JPS6227926A - Electrode for living body - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a metal electrode for measuring biological components,
More specifically, the present invention relates to improvements to the surface of metal electrodes that improve storage stability and measurement accuracy of such metal electrodes.

[Conventional technology]

BACKGROUND ART Conventionally, methods of electrically measuring biological components in blood and tissues using electrodes have been known. Among these methods, for example, a method of measuring oxygen gas components, various ions, etc., and in particular, a measurement method applying the principle of boularography has been widely used as a method of continuously measuring changes in the concentration of components. Various biological components in blood and tissues are measured using electrodes, and hereinafter, measurement of oxygen partial pressure will be described as an example. A measurement method that applies the principle of polarography uses an electrode made of a noble metal such as gold, platinum, or silver, and an indifferent electrode made of silver-silver chloride, etc., and applies a minute voltage between the two electrodes to create a different electrode (cathode). ) Oxygen gas concentration in the υ liquid is measured by reducing oxygen on the surface and measuring the reduction current flowing through the extermination.

On the other hand, the influence of oxygen gas concentration (oxygen partial pressure) in living organisms is significant, especially in neonatal, anesthesiology, cardiac surgery, and other areas.
As the importance of accurately and continuously capturing changes in oxygen partial pressure has been recognized in fields such as neurosurgery and gastrointestinal surgery, there has been a growing desire to measure changes in oxygen partial pressure in blood vessels or tissue at the desired site. ing.

However, although the above measurement method is based on the diffusion current based on the oxygen concentration gradient between the cathode surface and the liquid, the living body is constantly in motion due to the movement of the heart muscle and the pulsation of the blood, and the diffusion current is greatly affected by this. However, it has been difficult to accurately measure minute oxygen partial pressures. In order to improve this drawback, various studies have been carried out, and the so-called composite electrode, in which a related electrode, an indifferent electrode, and an electrolyte are housed in an oxygen-permeable membrane, or a related electrode surface made of hydrophilic water such as polyhydroxyethyl acrylate or cellophane, etc. A method has been proposed in which oxygen is transferred to the electrode surface through water trapped between the molecules by coating the electrode with a swelling film, and some of these methods have been put to practical use. However, the former has a large electrode shape, so it can only be inserted into a specific area, such as a large blood vessel, and the latter has the problem that measurement sensitivity changes when the retention state of the water-swollen membrane changes, making it impossible to obtain sufficient measurement accuracy. Furthermore, there is a problem that the membrane becomes brittle when dried, and the membrane is easily damaged.Therefore, there is an inconvenience that the membrane must be constantly immersed in water, and improvements are desired. In view of the current situation, the present inventors have developed a device that can be inserted into all parts of living tissues and blood vessels, and can continuously, stably and accurately supply oxygen partial pressure without being affected by the movement of tissues or blood. Metal wire electrode as a biological electrode capable of measurement [Problem to be solved by the invention] The biological electrode coated with the above porous membrane can be inserted into any part of the biological tissue or blood vessel, and can be inserted into any part of the biological tissue or blood vessel. Although it is excellent in that oxygen partial pressure can be measured continuously and stably without being affected, there is a risk that the oxygen reduction current value before and after sterilization may deviate. The current value tends to change over time, and there has been a need for a biological electrode that does not have these problems.

As a result of intensive investigation into the causes of the above-mentioned problems, the inventors of the present invention found that the phenomenon of not being able to obtain reproducibility in output values and the fact that it takes too long to achieve stable output is due to the following:
The inventors have discovered that the main reason for this is that the porous membrane covering the surface of the metal wire electrode dries during sterilization or storage, resulting in a change in the oxygen diffusion state, and has thus arrived at the present invention.

That is, the main reason for this is that drying requires a long time for rewetting the membrane (1), and that the pore shape such as the pore diameter of the υ porous membrane changes due to drying.

[Failure to solve the problem]

The above-mentioned problem is that the biological electrode of the present invention, that is, the tip and/or side surface of the noble metal wire with an insulating coating layer provided thereon, is coated with a porous membrane, The problem is solved by a biological electrode characterized in that at least the outside of the membrane is coated with a water-soluble compound that does not substantially evaporate at room temperature.

