JPS6248188B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a hydrogen ion sensitive FET converter (hereinafter referred to as a hydrogen ion sensitive FET converter) having a gate insulated field effect transistor structure.
This paper relates to a method for manufacturing a gas sensor using a FET converter (FET converter).

Measuring the concentration of gases such as carbon dioxide and ammonia gas is important in industrial applications. Furthermore, in recent years, the measurement of gas concentrations in living organisms has begun to be considered important in the fields of medicine and physiology. For example, in physiology, measuring the carbon dioxide concentration in a single cell provides important information, and in medicine, it is urgent to continuously measure the blood carbon dioxide concentration of anesthesia patients, critically ill patients, and patients in the recovery room. It helps in discovering the situation. Such a purpose requires an extremely small carbon dioxide sensor that can be inserted into cells or blood vessels.

Carbon dioxide sensors conventionally used for the above purpose use minute PH-sensitive glass electrodes. As schematically shown in Fig. 1, this sensor is composed of a PH-sensitive glass electrode 1, an Ag-AgCl reference electrode 2, a sodium bicarbonate (NaHCO ₃ ) aqueous solution 3, and a gas permeable membrane 4, and is called a Severinghans type carbon dioxide sensor. There is. This sensor utilizes the fact that carbon dioxide gas dissolved in water dissociates to produce H ⁺ ions and HCO ₃ ^- ions. That is, when CO ₂ dissolves in water, it produces carbonic acid, and its dissociation produces H ⁺ ions.

H ₂ O + CO ₂ H ₂ CO ₃ H ⁺ +HCO ₃ ^- (1) Therefore, the following relationship exists between the concentration of dissolved CO ₂ and the concentration of H ⁺ ions.

[ _HCO3 ^- ][H ⁺ ]/ _CO2 =K (2) On the other hand, the concentration of dissolved _CO2 is proportional to the partial pressure _Pco2 of gaseous _CO2 .

[CO ₂ ]=αPco ₂ (3) Using these equations, −log[H ⁺ ]=PH, logK=
If pK is used, a relationship well known as the so-called Henderson-Hasselbalch equation can be derived.

log (Pco ₂ ) = -PH + log [HCO ₃ ^- ] + pK - log α (4) Here, if the aqueous solution does not contain an electrolyte that produces bicarbonate ions such as NaHCO ₃ or a source of H ⁺ ions other than CO ₂ , [H ⁺ ]=[HCO ₃ ⁻ ] holds, so log(Pco ₂ )=−2PH+pK−logα (5). Since both K and α are constants under a constant temperature, equation (5) becomes PH=−1/2log(Pco ₂ )+constant (6). On the other hand, if an excess of NaHCO ₃ compared to dissolved CO ₂ is dissolved in the solution, [HCO ₃ ^- ] also remains constant, so from equation (4), PH=-log(Pco ₂ )+constant (7) Become. As is clear from the above explanation, the solution
PH changes in proportion to the logarithm of the partial pressure of carbon dioxide.
Taking advantage of this fact, dissolved CO ₂ can be removed using a PH-sensitive electrode.
The amount can be quantified. Here, as is clear from the comparison of equations (6) and (7), the effect of electrolytes such as NaHCO ₃ is to double the proportionality coefficient of the proportional relationship between PH and log(Pco ₂ ), that is, PH The purpose is to double the output of the electrode.

There are many gases such as carbon dioxide that dissolve in water to generate hydrogen ions and change the pH of the aqueous solution, as shown below.

CO ₂ +H ₂ OH ⁺ +HCO ₃ ^- NH ₃ +H ₂ ONH ₄ ⁺ +OH ^- SO ₂ +H ₂ OH ⁺ +HSO ₃ ^- 2NO ₂ +H ₂ O2H ⁺ +NO ₃ ^- +NO ₂ ^- X ₂ +H ₂ O2H ⁺ +XO ^- +X ^- ( (X = Cl, Br, l) Furthermore, as mentioned above, even if acids do not begin to dissolve in water to generate hydrogen ions, quantitative analysis using a PH-sensitive glass electrode is possible for acids that have a vapor pressure above a certain level. . For example, acetic acid gas dissolves in water and produces hydrogen ions.

