) does not lend itself to small size.
- The diffusion dependence is subject to calibration and drift problems.
- A strictly potentio etric (redox) electrode has specificity difficulties.
Haase, USP 4,201,222 discloses an optical catheter, including a fiber-optic bundle, adapted to be inserted into a blood vessel of a living body for measuring the partial pressure of oxygen gas in the blood stream. The catheter comprises a semi-permeable wall member for excluding the entry therethrough of blood liquid while permitting passage of blood gases. The intensity of a reflected visible light beam entering the optical fiber bundle, when compared to the intensity of the incident beam, is said to accurately correspond to the partial pressure of the oxygen gas in the bloodstream.
Mori, USP 3,814,081 discloses an optical catheter for measuring the percentage content of oxygen saturating the blood stream of a living animal body. An illuminating fiber optic system and a light receiving system are arranged closely adjacent to one another. The tip of the catheter is inserted into a blood-carrying organ of the animal body. The degree of oxygen saturation is measured by a light absorption spectroscopic determination of light waves which are reflected from the blood stream and received by an optical fiber bundle.
Ostrowski et al USP 3,807,390 disclose a fiber optic catheter for monitoring blood oxygen saturation in a human blood stream, in vivo, by insertion of the catheter tip into the cardiovascular system of the living body.
C.-
- ά -
Willis et al USP 4,033,330 is of general interest in showing a transcutaneous optical pH measuring device for determining blood pH or carbon dioxide σoncentraton in the blood. Fostick USP
4,041,932 is likewise of general interest in teaching an apparatus used to measure and monitor the concentration and partial pressure of gases, such as oxygen and carbon dioxide in arterial blood vessels, and the pH of the blood during various time periods.
The P electrode literature is enormous, °2 but there is still not a suitable electrode available.
Oxygen measurement by luminescence quenching has also been suggested. The idea originated in the 1930's, but has had relatively little use, although oxygen quenching of fluorescence is widely recognized as a nuisance. Stevens USP 3,612,866 discloses an apparatus for measuring the oxygen content concentration of liquids or gases based on the molecular luminescence quenching effect of gaseous oxygen on aromatic molecules, derivatives of such aromatics and aliphatic ketones.
Other applications of luminescence quenching for oxygen determination include:
1. Original observation of effect - dyes adsorbed on silica gel: H. Kautsky and A. Hirsch in early 1930fs, e.g. H. Kautsky and A. Hirsch, Z. fur anorg. u. allgem. Chemie 222, 126-34, 1935.
2. Measurement of 02 produced by illumination of algae: M. Pollack, P. Pringsheim and D. Terwood, J. Che . Phys. , 12, 295-9, 1944.
"
3. Catalog of oxygen quenching sensitivities of organic molecules of scintillation interest: I.B. Berlman, "Handbook of Fluorescence Spectra of Aromatic Molecules", Academic Press, 1965.
4. 02 measured down to 10~5 torr with acriflavin on acrylic sheet: Gy. Orban, Zs. Szentirmay and J. Patko, Proc. of the Intl. Conf. on Luminescence, 1966, v.l, 611-3, 1968.
5. Diffusion coefficient of 02 in acrylics measured by observing the phosphorescence of rods:
G. Shaw, Trans. Faraday Soc. _6 _, 2181-9, 1967.
6. 0 permeability of acrylic films measured by quench rate vs. PQ : P.F. Jones, Polymer Letters 6_, 487-91, 1968.
7. Pn measuring instrument based on υ2 fluoranthene adsorbed on plastic films and porous vycor: I. Bergman, Nature 218, 396, 1968.
8. Pyrenebutyric acid used as probe for measuring intracellular 0 : J.A. Knopp and I.A. Longmuir, Bioσhimica et Biophysica Acta, 279, 393-7, 1972.
9. Physiological PQ measurement using DMF solutions of pyrenebutyric acid in various membrane- enclosed forms, D.W. Lubber and N. Opitz, Z. Naturf. 30c, 532-3, 1975.
SUMMARY OF THE INVENTION
It is accordingly an object of the invention to overcome the defects of the prior art, such as above described.
Another object of the invention is to provide for improved Pn in vivo measurement.
°2 A further object of the invention is to provide for an improved PQ measurement device, particularly one based on oxygen measurement using luminescence quenching and including a fiber optic probe.
A still further object of the invention is to provide an improved PQ measurement device employing luminescence quenching as its operational principle and utilizing a fiber optic probe in combination with a relatively simple optical system in association with photomultiplier tubes and an electronic computing circuit driven by said photo¬ multiplier tubes and arranged to provide a direct analog computation of Q based on said luminescence quenching as detected by said optical system.
A typical fiber optic probe for measuring oxygen partial pressure according to the present invention, based on the principle of fluorescence quenching, comprises two 150-micrometer strands of plastic optical fiber ending in a section of porous polymer tubing about 5 mm long and 0.6 mm in diameter. The tubing is packed with a dye on an adsorptive particulate support. The general construction is similar to a physiological pH probe which has previously been described in the Peterson et al USP 4,200,110.
Development of the probe of the present invention required the solution of three major problems not encountered before in the application of the above-mentioned quenching principle:
1. A dye had to be found with the combined properties of suitable oxygen quench sensitivity (long activated state lifetime) , fluorescence excitation by visible light, and resistance to fading. Plastic optical fibers which transmit light sufficiently at wavelengths shorter than 450 nm are not available. Ultraviolet transmitting inorganic fibers are not desirable for this application because of their brittleness.
2. A suitable hydrophobic, high-oxygen- permeability envelope was necessary.
3. An adsorptive support was required which activated the dye without sensitivity to humidity.
The traditional silica dye support is not suitable for use in an aqueous medium.
The probe device of the present invention is intended to provide a small-size, low-cost probe suitable for tissue and blood vessel implantation through a hypodermic needle.
