JP3305398B2 - Optical fiber sensor - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an optical fiber sensor for detecting a chemical or physical parameter of a living body by using an optical fiber, and more particularly, to the field of blood pH and the like in a living body in the field of medicine and the like. The present invention relates to an optical fiber sensor capable of monitoring glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxyl ion concentration and the like in a body for a long time.

[0002]

2. Description of the Related Art Fiber optic sensors for sensing chemical or physical parameters using fiber optics include:
Conventionally, various proposals have been made, including those for industrial use and medical use. For example, a semipermeable membrane with a pH-sensitive dye is placed at the end of an optical fiber, and the test object is set to the pH of blood in a blood vessel.
(Japanese Patent Application Laid-Open No. 54-85588), chemical / physical parameter-sensitive chromophores are chemically bonded to the surface of the optical fiber core, and the test object is an industrial / medical chemical / physical parameter (eg, pH). Certain sensors (Japanese
77641), a sensor in which an oxygen-sensitive dye covered with a hydrophobic gas-permeable envelope is fixed to the tip of an optical fiber,
The test object is oxygen in the blood (Tables 59-50)
0896), a porous hydrophobic membrane supporting the indicator compound is arranged at the end of the optical fiber,
pH sensor (JP-A-60-35246), sensor containing an oxygen-sensing fluorescent agent in the core at the end of an optical fiber, and the test object being oxygen of blood in blood vessels (JP-A-61-178)
646), a film containing an oxygen-sensing fluorescent agent is applied to the end or side surface of the optical fiber, and the sensor to be tested is blood oxygen in a blood vessel (JP-A-61-182557). A sensor in which a sensing luminescent agent is arranged and the test object is oxygen of blood in a blood vessel
51) There is a sensor (JP-A-64-44834) in which a pH-sensing fluorescent molecule is fixed to the end of an optical fiber via a silane coupling agent and the test object is the pH of blood.

In addition, a gas-permeable sheath filled with an indicator is disposed at the tip of an optical fiber, and a sensor for testing oxygen and glucose of blood in a blood vessel (Japanese Patent Laid-Open No. 1-10777).
37), a phosphor is adhered to the end of the optical fiber via a protein, and the sensor to be tested is a liquid / gas pH (JP-A-2-57950). A sensor in which a test object is, for example, oxygen of blood (Japanese Patent Laid-Open No. 1831145/1990), a matrix containing a detection component is arranged at the tip of an optical fiber, and a test object is, for example, pH or hydroxyl ion of blood. (Japanese Unexamined Patent Publication (Kokai) No. 2-16435), a sensor in which a matrix made of a polymer to which an indicator molecule is bonded is disposed at the tip of an optical fiber, and a test target is blood, for example, pH, oxygen, carbon dioxide, or other ions ), A hydrophilic polymer matrix chemically bonded with an oxygen-sensitive fluorescent substance is disposed at the tip of an optical fiber, and a sensor whose test object is blood oxygen is disclosed in 1907448), and the like.

Further, a porous glass chip having a fluorescent substance bonded to the inner surface is disposed at the tip of the optical fiber, and a sensor whose test object is blood pH, oxygen, carbon dioxide or the like in a blood vessel (Japanese Unexamined Patent Publication No. Hei 2-265553). ), A vinylimidazole polymer with a reagent fixed inside is placed at the tip of the optical fiber, and the test target is pH, oxygen, carbon dioxide,
Other ion sensors (JP-A-3-65639),
A matrix in which sensor liquid vesicles are dispersed throughout is disposed at the tip of an optical fiber, and a sensor whose pH, oxygen, carbon dioxide, and other ions are to be inspected for industrial medical use (Japanese Patent Laid-Open No.
Japanese Patent Application Laid-Open No. 4-77651) discloses a sensor in which a sensor film containing a dye and a chemical substance-sensitive substance is disposed at the tip of a fiber, and the inspection target is a liquid / gas chemical substance.

