JPH06288829A - Optical fiber sensor - Google Patents

Abstract

PURPOSE:To give antithrombus property and to monitor in vivo blood pH, glucose concentration, etc., for a long time by laying out a sensor film where a compound with susceptibility is immobilized to a specific copolymer at an edge part. CONSTITUTION:A sensor film 1 where a compound with susceptibility for the chemical or physical parameters of a living body is immobilized to the ethylene - vinyl alcohol copolymer is laid out at the edge part of an optical fiber 2. The chemical or physical parameter of the living body is at least one type of parameter which is selected from pH inside blood, glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure etc. The optical fiber 2 to be used has a clad 4 and a core 3. When a sensor film 1 contacts the object to be measured of the living body, a compound with susceptibility to the chemical or physical parameter of the living body is discolored. Since the sensor film 1 is laid out at the edge part of the optical fiber 2, the optical fiber 2 transmits the optical change to the measurement system at the other edge.

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 specifically, in a field such as medical treatment, pH in blood in a living body, The present invention relates to an optical fiber sensor capable of monitoring glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxide ion concentration, etc. in the body for a long time.

[0002]

2. Description of the Related Art Regarding an optical fiber sensor for detecting a chemical or physical parameter using an optical fiber,
Various proposals have heretofore been made including those for industrial use and medical use. For example, a semipermeable membrane provided with a pH-sensitive dye is placed at the end of the optical fiber, and the test target is the pH of blood in a blood vessel.
Sensor (JP-A-54-85588), a chemical / physical parameter sensitive chromophore is chemically bonded to the core surface of an optical fiber, and an inspection target is a chemical / physical parameter for industrial / medical use (eg, pH). A sensor (Japanese Patent Laid-Open No. 58-
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 object to be inspected is oxygen in blood (Table 59-50)
0896), a porous hydrophobic film carrying an indicator compound is arranged at the end of the optical fiber, and the inspection target is in a solution / gas, for example,
A sensor having a pH (Japanese Patent Laid-Open No. 60-35246), a sensor containing an oxygen-sensing fluorescent agent in the core of the end of the optical fiber, and a test target being oxygen of blood in a blood vessel (Japanese Patent Laid-Open No. 61-178).
646), a film containing an oxygen-sensing fluorescent agent is applied to the end or the side of the optical fiber, and the sensor to be inspected is oxygen of blood in the blood vessel (Japanese Patent Laid-Open No. 61-182557), and the oxygen of the lanthanide complex is attached to the end of the optical fiber. A sensor in which a sensitizing luminescent agent is arranged and the test object is oxygen of blood in blood vessels (Japanese Patent Laid-Open No. 63-701
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 blood pH.

Further, a gas permeable sheath filled with an indicator is arranged at the tip of the optical fiber, and the sensors to be inspected are oxygen and glucose of blood in blood vessels (JP-A-1-10777).
37), a sensor in which a phosphor is attached to the end of an optical fiber through a protein, and an inspection target is a liquid / gas pH (Japanese Patent Laid-Open No. 2-57950), and a tip of the optical fiber on which a reagent layer is arranged is curved. A sensor in which the test object is blood such as oxygen (Japanese Patent Laid-Open No. 2-1831145), a matrix containing a detection component is arranged at the tip of the optical fiber, and the test object is blood such as pH or hydroxide ion. (JP-A-2-16435), a sensor in which a matrix made of a polymer to which an indicator molecule is bound is arranged at the tip of an optical fiber, and the test object is blood such as pH, oxygen, carbon dioxide, and other ions (JP-A-2-161338). ), A hydrophilic polymer matrix in which an oxygen-sensitive phosphor is chemically bonded is arranged at the tip of the optical fiber, and the sensor to be inspected is oxygen of blood (Japanese Patent Laid-Open No. HEI-2). 1907448), and the like.

Furthermore, a porous glass chip having a phosphor bonded to the inner surface is arranged at the tip of the optical fiber, and the sensor to be inspected is pH, oxygen, carbon dioxide, etc. of blood in a blood vessel (Japanese Patent Laid-Open No. 2-265531). ), The vinyl imidazole polymer having the reagent fixed inside is arranged at the tip of the optical fiber, and the test object is pH, oxygen, carbon dioxide,
Other ion sensors (JP-A-3-65639),
A matrix in which sensor liquid vesicles are dispersed is arranged at the tip of the optical fiber, and the sensor to be inspected is pH, oxygen, carbon dioxide, and other ions for industrial medical use (Japanese Patent Laid-Open No. HEI 3).
-85430), a sensor film containing a dye and a chemical substance sensitive substance is arranged at the tip of the fiber, and the inspection target is a liquid / gas chemical substance (JP-A-4-77651).