Fiber optic probes have substantial advantages, including the following: a. Very small size is possible, such as less than 0.5 mm θ. b. They are flexible, so that they can be threaded through small blood vessels or can be located in a variety of tissues. c. They are low in cost, disposable, and easy to fabricate. d. They introduce no electrical hazard. e. They are suitable for equilibrium measurement, rather than dynamic.
The s≤Iectionof luminescence quenching as the mechanism for oxygen measurement was based on the following factors:
1. A reversible indicator is needed for a
Pn probe. A reversible colorimetric (absorbance) u2 indicator for oxygen is not available. The transition metal complex oxygen absorbers do not have the required stability.
2, Aromatic molecules form charge-transfer complexes with oxygen upon activation by light absorption. This provides a mechanism for deactivation of the fluorescent state which is specific for oxygen. A high energy of activation of the molecule, sufficient to achieve formation of activated oxygen by collision transfer, is not needed, i.e., the quenching phenomenon can be observed with visible light activation of luminescence.
Fluorescence (and phosphorescence) quenching is the result of a non-luminescent decay mode competing with the luminescent decay of an activated molecule, thereby decreasing the mean lifetime of the activated state and decreasing the luminous intensity (see Figure 2) .
With constant illumination, the rate of decay of the excited state is the sum of the rates of the various decay modes? the collision decay rate is proportional to the activated state mean lifetime (approximately, the fluorescence lifetime) and the collision rate, which is in turn proportional to the pressure of the quench gas. These competing decay rates result in the Stern-Volmer relation for intensity I and pressure PQ of oxygen:
∑° + 1 + P°2
•*•
_ Q
(0. Stern and M. Volmer, Physikalische Zeitschrift 20, 183-8, 1919), where IQ is the intensity without quenching and P1 is a constant, the pressure at half- quench. The constant includes a proportionality of corresponding quench to mean fluorescence lifetime, so the same expression can be written in terms of observed luminescent lifetimes, TQ and T: 0 O + 1 +
P'
Good sensitivity to quenching requires a long mean lifetime of the excited state. Phosphorescence, with a very long lifetime (seconds) , is very sensitive to quenching, but is weakin intensity. Fluorescence is less sensitive to quenching, but has a high brightness (high quantum efficiency). P1 should be of the order of the pressure to be measured to best compromise brightness and sensitivity (see Figure 3) .
BRIEF DESCRIPTION OF THE DRAWINGS
Further objects and advantages of the invention will become apparent from the following description and claims, and from the accompanying drawings, wherein:
Figure 1 is a graph showing the classic concentration vs. pressure relationship of oxygen in human blood.
Figure 2 is a schematic representation of competing modes of deactivation of an optically excited molecule.
Figure 3 is a schematic representation showing the relationship between P' and PQ .
Figure 4 is a diagrammatic view of an embodiment of a Pn probe in accordance with the ϋ2 present invention.
Figure 5 is a graph comparing theoretical Stern-Volmer data with typically observed data according to the invention.
Figures 6 and 7 respectively show schematically the optical system and the electronic c-mputing system of a simple analog instrument employing testing probes according to the present invention.
DETAILED DESCRIPTION OF A PREFERRED EMBODIMENT
Referring to the drawings, and more particularly to Figure 4, a P0 probe according to the present invention is generally designated at 8. The PQ probe 8 is modelled after the pH probe previously developed by use (see Peterson et al, USP 4,200,110). In the PQ probe 8, the dye 15 on an adsorbent support 16, is contained inside a section of tubing 10 of porous polyethylene, providing rapid equilibration with the surrounding oxygen and isolating the dye packing 16 from contamination. The tubing 10 is
closed at one end, providing an axial tapered closure tip 9. A pair of flexible plastic optical fibers 12 and 14, for example, 150-micrometer strands of plastic optical fiber, are suitably secured in the other end of the tubing 10, with their ends optically exposed to the dye 15 in the packing 16. The tubing 10 may comprise a section of porous polymer tubing about 5 mm long and 0.6 mm in diameter.
Blue light illumination passes down one optical fiber 12 to excite the dye 15 to fluorescence. The green fluorescent light, along with scattered blue light, enters the other fiber 14 and passes to a measuring instrument (see Figures 6 and 7) . The blue light intensity I0 is used as the reference for optical compensation, and the green light intensity I is a measure of the oxygen quenching.
The Stern-Volmer relation provides a linear quantitative basis for measuring PQ by quenching (see Figure '5) . A curved relation is commonly observed (the literature with Stern-Volmer plotted data is large) and an exponent is often attached to the oxygen pressure to fit the data to the equation.
A theoretical interpretation o'f the exponential relation is difficult to understand; curved data can be equally well fitted by an offset constant on the intensity measurements, which can be explained as instrumental background or non-quenchable luminescence. For instrumental design purposes, however, using either an exponent m on the intensity ratio or an exponent n as the bracketed difference is more practical:
A simple analog instrument was constructed (see Figures 6 and 7) for evaluation of the probes. Measurement of PQ to the nearest ImmHg Q, requires better than 0.1% intensity measurement error. Instrumentally, the limiting factor is light source stability.
As noted above, there are three features of the above-described system which need to be properly selected, namely, the dye 15, the dye support 16 and the envelope 10.
A suitable dye 15 has the following characteristics: a. It must be capable of excitation by and generation of visible wavelengths which can be transmitted by plastic optical fibers of a type which is unbreakable when subjected to sharp bends, is highly flexible, and which can be formed to provide easy optical coupling, such as with flared ends. b. It must be stable to light and have adequate resistance to aging. c. It must be non-toxic. d. It must have sufficient oxygen quenching sensitivity (long mean lifetime of the excited state) as needed to attain measurement to the nearest 1 mm Ηtg
There is a problem in the selection of the dye 15 in that many UV-excited dyes have a high quench sensitivity (benzene has one of the highest) , but the requirement of visible light excitation makes it much more difficult to find a dye"which will meet the requirement. A suitable dye is perylene dibutyrate.
