JP5712910B2 - Electrochemical measuring device - Google Patents

Description

  The present invention relates to an electrochemical measurement device, and more particularly to an electrochemical measurement device that measures an oxidation-reduction reaction.

  Voltammetry is a method for measuring redox reactions using electrochemical reactions. In this method, the potential of the electrolyte and the electrode is controlled, and the electrons moving by the oxidation-reduction reaction are measured as current. Since the measurement method is simple, a lot of information can be obtained, and it is widely used. In particular, a method called cyclic voltammetry (CV) is well known.

  In recent years, such electrochemical measurement has been reduced in size so that a small amount of sample can be measured, and the measurement apparatus has been made into one chip as its ideal shape. This is because a region for holding an electrolyte solution is provided on a semiconductor substrate on which a circuit is formed, and an electrode is provided so as to be in contact with the electrolyte solution so that an electrochemical measurement can be performed using the circuit formed on the semiconductor substrate. is there.

  For example, Patent Document 1 describes a method of performing electrochemical analysis on a substrate and analyzing a gene based on the current value. In Patent Document 1, the substrate is not limited to a semiconductor, but Patent Document 2 describes a method in which electrochemical measurement is performed on a semiconductor chip. In the electrochemical measurement, the current value decreases as the sample becomes very small. As a result, a mechanism for amplifying current is required. Patent Document 2 describes a method of measuring a small current value using a current mirror type current amplifier circuit.

Japanese Patent No. 3917640 Japanese Patent No. 4177589

  In a current mirror type current amplification circuit, amplification is not possible unless the current value is greater than the current at which the transistor operates, but the value is on the order of nA. Therefore, it is difficult to measure current values below this, for example, current values on the order of pA or below fA. Therefore, the method using the current mirror type amplifier circuit has a problem that the size of the electrochemical reaction sample to be measured is restricted by the current value, and it is difficult to reduce it to a certain size or less.

Therefore, in the present invention,
A reaction region (100) formed in an insulating layer formed on a semiconductor substrate and holding an electrolyte to be measured;
A counter electrode (2) for applying a counter voltage to the electrolyte;
A reference electrode (3) for monitoring the voltage of the electrolyte;
A working electrode (4) formed in contact with the electrolyte;
A control circuit (101) for controlling the voltage value of the counter voltage so that the reference voltage monitored by the reference electrode coincides with a driving voltage given from the outside;
A capacitor (8) connected between the working electrode and a low-potential-side power supply line and storing electric charge flowing out through the working electrode;
An amplifying unit (110) for amplifying a working voltage generated in the capacitor and outputting a measurement voltage;
Feedback means (103) for feeding back the fluctuation of the working voltage to the control circuit,
The control circuit provides an electrochemical measurement device that maintains the voltage difference between the reference voltage and the working voltage constant by controlling the counter voltage based on a variation amount of the working voltage obtained by the feedback means. .

In the electrochemical measurement apparatus,
The control circuit (110)
A differential amplifier (102) having an inverting input terminal, a non-inverting input terminal, and an output terminal, and outputting the counter voltage from the output terminal;
A buffer circuit (104) for transmitting the reference voltage;
A first resistor (105) connected between the output of the buffer circuit and the inverting input terminal of the differential amplifier;
A second resistor (106) connected between an external input terminal to which the drive voltage is applied and the inverting input terminal of the differential amplifier;
An electrochemical measurement device is provided in which the working voltage is input to the non-inverting input terminal of the differential amplifier.

In the above electrochemical measurement apparatus,
The control circuit (110)
A differential amplifier having an inverting input terminal, a non-inverting input terminal, and an output terminal, a constant voltage is applied to the non-inverting input terminal, and the counter voltage is output from the output terminal;
A buffer circuit (104) for transmitting the reference voltage;
A first resistor (105) connected between the output of the buffer circuit and the inverting input terminal of the differential amplifier;
A second resistor (106) connected between an external input terminal to which the drive voltage is applied and the inverting input terminal of the differential amplifier;
The driving voltage provides an electrochemical measurement device in which a voltage value is controlled in accordance with a change in the measurement voltage.

In the above electrochemical measurement apparatus,
A reset switch (115) provided in parallel with the capacitor;
The reset switch is formed on a semiconductor substrate and provides an electrochemical measurement device in which a conduction state is switched by a mechanical operation.

In the above electrochemical measurement apparatus,
The reset switch is formed of a bimetallic material, and provides an electrochemical measurement device in which a contact state is switched by a thermal reaction.

