JPS6168030A - Minute sensor for measuring oxygen partial pressure - 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 [Field of Industrial Application] The present invention relates to an improved oxygen electrode for continuously measuring oxygen partial pressure in liquids, particularly changes in oxygen partial pressure in living organisms.

[Conventional technology]

The oxygen partial pressure of body fluids has a great effect on living organisms. In recent years C1
The advent of the Ark-type oxygen electrode has made it possible to measure oxygen in vitro with high precision, and has greatly improved the treatment of patients with respiratory disorders.

In addition, the ICU (intense i) for the purpose of cardiopulmonary resuscitation is
The development of ve care units also led to advances in oxygen partial pressure measurements.

In vitro measurements using such sample collection are limited by the frequency of sample collection, and changes may occur during sample storage, resulting in inaccurate measurements. Therefore, it goes without saying that the ideal method is to continuously measure oxygen partial pressure by directly inserting a snow shovel into a living body.

A method of continuously measuring the oxygen partial pressure in a living body has also been proposed. That is, using electrodes for manufacturing metals such as platinum, iridium, and gold and reference electrodes such as silver chloride, a voltage is applied between these electrodes, oxygen is reduced at the working bridge (cathode), and a diffusion current is generated. This is an application of the principle of measurement.

At this time, if the oxygen concentration gradient on the surface of the electrode changes due to the movement of the cardiac muscle or the pulsation of blood in the living body, the diffused electrolyte to be measured undergoes a large change, making it impossible to accurately measure the oxygen partial pressure. Various studies have been made to improve this problem. In other words, it is a miniaturized version of the so-called "Clark electrode," which separates both poles with an oxygen-permeable membrane and contains an electrolyte (see Bunji Hagiwara, "Oxygen Measurement by Electrode Method," Kodansha Scientific, 1977). ), or a method of creating a stable contact state between the cathode surface and the solution by coating the surface of a fine metal wire electrode with a porous membrane consisting of a multilayer structure (Japanese Patent Publication No. 117838/1983) has been proposed. has been done.

However, these methods require large electrodes and can only be inserted into specific areas, such as large blood vessels.
There were drawbacks such as the possibility of the porous membrane peeling off and causing iatrogenic diseases.

[Problem that the invention seeks to solve]

An object of the present invention is to provide a biological microsensor that can continuously, stably, and accurately measure the oxygen partial pressure in a living body, while eliminating these drawbacks.

[Means for solving problems]

That is, the present invention relates to a microsensor for measuring oxygen partial pressure, the surface of which is composed of a portion without oxygen reducing ability and a plurality of electrode portions having oxygen reducing ability.

All conventional electrochemical methods measure the diffusion current based on the oxygen concentration gradient that occurs between the solution and the cathode interface.

In this case, the interface between the electrode and the solution (diffusion layer) is difficult to keep stable due to the influence of the flow, so the measured value becomes unstable.

The inventors of the present invention have conducted extensive research into ways to overcome these problems and have arrived at the present invention.

That is, a diffusion layer is formed due to an oxygen concentration gradient between the cathode interface and the solution, and this diffusion layer is made as small as possible to substantially reduce the oxygen concentration in the solution and the oxygen concentration at the electrode interface. This is a method to make them equal.

In other words, if the surface area of the electrode is minute, the diffusion layer is minute, and the oxygen-reducing substance is quickly removed from the electrode surface by molecular motion, the oxygen concentration on the electrode surface will always be equal to the oxygen concentration in the solution. It should be.

Based on these considerations, the present inventors discovered that if an electrode portion having an oxygen reducing ability is minute and has a plurality of electrode portions, it would be substantially unaffected by the flow, and arrived at the present invention. .

The electrode portion used in the present invention may be of any type as long as it has the ability to reduce oxygen.

That is, the tip of carbon, platinum, iridium, gold, or the like can be microfabricated and used.

One of the preferred methods is to use carbon fibers for the electrodes. Therefore, the case of carbon fiber will be explained in more detail, but the present invention is not particularly limited thereto. Carbon fibers usually have a diameter of 30 μm or less, and have the ability to reduce oxygen by themselves, and can easily improve the ability to reduce oxygen.

As a method of improving the oxygen reduction ability of carbon fibers, there is a method of attaching various metals (platinum, iridium, gold, zinc, etc.) to the surface or surface layer. As the attachment method, commonly used methods such as a vacuum evaporation method, a spackle method, a plating method, an ion implantation method, etc. can be applied.

The type of carbon fiber used is not particularly limited, and carbon fibers made from polyacrylonitrile, pitch, rayon, phenol resin, etc. or carbon fibers produced by vapor phase growth are preferred. The diameter of the carbon fibers may be 30 μm or less, but preferably 20 μm or less.

When the diameter is 30 μm or more, it becomes susceptible to the influence of flow. In the case of carbon fiber, it is also possible to use one fiber instead of a plurality.

Furthermore, if too many carbon fibers are used, the shape of the sensor becomes large, which is not preferable. Usually, the total area of the electrode portions having oxygen reducing ability is in the range of 30 to 10,000 square microns, particularly preferably 100 to 10,000 square microns.

The shape of the electrode portion having oxygen reducing ability may be circular, oval, rectangular, irregular, etc., but it is preferable that its maximum diameter (longest distance) is 30 μm or less.

The minimum distance between the parts having oxygen reducing ability is preferably 6 μm or more. If it is shorter than this, it will be more susceptible to the influence of the flow. There is no problem with the spacing being wide, but it is not preferable for the total area of the parts with oxygen reduction ability to exceed 10,000 square microns because the sensor will become too large, so the spacing should be within that area. is preferred.