Another suitable dye is Pylam Products LX7878. Less suitable; but usable dyes are Terasil Brilliant Flavine 8GFF; Nylosan Brilliant Flavine; Acridine Yellow; Brilliant Sulfaflavine; 2,7-dichloro- fluorescein; Acridine Orange; Cou arin 34; Coumarin 6; sodium fluorescein (Auranine) , and some rhodamines. Others have appeared in the literature references given herein.
With regard to a suitable support 16, the quenching effect was classically observed on silica gel, and high sensitivity is achieved on this support. A high-permeability support is necessary to expose the individual dye molecules to oxygen collision. A solution of the dye in liquids or solids is insen¬ sitive because of the low oxygen permeability of such materials.
The problem with inorganic adsorbents is that the quenching is humidity-sensitive; quenching and/or fluorescence is destroyed at 100% humidity, the condition of physiologic measurement.
Organic adsorbents, such as porous polymers, avoid the humidity problem, with a sacrifice of quench sensitivity and these polymers determinable by routine testing in view of this disclosure, are desirably selected. A porous polymer, Rohm & Haas "Amberlite XAD4", a non-ionic hydrophobic polymer, is the preferred support 16. Examples of others are Gas Chrom Q, Amberlite XAD2, XAD8; Dow XFS4022; Johns-Manville Chromosorb, Nos. 101, 102, 103, 104, 105, 106, 107, 108; Waters Porapak Nos. N, P, PS, Q, R, S, QS, T; Hamilton Co. PRP-1.
In the illustrated embodiment of the ?
°2 probe 8, a liquid-water-impermeable container of high oxygen permeability is required for the permeable envelope 10. Porous polypropylene sheet Celanese
"Celgard", heat-sealed into tubing, has been found to be suitable.
The described embodiment works in aqueous media as well as in a gaseous system, and behaves- satisfactorily in test animals.
The combination of the use of luminescence quenching for oxygen determination, together with fiber optics is believed to be novel and highly advantageous. As noted above, the important features of the invention include the use of a porous polymer support, proper selection of dye, and the use of a porous jacket or envelope. The use of a porous polymer as the dye support 16 is essential for the best performance. As above mentioned, a suitable jacket 10 may be formed of Celgard, although other porous materials can be used.
Variations are possible. Thus, there are alternate ways of making the probe, e.g., a single fiber, rather than two fibers, could be used, with appropriate instrumentation modification, to reduce probe size.
In the typical optical system of Figure 7, the optical output of fiber 14 is transmitted through a collimating lens 13 to a 45°-inclined dichroic filter 19. The transmitted light component passes through a blue filter 20 to a first photomultiplier tube 21. The reflected light component passes through a green filter 22 to a second photomultiplier tube 23.
As shown in Figure 6, the output currents from the photomultiplier tubes 21 and 23 are fed to respective current-to-voltage converter circuits 24, 25, and the resultant voltage signals are passed through respective active filters 26, 27 to the inputs of divider circuit 23 provided with means to apply an exponent m to the quotient (Ifc>iue divided by Igrpen' as given above) . The PQ analog value is then computed by feeding the output of circuit 28 to a final computing circuit 29 which subtracts the quantity 1 from its input signal and applies the coefficient P', as indicated in Figure 6.
It will be obvious to those skilled in the art that various changes may be made without departing from the scope of the invention and that the invention is not to be considered limited to what is shown in the drawings and described in the specification.
Claims
1. A probe for determining PQ in the blood or tissue of a living animal, comprising: an oxygen- porous jacket of a size sufficiently small to be passed into a blood vessel; a porous dye support carried within said jacket and having high permeabilty to expose individual dye molecules carried thereby to oxygen collision; a non-toxic dye carried by said porous dye support, said dye being visibly lumi¬ nescent, having stability to light and aging, and being oxygen quenching-sensitive; and fiber optic means to pass excitation light to said dye within said jacket and collect luminescence therefrom. )
2. A probe according to claim 1, wherein said dye is perylene dibutyrate. (Color Index 59075) .
3. A probe according to claim 1 or claim 2, wherein said porous dye support is a porous organic polymer.
4. A probe according to claim 1, and wherein said porous dye support comprises silica gel.
5. A probe according to claim 1, and wherein said porous dye support comprises a porous adsorptive particulate polymeric material.
6. A probe according to claim 1, and wherein said porous dye support comprises Amberlite XAD4.
7. A probe according to claim 1, and wherein said oxygen-porous jacket comprises a tubular envelope of porous material.
8. A probe according to claim 7, and wherein said tubular envelope is formed of Celgard.
9. A probe according to claim 1, and wherein said oxygen-porous jacket comprises porous polypropylene sheet material heat-sealed into tubing, closed at one end and provided at said closed end with a tapered closure tip.
10. A probe according to claim 1, and wherein said fiber optic means comprises at least one strand of transparent plastic fiber with one end extending into said jacket and being optically exposed to said dye.
11. A probe according to claim 1, and wherein said fiber optic means comprises two strands of transparent flexible plastic fiber with ends extending into said jacket and being optically exposed to said dye.
12. A probe according to claim 1, and wherein said fiber optic means includes a strand of transparent plastic fiber with one end extending into said jacket and being optically exposed to said dye, optical beam-splitting means optically exposed to the
^ 3SJB
OMPI_ - 13 -
other end of said plastic fiber and forming two spaced optical beams from the light transmitted through the fiber, respective photoelectric signal generating means in the paths of said two optical beams, and
Pn computing circuit means connected to the output of υ2 said photoelectric signal generating means.
13. A probe according to claim 12, and respective different-color filter means optically interposed in the paths of the two optical beams between the beam-splitting means and the photo- electrical signal generating means.
