JP4528516B2 - Detection device - Google Patents

Description

  The present invention relates to a detection apparatus, and in particular, is used as an electrochemical reaction detection element that detects a chemical substance or the like by measuring a current generated according to an object to be detected by an electrochemical reaction.

  In recent years, there has been reported development of a chemical substance detection apparatus that can easily and quickly detect a chemical substance contained in a trace amount in a solution to be measured (see, for example, Patent Document 1). An electrochemical reaction detection element in which this chemical substance detection device is realized by a semiconductor device has also been proposed. For example, the use of this electrochemical reaction detecting element as a DNA sensor (biosensor) in which a difference in current generated by an electrochemical reaction is utilized for detection of DNA (Deoxyribo Nucleic Acid) has been studied.

  FIG. 6 shows a configuration example of a conventional electrochemical reaction detecting element. For example, as shown in FIG. 6, the electrochemical reaction detection element is configured by a reaction electrode unit 10, a control amplification unit 20, and a current measurement unit 30 provided on the semiconductor substrate 1. The reaction electrode unit 10 includes a counter electrode (CE1) 11, a reference electrode (RE1) 12, and a working electrode (WE1) 13. The control amplification unit 20 includes operational amplifiers (OA1) 21, (OA2) 22 and resistors (R_ce1) 23, (R_re1) 24, and the counter electrode 11 and the control electrode 20 according to the input voltage (OAIN1) applied to the terminal 2. The reference electrode 12 is controlled so as to always have the same potential. The current measuring unit 30 has an operational amplifier (OA3) 31 and a resistor (R_we1) 32, converts the current flowing through the working electrode 13 into an output voltage (OUT1), and outputs it from the terminal 3.

  In the electrochemical reaction detection element having such a configuration, for example, a solution or a substance containing a detection target to be detected is placed on the reaction electrode unit 10. In this state, when the input voltage (OAIN1) applied to the terminal 2 is changed, an electrochemical reaction occurs at the reaction electrode unit 10. As a result, a current corresponding to the object to be detected flows through the working electrode 13. The relationship between the current flowing through the working electrode 13 and the input voltage (OAIN1) depends on the type of the object to be detected and its concentration.

The current flowing through the working electrode 13 is output from the terminal 3 after being subjected to current-voltage conversion by the resistor 32 in the current measuring unit 30. That is, an output voltage (OUT 1) that is current-voltage converted according to the amount of current flowing through the working electrode 13 by the resistor 32 is output from the terminal 3. Thus, in this electrochemical reaction detection element, by detecting the current flowing through the working electrode 13, detection of the detection object, that is, acquisition of information for specifying or determining the detection object is performed.
JP 2001-99800 A

  In the electrochemical reaction detecting element having the above-described configuration, the value of the resistor 32 of the current measuring unit 30 may be increased in order to measure a minute current. However, when the value of the resistor 32 is increased, noise is easily applied to the output voltage (OUT1), and there is a problem in that the measurement accuracy is deteriorated.

  As described above, conventionally, when the resistance value is increased in order to measure a minute current, there is a problem that the measurement accuracy is deteriorated.

  The present invention has been made in order to solve the above-mentioned problems, and the object of the present invention is to improve the accuracy of measurement of the current generated according to the detected object by the electrochemical reaction, and to detect the detected object. An object of the present invention is to provide a detection device capable of detecting a high sensitivity.

According to one aspect of the present invention, there is provided a detection device that is provided on a semiconductor substrate and detects a detection target contained in a substance by measuring a current generated according to the detection target by an electrochemical reaction. An electrochemical reaction unit for causing an electrochemical reaction in the object to be detected; a mirror circuit unit for mirroring a current generated according to the object to be detected by an electrochemical reaction in the electrochemical reaction unit; A conversion unit that converts the current mirrored in the mirror circuit unit into a charge voltage, and the mirror circuit unit is connected to the positive power supply voltage, the gate is commonly connected, and provided on the non-mirror side and the mirror side, respectively. The p-channel first MOS transistor is connected to the negative power supply voltage, the gate is commonly connected, and the n-channel second MOS transistor provided on the non-mirror side and the mirror side, respectively. With the door, said conversion section to a connection point of said first 1MOS transistor and the 2MOS transistor mirror side is connected is connected, the current generated in response to the detected object by the electrochemical reaction, the conversion unit detection apparatus designed to measure the charge-to-voltage conversion in is provided.