In the above electrochemical measurement apparatus,
The reset switch provides an electrochemical measurement device in which a contact state is switched by an attractive force and a repulsive force due to an electrostatic field.

In the above electrochemical measurement apparatus,
The electrochemical measurement device provides an electrochemical measurement device formed on one semiconductor substrate.

  According to the electrochemical measurement apparatus according to the present invention, it is possible to improve the measurement accuracy for a small amount of sample.

1 is a cross-sectional view of a semiconductor device according to a first embodiment. 1 is a block diagram of an electrochemical measurement apparatus according to a first embodiment. It is a block diagram of the electrochemical measuring device concerning Embodiment 2. FIG. It is a block diagram of the electrochemical measuring device concerning Embodiment 4.

Embodiment 1
Embodiments of the present invention will be described below with reference to the drawings. In the electrochemical measurement apparatus according to the first embodiment, a reaction region in which a measurement sample (for example, an electrolytic solution) is put on one semiconductor substrate and a measurement circuit that measures an electrochemical reaction of the electrolytic solution are formed. Therefore, FIG. 1 shows a cross-sectional view of a semiconductor device in which the electrochemical measurement apparatus according to the first embodiment is formed.

  As shown in FIG. 1, in the electrochemical measurement apparatus according to the first embodiment, a circuit element is formed on the surface of a semiconductor substrate 23. The semiconductor substrate 23 is made of, for example, silicon. In the cross-sectional view shown in FIG. 1, MOSFETs (Metal Oxide Semiconductor Field Effect Transistors) 20 to 22 are shown as circuit elements. However, the electrochemical measurement apparatus according to the first embodiment has circuit elements such as transistors other than the MOSFETs 20 to 22 shown in FIG.

  An insulating layer 13 is formed on the upper layer of the semiconductor substrate 23. Then, wiring layers 10 to 12 are formed on the insulating layer 13. Wirings formed in the wiring layers 10 to 12 are connected to circuit elements or wirings of other wiring layers through via wirings 9. In the example shown in FIG. 1, the capacitor 8 is formed by the wiring and the insulating layer 13.

  Another insulating layer 6 is formed on the insulating layer 13. A depression is formed in the insulating layer 6. This depression becomes the reaction region 100. In the reaction region 100, the electrolytic solution 1 is placed. A counter electrode 2, a reference electrode 3, and a working electrode 4 are formed at the bottom of the reaction region 100. The counter electrode 2, the reference electrode 3, and the working electrode 4 are connected to the wiring formed in the insulating layer 13 through the via wiring 7. The counter electrode 2, the reference electrode 3, and the working electrode 4 are each formed of a material suitable for electrochemical measurement such as platinum or carbon. Since the counter electrode 2 is an electrode for applying a voltage to the electrolytic solution 1, it is connected to the drain of the MOSFET 20. Since the reference electrode 3 is for measuring the voltage of the electrolytic solution 1, it is connected to the gate of the MOSFET 21. Since the working electrode 4 is an electrode through which a current from the electrolytic solution 1 flows, it is connected to the gate of the MOSFET 22.

  As described above, in the electrochemical measurement apparatus according to the first embodiment, the reaction region and the measurement circuit are integrally formed on one semiconductor substrate. In this way, by forming the reaction region and the measurement circuit integrally, it is possible to accurately measure a small amount of sample and downsize the apparatus.

  Next, the configuration of the electrochemical measurement device according to the first embodiment will be described in detail. A block diagram of the electrochemical measurement apparatus 201 according to the first embodiment is shown in FIG. As shown in FIG. 2, the electrochemical measurement apparatus 201 includes a reaction region 100, a control circuit 101, a capacitor 8, and an amplification unit 110. The electrochemical measurement apparatus 201 includes an external input terminal 120 and an external output terminal 121. Furthermore, as shown in FIG. 2, the electrochemical measuring apparatus 201 receives a drive voltage from a drive signal control circuit 130 provided outside. This drive voltage is applied to the electrochemical measurement apparatus 201 via the external input terminal 120.

  The reaction region 100 is the reaction region 100 shown in FIG. 1, and is provided with the counter electrode 2, the reference electrode 3, and the working electrode 4. The counter electrode 2 is an electrode that applies a counter voltage to the electrolytic solution 1. The reference electrode 3 is an electrode that monitors the voltage of the electrolytic solution 1. The working electrode 4 is formed so as to be in contact with the electrolytic solution 1 and is an electrode for extracting a current from the electrolytic solution 1 to a measurement circuit.

