JPH02231559A - Field effect transistor type ion sensor - Google Patents

Abstract

PURPOSE:To miniaturize the sensor and to allow measurement even if the volume of the sample liquid to be measured is extremely slight by forming a sensitive film contg. an ion sensitive material in a polyurethane resin on an insulating gate film of the field effect transistor. CONSTITUTION:Copper wires coated with the polyurethane resin are connected to drain and source electrode taking-out parts 2', 3' of the FET element and after the element is put into a tube consisting of nylon, etc., the gate part is exposed and an epoxy resin is injected to the tube to seal the tube. The gate part 4 in the front end part of the FET element is immersed into the soln. of a sodium ion sensitive film and is rested for a while to allow tetrahydrofuran to evaporate and to form the uniform sodium ion sensitive film on the gate part 4. The ion sensor having such construction is capable of measuring the concn. of the sodium ions in a sodium ion concn. range of 10<-4> to 10<0>M.

Description

Detailed Description of the Invention (Field of Industrial Application) The present invention is a field effect transistor (field effect transistor) that is small, has good compatibility with living organisms and blood, and is capable of measuring even minute amounts of sample liquid.
The present invention relates to an applied ion sensor (hereinafter referred to as FET).

(Prior art and problems to be solved) Electrode-type ion sensors that use a sensitive membrane made of a mixture of various sensitive substances and polymers such as polyvinyl chloride resin and epoxy resin are known as ion sensors. .

However, such electrode-type ion sensors are large in size, and there are limits to the amount of sample liquid required to be measured.Moreover, in biological measurements, the sensitive membrane has poor compatibility with living organisms and blood; There are drawbacks such as the formation of blood clots and the tissue reaction of the living body itself against the membrane.

(Object of the Invention) The present invention not only solves the above-mentioned drawbacks of conventional ion sensors, but also improves the conventional electrode-type ion sensor, which is small and can measure even a minute amount of sample liquid, and is suitable for biological-related measurements. This was made with the aim of providing an alternative FET type sodium ion sensor.

(Means of the present invention for solving the problem) The present inventors focused on the fact that polyurethane resin has excellent blood and biocompatibility among polymeric materials, and developed this polyurethane resin with sodium ion sensitization. The present invention has been made based on the discovery that the above object can be achieved by forming a sensitive film containing a substance on the gate portion of a small FET type transistor that can be manufactured using ordinary semiconductor manufacturing techniques.

The present invention includes an ion-sensitive material comprising a FET as a signal conversion element manufactured by ordinary semiconductor manufacturing technology, a polyurethane resin, a sodium ion sensitive material, and a mixture of a liquid film solvent and a manion eliminating agent mixed as desired. is used.

FET type ion sensors can be manufactured using MOSFET, that is, semiconductor IC technology, so they are ultra-small and easy to mass produce.
An ion-sensitive film made of an ion-sensitive material is formed in place of the metal electrode of the MOSFET gate, which has advantages such as easy multiplication and IC integration and quick response. When this FET-type ion sensor and a reference electrode such as a liquid-junction type glass reference electrode are placed in a liquid to be measured, and a constant voltage V is applied to the drain electrode of the FET, the Drain current IIl changes. Drain current■. If the current is maintained at a constant current, the voltage between the reference electrode and the source (GS) will change depending on the ion concentration. M.O.
The reference electrode serves as the gate metal electrode of the SFET, and the ions in the liquid to be measured and the ion-sensitive membrane serve as the gate signal, resulting in an ion sensor.

FETs are manufactured by forming n- or p-type drain and source regions of opposite conductivity type on a p- or n-type semiconductor substrate, and forming an insulating film between the drain and source regions. As the semiconductor substrate, crystals such as St, Ge, and compound semiconductors, or non-quality semiconductors such as amorphous St can be used.

On the other hand, the ion sensitizer award goes to quaternary ammonium salts such as trioctylmethylammonium salt, higher alkyl phosphates such as calcium dodecyl phosphate, metal chelate compounds, crown ether, and valinomycin. Any other ionophores can be selected and used.