Carbon fibers can also be used as the sensor of the present invention by surrounding them with a substance (referred to as a matrix) that does not have oxygen reducing ability.

The matrix material is not particularly limited, but polymeric materials such as fluororesins (such as "Kel-F"), polyester resins, epoxy resins, polyphenylene oxide resins, polyphenylene sulfide resins, and urethane resins are used, and they have antithrombotic properties. It is preferable to use a resin with excellent properties. It is also possible to use ceramics or metal materials as a matrix.

When producing a microsensor in which the spacing between carbon fibers is 6 μm or more, a preferable method is to mix carbon fibers with fibers made from a material that does not have oxygen reduction ability to form a composite material and construct the microsensor. There is one.

Examples of fibers without oxygen reducing ability include glass fibers, aramid fibers (such as "Kevlar"), milicon carbide fibers, boron fibers, and alumina fibers, but are not particularly limited.

The composite material is manufactured according to a known method.

Another preferred method is to prepare a carbon fiber composite and locally apply an electric current.

Using carbon fiber as it is as an electrode part with oxygen reduction ability
Although it may be used, one preferable method is to modify the reactive surface of carbon fiber for the purpose of increasing the reduction current to be measured and making it easier to measure. When a metal material with oxygen reduction catalytic activity such as platinum, iridium, gold, or zinc is used as a modification material, conventional methods such as vacuum evaporation, sputtering, plating, and ion implantation are used.

At this time, the surface of the carbon fiber may be completely covered with these metals, but it may also be partially made to resist adhesion or injected.

It is also possible to use phthalocyanines or Prussian blue as a surface modification method.

When continuously measuring the oxygen partial pressure in a solution (living body) in which non-reducing substances such as catecholamines remain, a thin film that excludes these substances and allows only oxygen to pass through is applied to the electrode surface using a conventional method. is preferred.

Since the microsensor of the present invention is inserted directly into a living body,
The diameter is preferably 1 mm or less.

The sensor of the present invention can also be used as a biosensor in combination with enzymes or microorganisms.

〔Effect of the invention〕

The microsensor of the present invention is substantially unaffected by flow and can stably and accurately measure the oxygen concentration in a living body.

Dog Example 1 Carbon fiber (“Trading Card M-40”, diameter 5.1 μm) 60
(The total area of the electrode part with oxygen reduction ability is 1178μ
m) was divided into 6 equal parts of 10 pieces each, the 10 pieces were arranged at equal intervals as possible, and stacked in 6 layers with glass fiber scrim cloth (thickness 22.5 μm) placed between them.

An epoxy resin containing a curing agent was poured over this, and the resin was heated and cured under pressure. The tip of the resulting microsensor was cut to expose the carbon fiber cross section, and the cross section was polished until it was smooth.

In this way, two types of microsensors (samples A and B) of 60 carbon fibers with different spacing between each fiber were created.
was created.

The above carbon fiber electrode was used as a working electrode (cathode), a silver electrode was used as a counter electrode, and a silver/silver chloride electrode was used as a reference electrode.
The oxygen reduction current was measured by applying a voltage of -0.75 volts to the working electrode in (distilled water containing % by weight), and the results shown in Table 1 were obtained. The effect of the current was small. Similar results were obtained when 6 Torayca T-300'' (diameter 7 μm) was used as the carbon fiber.

Table 1 Effect of carbon fiber arrangement and flow on oxygen reduction current Example 2 Carbon fiber (“Torayca M-40”, diameter 5.1 μm) 19
Books and aramid fibers (“Kevlar 49”).

A bundle of 38 fibers (diameter: 12 μrd) uniformly mixed together was thoroughly impregnated with an epoxy resin containing a curing agent (the total area of the electrode portion having oxygen reducing ability was 372 μrd). Next, the impregnated fiber bundle was heated and cured while applying tension.

A wire-like composite with a diameter of about 100 μm was obtained.

The spacing between carbon fibers was 6-15 μm.

The sides were insulated with a polyurethane thin film. One tip was cut with a sharp knife, and the cross section was polished with sandpaper and then with fine aluminum powder. The polymer coating on the other end was peeled off and connected to the working electrode terminal of an oxygen gas partial pressure measuring device. Further, a silver-silver chloride electrode was connected to the reference electrode terminal.

Physiological saline was circulated at 37° C. and 100 m 6 /min 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 current value was not affected by the liquid flow and showed a constant value. When nitrogen gas was introduced into the gas exchange section of the circulation system instead of air, the current value decreased. A calibration curve was obtained using a conventional method, and the oxygen partial pressure in the fluid could be determined.

Example 3 A cross-section of the composite obtained in Example 2 with a polished cross-section was immersed in a plating solution (a mixed solution of 4 parts of platinum chloride, 720 parts of ammonium phosphate, and 100 parts of sodium phosphate).
Platinum plating was carried out at a current of about IA/drrf and a temperature of 70 to 90°C.

This electrode was inserted directly into the dog's heart muscle to measure oxygen partial pressure. Stable values were obtained without being affected by the intense movement of the myocardium.

Claims (4)

[Claims] (1) A microsensor for measuring oxygen partial pressure whose surface consists of a portion without oxygen reduction ability and a plurality of electrode portions with oxygen reduction ability. (2) The maximum diameter of the electrode part with oxygen reduction ability is 30 μm
A microsensor according to claim (1) below. (3) The microsensor according to claim (1), wherein the electrode portion having oxygen reduction ability is carbon fiber or carbon fiber modified with an oxygen reduction catalyst. (4) The microsensor according to claim (1), wherein the shortest distance between the electrode portions having oxygen reducing ability is 6 μm or more.