14. A probe according to claim 13, and wherein one color filter means passes only light corresponding to the luminescence wavelength of the dye, and the other color filter means passes light only of a color corresponding to that of scattered incident light to which the dye is exposed and which is reflected from the dye.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP50331582A JPS59500896A (en) | 1982-03-30 | 1982-10-15 | Oxygen partial pressure measuring device using optical fiber |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US36342582A | 1982-03-30 | 1982-03-30 | |
US363,425 | 1982-03-30 | ||
US396,055820707 | 1982-07-07 | ||
US06/396,055 US4476870A (en) | 1982-03-30 | 1982-07-07 | Fiber optic PO.sbsb.2 probe |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1983003344A1 true WO1983003344A1 (en) | 1983-10-13 |
Family
ID=27002060
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1982/001418 WO1983003344A1 (en) | 1982-03-30 | 1982-10-15 | Fiber optic p¿o2? probe |
Country Status (7)
Country | Link |
---|---|
US (1) | US4476870A (en) |
EP (1) | EP0091390B1 (en) |
AU (1) | AU565949B2 (en) |
CA (1) | CA1187386A (en) |
CH (1) | CH665345A5 (en) |
DE (1) | DE3381613D1 (en) |
WO (1) | WO1983003344A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0126600A2 (en) * | 1983-05-17 | 1984-11-28 | Elf U.K. Plc | Optical fibre probe |
WO1986005589A1 (en) * | 1985-03-20 | 1986-09-25 | Monash University | Fibre optic chemical sensor |
EP0251475A1 (en) * | 1986-06-26 | 1988-01-07 | Becton, Dickinson and Company | Apparatus for monitoring glucose |
US4842783A (en) * | 1987-09-03 | 1989-06-27 | Cordis Corporation | Method of producing fiber optic chemical sensors incorporating photocrosslinked polymer gels |
US5151603A (en) * | 1987-09-03 | 1992-09-29 | Terumo Kabushiki Kaisha | Method for optical determination of concentration of substance and apparatus for the determination |
US5152287A (en) * | 1990-08-15 | 1992-10-06 | Cordis Corporation | Cross-linked fluorinated polymers for use in gas sensors |
Families Citing this family (179)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4626693A (en) * | 1980-10-06 | 1986-12-02 | The Regents Of The University Of California | Remote multi-position information gathering system and method |
US4577109A (en) * | 1980-10-06 | 1986-03-18 | Regents Of The University Of California | Remote multi-position information gathering system and method |
US4586819A (en) * | 1982-07-09 | 1986-05-06 | Hitachi, Ltd. | Laser Raman microprobe |
CA1261717A (en) * | 1982-12-23 | 1989-09-26 | John R. Bacon | Method and apparatus for oxygen determination |
US5030420A (en) * | 1982-12-23 | 1991-07-09 | University Of Virginia Alumni Patents Foundation | Apparatus for oxygen determination |
US4553034A (en) * | 1983-12-02 | 1985-11-12 | Westinghouse Electric Corp. | Ion exchange resin intrusion monitor |
US4622974A (en) * | 1984-03-07 | 1986-11-18 | University Of Tennessee Research Corporation | Apparatus and method for in-vivo measurements of chemical concentrations |
GB2159620A (en) * | 1984-05-29 | 1985-12-04 | Norman Barrie Jones | Photoelectric pressure transducer without elastic diaphragm |
EP0175352B1 (en) * | 1984-09-19 | 1991-06-12 | Siemens-Elema AB | Method and device for rapidly ascertaining the parameters of a sample medium |
EP0187283B1 (en) * | 1984-12-26 | 1989-04-26 | Nivarox-FAR S.A. | Device to locate in situ through-holes in a hollow pin that is implanted into the medullary canal for the retention of the fragments of a fractured bone |
EP0190830A3 (en) * | 1985-02-04 | 1988-04-27 | Gould Inc. | Single optical fiber sensor for measuring the partial pressure of oxygen |
US4752115A (en) * | 1985-02-07 | 1988-06-21 | Spectramed, Inc. | Optical sensor for monitoring the partial pressure of oxygen |
US4666672A (en) * | 1985-04-08 | 1987-05-19 | University Of California | Optrode for sensing hydrocarbons |
US5354825A (en) * | 1985-04-08 | 1994-10-11 | Klainer Stanley M | Surface-bound fluorescent polymers and related methods of synthesis and use |
US4801655A (en) * | 1985-06-21 | 1989-01-31 | Gould, Inc. | Fiber optic pH sensor having low drift rate |
US5043286A (en) * | 1985-07-03 | 1991-08-27 | Abbott Laboratories | Method and sensor for measuring oxygen concentration |
US4810655A (en) * | 1985-07-03 | 1989-03-07 | Abbott Laboratories | Method for measuring oxygen concentration |
EP0227815A4 (en) * | 1985-07-03 | 1988-06-23 | Internat Biomedics Inc | Methods of measuring oxygen concentration. |
US4613237A (en) * | 1985-08-22 | 1986-09-23 | United Technologies Corporation | Method for determining the temperature of a fluid |
US5034189A (en) * | 1985-08-27 | 1991-07-23 | The Regents Of The University Of California | Fluorescent probe for rapid measurement of analyte concentration |
AT387860B (en) * | 1985-09-16 | 1989-03-28 | Optical Sensing Technology | METHOD AND DEVICE FOR TUMOR DIAGNOSIS BY MEANS OF SERA |
US4936679A (en) * | 1985-11-12 | 1990-06-26 | Becton, Dickinson And Company | Optical fiber transducer driving and measuring circuit and method for using same |
US4737343A (en) * | 1986-01-21 | 1988-04-12 | The Regents Of The University Of California | Gas-sensing optrode |