  According to the present invention, it is possible to measure even a minute current with high accuracy without using a high resistance, and as a result, the accuracy of measurement of current generated according to an object to be detected by an electrochemical reaction is improved. And a detection device capable of detecting an object to be detected with high sensitivity.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

[First Embodiment]
FIG. 1 shows a basic configuration of an electrochemical reaction detection element according to the first embodiment of the present invention. This electrochemical reaction detecting element can measure a current generated according to an object to be detected by an electrochemical reaction by charge-voltage conversion without using a resistor.

  That is, a reaction electrode portion 10 that is an electrochemical reaction portion is formed on the semiconductor substrate 1. The reaction electrode unit 10 is provided with a counter electrode (CE1) 11, a reference electrode (RE1) 12, and a working electrode (WE1) 13. Each of these electrodes 11, 12, and 13 is formed by sputtering using a metal, for example, gold (Au) having a good S (signal) / N (noise) ratio.

  A control amplification unit 20 is connected to the counter electrode 11 and the reference electrode 12. The control amplifier 20 is provided on the semiconductor substrate 1 and includes operational amplifiers (OA1) 21 and (OA2) 22 and resistors (R_ce1) 23 and (R_re1) 24. In other words, the output terminal of the operational amplifier 21 is connected to the counter electrode 11. A common input (COM) is connected to the non-inverting input terminal (+) of the operational amplifier 21. The inverting input terminal (−) of the operational amplifier 21 is connected to one end of each of the resistors 23 and 24. The other end of the resistor 23 is connected to a terminal 2 to which an input voltage (OAIN1) is applied. On the other hand, the other end of the resistor 24 is connected to the output terminal and the inverting input terminal (−) of the operational amplifier 22. The reference electrode 12 is connected to the non-inverting input terminal (+) of the operational amplifier 22.

  An operational amplifier (OA3) 31 and a current mirror circuit (mirror circuit unit) 40 are connected to the working electrode 13. The operational amplifier 31 is provided on the semiconductor substrate 1 and the working electrode 13 is connected to the inverting input terminal (−) thereof. A common input is connected to the non-inverting input terminal (+) of the operational amplifier 31. The current mirror circuit 40 is connected to the output terminal of the operational amplifier 31.

  The current mirror circuit 40 is provided on the semiconductor substrate 1, and P channel MOS (PMOS) transistors TRC1, TRC2, TRC4, TRC7, TRC8 and N channel MOS (NMOS) transistors TRC3, TRC5, TRC6, TRC9, TRC10. have. Among the transistors TRC1 to TRC10, the PMOS transistors TRC1, TRC2, and TRC4 and the NMOS transistors TRC3, TRC5, and TRC6 are connected in series between the positive power supply voltage VDD and the negative power supply voltage VSS (non-current). Mirror side). The PMOS transistors TRC7 and TRC8 and the NMOS transistors TRC9 and TRC10 are connected in series between the positive power supply voltage VDD and the negative power supply voltage VSS (mirror side).

  The PMOS transistors TRC1 and TRC7 are mirror-connected, that is, the gates are connected in common, and the common gate is connected to the connection point of the PMOS transistors TRC1 and TRC2. Similarly, the PMOS transistors TRC2 and TRC8 are mirror-connected, that is, the gates are connected in common, and the common gate is connected to the connection point between the PMOS transistor TRC2 and the NMOS transistor TRC3. The NMOS transistors TRC5 and TRC9 are mirror-connected, that is, the gates are connected in common, and the common gate is connected to the connection point between the PMOS transistor TRC4 and the NMOS transistor TRC5. Similarly, the NMOS transistors TRC6 and TRC10 are mirror-connected, that is, the gates are connected in common, and the common gate is connected to the connection point of the NMOS transistors TRC5 and TRC6.