In the present invention, "noble metal wire" refers to a metal wire made of noble metals such as gold, silver, and platinum metal elements, or a transition metal contained around the metal wire from atomic number 21 (scandium) to atomic number 30 (zinc). A metal wire with a layer of In consideration of the hearing loss when inserted into the body as a biological electrode, the diameter of the noble metal wire is preferably thinner, and in consideration of workability, the diameter is preferably 20 to 500 μm, and 50 to 300 μm. More preferably 0 When the noble metal wire is a wire provided with a transition metal layer on its outer periphery, the transition metal used may be one type or two or more types, and a plurality of types may have a multilayer structure. Good too. The type of transition metal to be used can be selected appropriately taking into consideration the type of noble metal used and the material of the insulating coating layer. It is better to form the transition metal layer as thin as possible in terms of electrode performance.
Particularly from the viewpoint of stability in the initial stage of measurement, it is preferable that the thickness be less than 10 times the diameter of the noble metal wire, and it is preferable that the thickness be uniform. As a method for forming the transition metal layer, methods for forming a normal metal layer such as electrolytic plating, electroless plating, and sputtering can be adopted. Materials for the insulating coating layer include normal metals such as polyurethane, polyester, polyamide, and epoxy resin. A polymer compound used for line liquid temperature is used.

This insulating coating layer may be made of a single polymer compound, or may have a multilayer structure.

In view of the bending resistance of the electrode, the outermost layer of the insulating coating layer is preferably made of polyurethane. The thickness of the insulating coating layer can maintain electrical insulation and resist external forces during use.
For example, it only needs to be thick enough to maintain an insulating state even if it is bent.

If it is too thick, the electrode will become unnecessarily thick, so the thickness should be 5 to 30 μm.
The thickness is good.

The biological electrode of the present invention requires that the tip and/or part of the side surface of the noble metal wire be covered with a porous membrane instead of an insulating coating layer. To cover with a porous film, cut a noble metal wire with an insulating coating layer around it at right angles to the length, and then peel off the exposed metal surface or the insulating coating layer in the vicinity to expose the metal. can be covered with a porous membrane.

In the present invention, the porous membrane has a dense layer having an average pore size of at least 0.7 μm or less in the outermost layer (~, and the outermost layer has a dense layer having a pore size equal to or larger than the pore size of the outermost layer). Preferably, it is a porous membrane comprising an inner layer.

When an electrode covered with this highly porous membrane is inserted into blood or tissue, the i! The electrode surface is protected by a porous membrane to form a stable water film layer, and after passing through the pores in the outermost layer, oxygen gas quickly reaches the electrode surface via this water film layer. When the average pore diameter of the outermost layer becomes 0.7 μm (l:#), high molecular weight substances and solid components in the blood can pass through the pores and adhere to the metal wire surface, or block the pores. This may impede the permeation of oxygen gas and reduce the performance of the electrode. From this point of view, the average pore diameter is more preferably 0.5 μm or less.

The thickness of the porous membrane varies depending on the site where the electrode is inserted.
It is determined based on the required physical strength and the thickness required for a stable water film layer formed within the porous membrane, but approximately 5 to 2
00 μm is preferable, and 20 to 100 μm is more preferable. The higher the porosity of the porous membrane, the better from the viewpoint of electrode sensitivity, but it may be determined as appropriate in view of the physical strength of the membrane.

Any material can be used for the porous membrane, but
It is preferable that the material does not swell excessively when immersed in water. Examples of such materials include cellulose acetate, cellulose, and polyurethane. Among these, polyurethane is preferred in terms of film strength and the like. The polyurethane may be either a polyester type or a polyether type, but when polyurethane is made into a homogeneous film, the modulus of the film is 10 kg /
Those having c11i or more are preferable from the viewpoint of stability of the porous membrane.

The method for forming a porous membrane is to apply a solution prepared by dissolving a polymer compound forming a porous membrane in an appropriate solvent to the entire surface of the metal electrode where the metal is exposed, and then to A method can be used in which the core polymer compound is coagulated by desolvation in a nonsolvent of the polymer compound that is compatible with the solvent. The pore size can be adjusted by adjusting the solution composition and concentration, for example, the desolvation rate by adjusting the coagulation bath composition, or by adding a third component such as a salt or a surfactant to the solution. Various methods such as dipping, coating, and spraying can be used to attach the solution to the metal surface.

The above-mentioned porous film is used to cover the above-mentioned exposed metal surface for 1 hour, but in order to prevent the porous film from shifting or falling off, it is preferable to partially cover the nearby insulating coating layer as well. The vicinity here refers to a portion within 0.5 mm or more from the boundary between the insulating coating and the exposed metal portion. From the viewpoint of adhesion between the membrane and the insulating coating layer, both the porous membrane and the outermost insulating coating layer are preferably made of polyurethane.

The biological electrode of the present invention is characterized in that at least the outside of the porous membrane is coated with a water-soluble compound that does not substantially evaporate at room temperature, thereby preventing the porous membrane from drying out. .