[0005]

However, in a conventional medical optical fiber sensor, if the tip of the optical fiber sensor is inserted into a body, for example, a blood vessel as a probe for a long time, platelets may be deposited on the sensor surface. It adheres and exhibits thrombotic properties, in which the platelets are denatured, and they are taken in with the red blood cells to form blood clots and coagulate. The present invention has been made on the basis of the above-described background, and has an object to show antithrombotic properties, and in the fields of medicine and the like, to measure the pH, glucose concentration, cholesterol concentration, oxygen partial pressure in blood in a living body. It is an object of the present invention to provide an optical fiber sensor that can monitor the carbon dioxide partial pressure, the hydroxyl ion concentration, and the like in the body for a long time.

[0006]

SUMMARY OF THE INVENTION An optical fiber sensor according to the present invention is an optical fiber sensor for detecting a chemical or physical parameter of a living body using an optical fiber, wherein the compound having sensitivity to the parameter is ethylene-vinyl. A sensor film fixed to an alcohol copolymer, and an optical fiber, preferably a plastic optical fiber, wherein the sensor film is disposed at an end and detects a change in the sensor film due to the parameter. It is.

In a preferred embodiment according to the present invention, the chemical or physical parameters of the living body are determined from the pH, glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxyl ion concentration, and hemoglobin content in blood. At least one parameter selected. In a preferred aspect of the present invention, the sensor film is provided on the end surface or side surface of the end of the optical fiber, or a porous body is provided on the end surface or side surface of the end of the optical fiber, and Carried on the substrate, or
The end of the optical fiber including the sensor membrane is covered with a porous separation membrane.

The optical fiber used in the present invention has a cladding (sheath) and a core (core). The structure thereof is a step index type multimode optical fiber in which a refractive index changes stepwise, There are a step-index single-mode optical fiber whose rate changes stepwise and consists of a single mode, and a graded-index multimode optical fiber that propagates different modes. Examples of the material constituting the core (core) material include inorganic materials such as multi-component glass and quartz glass, and polymethyl methacrylate-based resins (PMMA, including homopolymers and copolymers of methyl methacrylate in the present specification). ), Deuterated PM
Organic materials such as MA, polycarbonate resin, polystyrene resin, deuterated polystyrene resin, poly-4-methylpentene-1, and silicon polymer can be used.

Among these organic materials, a polymethyl methacrylate resin is particularly preferred, and a copolymer containing polymethyl methacrylate and methyl methacrylate units as main components and preferably containing at least 70% by weight, or a deuterium-containing copolymer. Resin can be used. As the copolymerization component with methyl methacrylate, for example,
Examples include acrylates such as methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, and 2-ethylhexyl acrylate, and methacrylates such as cyclohexyl methacrylate, benzyl methacrylate, ethyl methacrylate, propyl methacrylate, and butyl methacrylate. As the polymethyl methacrylate-based resin, for example, it is preferable to use a resin obtained by a continuous bulk polymerization method as disclosed in JP-B-53-42260.

The clad (sheath) material used in the present invention has a lower refractive index than the core material. When a PMMA-based resin is used as the core material, the sheath material is, for example, a fluorine-based polymer, specifically, a vinylidene fluoride-based polymer (including a copolymer in the present specification; A vinylidene-tetrafluoroethylene copolymer (for example, a copolymer containing 50% by weight or more, preferably 70% by weight to 90% by weight of vinylidene fluoride), a vinylidene fluoride-propylene hexafluoride copolymer, Vinylidene fluoride-hexafluoroacetone copolymer, vinylidene fluoride-trifluoroethylene copolymer, tertiary or higher copolymer of vinylidene fluoride), perfluoroalkyl methacrylate-based polymer,
Examples include methacrylic acid ester-based polymers.

The ethylene-vinyl alcohol copolymer used in the present invention may be any of a random copolymer, a graft copolymer and a block copolymer as long as it has antithrombotic properties. Ethylene content is 1% to 80%,
Preferably, 5% to 70%, more preferably, 15% to
50%. This is because the more hydroxyl groups, the better the chemical modification to the sensitive compound.

[0012]

According to the present invention having the above configuration, the operation and operation are performed as follows. A sensitive compound is immobilized on the ethylene-vinyl alcohol copolymer of the sensor film. The compound is sensitive to biological chemical or physical parameters. When the sensor membrane comes into contact with the measurement target of the living body, a compound having sensitivity to a chemical or physical parameter of the living body changes color according to the parameter. Since the sensor film is disposed at the end of the optical fiber, the optical change transmits the optical change to the measurement system at the other end.