US5019350A (en) * | 1986-02-13 | 1991-05-28 | Pfizer Hospital Products, Inc. | Fluorescent polymers |
US4710623A (en) * | 1986-02-27 | 1987-12-01 | Eli Lilly And Company | Optical fiber catheter with fiber-contained reactive element |
US5006314A (en) * | 1986-04-18 | 1991-04-09 | Minnesota Mining And Manufacturing Company | Sensor and method for sensing the concentration of a component in a medium |
US4927222A (en) * | 1986-06-16 | 1990-05-22 | Shiley Incorporated | Dual optical fiber device |
US4822127A (en) * | 1986-06-16 | 1989-04-18 | Shiley Incorporated | Multi-channel optical transmission system |
US4854321A (en) * | 1986-06-18 | 1989-08-08 | Medex, Inc. | Integrated optic system for monitoring blood gases |
US5001054A (en) * | 1986-06-26 | 1991-03-19 | Becton, Dickinson And Company | Method for monitoring glucose |
US4895156A (en) * | 1986-07-02 | 1990-01-23 | Schulze John E | Sensor system using fluorometric decay measurements |
US4800886A (en) * | 1986-07-14 | 1989-01-31 | C. R. Bard, Inc. | Sensor for measuring the concentration of a gaseous component in a fluid by absorption |
US4929562A (en) * | 1986-08-20 | 1990-05-29 | The Regents Of The University Of California | Method and apparatus for detecting gem-polyhalogenated hydrocarbons |
US4861727A (en) * | 1986-09-08 | 1989-08-29 | C. R. Bard, Inc. | Luminescent oxygen sensor based on a lanthanide complex |
US4900933A (en) * | 1986-09-08 | 1990-02-13 | C. R. Bard, Inc. | Excitation and detection apparatus for remote sensor connected by optical fiber |
US4760250A (en) * | 1986-09-29 | 1988-07-26 | Spectramed, Inc. | Optoelectronics system for measuring environmental properties having plural feedback detectors |
US4886338A (en) * | 1986-10-10 | 1989-12-12 | Minnesota Mining And Manufacturing Company | Optical fiber event sensor |
US5120510A (en) * | 1986-10-10 | 1992-06-09 | Minnesota Mining And Manufacturing Company | Sensor and method for sensing the concentration of a component in a medium |
US5012809A (en) * | 1986-10-10 | 1991-05-07 | Shulze John E | Fiber optic catheter system with fluorometric sensor and integral flexure compensation |
US4830013A (en) * | 1987-01-30 | 1989-05-16 | Minnesota Mining And Manufacturing Co. | Intravascular blood parameter measurement system |
US4989606A (en) * | 1987-01-30 | 1991-02-05 | Minnesota Mining And Manufactoring Company | Intravascular blood gas sensing system |
US4951669A (en) * | 1987-01-30 | 1990-08-28 | Minnesota Mining And Manufacturing Company | Blood parameter measurement system |
US4934369A (en) * | 1987-01-30 | 1990-06-19 | Minnesota Mining And Manufacturing Company | Intravascular blood parameter measurement system |
US5462052A (en) * | 1987-01-30 | 1995-10-31 | Minnesota Mining And Manufacturing Co. | Apparatus and method for use in measuring a compositional parameter of blood |
US5048525A (en) * | 1987-01-30 | 1991-09-17 | Minnesota Mining And Manufacturing Company | Blood parameter measurement system with compliant element |
US4833091A (en) * | 1987-02-06 | 1989-05-23 | Shiley Incorporated | Sensor system |
US5093266A (en) * | 1987-02-06 | 1992-03-03 | Shiley Inc. | Sensor system |
US4852579A (en) * | 1987-04-20 | 1989-08-01 | Karl Storz Endoscopy Gmbh And Company | Photocharacterization and treatment of normal abnormal and ectopic endometrium |
AT389590B (en) * | 1987-05-27 | 1989-12-27 | Avl Verbrennungskraft Messtech | METHOD FOR THE CONTINUOUS, QUANTITATIVE DETERMINATION OF SULFUR DIOXIDE AND ARRANGEMENT FOR IMPLEMENTING THE METHOD |
US5043285A (en) * | 1987-07-09 | 1991-08-27 | Allied-Signal Inc. | Optical detection of oxygen |
US4785814A (en) * | 1987-08-11 | 1988-11-22 | Cordis Corporation | Optical probe for measuring pH and oxygen in blood and employing a composite membrane |
EP0309214A3 (en) * | 1987-09-22 | 1990-03-14 | BAXTER INTERNATIONAL INC. (a Delaware corporation) | Fiber optical probe connector for physiologic measurement devices |
US4974929A (en) * | 1987-09-22 | 1990-12-04 | Baxter International, Inc. | Fiber optical probe connector for physiologic measurement devices |
EP0312293A3 (en) * | 1987-10-16 | 1990-03-14 | O.C.T. Optical Chemical Technologies Limited | Sensing device for analysis |
US5037615A (en) * | 1987-10-30 | 1991-08-06 | Cordis Corporation | Tethered pair fluorescence energy transfer indicators, chemical sensors, and method of making such sensors |
US5242835A (en) * | 1987-11-03 | 1993-09-07 | Radiometer A/S | Method and apparatus for determining the concentration of oxygen |
DK163194C (en) * | 1988-12-22 | 1992-06-22 | Radiometer As | METHOD OF PHOTOMETRIC IN VITRO DETERMINING A BLOOD GAS PARAMETER IN A BLOOD TEST |
US4994396A (en) * | 1987-12-14 | 1991-02-19 | The Dow Chemical Company | Method for measuring the concentration or partial pressure of oxygen |
US4929049A (en) * | 1988-01-29 | 1990-05-29 | Fiberchem, Inc. | Fiber optic refractive index sensor using a metal clad |
US5217876A (en) * | 1988-03-15 | 1993-06-08 | Akzo N.V. | Method for detecting microorganisms |
US5518895A (en) * | 1990-02-15 | 1996-05-21 | Akzo N.V. | Device for detecting microorganisms using piezoelectric means |
US5127077A (en) * | 1988-07-25 | 1992-06-30 | Abbott Laboratories | Fiber-optic physiological probes |