The water-soluble compound that does not substantially evaporate at room temperature as used in the present invention has a boiling point of at least 100°C or higher, is easily soluble in water, and has a very low vapor pressure at room temperature.
Refers to items that hardly lose weight even if left open at room temperature. Such compounds should be selected to be safe for living organisms. Specific examples include glycerin, polyethylene glycol, and fluoropylene gellicol.

Generally, as a method of preventing drying of a porous membrane, for example, a method of treating hollow fibers with glycerin is known.

However, when this membrane is used, the adhering glycerin must be washed off, otherwise the separated product will be contaminated with glycerin, causing problems.

In biological electrodes such as those of the present invention, the electrodes are generally not cleaned before use. Conventionally, it has been thought that it is difficult to remove the compounds treated with compounds such as those used in the present invention, and that this poses a problem in electrode stabilization and reproducibility. However, in the biological electrode of the present invention, the present inventors have found that the above-mentioned compounds are either quickly removed to the extent that they do not interfere with the electrode's use, or that water is retained and the inside of the porous membrane is substantially reduced. It has been found that when the container is filled with clean water, it quickly absorbs water within a period of time that does not interfere with its use.

The above compound needs to coat at least the outside of the porous membrane. As a result, υ, which retains the water trapped within the membrane, functions to make it easier to absorb water.

When using polyurethane for the porous membrane, it is most preferable to use glycerin as the above compound from the viewpoint of output reproducibility. For example, in the case of polyethylene glycol, if the polyurethane film is left coated with polyethylene glycol for a long time, the polyurethane film will swell slightly, so reproducibility of output values before and after storage may not be obtained. However, even in this case, it can be used as is when continuously measuring changes in output values. Furthermore, when determining the accuracy of the absolute value, by measuring and calibrating a liquid with a known concentration before measurement, the measurement after calibration can be performed with the same accuracy.

Examples of coating methods include filling the porous membrane in advance with water or water containing an electrolyte, and then coating with the above compound, for example, immersing it in the above compound or its solution. .

A biological electrode coated with the above compound needs to be sterilized when used on a living body, especially a human body, and examples of sterilization methods include ethylene oxide gas sterilization and γ-ray sterilization.

〔Example〕

Hereinafter, the present invention will be explained in more detail with reference to Examples.

Example 1 A platinum wire having a diameter of 100 μm was coated with nickel to a thickness of approximately 0.5 μm by electrolytic plating. Next, apply and bake epoxy resin to a thickness of 10 μm on the outside, and then apply 4 μm of polyurethane on the outside.
It was coated and baked to form an insulating coating layer. This metal wire was cut perpendicularly to the length direction with a sharp knife to a length of 20 cm to expose a new metal surface.

On the other hand, polyester type polyurethane contains Tuboran 5109,
Product name, manufactured by Nippon Polyurethane Co., Ltd.) with a solid content concentration of 20 qb
Prepare a homogeneous solution by dissolving it in dimethylformamide so that Only the tip portion was brought into contact with the polyurethane solution again to adhere the polyurethane solution, and then immersed in ion-exchanged water at room temperature to completely remove the solvent. As a result of analyzing the surface and cross section of the polyurethane porous membrane of this electrode and the cross section of the metal wire using a scanning electron microscope and an X-ray microanalyzer, it was found that pores with an average diameter of 0.3 μm were uniformly dispersed in the outermost layer of the porous membrane. Please leave it to me9
, the pores become larger towards the inner layer, and the film thickness is 2.
The porous film, which was found to have a thickness of 5 μm, and the insulating coating layer were well bonded, and a nickel layer was interposed between the insulating coating layer and the platinum, and no peeling was observed between them. won.

Approximately 2 cm of the insulating coating layer on the end of the electrode obtained in this way that was not covered with the polyurethane porous membrane was peeled off.
A silver-silver chloride electrode was used as an indifferent electrode in an oxygen partial pressure measuring device.

Physiological saline was circulated at 37° C. and 100 ml/m using a circulation device having a gas exchange section and a heating section, and the tips of the two electrodes were inserted into the circulation system. Next, air was introduced into the gas exchange section so that the physiological saline was constantly saturated with air, and then measurement was started. The measured value was not affected by the flow of the liquid and showed a constant value. After reading the current value due to saturated air as an oxygen partial pressure of 150 mm Hg, nitrogen gas is introduced into the gas exchange section of the circulation system instead of air, and at the same time the value measured by the electrode is linearly calculated from the current value corresponding to 150 mm Hg. The partial pressure of oxygen decreases to On+mHg
It reached a stable value at a point corresponding to . Set this value to O+++
A calibration curve was determined as +nHg. Next, various gases with appropriately selected ratios of oxygen gas and nitrogen gas were introduced into the gas exchange section of the circulation system, and the respective values were determined.
It almost matched the calibration curve obtained earlier, and it was possible to measure oxygen partial pressure with high accuracy.