  The control circuit 101 controls the voltage value of the counter electrode 2 so that the reference voltage monitored by the reference electrode 3 matches the drive voltage given from the outside. More specifically, the control circuit 101 includes a differential amplifier 102, a feedback wiring 103, a buffer circuit 104, a first resistor 105, and a second resistor 106.

  The differential amplifier 102 has an inverting input terminal, a non-inverting input terminal, and an output terminal, and outputs a counter voltage from the output terminal. A feedback wiring 103 is connected to the non-inverting input terminal of the differential amplifier 102. The feedback wiring 103 applies a voltage generated by the electric charge accumulated in the capacitor 8 to the non-inverting input terminal of the differential amplifier 102. That is, the feedback wiring 103 becomes the feedback means in the first embodiment.

  A reference voltage is applied from the reference electrode 3 to the non-inverting input terminal of the buffer circuit 104. The inverting input terminal of the buffer circuit 104 is connected to the output terminal of the buffer circuit 104. Then, the buffer circuit 104 outputs the reference voltage measured by the reference electrode 3 to the first resistor 105.

  The inverting input terminal of the differential amplifier 102 is connected to the external input terminal 120 through the second resistor 106, and is connected to the output terminal of the buffer circuit 104 through the first resistor 105. That is, a voltage obtained by dividing the voltage difference between the reference voltage and the drive voltage by the first resistor 105 and the second resistor 106 is applied to the inverting input terminal of the differential amplifier 102. The first resistor 105 and the second resistor 106 are set to the same resistance value.

  The capacitor 8 is connected between the working electrode 4 and the low potential side power supply wiring (for example, ground wiring). The capacitor 8 accumulates the electric charge given from the working electrode 4 and generates a working voltage.

  The amplifying unit 110 amplifies the working voltage generated in the capacitor 8 to generate a measurement voltage, and outputs the measurement voltage via the external output terminal 121. The reaction of the electrolytic solution 1 can be measured by measuring this measurement voltage with an external measuring instrument.

  The amplifying unit 110 includes a MOSFET 22, a resistor 111, and an amplifier 112. The MOSFET 22 is, for example, an NMOS transistor. A constant voltage Vconst1 is supplied to the drain of the MOSFET 22. A constant voltage Vconst2 is supplied to the source of the MOSFET 22 via the resistor 111. The constant voltage Vconst1 is, for example, a power supply voltage, and the constant voltage Vconst2 is, for example, a ground voltage. The MOSFET 22 functions as a source follower amplifier. The amplifier 112 amplifies the voltage generated at the source of the MOSFET 22 and outputs the amplified voltage.

  Subsequently, the operation of the electrochemical measurement apparatus 201 according to the first embodiment will be described. In the electrochemical measuring device 201, 0V is generated as the working voltage when no charge is accumulated in the capacitor 8. At this time, if the drive voltage is a (V), the control circuit 101 controls the counter voltage so that the reference voltage is a (V).

  As described above, the control circuit 101 drives the counter electrode 2, whereby a voltage is applied to the electrolytic solution 1. As a result, a current e− flows from the working electrode 4. The current e− is accumulated in the capacitor 8, and an operating voltage is generated in the capacitor 8. At this time, when the working voltage is b (V), the control circuit 101 controls the counter voltage so that the reference voltage becomes a + b (V). That is, the control circuit 101 performs control so that a (V) is always applied to the electrolytic solution 1. Thus, the oxidation-reduction reaction of the electrolytic solution 1 can be stably continued by keeping the voltage applied to the electrolytic solution 1 constant regardless of the fluctuation of the working voltage.

  In addition, the electrochemical measurement apparatus 201 according to the first embodiment amplifies the working voltage generated in the capacitor 8 by the amplifying unit 110 and outputs the measurement voltage (voltage of the external output terminal 121). In the electrochemical measurement apparatus 201, when the amplification factor of the amplification unit 110 (the total amplification factor of the source follower amplifier and the amplifier 112) is A, the current value of the current e− flowing through the working electrode 4 is a differential value (ΔV / Δt) equal to 1 / A times. That is, the electrochemical measurement apparatus 201 facilitates observation of a minute current change by amplifying the working voltage, and realizes a minute current measurement by calculating a current value from the measured measurement voltage.

