JPH063539Y2 - Biomaterial-immobilized electrode - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention relates to a biomaterial-immobilized electrode used as a sensor in artificial organs in the fields of medicine and medicine.

(Problems to be Solved by Conventional Techniques and Inventions) In recent years, in the fields of medicine and medical care, development of artificial organs has been required as an active treatment means for damaged organs.

The artificial organ is composed of a sensor, a control unit, and an operation unit. In order to measure the in-vivo condition in real time and immediately perform a therapeutic operation, at least the sensor is
It must be implantable.

However, although conventionally developed for this purpose, it can be placed in the body within a certain period,
When implanted in the body, there is a problem that incision surgery on the body surface is required and maintenance of the sensor is not easy.

As a measure to solve the above-mentioned problems, it is conceivable that the shape of the sensor is formed in a needle shape so that it can be inserted from the body surface and that it can be easily replaced. Membrane-bonded wire-type electrodes are known.

However, since this wire-type electrode has a structure in which the tip of the wire is covered with a biological substance-immobilized film, there is a problem that the biological substance-immobilized film is easily peeled off or damaged during insertion from the body surface. Have

It is an object of the present invention to provide a structure of a biomaterial-immobilized electrode that is easy to insert from the body surface and does not cause peeling or damage of the biomaterial-immobilized membrane.

(Means for Solving the Problems) The present invention considers the problems in the conventional wire type electrode used as a sensor for artificial organs, and considers the biological material inside the hollow needle made of a metal material. The metal thin wire coated with the immobilization film is detachably inserted.

The thin metal wire coated with the biological substance-immobilized membrane can be inserted into the hollow needle either before or after the hollow needle is inserted into the inspection target, and the thin metal wire can be freely moved inside the hollow needle. Operated.

Both the hollow needle and the thin metal wire must be electrochemically stable, and examples of the hollow needle include platinum, silver, and gold, and examples of the thin metal wire include platinum and gold.

The outer diameter of the hollow needle is preferably 1 mm or less from the surface of insertion into the body.

Biological substances to be fixed on the biological substance-immobilized film covering the tip of the thin metal wire include various enzymes, antigens, antibodies, antibiotics, hormones, receptors, organelles, channels, microorganisms (actinomycetes, filamentous fungi, yeasts, bacteria). ) And the like are used, and further, although they are artificial substances, complexes such as phthalocyanine are also included.

Examples of substances that immobilize these biological substances include photosensitive resins, general-purpose polymers such as polyvinyl butyral, natural materials such as cellulose, chitins, and biologically-derived substances such as albumin.

As the immobilization method, for example, a covalent bond method using glutaraldehyde, carbodiimide or the like is effective, and in addition, an ionic bond method, an adsorption method, a cross-linking method or the like can be used.

The binding of the biomaterial-immobilized membrane to the metal thin wire is performed by dispersing the above-mentioned biomaterial in the biomaterial-immobilized material before or during the reaction and applying it to the tip of the metal wire by the dipping method or the like. Easy to implement.

In order to prevent a short circuit between the hollow needle and the thin metal wire, a film of an electrical insulating material is applied to the surface of the thin metal wire portion which is not covered with the biological substance-immobilized film.

(Operation) When the hollow needle and the thin metal wire of the biological material-immobilized electrode according to the present invention having the above-mentioned structure are used as the electrochemical electrode,
The chemical change induced by the biological substance is detected as an electric signal.

(Example) FIG. 1 shows an example of the structure of a biomaterial-immobilized electrode according to the present invention. The hollow needle 1 used in an ordinary syringe is coated with a biomaterial-immobilized membrane 3 at the tip thereof. Then, the thin metal wire 2 coated with the electrical insulating film 4 is inserted into the surface of the portion not covered with the biological substance fixing film 3.

[Example] Glucose oxidase (GOD) was fixed to the tip of a platinum wire having an outer diameter of 0.4 mm according to the following procedure.