Next, this electrode was taken out of the physiological saline and soaked in a local glycerin solution (glycerate 970 degrees 98%) at 25 degrees Celsius for 3 minutes.
It was immersed for 0 minutes. At this time, the glycerin solution was kept in a well-stirred state. After immersion treatment for 0.30 minutes, the electrode was taken out from the glycerin solution, sterilized with ethylene oxide gas, and stored at room temperature for about one month. After storage, we performed the same measurements as before the glycerin treatment using the measurement temperature and equipment described above, and the measured values matched the previously created calibration curve within ±5 degrees of the previous measurement, indicating that the measurements were accurate. I was able to do this. The time required for stabilization at this time was as quick as about 15 minutes.

Example 2゜Example 1. An electrode of a polyurethane porous membrane prepared by the same method as in Example 1. The output value of the electrode was measured using the measurement system used in . Next, this electrode was removed from the physiological saline and immersed in polyethylene glycol molecules: ji:400 heated to 40°C with stirring for 30 minutes. After leaving the electrode at room temperature for 2 weeks, the output value of the electrode was measured again. I measured it. As a result, the output values agreed within ±10%, and a stable output was obtained even after 8 hours of continuous measurement. It responded instantaneously to changes to gas and even to 50% oxygen gas, and its output value matched the value calculated based on the output value at equilibrium with air.

The stabilization time of the electrode was approximately 15 minutes.

Example 3: Platinum wire with a diameter of 150 μm and polyurethane coated with a thickness of 10 μm
It was painted and baked to form an insulating coating layer. This precious metal wire was cut perpendicularly to the longitudinal direction with a sharp knife to a length of 20 cm to expose a new platinum cross section.

On the other hand, polyether type polyurethane (Crisbon 1367
, trade name, manufactured by Dainippon Ink Chemical Co., Ltd.) in dimethylformamide to a solid content concentration of 15, and polyethylene glycol with an average molecular weight of 400 was further added to this in an amount equal to the solid content of polyurethane. A polyurethane solution was prepared. Using this solution, Example 1. A porous polyurethane film was formed on the tip of the metal wire in the same manner as O.As a result of observing this polyurethane porous film-covered electrode with an operating electron microscope, the outermost layer of the porous film had an average thickness of 0.2 μm.
The pores were uniformly dispersed, and the pores became larger toward the inner layer, and the film thickness was about 50 μm at the thickest point. The thickness of the insulation coating layer of this product is 12
It was a μ door.

Example 1 was performed using an electrode obtained by the same method as this electrode. Oxygen partial pressure was measured in the same manner as above. Furthermore, Example 1. After treating the porous membrane with glycerin in the same manner as above, it was stored at room temperature for 2 months. Two months later, the oxygen partial pressure was measured using the same method as above, and the measured value was almost the same as the previous time.

Example 4 Polyurethane was applied to a thickness of 1 around a platinum wire with a diameter of 150 μm.
It was painted and baked to a thickness of 0 μm to form an insulating coating layer.

This precious metal wire was cut perpendicularly to the length direction with a sharp knife to a length of 30 m, and the new platinum layer i-side was exposed.Meanwhile, cellulose acedate with an acetyl content of 42 parts or more was cut at right angles to the length direction with a sharp knife. % formic acid to a solid content concentration of 5% to obtain a uniform solution. After bringing the tip of the noble metal wire into contact with this solution and adhering the solution to the tip, it was immediately immersed in ion-exchanged water at 50°C, and the process with desolvated 0 was repeated twice. , wash thoroughly with deionized water at room temperature,
Oxygen partial pressure was measured in the same manner as in Example 1. Then,
After immersing this electrode in 98% glycerin at room temperature for 60 minutes,
After one month of storage at room temperature, the oxygen partial pressure was measured in the same manner as above. The stabilization time at this time was about 20 minutes, and the output values almost matched.

〔Effect of the invention〕

The electrode of the present invention has no deviation in the oxygen reduction current value before and after sterilization, the oxygen reduction current value does not change even after long-term storage, the stabilization time is short, and the response is fast. It is a highly accurate and reliable electrode.

Claims (1)

[Claims] The tip and/or side parts of a noble metal wire with an insulating coating layer around it and the parts without the insulating coating layer are covered with a porous membrane, and at least the outside of the porous membrane is water-soluble and does not substantially evaporate at room temperature. A biological electrode characterized by being coated with a compound.