US5000901A (en) * | 1988-07-25 | 1991-03-19 | Abbott Laboratories | Fiber-optic physiological probes |
US4925268A (en) * | 1988-07-25 | 1990-05-15 | Abbott Laboratories | Fiber-optic physiological probes |
US4889407A (en) * | 1988-12-02 | 1989-12-26 | Biomedical Sensors Limited | Optical waveguide sensor and method of making same |
US5047350A (en) * | 1989-01-19 | 1991-09-10 | Eastman Kodak Company | Material and method for oxygen sensing |
EP0381026A3 (en) * | 1989-02-03 | 1991-05-02 | F. Hoffmann-La Roche Ag | Optical oxygen sensor |
US4892383A (en) * | 1989-02-17 | 1990-01-09 | Fiberchem Inc. | Reservoir fiber optic chemical sensors |
US4906249A (en) * | 1989-02-23 | 1990-03-06 | Medtronic, Inc. | Terpolymer composition with bound indicator dye for fiber optic probe |
US5094959A (en) * | 1989-04-26 | 1992-03-10 | Foxs Labs | Method and material for measurement of oxygen concentration |
US5858769A (en) * | 1989-05-15 | 1999-01-12 | Akzo Nobel N.V. | Device for detecting microorganisms |
US5434084A (en) * | 1989-09-06 | 1995-07-18 | The Washington Research Foundation | Flow optrode having separate reaction and detection chambers |
CA2022558A1 (en) * | 1989-09-11 | 1991-03-12 | Richard Barner | Optical oxygen sensor |
JP2798450B2 (en) * | 1989-12-08 | 1998-09-17 | 株式会社日立製作所 | Biological measurement device |
US5244810A (en) * | 1990-01-12 | 1993-09-14 | Gottlieb Amos J | Analytical method |
US5102625A (en) * | 1990-02-16 | 1992-04-07 | Boc Health Care, Inc. | Apparatus for monitoring a chemical concentration |
US5127405A (en) * | 1990-02-16 | 1992-07-07 | The Boc Group, Inc. | Biomedical fiber optic probe with frequency domain signal processing |
US5175016A (en) * | 1990-03-20 | 1992-12-29 | Minnesota Mining And Manufacturing Company | Method for making gas sensing element |
EP0447949A1 (en) * | 1990-03-22 | 1991-09-25 | F. Hoffmann-La Roche Ag | Optical oxygen sensor |
US5115133A (en) * | 1990-04-19 | 1992-05-19 | Inomet, Inc. | Testing of body fluid constituents through measuring light reflected from tympanic membrane |
US5115811A (en) * | 1990-04-30 | 1992-05-26 | Medtronic, Inc. | Temperature measurement and compensation in a fiber-optic sensor |
US5047627A (en) * | 1990-05-18 | 1991-09-10 | Abbott Laboratories | Configuration fiber-optic blood gas sensor bundle and method of making |
US5124130A (en) * | 1990-05-22 | 1992-06-23 | Optex Biomedical, Inc. | Optical probe |
US5271073A (en) * | 1990-08-10 | 1993-12-14 | Puritan-Bennett Corporation | Optical fiber sensor and method of manufacture |
US5186173A (en) * | 1990-08-14 | 1993-02-16 | Drexel University | Method for in vivo measurement of oxygen concentration levels |
WO1992005441A1 (en) * | 1990-09-17 | 1992-04-02 | Baxter International Inc. | Water insensitive tissue oxygen sensor |
US5176882A (en) * | 1990-12-06 | 1993-01-05 | Hewlett-Packard Company | Dual fiberoptic cell for multiple serum measurements |
US5273716A (en) * | 1991-01-14 | 1993-12-28 | Electric Power Research Institute, Inc. | pH optrode |
US5142155A (en) * | 1991-03-11 | 1992-08-25 | Hewlett-Packard Company | Catheter tip fluorescence-quenching fiber optic pressure sensor |
US5435307A (en) * | 1991-03-29 | 1995-07-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Surface fluorescent monitor |
US5119463A (en) * | 1991-04-09 | 1992-06-02 | Abbott Laboratories | Compound optical probe employing single optical waveguide |
DE4120688A1 (en) * | 1991-06-22 | 1993-01-14 | Wienert Volker | Quantitative detection appts. for fluorescent material in human skin tissue - uses measurement head with stimulation light source and tuned photodiode fluorescent light receiver |
US5241184A (en) * | 1991-09-26 | 1993-08-31 | Electric Power Research Institute | Apparatus and method for quantizing remaining lifetime of transmission cable insulation |
US5204922A (en) * | 1991-10-22 | 1993-04-20 | Puritan-Bennett Corporation | Optical signal channel selector |
US5335305A (en) * | 1991-12-19 | 1994-08-02 | Optex Biomedical, Inc. | Optical sensor for fluid parameters |
US5335658A (en) * | 1992-06-29 | 1994-08-09 | Minnesota Mining And Manufacturing Company | Intravascular blood parameter sensing system |
US5326531A (en) * | 1992-12-11 | 1994-07-05 | Puritan-Bennett Corporation | CO2 sensor using a hydrophilic polyurethane matrix and process for manufacturing |
US5515864A (en) * | 1994-04-21 | 1996-05-14 | Zuckerman; Ralph | Method and apparatus for the in vivo measurement of oxygen concentration levels by the indirect determination of fluoescence lifetime |
US5605152A (en) * | 1994-07-18 | 1997-02-25 | Minimed Inc. | Optical glucose sensor |
US5718842A (en) * | 1994-10-07 | 1998-02-17 | Joanneum Reserach Forschungsgesellschaft Mbh | Luminescent dye comprising metallocomplex of a oxoporphyrin |
US5706808A (en) * | 1995-01-31 | 1998-01-13 | Kleinerman; Marcos Y. | Fiber optic system for measuring cardiac output |
US5490490A (en) * | 1995-04-27 | 1996-02-13 | Ford Motor Company | On-board gas composition sensor for internal combustion engine exhaust gases |
US5902246A (en) * | 1996-03-26 | 1999-05-11 | Lifespex, Incorporated | Method and apparatus for calibrating an optical probe |
US5863460A (en) * | 1996-04-01 | 1999-01-26 | Chiron Diagnostics Corporation | Oxygen sensing membranes and methods of making same |