  Further, the output terminal of the operational amplifier 31 is connected to the gates of the NMOS transistor TRC3 and the PMOS transistor TRC4. The working electrode 13 is connected to a connection point between the NMOS transistor TRC3 and the PMOS transistor TRC4.

  A charge-voltage converter 50 is connected to a connection point between the PMOS transistor TRC8 and the NMOS transistor TRC9 via a sampling (control) transistor TRS1 composed of an N-channel MOS (NMOS) transistor. The sampling transistor TRS1 is provided on the semiconductor substrate 1, and a sampling pulse (SP) is supplied to its gate.

  The charge-voltage conversion unit 50 is provided on the semiconductor substrate 1, and includes a capacitor C1, a reset transistor TR1 including an N-channel MOS (NMOS) transistor, and an N-channel MOS (NMOS) transistor constituting a source follower circuit. TR2 and TR3. That is, the capacitor C1 is for holding electric charge, and the negative power supply voltage VSS is supplied to one electrode thereof. The other electrode of the capacitor C1 is connected to the sampling transistor TRS1, one diffusion layer forming the source / drain of the reset transistor TR1, and the gate of the NMOS transistor TR2.

  The reset transistor TR1 is for resetting the charge held in the capacitor C1. A reset control pulse (RST_C) is supplied to the gate of the reset transistor TR1, and a reset voltage (VRS) is supplied to the other diffusion layer.

  The NMOS transistors TR2 and TR3 are connected in series between the positive power supply voltage VDD and the negative power supply voltage VSS. The gate of the NMOS transistor TR3 is also connected to the negative power supply voltage VSS. The connection point between the NMOS transistors TR2 and TR3 is connected to a terminal 3 from which an output voltage (OUT1) is taken.

  The positive power supply voltage VDD and the negative power supply voltage VSS are also supplied to the operational amplifiers 21, 22, and 31, respectively.

  Next, a method for detecting an object to be detected by the electrochemical reaction detecting element having the above configuration will be described. That is, in the electrochemical reaction detection element having the above-described configuration, for example, a solution or a substance containing a detection target to be detected is placed on the reaction electrode unit 10. In this state, the input voltage (OAIN1) applied to the terminal 2 is changed. Then, the potential of the counter electrode 11 is controlled by the control amplifier 20 according to the input voltage (OAIN1) and the feedback potential of the reference electrode 12. As a result, an electrochemical reaction takes place at the reaction electrode section 10, and a current (charge) corresponding to the input voltage (OAIN1) and the type and concentration of the detected object is generated.

  A current (charge) generated according to the object to be detected by the electrochemical reaction flows through the working electrode 13. The current (charge) is supplied to the current mirror circuit 40 connected to the working electrode 13 and copied to the mirror side. At that time, the potential on the non-mirror side of the current mirror circuit 40 is kept constant by the output of the operational amplifier 31.

  For example, when the current (charge) flowing through the working electrode 13 is smaller than the common input, the current (charge) copied by the current mirror circuit 40 flows to the sampling transistor TRS1. At this time, if the gate of the sampling transistor TRS1 is open, the current (charge) is held by the capacitor C1 of the charge-voltage converter 50. The charge held by the capacitor C1 is converted into a charge voltage by the source follower circuits (NMOS transistors) TR2 and TR3.

  In the case of this embodiment, the current (charge) flowing through the working electrode 13 is measured by charge-voltage conversion. For this reason, even if the current (charge) flowing through the working electrode 13 is a minute value, it can be measured with high accuracy, and the measurement accuracy can be remarkably improved as compared with the case where high resistance is used.

  Thus, the current (charge) flowing through the working electrode 13 becomes the output voltage (OUT1) and is output from the terminal 3. This output voltage (OUT1) is subjected to processing such as identification and determination of the detected object as information for detecting the detected object. By opening the gate of the reset transistor TR1, the charge held by the capacitor C1 becomes the same potential as the reset voltage VRS, that is, is reset.