The ethylene-vinyl alcohol copolymer, which is the material of the sensor membrane, adsorbs relatively stable proteins, mainly albumin in blood, on the membrane surface.
It has weak activity on various blood coagulation factors and platelet factors. Therefore, even if the optical fiber sensor is inserted into the body, for example, a blood vessel for a long time as a probe, the platelet adheres or denatures to the sensor surface, and the optical fiber sensor and the red blood cells are used for medical purposes. It does not exhibit the thrombotic property of being taken up to form a blood clot and coagulation.

[0014]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be specifically described below with reference to embodiments. Example 1 -Preparation of pH Sensor Film- Congo Red and Neutral Red pH indicators were added to a random copolymerized ethylene-vinyl alcohol copolymer film having an ethylene content of 32% and 44% and a film thickness of 15 μm and 50 μm. Immobilized. This immobilization was carried out by washing the ethylene-vinyl alcohol copolymer membrane with methanol and then chemically modifying the polymer membrane for 10 minutes while stirring in a pH indicator solution containing bowel nitrate.

Example 2-Evaluation of pH Sensor Film- The obtained sensor film was evaluated. As a result, an ethylene-vinyl alcohol copolymer film having an ethylene content of 32% and a film thickness of 15 μm was chemically modified well. I was The sensor membrane to which Congo Red is immobilized has a pH of 1 to 5,
The sensor membrane on which neutral red was immobilized had a sensitivity at pH 6 to 8. A sensor film is placed inside a socket attached to the tip of an optical fiber sensor, and two types of p
An optical fiber sensor is immersed in a flow cell in which H buffer solutions (pH 1 and 4) alternately flow at a certain time interval, and the response speed until the reflection intensity of each buffer solution reaches a steady state at a predetermined wavelength is determined. And the reversibility was evaluated.
As a result, the response time until the reflection intensity becomes constant is p
It was about 5 minutes from H1 to pH4, and about 2 minutes from pH4 to pH1, and the reflection intensity which became constant in each repetition was almost equal. From this, it has a response speed that can be put to practical use and reversibility.

Example 3-Antithrombotic Properties of pH Sensor Membrane Ethylene having an ethylene content of 32% and a film thickness of 15 μm
A platelet suspension of rat blood was dropped on each of a vinyl alcohol copolymer film, a sensor film having Congo Red immobilized on the film, and a polypropylene film, and the mixture was allowed to stand for 1 hour. Then, the cells were washed with physiological saline, fixed in 2.5% glutaraldehyde physiological saline for 3 hours, washed with purified water, and freeze-dried. The obtained dried membrane was observed with a scanning electron microscope, and the antithrombotic properties of each membrane were evaluated. Scanning electron microscopy revealed that platelets had undergone a morphological change in the polypropylene membrane, causing pseudopods and sticking. On the other hand, in the ethylene-vinyl alcohol copolymer film and the Congo Red-immobilized sensor film, platelets slightly giving pseudopodia were observed.
It was found to be antithrombotic. Therefore, from the antithrombotic properties, it is possible to monitor blood pH, glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxyl ion concentration, etc. in the living body for a long time in the field of medicine and the like. it can.

Embodiment 4-Optical Fiber Sensor-An embodiment of an optical fiber sensor head is shown in FIG. The sensor head of this example includes a plastic optical fiber 1 composed of a core 3 and a clad 4,
The sensor film 1 is attached. Light from a light source such as a xenon lamp is incident on the optical fiber, light transmitted through the core 3 is reflected by the sensor film, and the reflected light returns within the same optical fiber. The reflected light is measured by, for example, a spectrophotometer, and if necessary, processed by a computer for various purposes. The present invention is not limited to the above embodiment, and various modifications are possible within the scope of the present invention.

[Embodiment 5-Optical fiber sensor-] Another embodiment of an optical fiber sensor head is shown in FIG.
Shown in In this embodiment, the sensor film is disposed on the side of the core 3 from which the cladding 4 at the tip of the optical fiber has been removed,
It is stuck. The use of this sensor is similar to the above example.