US7335164B2 (en) | 1996-07-15 | 2008-02-26 | Ntc Technology, Inc. | Multiple function airway adapter |
US6325978B1 (en) | 1998-08-04 | 2001-12-04 | Ntc Technology Inc. | Oxygen monitoring and apparatus |
US6815211B1 (en) | 1998-08-04 | 2004-11-09 | Ntc Technology | Oxygen monitoring methods and apparatus (I) |
US6274086B1 (en) | 1996-12-16 | 2001-08-14 | The Trustees Of The University Of Pennsylvania | Apparatus for non-invasive imaging oxygen distribution in multi-dimensions |
US5830138A (en) * | 1996-12-16 | 1998-11-03 | Trustees Of The University Of Pennsylvania | Intravascular catheter probe for clinical oxygen, pH and CO2 measurement |
US6048359A (en) * | 1997-08-25 | 2000-04-11 | Advanced Photodynamic Technologies, Inc. | Spatial orientation and light sources and method of using same for medical diagnosis and photodynamic therapy |
US6306347B1 (en) | 1998-01-21 | 2001-10-23 | Bayer Corporation | Optical sensor and method of operation |
US6190612B1 (en) | 1998-01-21 | 2001-02-20 | Bayer Corporation | Oxygen sensing membranes and methods of making same |
US6254831B1 (en) | 1998-01-21 | 2001-07-03 | Bayer Corporation | Optical sensors with reflective materials |
CA2329783A1 (en) | 1998-05-13 | 1999-11-18 | Yellow Springs Optical Sensor Co. Pll. | System and method for optical chemical sensing |
US6107083A (en) * | 1998-08-21 | 2000-08-22 | Bayer Corporation | Optical oxidative enzyme-based sensors |
US6219566B1 (en) * | 1999-07-13 | 2001-04-17 | Photonics Research Ontario | Method of measuring concentration of luminescent materials in turbid media |
US6395555B1 (en) | 1999-10-14 | 2002-05-28 | David F. Wilson | Method and apparatus for determining the effect of a drug on cells |
US6701168B1 (en) | 1999-10-14 | 2004-03-02 | Trustees Of The University Of Pennsylvania | Apparatus for measuring an oxygen concentration gradient and method of use thereof |
US6925328B2 (en) | 2000-04-20 | 2005-08-02 | Biophan Technologies, Inc. | MRI-compatible implantable device |
US8527046B2 (en) | 2000-04-20 | 2013-09-03 | Medtronic, Inc. | MRI-compatible implantable device |
US20020116029A1 (en) | 2001-02-20 | 2002-08-22 | Victor Miller | MRI-compatible pacemaker with power carrying photonic catheter and isolated pulse generating electronics providing VOO functionality |
US6829509B1 (en) | 2001-02-20 | 2004-12-07 | Biophan Technologies, Inc. | Electromagnetic interference immune tissue invasive system |
US7054686B2 (en) | 2001-08-30 | 2006-05-30 | Biophan Technologies, Inc. | Pulsewidth electrical stimulation |
US6731979B2 (en) | 2001-08-30 | 2004-05-04 | Biophan Technologies Inc. | Pulse width cardiac pacing apparatus |
US20030077205A1 (en) * | 2001-10-24 | 2003-04-24 | Xu Tom C. | Diagnostic test optical fiber tips |
WO2003037399A2 (en) | 2001-10-31 | 2003-05-08 | Biophan Technologies, Inc. | Hermetic component housing for photonic catheter |
US6968236B2 (en) * | 2002-01-28 | 2005-11-22 | Biophan Technologies, Inc. | Ceramic cardiac electrodes |
US6711440B2 (en) | 2002-04-11 | 2004-03-23 | Biophan Technologies, Inc. | MRI-compatible medical device with passive generation of optical sensing signals |
US6725092B2 (en) | 2002-04-25 | 2004-04-20 | Biophan Technologies, Inc. | Electromagnetic radiation immune medical assist device adapter |
JP3653536B2 (en) * | 2002-06-21 | 2005-05-25 | 独立行政法人航空宇宙技術研究所 | Optical oxygen concentration measuring method and optical oxygen concentration measuring sensor |
US6925322B2 (en) | 2002-07-25 | 2005-08-02 | Biophan Technologies, Inc. | Optical MRI catheter system |
US6999807B2 (en) * | 2003-01-23 | 2006-02-14 | Scimed Life Systems, Inc. | pH measuring balloon |
DE102005024578A1 (en) * | 2005-05-25 | 2006-11-30 | Raumedic Ag | Probe for measuring oxygen content in biological material comprises distal fiber section inclusive of distal end face along with dye enclosed by oxygen-penetrable, fluid-impenetrable membrane which in enclosed area provides gas space |
US7611621B2 (en) * | 2005-06-13 | 2009-11-03 | Nova Biomedical Corporation | Disposable oxygen sensor and method for correcting oxygen effect on oxidase-based analytical devices |
US20060289796A1 (en) * | 2005-06-22 | 2006-12-28 | Cryovac, Inc. | UV-C sensitive composition and dosimeter |
US7648624B2 (en) * | 2005-07-26 | 2010-01-19 | Nova Biomedical Corporation | Oxygen sensor |
DE102005036410A1 (en) * | 2005-07-29 | 2007-02-01 | Biocam Gmbh | Method for determining the oxygen partial pressure distribution in at least one tissue surface section, in particular skin tissue surface section |
EP2679155A1 (en) | 2006-01-04 | 2014-01-01 | The Trustees of The University of Pennsylvania | Oxygen sensor for internal monitoring of tissue oxygen in vivo |
US8129105B2 (en) * | 2006-04-13 | 2012-03-06 | Ralph Zuckerman | Method and apparatus for the non-invasive measurement of tissue function and metabolism by determination of steady-state fluorescence anisotropy |
US8088097B2 (en) | 2007-11-21 | 2012-01-03 | Glumetrics, Inc. | Use of an equilibrium intravascular sensor to achieve tight glycemic control |
US8738107B2 (en) | 2007-05-10 | 2014-05-27 | Medtronic Minimed, Inc. | Equilibrium non-consuming fluorescence sensor for real time intravascular glucose measurement |