CH ₃ COOHH ⁺ + CH ₃ COO ^-Using such a reaction, an ammonia gas sensor can be fabricated from a gas-permeable membrane, an aqueous phase containing a salt or polyion with ammonium ions, an Ag-AgCl electrode, and a PH-sensitive electrode. can.

Further, the sulfur dioxide gas sensor may use an aqueous phase containing a salt or polyion containing sulfite ions.

Various gas sensors using such a principle are inserted into living tissue when used in the medical and physiological fields, particularly for measuring gas concentrations in living bodies. Therefore, it is necessary to downsize the gas sensor, or in other words, downsize the PH-sensitive electrode. However, it is known that the following problems occur when conventional glass electrodes are miniaturized.

(a) Since the resistance value of the glass membrane is approximately 10MΩ, an amplifier with a high input resistance value is required.

(b) Glass membranes are thin and have low mechanical strength.

(c) Since the electrode area becomes smaller, the resistance value of the glass film increases.

As a result, the measuring device is large and complicated, and the electrode itself is fragile and easily damaged, which poses practical problems, particularly as a sensor for measuring gas concentrations in living organisms by inserting them into living tissues.

On the other hand, a carbon dioxide sensor using a solid PH electrode made of metal oxide instead of a glass electrode is disclosed in US Patent No. 3719576.
It is disclosed in the issue. This sensor is smaller and thinner than a sensor using a glass electrode, and is suitable for use as a sensor inserted into living tissue, but (a) the sensor is inflexible because it uses a solid electrode.

(b) Electrical resistance increases due to miniaturization.

It has drawbacks such as: Therefore, there was a limit to miniaturization.

These problems have been solved by using a recently developed hydrogen ion sensitive FET converter having a gate insulated field effect transistor structure instead of glass and solid electrodes. Such PH sensitivity
Gas sensors using FET converters are PH sensitive as disclosed by the applicant in Japanese Patent Application Laid-open No. 149396/1983.
The FET converter and reference electrode are separated and inserted into the tube, electrically insulating resin is injected between the lead wire connection and the tube wall to close the tube, and the tip of the tube is covered with a gas permeable membrane. It has a structure in which electrolyte is injected into the space formed by the membrane and tube wall. But above
Gas sensors using FET converters have various structural problems that need to be solved. That is, (a) in order to downsize the gas sensor, it is necessary to make the electrolyte chamber smaller, but this will reduce the amount of electrolyte sealed in this chamber. Therefore, continuous measurement over a long period of time is difficult due to leakage or evaporation of the electrolyte during measurement.

(b) When a polymer electrolyte solution is used as the electrolyte, the polymer serves both as a cationic electrolyte and as an electrolyte holder, so in such a system, due to the buffering effect of the polymer electrolyte, This causes the disadvantage that the sensitivity at low gas concentrations decreases.

Matsuo et al. have developed a carbon dioxide gas sensor that eliminates the above-mentioned drawbacks of gas sensors using PH-sensitive FET converters.
It was proposed at the 18th Japan ME Society Conference (May 1978). This sensor is PH sensitive as shown in Figure 2.
An Ag-AgCl comparison electrode 6 is vapor-deposited on the surface of the FET converter 5 and inserted into the glass tube 7, and an electrically insulating resin 8 is filled between the lead wire connection part and the inner wall of the tube to close the tube and make it gas permeable. It has a structure in which a sodium bicarbonate aqueous solution is sealed in a space 9 formed between the membrane 10 and the Ag-AgCl and gate portions of the FET. The above sensor is manufactured in the following manner. After depositing the Ag-AgCl comparison electrode 6 on the surface of the FET converter 5, aluminum is evaporated, the surface is coated with a fluororesin for a gas permeable membrane, and then the aluminum layer is removed by electrolysis.
After forming a space between the fluororesin coating, the gate part of the FET converter, and a part of the reference electrode, an electrolytic solution is injected into this space using a syringe, and the injection hole is sealed with silicone resin. However, when forming the electrolyte injection space, the silver of the reference electrode becomes contaminated with aluminum, resulting in unstable signals, and the manufacturing method is complicated, making it extremely difficult to produce a sensor with reproducibility.

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a method for manufacturing a gas sensor that always provides stable and correct measurement values over a long period of time.

Another object of the present invention is to provide a method for manufacturing a small gas sensor that can be inserted into a living body.

