JPS6134619B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides chemically sensitive elements having a plurality of insulated gate transistor structures formed on the same or different substrates and each having a chemically sensitive part selectively sensitive to different specific substances. A method for detecting a chemical substance using a chemical sensitive element having an insulated gate transistor structure, in which the chemical sensitive element is brought into contact with the same test substance together with one reference electrode to detect various specific substances in the test substance. It is related to.

Conventionally, in the gate part of a field effect transistor,
Various chemically sensitive elements have been proposed that detect various ions, gases, enzymes, antigens, antibodies, etc. by forming chemically sensitive portions that are sensitive to specific chemical substances. Such chemically sensitive elements include those in which a chemically sensitive part selectively sensitive to one specific chemical substance is formed on one semiconductor substrate, and those in which a plurality of chemically sensitive parts each selectively sensitive to different chemical substances are formed. There are some things that I did. Various methods have been proposed in the past for detecting the concentration and activity of specific ions in test liquids such as serum using such chemically sensitive elements, such as ion sensors. Figure 1 is a diagram showing the configuration of an example of an ion concentration measurement circuit proposed earlier by the applicant in Japanese Patent Application No. 53-43862 (Japanese Patent Publication No. 60-21344). The bias voltage applied to the reference electrode is controlled so that a predetermined current flows between the source and drain of the concentration-sensitive ion sensor, and the concentration and activity of specific ions in the sample solution are determined based on the bias voltage value. It is designed to be detected. In the first step, the test liquid 2 contained in the container 1
Inside, an ion sensor 3 and a chemically sensitive part 4 are immersed together with a reference electrode 5. A power source 7 is connected to the drain terminal 6 of the ion sensor 3 to apply a constant voltage, and the source terminal 8 and the semiconductor substrate 9 constituting the ion sensor 3 are grounded via a resistor 10. Further, the reference electrode 5 includes a potential control circuit 11 including a bias power supply.
is connected, and the bias voltage is controlled by the potential control circuit 11 so that the potential of the source terminal 8 becomes a predetermined potential, that is, a predetermined current flows between the source and drain, and the voltage value at that time is output. It is configured to detect with a bulb or the like between the terminals 12 and 13. According to such an ion concentration measurement circuit, since the ion sensor 3 is operated with a constant current, the operation is stable and minute changes in the interfacial potential depending on the ion concentration can be detected with high precision. There are advantages.

On the other hand, in the field of biochemistry, it is common to measure multiple ion concentrations and activities from the same sample solution. One possible measurement method in this case is to dispense the same test liquid into a plurality of containers, configure a measurement circuit as shown in FIG. 1 in each container, and perform multichannel measurement. However, this method requires a large amount of test liquid to measure the ion concentration and activity of each item independently, and is cumbersome to operate. When using an ion sensor in which a sensitive part is formed, there is a drawback that its function cannot be fully demonstrated. These drawbacks apply not only to ion sensors, but also to gas sensors, enzyme sensors, immunosensors, and the like.

An object of the present invention is to provide a chemically sensitive element with an insulated gate transistor structure that eliminates the above-mentioned drawbacks and can easily detect multiple specific chemical substances in the same cell with a small amount of analyte. The purpose is to provide a method for detecting the chemical substances used.

The invention may be formed on the same or different substrates,
A plurality of chemically sensitive elements each having a chemically sensitive part selectively sensitive to different specific substances, each having a structure of an insulated gate transistor, are brought into contact with the same test substance, at least all of the chemically sensitive parts together with one reference electrode, In detecting various specific substances in the test substance, the bias voltage applied to the reference electrode is selectively controlled so that a predetermined current flows between the source and drain of each chemically sensitive element. This method is characterized in that various specific substances in the test substance are selectively detected based on the bias voltage value.

The present invention will be described in detail below with reference to the drawings.

FIG. 2 is a diagram showing the configuration of an example of a detection device that implements the method of the present invention. This detection device
The ion concentrations and activities of three items in the test liquid 21 contained in the test liquid 21 are measured. Inside the container 20, in this example, each ion sensing part 23, 24, and 25 of an ion sensor 22 of an insulated gate transistor structure, which is formed on the same semiconductor substrate and selectively senses three different desired types of ions, are installed. The reference electrode 2 is placed in contact with the test liquid 21 and
6 is placed immersed in the test liquid 21. A common power source 27 is connected to the drain terminal D of the ion sensor constituting each ion sensing section to apply a constant DC voltage, and the source terminal S and the semiconductor substrate K
is grounded via the changeover switch 28 and the reference resistor 29. On the other hand, a potential control circuit 30 is connected to the reference electrode 26, and the bias voltage value applied to the reference electrode 26 is controlled by the potential control circuit 30 so that the potential at the point of the reference resistor 29 is applied to the ion sensor constituting each ion sensing section. In other words, control is performed so that a predetermined potential is applied to the ion sensor, that is, a predetermined current flows between the source and drain of the ion sensor constituting each ion sensing section. Therefore, in this example, the voltage at the point is supplied to one input terminal of the differential amplifier 32, and the voltage at the other input terminal is supplied to the other input terminal via the changeover switch 33, and is applied to the reference voltage corresponding to the ion sensor constituting each ion sensing section. Voltage sources 34, 35, and 36 are connected to each switch to supply a predetermined voltage, and the output of the differential amplifier 32 is used to bring the potential at a point to a predetermined potential via a drive circuit 37. The bias voltage source 31 was configured to be controlled. The bias voltage value at this time is measured at the output terminals 38 and 39 by a recorder, digital voltmeter, etc. via a measuring means (not shown) such as a voltmeter or an amplifier. In addition, the changeover switches 28 and 33
are configured to be switched synchronously by the control device 40 in accordance with the operation of the ion sensors constituting each ion sensing section.