EP2989975B1 (en) | 2007-02-06 | 2018-06-13 | Medtronic MiniMed, Inc. | Optical systems and methods for rationmetric measurement of blood glucose concentration |
WO2008118042A1 (en) * | 2007-03-23 | 2008-10-02 | St. Jude Medical Ab | Implantable medical device |
US20100130839A1 (en) * | 2007-04-27 | 2010-05-27 | St. Jude Medical Ab | Implantable devices and method for determining a concentration of a substance and/or molecule in blood or tissue of a patient |
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3612866A (en) * | 1969-07-08 | 1971-10-12 | Brian Stevens | Instrument for determining oxygen quantities by measuring oxygen quenching of fluorescent radiation |
US3807390A (en) * | 1972-12-04 | 1974-04-30 | American Optical Corp | Fiber optic catheter |
US3814081A (en) * | 1971-04-02 | 1974-06-04 | Olympus Optical Co | Optical measuring catheter |
US4003707A (en) * | 1975-02-28 | 1977-01-18 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Method and arrangement for measuring the concentration of gases |
US4200110A (en) * | 1977-11-28 | 1980-04-29 | United States Of America | Fiber optic pH probe |
US4201222A (en) * | 1977-08-31 | 1980-05-06 | Thomas Haase | Method and apparatus for in vivo measurement of blood gas partial pressures, blood pressure and blood pulse |
US4215940A (en) * | 1976-07-20 | 1980-08-05 | Max Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Optode arrangement |
US4269516A (en) * | 1976-07-21 | 1981-05-26 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Optode |
US4306877A (en) * | 1978-07-29 | 1981-12-22 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Optical measurement of concentration |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DD106086A1 (en) * | 1973-07-16 | 1974-05-20 | ||
GB2003050B (en) * | 1977-08-25 | 1982-02-10 | Medishield Corp Ltd | Apparatus for analysis of absorbed gases |
JPS54155682A (en) * | 1978-05-29 | 1979-12-07 | Sumitomo Electric Industries | Sensor for measuring oxygen concentration in percutaneous blood |
-
1982
- 1982-07-07 US US06/396,055 patent/US4476870A/en not_active Expired - Lifetime
- 1982-10-15 CH CH6521/83A patent/CH665345A5/en not_active IP Right Cessation
- 1982-10-15 WO PCT/US1982/001418 patent/WO1983003344A1/en unknown
- 1982-10-15 AU AU90592/82A patent/AU565949B2/en not_active Ceased
- 1982-12-07 CA CA000417127A patent/CA1187386A/en not_active Expired
-
1983
- 1983-03-28 EP EP83450008A patent/EP0091390B1/en not_active Expired - Lifetime
- 1983-03-28 DE DE8383450008T patent/DE3381613D1/en not_active Expired - Fee Related
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3612866A (en) * | 1969-07-08 | 1971-10-12 | Brian Stevens | Instrument for determining oxygen quantities by measuring oxygen quenching of fluorescent radiation |
US3814081A (en) * | 1971-04-02 | 1974-06-04 | Olympus Optical Co | Optical measuring catheter |
US3807390A (en) * | 1972-12-04 | 1974-04-30 | American Optical Corp | Fiber optic catheter |
US4003707A (en) * | 1975-02-28 | 1977-01-18 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Method and arrangement for measuring the concentration of gases |
US4215940A (en) * | 1976-07-20 | 1980-08-05 | Max Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Optode arrangement |
US4269516A (en) * | 1976-07-21 | 1981-05-26 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Optode |
US4201222A (en) * | 1977-08-31 | 1980-05-06 | Thomas Haase | Method and apparatus for in vivo measurement of blood gas partial pressures, blood pressure and blood pulse |
US4200110A (en) * | 1977-11-28 | 1980-04-29 | United States Of America | Fiber optic pH probe |
US4306877A (en) * | 1978-07-29 | 1981-12-22 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Optical measurement of concentration |
Non-Patent Citations (1)
Title |
---|
Rev. Sci. Instrum., May 1980, John Peterson and Raphael V. Fitzgerald; New Technique of Surface Flow Based on Oxygen Quenching of Fluorescence, pages 670-671 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0126600A2 (en) * | 1983-05-17 | 1984-11-28 | Elf U.K. Plc | Optical fibre probe |
EP0126600A3 (en) * | 1983-05-17 | 1985-10-30 | Elf U.K. Plc | Optical fibre probe |
WO1986005589A1 (en) * | 1985-03-20 | 1986-09-25 | Monash University | Fibre optic chemical sensor |
EP0251475A1 (en) * | 1986-06-26 | 1988-01-07 | Becton, Dickinson and Company | Apparatus for monitoring glucose |
US4842783A (en) * | 1987-09-03 | 1989-06-27 | Cordis Corporation | Method of producing fiber optic chemical sensors incorporating photocrosslinked polymer gels |
US5151603A (en) * | 1987-09-03 | 1992-09-29 | Terumo Kabushiki Kaisha | Method for optical determination of concentration of substance and apparatus for the determination |
US5152287A (en) * | 1990-08-15 | 1992-10-06 | Cordis Corporation | Cross-linked fluorinated polymers for use in gas sensors |
Also Published As
Publication number | Publication date |
---|---|
US4476870A (en) | 1984-10-16 |
EP0091390B1 (en) | 1990-05-30 |
EP0091390A1 (en) | 1983-10-12 |
CA1187386A (en) | 1985-05-21 |
AU9059282A (en) | 1983-10-24 |
CH665345A5 (en) | 1988-05-13 |
AU565949B2 (en) | 1987-10-01 |
DE3381613D1 (en) | 1990-07-05 |
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