[0005]

However, in the conventional optical fiber sensor for medical use, when the tip of the optical fiber sensor is inserted as a probe into the body, for example, the blood vessel, for a long time, platelets are deposited on the sensor surface. It adheres and exhibits thrombotic properties in which the platelets are denatured and the red blood cells and the red blood cells are taken into the blood clot to cause coagulation. The present invention has been made based on the above-mentioned background, and an object thereof is to exhibit antithrombotic property, and in the fields of medical treatment and the like, pH in blood in vivo, glucose concentration, cholesterol concentration, oxygen partial pressure. Another object of the present invention is to provide an optical fiber sensor capable of monitoring the partial pressure of carbon dioxide, the concentration of hydroxide ion, etc. in the body for a long time.

[0006]

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 by using an optical fiber, and a 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, having a sensor film disposed at an end and detecting a change in the sensor film due to the above-mentioned parameter. Is.

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

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

Among these organic materials, polymethylmethacrylate resin is particularly preferable, and polymethylmethacrylate, a copolymer containing methylmethacrylate unit as a main component, preferably at least 70% by weight, or deuterium thereof is used. It is possible to use a resin that has been converted into a resin. As the copolymerization component with methyl methacrylate, for example,
Examples thereof include acrylic acid esters such as methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate and 2-ethylhexyl acrylate, and methacrylic acid esters such as cyclohexyl methacrylate, benzyl methacrylate, ethyl methacrylate, propyl methacrylate and butyl methacrylate. As the polymethylmethacrylate resin, it is preferable to use, for example, 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 smaller refractive index than the core material. When a PMMA-based resin is used as the core material, the sheath material may be, for example, a fluoropolymer, specifically, a vinylidene fluoride-based polymer (in this specification, including a copolymer, for example, a fluoropolymer). Vinylidene-tetrafluoroethylene copolymer (for example, a copolymer containing 50% by weight or more, preferably 70% by weight or more and 90% by weight or less of vinylidene fluoride), vinylidene fluoride-hexafluoropropylene copolymer, fluorine Vinylidene fluoride-hexafluoroacetone copolymer, vinylidene fluoride-trifluoroethylene copolymer, vinylidene fluoride ternary or more copolymers, etc.), perfluoroalkyl methacrylate-based polymer,
There are methacrylic acid ester-based polymers and the like.

The ethylene-vinyl alcohol copolymer used in the present invention may be a random copolymer, a graft copolymer or 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 of the sensitive compound.

[0012]

According to the present invention having the above-described structure, the operation and action are as follows. The sensitive compound is immobilized on the ethylene-vinyl alcohol copolymer of the sensor film. This compound is sensitive to the chemical or physical parameters of the organism. When the sensor film comes into contact with an object to be measured of a living body, a compound having sensitivity to a chemical or physical parameter of the living body changes its color according to the parameter. Since this sensor film is arranged at the end of the optical fiber, the optical fiber transmits this optical change to the measuring system at the other end.

Since the ethylene-vinyl alcohol copolymer, which is the material for the sensor film, adsorbs a relatively stable protein centered on blood albumin on the film surface,
It has weak activity against various blood coagulation factors and platelet factors. Therefore, even if the optical fiber sensor for medical use is inserted into the body, for example, a blood vessel for a long time, as a probe, the tip of the optical fiber sensor is attached to the sensor surface by platelets to denature it and red blood cells. It does not show the thrombotic property of being taken up to form a blood clot and causing coagulation.

[0014]

EXAMPLES The present invention will be specifically described below with reference to examples. [Example 1-Preparation of pH sensor membrane-] Congo red and neutral red pH indicators were added to a random copolymer ethylene-vinyl alcohol copolymer membrane having ethylene contents of 32% and 44% and film thicknesses of 15 µm and 50 µm. It was fixed. This immobilization was performed 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 Glauber's salt.

[Example 2-Evaluation of pH sensor film-] As a result of evaluation of the obtained sensor film, an ethylene-vinyl alcohol copolymer film having an ethylene content of 32% and a film thickness of 15 μm was satisfactorily chemically modified. Was there. Further, the sensor membrane on which Congo Red is immobilized has a pH of 1 to 5,
The sensor membrane having the neutral red immobilized thereon had a sensitivity of pH 6-8. The sensor membrane is placed inside the socket attached to the tip of the optical fiber sensor, and two types of p
The response speed until the optical fiber sensor is immersed in the flow cell in which the H buffer solutions (pH 1 and 4) alternately flow at a certain time, and the reflection intensity reaches a steady state at the wavelength determined by each buffer solution, And reversibility were 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 that became constant at each repetition was almost equal. From this fact, it has a response speed that can be practically used and reversibility.