In the detection device shown in FIG.
If the changeover switches 28 and 33 are switched synchronously and sequentially with 0, the reference electrode 26
A bias voltage is applied so that the potential at the point becomes a predetermined potential. Therefore, for two types of liquids whose concentrations are known for each of the liquids to be measured, in a detection device having the same configuration as that shown in FIG. In other words, by measuring the bias voltage values when a predetermined current flows between the source and drain, the bias voltage value can be calculated from these bias voltage values and the bias voltage value measured for the test liquid 21 with unknown ion concentration. , the specific ion concentration and activity in the test liquid 21 can be determined.

The bias voltage values at the output terminals 38 and 39 can also be measured after the control device 40 repeatedly controls the changeover switches 28 and 33 a desired number of times. In this case, output terminals 38, 39
Since the bias voltage values for the ion sensors constituting each ion sensing section are repeatedly measured in sequence, the changeover switches 28 and 33 are repeatedly controlled according to the response speed of each ion sensing section, and then each ion sensing section is Read the bias voltage value for the section. In this way, the time required for each ion sensing section to reach an equilibrium state can be shortened, and the bias voltage values for each ion sensor can be measured almost simultaneously at the desired number of repeated controls.

FIGS. 3 and 4 are diagrams showing the configurations of two other examples of the detection apparatus for carrying out the method of the present invention, and the detection apparatus shown in FIG. The only difference from the detection device shown in FIG. 2 is that it is provided between the drain terminal D of the ion sensor and the power source 27.
Furthermore, the detection device shown in FIG. 4 is designed to operate the ion sensors constituting each ion sensing section with a desired source/drain current according to its impedance, and for this purpose, the source terminal S of each sensor is It is grounded via a changeover switch 28 and reference resistors 29A, 29B, and 29C depending on the impedance. In this case, the voltage drops in each reference resistor, that is, the potentials at the points, can be made equal to each other, and therefore one reference voltage source 41 is connected to the other input terminal of the differential amplifier 32 of the potential control circuit 30. All you have to do is connect.

As described above, according to the present invention, a plurality of ion sensors selectively sensitive to different ions and a common reference electrode are simultaneously immersed in a test liquid housed in the same cell, and each ion sensor is Since the bias voltage applied to the reference electrode is selectively controlled so as to operate the reference electrode with a constant current, highly accurate detection can be performed with simple operations, and the amount of sample liquid required is small.

Note that the present invention is not limited to the above-mentioned example, and can be modified or modified in many ways. For example, the above-mentioned detection devices all use ion sensors in which multiple ion-sensing parts that are selectively sensitive to different ions are formed on the same semiconductor substrate, but each ion-sensing part is formed on an independent semiconductor substrate. A formed ion sensor can also be used. Furthermore, the present invention can be effectively applied even when a test liquid is introduced into a flow cell for measurement. Furthermore, the potential control circuit 30 is not limited to the above-described configuration;
Various modifications are possible. Furthermore, in addition to detecting the various ion concentrations and activities described above, the present invention can effectively detect desired chemical substances by using gas sensors, enzyme sensors, immunosensors, etc. as chemically sensitive elements. .

[Brief explanation of the drawing]

FIG. 1 is a diagram showing the configuration of an example of an ion concentration measuring circuit previously proposed by the applicant, FIG. 2 is a diagram showing the configuration of an example of a detection device implementing the method of the present invention,
FIG. 3 is a diagram showing the configuration of another example, and FIG. 4 is a diagram showing the configuration of still another example. 20... Container, 21... Test liquid, 22... Ion sensor, 23, 24, 25... Ion sensing section, 26...
Reference electrode, 27... Power supply, 28... Changeover switch, 2
9, 29A, 29B, 29C...Reference resistance, 30...
Potential control circuit, 31... Bias voltage source, 32... Differential amplifier, 33... Changeover switch, 34, 35, 3
6, 41... Reference voltage source, 37... Drive circuit, 38,
39...Output terminal, 40...Control device.

Claims (1)

[Scope of Claims] 1 A plurality of chemically sensitive elements each having a chemically sensitive portion having a chemically sensitive portion selectively sensitive to different specific substances formed on the same or different substrates, each having a plurality of chemically sensitive elements each having a chemically sensitive portion selectively sensitive to different specific substances. in contact with the same test substance together with one reference electrode to detect various specific substances in the test substance, so that a predetermined current flows between the source and drain of each of the chemically sensitive elements, Chemistry of an insulated gate transistor structure, characterized in that a bias voltage applied to the reference electrode is selectively controlled, and various specific substances in the test substance are selectively detected based on the bias voltage value. A method for detecting chemical substances using a sensing element.