  As described above, the current generated according to the object to be detected by the electrochemical reaction can be measured without using the resistance. That is, in the electrochemical reaction detection element, the current flowing through the working electrode is measured by charge detection (charge-voltage conversion). As a result, a minute current can be measured with high accuracy without using a high resistance. Therefore, it is possible to detect the detection object with high sensitivity without being affected by noise.

  In particular, in the electrochemical reaction detection element having the above-described configuration, it is possible to measure a smaller current by changing the capacitance value of the capacitor (C1) in the charge-voltage conversion unit 50 according to the amount of current to be measured. is there.

  In the present embodiment, the current mirror circuit 40 may be constituted by only the PMOS transistors TRC1, TRC2, TRC7, TRC8 and the NMOS transistor TRC3. That is, when the output of the operational amplifier 31 is fixed to the positive side (+), the PMOS transistor TRC4 and the NMOS transistors TRC5, TRC6, TRC9, and TRC10 in the current mirror circuit 40 can be omitted.

  Further, in the electrochemical reaction detecting element having the above-described configuration, it is possible to measure a smaller current by changing the amplification degree of the current (charge) to be mirrored in the current mirror circuit 40.

[Second Embodiment]
2 and 3 show examples of the configuration of the current mirror circuit according to the second embodiment of the present invention. That is, in the case of the current mirror circuit 40a shown in FIG. 2, for example, at least the PMOS transistor TRC7 is composed of a plurality of PMOS transistors TRC7a, TRC7b,..., TRC7n connected in parallel. In this example, at least the NMOS transistor TRC10 includes a plurality of NMOS transistors TRC10a, TRC10b,..., TRC10n connected in parallel.

  According to the current mirror circuit 40a having this configuration, the current (charge) flowing through the working electrode 13 depends on the number of the PMOS transistors TRC7a, TRC7b,..., TRC7n, or the NMOS transistors TRC10a, TRC10b,. Depending on the number of TRCs 10n, they are amplified and copied to the mirror side. Thereby, it is possible to measure a smaller current.

  In the case of the current mirror circuit 40b shown in FIG. 3, for example, the PMOS transistor TRC7 is composed of a plurality of PMOS transistors TRC7a, TRC7b,..., TRC7n connected in parallel, and the PMOS transistor TRC8 is connected in parallel. Are constituted by a plurality of PMOS transistors TRC8a, TRC8b,..., TRC8n. In this example, the NMOS transistor TRC10 includes a plurality of NMOS transistors TRC10a, TRC10b,..., TRC10n connected in parallel, and the NMOS transistor TRC9 includes a plurality of NMOS transistors connected in parallel. TRC9a, TRC9b,..., TRC9n.

  According to the current mirror circuit 40b having this configuration, the current (charge) flowing through the working electrode 13 depends on the number of the PMOS transistors TRC7a, TRC7b,..., TRC7n and the number of the PMOS transistors TRC8a, TRC8b,. Alternatively, each of the NMOS transistors TRC9a, TRC9b,..., TRC9n and the NMOS transistors TRC10a, TRC10b,. Thereby, it is possible to measure a smaller current.

[Third Embodiment]
FIGS. 4 and 5 show configuration examples of the current mirror circuit according to the third embodiment of the present invention. That is, in the case of the current mirror circuit 40c shown in FIG. 4, for example, at least the PMOS transistor TRC7 is composed of a plurality of PMOS transistors TRC7a, TRC7b,..., TRC7n connected in series. In this example, at least the NMOS transistor TRC10 includes a plurality of NMOS transistors TRC10a, TRC10b,..., TRC10n connected in series.

  According to the current mirror circuit 40c having this configuration, the current (charge) flowing through the working electrode 13 depends on the number of the PMOS transistors TRC7a, TRC7b,..., TRC7n, or the NMOS transistors TRC10a, TRC10b,. Depending on the number of TRCs 10n, each is amplified (one times the number) and copied to the mirror side. As described above, the current mirror circuit can be configured so that the amplification degree of the current (charge) to be mirrored becomes small as necessary.