GOD 5 mg, human serum albumin 40 ml, 50% glutaraldehyde aqueous solution 20 in 1 ml phosphate buffer (pH 7.0) 20
After dissolving 1 μl of the solution and 1 minute after preparing the solution, the tip of the platinum wire was added, and the prepared solution was immersed in the solution for 1 minute with stirring, pulled up, and left at 4 ° C. for 24 hours.

As a means for fixing GOD, a method using a photocrosslinkable polymer shown below is also effective.

That is, GOD is added to a water-soluble polymer having a stilbazolium group or a diazo group as a photosensitive group in the molecule.
Is dispersed, coated on a platinum wire, naturally dried and then irradiated with ultraviolet rays to be photocrosslinked, and GOD is entrapped and fixed in the film.

For example, 0.4 ml of distilled water prepared by dissolving 30 mg of glucose oxidase enzyme in 0.5 g of a 11.7% by weight aqueous solution of photocrosslinkable polyvinyl alcohol (photocrosslinkable stilbazolium group content 1.4 mol%, saponification degree 88%, polymerization degree 1400). Add
Stir and mix for several minutes to prepare a coating solution, immerse the tip of the platinum wire in this coating solution and pull it up.
After natural drying, UV irradiation (250 W) is performed for 30 seconds to form a GOD-immobilized film by photocrosslinking.

Next, a platinum wire with this GOD fixed was
It was inserted into a platinum injection needle having an inner diameter of 0.8 mm to obtain a biomaterial-immobilized electrode as shown in FIG.

The biomaterial-immobilized electrode manufactured in this way was used at 37 ℃ and pH.
The sample was immersed in 7.0 phosphate buffer, various concentrations of glucose were added, and the increase in current at an applied voltage of 0.7 V was measured using the hollow needle as the cathode and the platinum wire as the anode.

Glucose diffuses from the tip of the needle into the GOD-immobilized membrane, and G
It is decomposed into gluconic acid and hydrogen peroxide by OD. At this time, both electrodes of the hollow needle and the platinum thin wire act as hydrogen peroxide electrodes, and a current proportional to the amount of hydrogen peroxide produced flows between both electrodes. . Therefore, the glucose concentration can be obtained from this current value.

From the measurement results shown in FIG. 2, a good correlation was observed between the glucose concentration and the output current.

(Effect of the Invention) The biological material-immobilized electrode according to the present invention, as described above,
By having a structure in which a thin metal wire coated with a biomaterial-immobilized film is inserted into the hollow needle at the tip portion, a voltage is applied using the hollow needle and the metal thin wire inserted in the biomaterial as both electrodes. At that time, the chemical change induced by the biological substance is detected as an electric signal, so that it can effectively function as a sensor for an artificial organ.

Since the size of the biomaterial-immobilized electrode is about the same as a normal injection needle, it can be easily inserted into and removed from the body when used as a sensor for implanting in the body, facilitating maintenance of the sensor. In addition, since the thin metal wire coated with the biomaterial immobilization membrane is held in the center of the hollow needle or extracted from the hollow needle, the biomaterial is immobilized at the time of insertion and extraction. There is no risk of film peeling or damage.

Since the biological material-immobilized film is coated only on the tip portion of the thin metal wire, the thickness of the immobilization material film is reduced to provide a high-speed response.

[Brief description of drawings]

FIG. 1 is a cross-sectional view of a structural example of a biological material-immobilized electrode according to the present invention, and FIG. 2 is a chart of measurement results using the biological material-immobilized electrode according to the present invention. 1 ... Hollow needle, 2 ... Metal wire, 3 ... Biomaterial immobilization film, 4 ... Insulation film.

Claims (1)

[Scope of utility model registration request] 1. A biomaterial having a hollow needle (1) and a thin metal wire (2) which is detachably inserted into the hollow needle (1) with a biomaterial-immobilized film (3) coated on the surface of the tip. Fixed electrode.