Another object of the present invention is to provide a method for manufacturing a gas sensor that is easy to manufacture and suitable for mass production.

The present invention relates to a step of arranging a reference electrode on a substrate of a hydrogen ion sensitive FET converter having a gate insulated field effect transistor structure in close proximity to the gate thereof, and a step of arranging a reference electrode on a substrate of a hydrogen ion sensitive FET converter having a gate insulated field effect transistor structure. The step of insulating the connection part is to accommodate the gate part of the FET converter to which the lead wire is connected and a part of the reference electrode to be located in the opening part of the flexible tube.
and a process of filling at least an electrically insulating resin between the inner wall of the tube and the lead wire connection part to close the tube, and coating a part of the gate part of the FET converter and the reference electrode with a non-electrolytic hydrophilic polymer containing an electrolyte. a step of drying the hydrophilic polymer, a step of coating the surface of the dried hydrophilic polymer layer with a gas permeable polymer, and a step of allowing the hydrophilic polymer layer to absorb moisture.
This is a method for manufacturing a gas sensor using a FET converter.

Figure 3 shows the PH sensitivity used in the gas sensor of the present invention.
2 is a plan view showing an example of a FET converter 21. FIG. This FET converter 21 has a width of 0.4 mm and a length of 5 mm, for example.
It has an elongated shape with a gate part 22 at one end,
A drain terminal 23 and a source terminal 24 are provided at the other end. The specific structure of such a FET converter is described in Japanese Patent Application Laid-Open No. 1983-66194, which was proposed by the applicant of the present invention. The gate portion 22 is shown in FIG. 4 and A- in FIG. 3.
As shown in cross-sectional view A, a drain diffusion region 26 and a source diffusion region 27 are formed in a silicon substrate 25, and the entire structure is sequentially covered with an oxide film 29 and a silicon nitride film 30. The sensor with the membrane described above is sensitive to hydrogen ions.

FIG. 5 shows the gate section 22 of the FET converter 21.
FIG. 3 is a plan view showing an example in which a comparison electrode 31 is placed on the FET substrate in close proximity to the FET substrate. The comparison electrode may be integrally deposited on the FET substrate as shown in FIG. 5, or the comparison electrode may be placed on the FET substrate. This comparison electrode 31 is shown in FIG.
As shown in the -B cross-sectional view, it is made of, for example, silver 32 and silver chloride 33. The above Ag-AgCl can be produced by vapor deposition, plating, and electrolysis.
For example, the Ag-AgCl layer is formed by depositing or plating a silver layer on the Si ₃ N ₄ layer on the FET surface, and then electrolyzing this layer in a NaCl solution using the Ag electrode deposited on the Si ₃ N ₄ as an anode. By doing so, the surface of the silver layer is chlorinated and an Ag-AgCl comparison electrode can be produced. The shape and arrangement of the reference electrode are also important; if the distance L between the gate part and the reference electrode (Fig. 5) is large, it will be easier to pick up noise due to induction, so the distance L between the gate part and the reference electrode should be 2 mm or less. It is preferable. When this distance is 2 mm or less, noise poses no practical problem. In order to prevent a short circuit between the lead wire connection part of the reference electrode and the gate part of the FET, the reference electrode has an elongated shape similar to the shape of the FET converter, and the lead wire is connected to the end of the reference electrode to prevent a short circuit between the lead wire connection part of the reference electrode and the gate part of the FET. It is preferable to make the distance between the lead wire connection part and the lead wire connection part as large as possible.

FIG. 7 is a sectional view of essential parts showing the configuration of the gas sensor of the present invention. This sensor is a flexible tube 4
A PH-sensitive FET converter 21 in which a reference electrode 31 shown in FIGS. 5 and 6 is deposited on a substrate within the tip of the
is housed with its gate portion 22 exposed at the tip opening of the tube 40. The reference electrode 31 and
Each lead wire 41 connected to the FET converter 21 is insulated and passed through the tube and led out from the rear end (not shown). The opening at the tip of the tube 40 is made to protrude slightly beyond this in order to protect the FET converter 21 from damage, and is cut out diagonally so that it can be easily inserted into a living body, for example. Then, the gap between the lead wire connection portion of the FET converter 21 and the reference electrode 31, and the inner wall of the tube is filled with electrically insulating resin 42, such as epoxy resin or silicone resin, to close the tip of the tube.