  In the case of the current mirror circuit 40d shown in FIG. 5, for example, the PMOS transistor TRC7 is composed of a plurality of PMOS transistors TRC7a, TRC7b,..., TRC7n connected in series, and the PMOS transistor TRC8 is connected in series. Are constituted by a plurality of PMOS transistors TRC8a, TRC8b,..., TRC8n. In this example, the NMOS transistor TRC9 includes a plurality of NMOS transistors TRC9a, TRC9b,..., TRC9n connected in series, and the NMOS transistor TRC10 includes a plurality of NMOS transistors connected in series. It is comprised by TRC10a, TRC10b, ..., TRC10n.

  In the case of the current mirror circuit 40d, the current (charge) flowing through the working electrode 13 depends on the number of the PMOS transistors TRC7a, TRC7b,..., TRC7n and the PMOS transistors TRC8a, TRC8b,. Depending on the number of NMOS transistors TRC9a, TRC9b,..., TRC9n and the NMOS transistors TRC10a, TRC10b,..., TRC10n, they are respectively amplified (one times the number) and copied to the mirror side. As described above, the current mirror circuit can be configured to further reduce the amplification degree of the current (charge) to be mirrored, if necessary.

  In the second and third embodiments, the gate width (W) and the gate length (L) of the PMOS transistors TRC7 and TRC8 and the NMOS transistors TRC9 and TRC10 are the same in any case. ) Ratio (W / L) is preferably not changed. That is, the PMOS transistor TRC7 is constituted by using a plurality of transistors TRC7a, TRC7b,..., TRC7n having the same gate width and gate length. Similarly, the PMOS transistor TRC8 is configured by using a plurality of transistors TRC8a, TRC8b,..., TRC8n having the same gate width and gate length. Similarly, the NMOS transistor TRC9 is configured by using a plurality of transistors TRC9a, TRC9b,..., TRC9n having the same gate width and gate length. Similarly, the NMOS transistor TRC10 is configured by using a plurality of transistors TRC10a, TRC10b,..., TRC10n having the same gate width and gate length. By doing so, it is possible to reduce variations in the degree of amplification and to suppress a reduction in measurement accuracy.

  In addition, the present invention is not limited to the above (each) embodiment, and various modifications can be made without departing from the scope of the invention in the implementation stage. Further, the above (each) embodiment includes various stages of the invention, and various inventions can be extracted by appropriately combining a plurality of disclosed constituent elements. For example, even if several constituent requirements are deleted from all the constituent requirements shown in the (each) embodiment, the problem (at least one) described in the column of the problem to be solved by the invention can be solved. When the effect (at least one of the effects) described in the “Effect” column is obtained, a configuration from which the constituent requirements are deleted can be extracted as an invention.

1 is a circuit diagram showing a basic configuration of an electrochemical reaction detection element according to a first embodiment of the present invention. The circuit diagram which shows the structural example of the current mirror circuit according to the 2nd Embodiment of this invention. The circuit diagram which shows the other structural example of the current mirror circuit according to the 2nd Embodiment of this invention. The circuit diagram which shows the structural example of the current mirror circuit according to the 3rd Embodiment of this invention. The circuit diagram which shows the other structural example of the current mirror circuit according to the 3rd Embodiment of this invention. The circuit diagram of the electrochemical reaction detection element shown in order to demonstrate a prior art and its problem.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Semiconductor substrate, 2 ... Terminal (input side), 3 ... Terminal (output side), 10 ... Reaction electrode part, 11 ... Counter electrode (CE1), 12 ... Reference electrode (RE1), 13 ... Working electrode (WE1) , 20 ... control amplification unit, 21, 22, 31 ... operational amplifier, 23, 24 ... resistor, 40, 40a, 40b, 40c, 40d ... current mirror circuit, 50 ... charge voltage conversion unit, COM ... common input, OAIN1 ... input Voltage, OUT1... Output voltage, TRC1, TRC2, TRC4, TRC7, TRC7a, TRC7b,..., TRC7n, TRC8, TRC8a, TRC8b,..., TRC8n. TRC9n, TRC10, TRC10a, TRC10b, ..., TRC10n ... NMOS transistor VDD, positive power supply voltage, VSS, negative power supply voltage, TRS1, sampling transistor, SP, sampling pulse, TR2, TR3, NMOS transistor (source follower circuit), C1, capacitor, TR1, reset transistor, RST_C ... reset control pulse, VRS ... reset voltage, W ... gate width, L ... gate length.