[Embodiment 6-Optical fiber sensor-] Another embodiment of the optical fiber sensor head is shown in FIG.
Shown in In this embodiment, a socket 5 is mounted on the tip of the optical fiber 2, and the sensor film 1 is fixed inside the socket 5. The sensor film 1 responding to the chemical or physical parameters of the living body is irradiated with light from the end face of the optical fiber, and the reflected light is received by the same optical fiber.

[Embodiment 7-Optical fiber sensor-] Another embodiment of the optical fiber sensor head is shown in FIG.
Shown in In this embodiment, two optical fibers 2a and 2b are used for light transmission and light reception. A socket 5 is mounted on the tip of the two aligned optical fibers, and the sensor film 1 is fixed inside the socket 5. The sensor film 1 responding to the parameters of the living body is irradiated with light from the end face of the light transmitting optical fiber 2a, and the reflected light is received by the light receiving optical fiber 2b.

[Embodiment 8-Optical fiber sensor-] Another embodiment of the optical fiber sensor head is shown in FIG.
Shown in In the optical fiber sensor of this embodiment, a porous body 6 is fixed to an end of an optical fiber, and a sensor film according to the present invention is provided in a hole inside the porous body. A liquid to be inspected, such as blood or tissue fluid, enters the inside of the porous body and reacts with the sensor film inside the porous body. The changed sensor film is detected by light from the optical fiber.

[Embodiment 9-Optical fiber sensor-] Another embodiment of the optical fiber sensor head is shown in FIG.
Shown in In the optical fiber sensor of this embodiment, two optical fibers 2a and 2b are used for light transmission and light reception. The end portions of the two aligned optical fibers are covered with a porous separation membrane 7 together with the sensor membrane 1 to fix the sensor membrane 1. The sensor membrane 1 responding to the parameters of the living body is
The light is emitted from the end face of the light transmitting optical fiber 2a, and the reflected light is received by the light receiving optical fiber 2b.

[0023]

The optical fiber sensor according to the present invention has antithrombotic properties, and is useful in the field of medicine and the like in blood in vivo.
H, glucose concentration, cholesterol concentration, oxygen partial pressure,
It is possible to monitor the partial pressure of carbon dioxide and the concentration of hydroxyl ions in the body for a long time.

[Brief description of the drawings]

FIG. 1 is a longitudinal sectional view showing one embodiment of a head of an optical fiber sensor according to the present invention.

FIG. 2 is a longitudinal sectional view showing one embodiment of the head of the optical fiber sensor according to the present invention.

FIG. 3 is a longitudinal sectional view showing one embodiment of the head of the optical fiber sensor according to the present invention.

FIG. 4 is a longitudinal sectional view showing one embodiment of the head of the optical fiber sensor according to the present invention.

FIG. 5 is a longitudinal sectional view showing one embodiment of the head of the optical fiber sensor according to the present invention.

FIG. 6 is a longitudinal sectional view showing one embodiment of the head of the optical fiber sensor according to the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Sensor membrane 2 ... Optical fiber 3 ... Core 4 ... Cladding 5 ... Socket 6 ... Porous body 7 ... Porous separation membrane

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. ⁷ , DB name) G01N 21/78 G01J 1/02 G02B 6/00

Claims (5)

(57) [Claims] 1. An optical fiber sensor for detecting a chemical or physical parameter of a living body using an optical fiber, wherein a compound having sensitivity to the parameter is immobilized on an ethylene-vinyl alcohol copolymer. An optical fiber sensor, comprising: a film; and an optical fiber having the sensor film disposed at an end and detecting a change in the sensor film due to the parameter. 2. The biological or chemical parameter of the living body is at least one selected from pH, glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxyl ion concentration and hemoglobin amount in blood. The optical fiber sensor according to claim 1, wherein: 3. The optical fiber sensor according to claim 1, wherein the sensor film is disposed on an end face or a side face of the end of the optical fiber. 4. The optical fiber sensor according to claim 1, wherein a porous body is disposed on an end face or a side face of the end of the optical fiber, and the sensor film is supported on the porous body. 5. The optical fiber sensor according to claim 1, wherein an end of the optical fiber including the sensor membrane is covered with a porous separation membrane.