Example 3 Antithrombogenicity of pH Sensor Membrane Ethylene with 32% Ethylene Content and 15 μm Thickness
A platelet suspension of rat blood was added dropwise to each of the vinyl alcohol copolymer membrane, the sensor membrane having Congo red immobilized on the membrane, and the polypropylene membrane, and the mixture was allowed to stand for 1 hour. Then, it was washed with physiological saline, fixed in 2.5% glutaraldehyde physiological saline for 3 hours, washed with purified water, and lyophilized. The obtained dry film was observed with a scanning electron microscope to evaluate the antithrombotic property of each film. By scanning electron microscope observation, it was found that in the polypropylene film, the platelets undergo a morphological change, causing pseudopods and adhesion. On the other hand, in the ethylene-vinyl alcohol copolymer film and the Congo red-immobilized sensor film, platelets with a slight false limb were observed, but there was almost no morphological change in the platelets,
It was found to have antithrombotic properties. Therefore, due to this antithrombotic property, it is possible to monitor in-body blood pH, glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxyl ion concentration, etc. in the body for a long time in the fields such as medical treatment. it can.

[Fourth Embodiment-Optical Fiber Sensor] An embodiment of an optical fiber sensor head is shown in FIG. 1 which is a longitudinal sectional view. In the sensor head of this example, the end face of the tip of the plastic optical fiber 1 including the core 3 and the clad 4 is
The sensor film 1 is attached. Light from a light source such as a xenon lamp is incident on the optical fiber, the light transmitted in the core 3 is reflected by the sensor film, and the reflected light returns in the same optical fiber. This reflected light is measured by, for example, a spectrophotometer, and if necessary, data processed by a computer and used for various purposes. The present invention is not limited to the above embodiments, and various modifications are possible within the scope of the present invention.

[Embodiment 5: Optical Fiber Sensor] Another embodiment of the head of the optical fiber sensor is shown in FIG.
Shown in. In this embodiment, the sensor film is arranged on the side surface of the core 3 in which the cladding 4 at the tip of the optical fiber is removed,
It is attached. The use of this sensor is similar to the above example.

[Embodiment 6-Optical Fiber Sensor] Another embodiment of the head of the optical fiber sensor is shown in FIG.
Shown in. In this mode, the socket 5 is capped on the tip of the optical fiber 2, and the sensor film 1 is fixed inside the socket 5. The sensor film 1 that responds to the chemical or physical parameters of the living body is irradiated with the 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 head of the optical fiber sensor is shown in FIG.
Shown in. In this aspect, the two optical fibers 2a and 2b are used for transmitting light and receiving light. A socket 5 is capped on the tips of the two aligned optical fibers, and the sensor film 1 is fixed inside the socket 5. The sensor film 1 that has responded to the parameters of the living body is irradiated with the 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 head of the optical fiber sensor is shown in FIG.
Shown in. In the optical fiber sensor of this aspect, the porous body 6 is fixed to the end portion of the optical fiber, and the sensor film according to the present invention is arranged in the hole inside the porous body. The 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 the light from the optical fiber.

[Embodiment 9-Optical Fiber Sensor] Another embodiment of the head of the optical fiber sensor is shown in FIG.
Shown in. In the optical fiber sensor of this aspect, two optical fibers 2a and 2b are used for transmitting light and receiving light. The tip ends of the two aligned optical fibers are covered with the sensor membrane 1 by the porous separation membrane 7 to fix the sensor membrane 1. The sensor membrane 1 that responds to the biological parameters
The light from the end face of the light transmitting optical fiber 2a is emitted, and the reflected light is received by the light receiving optical fiber 2b.

[0023]

INDUSTRIAL APPLICABILITY The optical fiber sensor according to the present invention exhibits antithrombogenicity and is used in blood in vivo in the field of medicine and the like.
H, glucose concentration, cholesterol concentration, oxygen partial pressure,
The carbon dioxide partial pressure and the hydroxide ion concentration can be monitored in the body for a long time.

[Brief description of drawings]

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

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

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

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

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

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

[Explanation of symbols]

 1 ... Sensor membrane 2 ... Optical fiber 3 ... Core 4 ... Clad 5 ... Socket 6 ... Porous body 7 ... Porous separation membrane

Claims (5)

[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 thereof and detecting a change in the sensor film due to the parameter. 2. A chemical or physical parameter of a living body is at least one selected from blood pH, glucose concentration, cholesterol concentration, oxygen partial pressure, carbon dioxide partial pressure, hydroxyl ion concentration, and hemoglolobin amount. The optical fiber sensor according to claim 1, which is a parameter of 3. The optical fiber sensor according to claim 1, wherein the sensor film is provided on an end surface or a side surface of the end portion of the optical fiber. 4. The optical fiber sensor according to claim 1, wherein a porous body is provided on an end surface or a side surface of the end portion of the optical fiber, and the sensor film is carried on the porous body. 5. The optical fiber sensor according to claim 1, wherein an end portion of the optical fiber including the sensor film is covered with a porous separation film.