  From the above description, in the electrochemical measurement apparatus 201 according to the first embodiment, the amplifying unit 110 amplifies and outputs the working voltage generated in the capacitor 8 by the minute current from the working electrode 4. In such a system in which electric charge is accumulated in the capacitor, a voltage corresponding to the current value can be generated without causing a problem of leakage current due to the transistor. In addition, a minute voltage change can be accurately measured by amplifying the working voltage and generating a measurement voltage. As a result, the electrochemical measurement apparatus 201 according to the first embodiment can measure a very small amount of current that is difficult to measure due to the influence of the leakage current of the transistor and the like in the conventional method employing the current mirror type current amplification circuit. .

  In addition, since the working voltage generated in the capacitor 8 must be within a certain range, it is necessary to perform a reset process when the working voltage exceeds the range. In the block diagram of the electrochemical measurement apparatus 201 shown in FIG. 2, the reset switch is not turned on. In this case, the electric charge of the capacitor 8 is extracted from the counter electrode 2 through the electrolytic solution 1. This resetting operation is better performed before measurement. The reason why the reset circuit is not included in the capacitor 8 is that a switch using a MOSFET has a leakage current, and it becomes a noise and a minute amount of current cannot be measured.

  Further, in the electrochemical measurement device 201 according to the first embodiment, the voltage of the working electrode 4 increases as the working voltage generated in the capacitor 8 increases. Therefore, when the voltage applied to the non-inverting input terminal of the differential amplifier 102 of the control circuit 101 is fixed, the voltage of the reference electrode 3 and the voltage of the working electrode 4 are increased as the voltage of the working electrode 4 increases. There is a problem that the voltage difference from the voltage becomes small, and the oxidation-reduction reaction of the electrolytic solution 1 becomes unstable. However, in the electrochemical measurement apparatus 201 according to the first embodiment, the voltage of the working electrode 4 (for example, working voltage) is applied to the non-inverting input terminal of the differential amplifier 102 of the control circuit 101. Therefore, even when the working voltage fluctuates, the control circuit 101 can keep the voltage difference between the reference electrode 3 and the working electrode 4 constant according to the fluctuation of the working voltage. By performing such control, the electrochemical measurement apparatus 201 according to the first embodiment can maintain the same oxidation-reduction reaction as when there was no voltage fluctuation of the working electrode 4.

Embodiment 2
FIG. 3 shows a block diagram of the electrochemical measurement apparatus 202 according to the second embodiment. As shown in FIG. 3, the electrochemical measurement apparatus 202 according to the second embodiment applies the low voltage Vconst3 to the non-inverting input terminal of the differential amplifier 102 by deleting the feedback wiring 103. In addition, the electrochemical measurement apparatus 202 according to the second embodiment applies the measurement voltage output from the external output terminal 121 to the drive signal control circuit 130 via the feedback wiring 131. That is, the electrochemical measurement apparatus 202 according to the second embodiment performs feedback of the working voltage via the drive signal control circuit 130 provided outside. That is, the feedback wiring 131 and the drive signal control circuit 130 serve as feedback means in the first embodiment.

  The drive signal control circuit 130 determines the voltage of the working electrode 4 from the measured voltage, and outputs a voltage obtained by adding the voltage value of the working voltage as a new drive voltage. For example, when the working voltage is b (V) in a state where the initial driving voltage is a (V), the new driving voltage is set to a + b (V). Thus, the merit of feeding back the working voltage via the drive signal control circuit 130 is that the drive signal control circuit 130 can determine whether the measurement system is likely to become unstable by monitoring the change of the working voltage. It is. For example, if the change in the working voltage is too large, it can be determined that the measurement is interrupted.

  From the above description, as shown in the electrochemical measurement apparatus 202 according to the second embodiment, the feedback of the working voltage can also be performed via the external drive signal control circuit 130. In addition, the stability of the measurement system can be determined by feeding back the working voltage via the drive signal control circuit 130.

Embodiment 3
FIG. 4 shows a block diagram of the electrochemical measurement apparatus 203 according to the third embodiment. As shown in FIG. 4, an electrochemical measurement device 203 according to the third embodiment is obtained by adding a reset switch 115 to the electrochemical measurement device 202 according to the second embodiment.

  The reset switch 115 is provided in parallel with the capacitor 8. The reset switch 115 controls the conduction state by a mechanical contact formed on the semiconductor substrate. The reset switch 115 extracts the electric charge of the capacitor 8 in a conductive state, and resets the working voltage to the ground voltage. The reset switch 115 can be formed of, for example, a bimetal material or a magnetic material.