Further, as the polyurethane resin, a solvent-soluble thermoplastic polyurethane is preferable. This polyurethane is obtained by polyaddition reaction of diol and diisocyanate. The diol used is polyester, polyether, etc., which have hydroxyl groups at both terminals and have a molecular weight of about several hundred to several thousand. As the diisocyanate, hexamethylene diisocyanate having a ratio of 4.4'-diphenylmethane diisocyanate is used. Furthermore, if desired, low-molecular diols such as ethylene glycol or low-molecular diamines such as ethylene diamine may be polyaddition-reacted with diisocyanate, followed by chain extension reaction to increase the molecular weight. In addition to these components, polyurethanes obtained by adding a third component and so-called medical polyurethanes [described in Kobunshi Kako, Vol. 35, p. 158 (1986)] can also be used. These polyurethane resins not only have excellent antithrombotic properties, but also prevent red blood cell destruction. It has extremely little effect on blood physiological functions such as decreased platelet function and temporary decrease in white blood cells, and has excellent blood compatibility and biocompatibility.

In the present invention, improvements in the mixability of the polyurethane resin and the ion-sensitive material, improvement in the adhesion between the gate film and the sensitive film, and the scientific improvement of the sensitive film are achieved. For the purpose of improving mechanical properties, response properties and electrical properties of the resulting ion sensor, a liquid film solvent such as an alkyl phosphate, Esters, ethers. Alcohols and ketones may be added, and an anion scavenger such as tetraphenyl borate may be added to improve ion selectivity.

As an example of a method for forming a sensitive film on the gate part of an FET, a polyurethane resin is dissolved in a suitable solvent, an ion sensitive material and a third component added as required are mixed therein, and then this mixture is mixed. It is applied to the gate area and the solvent is evaporated to form a film. Methods for applying the mixture to the gate include dropping the mixture onto the gate, brushing, or dipping the gate into the mixture. After application, shake off, rotate, etc. to form a uniform film. , adjustments such as overcoating, etc.

In the ion-selective sensitive membrane thus formed at the gate of the FET, the ion-sensitive substance is completely retained in the polyurethane resin, so changes in the electrolyte concentration in the liquid to be measured will be caused by the ion-selective sensitive membrane. This is converted into a potential by the film, becomes the potential of the gate of the FET in contact with it, generates electrons or holes between the drain and source directly under the gate, forms a channel, and changes the drain current I. Therefore, if the drain current I is set as a constant current, the ion concentration is detected as a change in the voltage VCS between the reference electrode and the source.

Next, an example of the FET type sodium ion sensor will be described.

(Example) An impurity that forms an n-type, such as phosphorus, is diffused into a P-type silicon substrate in a predetermined pattern using normal semiconductor manufacturing technology to form drain and source regions, and
A channel stopper is formed by diffusing an impurity that forms a P'' type, such as boric acid, into the type region to form a P'' region.Then, the drain electrode extraction portion is made N'' as before, and the source electrode extraction portion is made source. N' and P' are formed to make it a floor type FET. Also, in order to insulate at least the part that comes into contact with the liquid to be measured from the liquid, the front, back, and side surfaces are insulated with a silicon oxide film, a silicon nitride film, etc. Afterwards, these insulating films in the gate area are removed by etching, and a silicon oxide film and a silicon nitride film with low impurities are formed again to form an insulating gate film.Then, the insulating film in the drain and source electrode extraction areas is removed. After forming chrome and nickel electrode metals and placing lead-tin solder on top of them, an electrode extraction part is formed to fabricate an FET element. Figure 1 shows the FET element thus fabricated. The overall structure and the cross-sectional structure of the gate part of the FET element are shown in Figure 2. In each figure, (1) is a P-type silicon substrate, (2) and (3) are n-type drain and source regions, (2)゛) and (3゛) are the extraction parts of the drain and source electrodes, (4
) is the gate part, (5) is the P' type channel stopper region, (6) is the diode electrode for detecting the temperature using the temperature dependence of the forward voltage of the diode, (7
) is an insulating film for insulating the liquid to be measured, (8) is a silicon oxide film, and (9) is a silicon nitride film. 00) indicates a sensitive film when an ion-sensitive film described later is formed.