A hydrophilic polymer layer 43 containing an electrolytic solution whose pH changes by absorbing gas is provided so as to span both the gate portion 22 of the PH-sensitive FET converter 21 and the comparison electrode 31 . The thickness of this polymer layer is 0.5-100μ in wet state, preferably 0.1
~10μ is appropriate. The thickness of this polymer layer is
If it exceeds 100μ, the response speed will decrease and
Below 0.5 μ, the signal becomes unstable. Therefore, the polymer layer needs to be thin and uniform.

The polymer used here preferably has an appropriate water absorbency, for example, 60% by weight or more at a temperature of 37°C. If the water absorption is low, the response speed will be low. Such polymers include polyvinyl alcohol (hereinafter referred to as
PVA), cellulose, polyhydroxyethyl methacrylate, polyvinylpyrrolidone, agar, etc. These polymers may be copolymerized with other monomers and may also contain plasticizers and the like. Among these polymers, especially
PVA is superior in terms of stability.

Also, the amount of electrolyte contained in this polymer layer is
If the concentration is low relative to the polymer, a decrease in sensitivity tends to occur and the signal becomes unstable. Moreover, if the concentration is large, the response speed will decrease. Therefore, it is necessary to contain the electrolyte in an amount that does not cause the above-mentioned troubles. A polymer layer containing such an electrolyte may be formed by dissolving the polymer in a solvent that dissolves both the polymer and the electrolyte, such as water, and applying and drying the solution.
In addition, a polymer layer obtained by applying a solution of polymer alone in advance or polymerizing on the gate,
If necessary, after crosslinking, it may be immersed in an electrolyte solution, swollen, and then dried. In either case, freeze-drying is preferred in order to maintain the thickness of the swollen state.

The hydrophilic polymer layer 43 is further coated with a gas permeable polymer 44.

A known gas permeable membrane can be used for this polymer. These include, for example, fluorocarbon resins such as polymers and copolymers such as tetrafluoroethylene, trifluoroethylene, hexafluoropropylene, and chlorotrifluoroethylene, polyolefins such as polyethylene, polypropylene, polypentene-1, and silicone resins. Among these, polytetrafluoroethylene and silicone resin are particularly preferred; the former provides a sensor with little change over time, and the latter provides a sensor with a short response time. In addition, from the viewpoint of strength and response time, the thickness of the film is 3 to 3.
For rubber such as silicone resin, 50 to 300μ is preferable.

The coating method for the gas permeable membrane 44 is as follows:
Methods such as dip coating, spray coating, vacuum deposition, ultraviolet polymerization, plasma polymerization, and sputtering can be used. Gas-permeable membranes need to be uniform and thin in order to obtain sufficient response speed, and in particular non-rubber-like polymers such as polytetrafluoroethylene and polyethylene/polypropylene need to be thin. vapor deposition,
It is preferable to use a gas phase polymerization method such as ultraviolet polymerization, plasma polymerization, or sputtering method.

The hydrophilic polymer layer of the gas sensor produced in this way is dry and will not work as it is, so the sensor is used after the hydrophilic polymer absorbs moisture and swells in water or steam. Even if this sensor dries out, it can be used again by immersing it in water for a long time.

The above gas sensor can be manufactured as follows.

(1) A comparison electrode 31 is placed on the surface of the PH-sensitive FET converter 21 shown in FIG. 3 as shown in FIG. 5.
(In Fig. 5, it is vapor deposited.) (2) Next, the lead wire 41 is attached to the comparison electrode 31 and the FET converter 21. When placing the reference electrode on the surface of the FET converter, the reference electrode and FET
For handling purposes, it is preferable to connect the lead wires to the converter in advance. Next, apply epoxy resin 4 to the area around the reference electrode and the lead wire connection part of the FET converter.
After insulating at step 5 (FIG. 8), the FET converter 21 is housed in the catheter 40 so that the gate part 22 is located at the distal end opening. Then, epoxy resin 46 is injected into the lead wire attachment portion and the inner wall surface of the catheter to close the catheter tip.
(Figure 9) (3) Cover the gate part and a part of the reference electrode with hydrophilic polymer 43 and dry. (FIG. 10) At this time, the polymer must cover the entire surface of the gate portion and a portion of the reference electrode.