  When the reset switch 115 is formed of a bimetal material, the conduction state of the contact is switched by a thermal reaction. Further, when the reset switch 115 is formed of a magnetic material, the conduction state of the contact is switched by the attractive force and the repulsive force due to the electrostatic field.

  As described above, the capacitor 8 is reset while preventing the influence of the leakage current flowing through the reset switch by using the reset switch 115 that can switch the conduction state of the contact by mechanical operation on the semiconductor substrate. Can do. Further, by providing the reset switch 115, when the measurement system becomes unstable, a reset operation can be performed and measurement can be continued.

  Note that the present invention is not limited to the above-described embodiment, and can be changed as appropriate without departing from the spirit of the present invention. For example, the resistance values of the first and second resistors are the same, but if the degree of influence of the reference electrode voltage is to be changed, the ratio of the resistance values of the first and second resistors is changed accordingly. May be. Further, the first and second resistors may be combined with a capacitor or the like to have a frequency characteristic such as a low-pass filter.

DESCRIPTION OF SYMBOLS 1 Electrolytic solution 2 Counter electrode 3 Reference electrode 4 Working electrode 6, 13 Insulating layer 7 Via wiring 8 Capacitor 9 Via wiring 10-12 Wiring layer 13 Insulating layer 20-22 MOSFET
23 Semiconductor substrate 100 Reaction region 101 Control circuit 102 Differential amplifier 103, 131 Feedback wiring 104 Buffer circuit 105, 106 Resistor 110 Amplifier 111 Resistor 112 Amplifier 115 Reset switch 120 External input terminal 121 External output terminal 130 Drive signal control circuit 201- 203 Electrochemical measuring device

Claims (7)

A reaction region formed on an insulating layer formed on a semiconductor substrate and holding an electrolyte to be measured;
A counter electrode for applying a counter voltage to the electrolyte;
A reference electrode for monitoring the voltage of the electrolyte;
A working electrode formed in contact with the electrolyte;
A control circuit that controls the voltage value of the counter voltage so that the reference voltage monitored by the reference electrode matches the drive voltage applied from the outside;
A capacitor for accumulating charge flowing out through the working electrode ;
An amplifying unit for amplifying the working voltage generated in the capacitor and outputting a measurement voltage;
Feedback means for feeding back the fluctuation of the working voltage to the control circuit,
The control circuit is an electrochemical measurement device that maintains the voltage difference between the reference voltage and the working voltage constant by controlling the counter voltage based on a variation amount of the working voltage obtained by the feedback means. The control circuit includes:
A differential amplifier having an inverting input terminal, a non-inverting input terminal, and an output terminal, and outputting the counter voltage from the output terminal;
A buffer circuit for transmitting the reference voltage;
A first resistor connected between the output of the buffer circuit and the inverting input terminal of the differential amplifier;
A second resistor connected between an external input terminal to which the drive voltage is applied and the inverting input terminal of the differential amplifier;
The electrochemical measurement device according to claim 1, wherein the working voltage is input to the non-inverting input terminal of the differential amplifier. The control circuit includes:
A differential amplifier having an inverting input terminal, a non-inverting input terminal, and an output terminal, a constant voltage is applied to the non-inverting input terminal, and the counter voltage is output from the output terminal;
A buffer circuit for transmitting the reference voltage;
A first resistor connected between the output of the buffer circuit and the inverting input terminal of the differential amplifier;
A second resistor connected between an external input terminal to which the drive voltage is applied and the inverting input terminal of the differential amplifier;
The electrochemical measurement device according to claim 1, wherein a voltage value of the drive voltage is controlled according to a change in the measurement voltage. A reset switch provided in parallel with the capacitor;
The electrochemical measurement device according to any one of claims 1 to 3, wherein the reset switch is formed on a semiconductor substrate and the conduction state is switched by a mechanical operation.   The electrochemical measurement device according to claim 4, wherein the reset switch is formed of a bimetal material, and a contact state is switched by a thermal reaction.   The electrochemical measurement device according to claim 4, wherein the reset switch has a contact conducting state switched by an attractive force and a repulsive force due to an electrostatic field.   The electrochemical measurement apparatus according to any one of claims 1 to 6, wherein the electrochemical measurement apparatus is formed on a single semiconductor substrate.

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