Claims (6)

A detection device that is provided on a semiconductor substrate and detects a detection object contained in a substance by measuring a current generated according to the detection object by an electrochemical reaction,
An electrochemical reaction section for causing an electrochemical reaction to the object to be detected;
A mirror circuit unit that mirrors a current generated according to the object to be detected by an electrochemical reaction in the electrochemical reaction unit;
A conversion unit that converts a current mirrored by the mirror circuit unit into a charge voltage, and
The mirror circuit section is connected to the positive power supply voltage, the gate is commonly connected, and a p-channel first MOS transistor provided on each of the non-mirror side and the mirror side,
An n-channel second MOS transistor connected to the negative power supply voltage, having a common gate, and provided on the non-mirror side and the mirror side, respectively
The conversion unit is connected to a connection point where the first MOS transistor and the second MOS transistor on the mirror side are connected,
A detection apparatus characterized in that a current generated according to the object to be detected by the electrochemical reaction is measured by charge-voltage conversion in the conversion unit. Each of the first MOS transistors on the non-mirror side and the mirror side includes p-channel third and fourth MOS transistors connected in series,
The third of the mirror side, at least one of the first 4MOS transistor, Ri Na by connecting a plurality of p-channel transistors in parallel,
Each of the second MOS transistors on the non-mirror side and the mirror side includes n-channel fifth and sixth MOS transistors connected in series,
The fifth of the mirror side, at least one of the first 6MOS transistor, detecting device according to claim 1, characterized in Rukoto such by connecting a plurality of n-channel transistors in parallel. Each of the first MOS transistors on the non-mirror side and the mirror side includes p-channel third and fourth MOS transistors connected in series,
The mirror side of the third, each of the 4MOS transistor, Ri Na by connecting a plurality of p-channel MOS transistors in parallel,
Each of the second MOS transistors on the non-mirror side and the mirror side includes n-channel fifth and sixth MOS transistors connected in series,
The fifth of the mirror side, each of the 6MOS transistor, the detection apparatus according to claim 1, characterized in Rukoto such by connecting a plurality of n-channel transistors in parallel. Each of the first MOS transistors on the non-mirror side and the mirror side includes p-channel third and fourth MOS transistors connected in series,
The mirror side of the third, at least one of the first 4MOS transistor, Ri Na by connecting a plurality of p-channel MOS transistor in series,
Each of the second MOS transistors on the non-mirror side and the mirror side includes n-channel fifth and sixth MOS transistors connected in series,
The fifth of the mirror side, at least one of the first 6MOS transistor, detecting device according to claim 1, characterized in Rukoto such by connecting a plurality of n-channel transistor in series. Each of the first MOS transistors on the non-mirror side and the mirror side includes p-channel third and fourth MOS transistors connected in series,
The mirror side of the third, each of the 4MOS transistor, Ri Na by connecting a plurality of p-channel transistor in series,
Each of the second MOS transistors on the non-mirror side and the mirror side includes n-channel fifth and sixth MOS transistors connected in series,
The fifth of the mirror side, each of the 6MOS transistor, the detection apparatus according to claim 1, characterized in Rukoto such by connecting a plurality of n-channel transistor in series.   2. The conversion unit according to claim 1, further comprising a capacitor that holds a charge corresponding to the current mirrored by the mirror circuit unit, and a source follower circuit that converts the charge held by the capacitor into a voltage. The detection device according to 1.

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