(4) Next, the dried hydrophilic polymer layer 43 is covered with a gas permeable membrane 44. (Figure 7) (5) Since the gas sensor produced in this way will not work as it is, the hydrophilic polymer is allowed to absorb moisture and swell in water or steam.

The above-mentioned sensor can then measure the gas concentration in the liquid to be measured using, for example, the measuring circuit described in Japanese Patent Application Laid-Open No. 52-26292. That is, when the gas sensor is inserted into a measurement liquid, for example, a blood vessel, the gas that has passed through the gas permeable membrane 44 is absorbed by the electrolyte contained in the hydrophilic polymer layer 43, changing the hydrogen ion concentration of the electrolyte, and the polymer layer exposed to
The interface potential of the gate portion 22 of the FET converter 21 is changed. Since this circuit uses a source follower circuit, changes in the interfacial potential are directly extracted as an output voltage, and by measuring this potential, the hydrogen ion concentration in the polymer layer, in other words, the gas concentration in the solution can be measured. .

Example 1 An Ag layer was deposited on the surface of a PH-sensitive FET transducer as shown in FIGS. 5 and 6, and an AgCl layer was further formed thereon by electrolytic plating, followed by insertion into a catheter. After sealing epoxy resin into the gap between the inner wall of the catheter and the FET converter and reference electrode lead wire connections, the center gate and part of the reference electrode were soaked with 10μ of 0.1N NaCl and 0.1N _NaHCO3.
It was coated with a layer of polyvinyl alcohol (degree of polymerization 1700) with a degree of saponification of 98%. Furthermore, the above PVA layer was coated with a silicone resin having a thickness of 50 μm using a dip coating method to produce a carbon dioxide gas sensor.

The above gas sensor is immersed in water and the PVA layer is 37 cm.
It was allowed to swell until the moisture content at ℃ reached 60% or more.

When this sensor was inserted into a nitrogen stream containing 5% and 12% carbon dioxide gas at 25°C and measured, the signal difference was 18 mV (theoretical value 22 mV), and the response rate was 50%.
An excellent carbon dioxide gas sensor was obtained that lasted for 30 seconds. Additionally, this sensor maintains stable output day and night at room temperature.
Furthermore, even if this gas sensor had been dried once, it could be used again by immersing it in water at 50°C for 2 hours.

[Brief explanation of the drawing]

Fig. 1 is a schematic diagram explaining the measurement principle of a carbon dioxide sensor using a glass electrode, Fig. 2 is a sectional view of the main part of a conventional carbon dioxide sensor using a PH-sensitive FET converter, and Fig. 3 is a schematic diagram illustrating the measurement principle of a carbon dioxide gas sensor using a glass electrode. FIG. 2 is a plan view of a PH-sensitive FET converter used in the gas sensor of the present invention. FIG. 4 is a sectional view taken along the line A-A of the FET converter shown in FIG. 3, FIG. 5 is a plan view of the FET converter shown in FIG. 6 is a cross-sectional view taken along line BB of the FET converter shown in FIG. 5. FIG. FIG. 7 is a cross-sectional view of a main part of a gas sensor manufactured by the method of the present invention, and FIGS. 8 to 10 are cross-sectional views of main parts for explaining the method of manufacturing a gas sensor of the present invention.

Claims (1)

[Claims] 1. A step of arranging a reference electrode on the substrate close to the gate portion of a hydrogen ion sensitive FET converter having a gate insulated field effect transistor structure,
The process of insulating the connection part of the lead wire connected to the FET converter and reference electrode.
The gate part of the FET converter and a part of the reference electrode are housed in the opening of the flexible tube, and at least the inner wall of the tube and the lead wire connection part are filled with electrically insulating resin. the process of occlusion;
A process of coating the gate part of the FET converter and a part of the reference electrode with a non-electrolytic hydrophilic polymer containing an electrolyte, a process of drying the hydrophilic polymer, and a process of making the surface of the dried hydrophilic polymer layer gas permeable. A method for manufacturing a gas sensor using a hydrogen ion sensitive FET converter, comprising a step of coating a polymer and a step of making the hydrophilic polymer layer absorb moisture.