The drain and source electrode extraction portions of this FET element (
2') (3"), connect a copper wire coated with a resin such as polyurethane with lead-tin solder and place it in a tube made of silicone resin. After exposing the gate part, insert it inside the tube. The FET element part is sealed by injecting room temperature curable (RTV) silicone rubber, epoxy resin, etc.

Further, the end of the tube on the opposite side of the FET element from which the electrode lead-out insulated copper wire comes out is also sealed with resin in the same manner as described above.

On the other hand, O-nitrophenyl containing 40 mg of sodium ionophore as a sodium ion-sensitive substance, 600 cm of polyurethane resin KP-13 (manufactured by Kanebuchi Chemical Co., Ltd.) as a polyurethane resin, and 1.8 μ of sodium tetraphenyl borate as an anion scavenger. Octyl ether 360■
was dissolved in 6000 ml of tetrahydrofuran and adjusted to a uniform solution to prepare a solution in which the sodium ion sensitive membrane was dissolved. Then, the tip of the FET element (gate portion (4)) is immersed in the solution of this sodium ion sensitive membrane, pulled up, and then shaken several times to obtain a uniform membrane.

Then, leave it for a while to volatilize the tetrahydrofuran.

This operation is repeated several times to form a uniform sodium ion sensitive film θ0 without any via holes at the gate portion (4) of the FET. Note that the ion-sensitive film may be formed on the gate portion of the FET element before it is assembled into a tube.

The FET type sodium ion sensor thus produced was immersed in a sodium chloride aqueous solution with the glass comparison electrode as the reference electrode, and the drain voltage was set to ■.

= 3■, drain current L = 50 μA, voltage between the reference electrode and the source electrode at a liquid temperature of 25°C. , were measured to determine the response characteristics. The results are shown in FIG. FIG. 3 is a graph showing the relationship between sodium ion concentration and FET output voltage VGS.
' Sodium ion concentration can be measured within the sodium ion concentration range of M. Furthermore, the ion selectivity of this sodium ion sensor was also measured. The results are shown in Table 1. The ion selectivity was determined by a known mixed solution method and by calculating the selectivity coefficient defined by the Nikolsky and Eisenman equations. In addition, to check compatibility with blood, measurements were performed in serum.

The result is shown in Figure 4. For reference, polyvinyl chloride P
Figure 5 shows the measurement results in serum of a FET-type sodium sensor fabricated using VC and a sodium ionophore. Considering the concentration of each interfering ion in serum, the sodium ion concentration in serum can be measured without interference.
Regarding compatibility with blood, as can be seen from FIGS. 4 and 5, the sodium ion sensor using the polyurethane resin of the present invention is superior to the one using PVC. Note that the measurement in serum shown in Figure 4 does not use a constant temperature bath, so there is some drift, but a potential response appears corresponding to the difference in sodium ion concentration, and it is possible to measure sodium ions in blood. It shows.

(Effects of the Invention) As described above, the FET type ion sensor of the present invention uses polyurethane resin as the base resin of the sensitive membrane and FET as the signal conversion element, so it is small and can measure an extremely large amount of sample liquid. It can be used to measure even minute amounts and is also suitable for measuring electrolyte components in blood, making it highly effective for measuring various ion concentrations.

[Brief explanation of the drawing]

FIG. 1 is an overall diagram of an FET device showing an embodiment of the present invention;
Figure 2 is a cross-sectional view of the gate part of the FET element in Figure 1;
The figure shows sodium ion concentration and FET output voltage vc. s
FIGS. 4 and 5 are diagrams showing the results of sodium ion measurement in serum of the present invention and the polyvinyl chloride resin-based sensitive membrane. (1)...Silicon substrate, (2) and (3)...Drain and source regions, (2') (3')...Drain and source electrode extraction parts, (4)...Gate Part, (5)...Channel stopper area, (6)...
Diode electrode, (7)...insulating film, (8)...silicon oxide film, (9)...silicon nitride film, 00)
...Ion-sensitive membrane. 1st mouth

Claims (1)

[Claims] A field effect transistor type ion sensor characterized in that a sensitive film containing an ion sensitive substance made of polyurethane resin is formed on an insulated gate film of a field effect transistor.