JP4413060B2 - Chemical sensor and method for measuring concentration of chemical substance using the same - Google Patents

Chemical sensor and method for measuring concentration of chemical substance using the same Download PDF

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JP4413060B2
JP4413060B2 JP2004113701A JP2004113701A JP4413060B2 JP 4413060 B2 JP4413060 B2 JP 4413060B2 JP 2004113701 A JP2004113701 A JP 2004113701A JP 2004113701 A JP2004113701 A JP 2004113701A JP 4413060 B2 JP4413060 B2 JP 4413060B2
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善孝 伊藤
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Shindengen Electric Manufacturing Co Ltd
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本発明は、主に人体の血液や体液から、例えば水素イオン濃度（以下「ｐＨ」という。）などの化学的物質の濃度を測定し、酵母や細菌などの微生物による感染の有無を判定するケミカルセンサ及びこれを用いた化学的濃度の測定方法に関するものである。 The present invention is a chemical that measures the concentration of a chemical substance such as hydrogen ion concentration (hereinafter referred to as “pH”) mainly from human blood or body fluid to determine the presence or absence of infection by microorganisms such as yeast and bacteria. The present invention relates to a sensor and a chemical concentration measurement method using the sensor.

従来、人体が酵母や細菌などの微生物（バクテリア）による感染を受けた場合、その感染の有無につき血液のｐＨ値の変化を調べることで行われていた。例えば、人体の血液のｐＨ値は通常ｐＨ7.35からｐＨ7.45であるが、バクテリア感染をしている場合にはｐＨ7.0以下になるので、ｐＨ計を用いてｐＨで検定する方法がある（例として非特許文献１参照）。
日本光電株式会社 技術情報 ウレアーゼ活性の測定 ［平成１６年３月２４日検索］ インターネット ＜ URL : http://www.nihonkohden.co.jp/techinfo/pylori/pyl_genri_ureaze.html＞ Conventionally, when a human body is infected by microorganisms (bacteria) such as yeast and bacteria, it has been carried out by examining changes in the pH value of blood for the presence or absence of the infection. For example, the pH value of human blood is usually pH 7.35 to pH 7.45, but it is pH 7.0 or lower when there is a bacterial infection, so there is a method to test with pH using a pH meter (See Non-Patent Document 1 as an example).
Nihon Kohden Co., Ltd. Technical Information Measurement of urease activity [Search on March 24, 2004] Internet <URL: http://www.nihonkohden.co.jp/techinfo/pylori/pyl_genri_ureaze.html>

この測定方法の一例に次のようなものがある。先ず、抗原抗体反応させた固相チップを測定部にセットすると、先ず尿素の入った基質溶液が流れてピロリ菌ウレアーゼと酵素反応する。尿素とピロリ菌ウレアーゼが反応することにより、アンモニアと炭酸ガスが生成する。次に基質溶液が逆流して、ｐＨセンサによって、ｐＨの変化が測定される。ピロリ菌ウレアーゼの量が多いほど、上記の反応によるアンモニアの生成量が増大し、それに伴って固相チップ内部の基質溶液のｐＨはアルカリ側に上昇する。実際は、逆流前後の基質溶液のｐＨを測定して、その差をΔｐＨとして表示する。   An example of this measuring method is as follows. First, when a solid-phase chip subjected to antigen-antibody reaction is set in the measurement part, first, a substrate solution containing urea flows and reacts with H. pylori urease. Reaction of urea and H. pylori urease produces ammonia and carbon dioxide. The substrate solution then flows back and the pH change is measured by the pH sensor. As the amount of H. pylori urease increases, the amount of ammonia produced by the above reaction increases, and the pH of the substrate solution in the solid-phase chip rises to the alkali side accordingly. Actually, the pH of the substrate solution before and after the backflow is measured, and the difference is displayed as ΔpH.

また、ｐＨ計のセンサ部を血液サンプルに浸漬するか、センサ部に直接滴下して、そのｐＨ値を読みとる測定方法もある。   In addition, there is a measurement method in which the pH value is read by immersing the sensor unit of the pH meter in a blood sample or by dropping it directly on the sensor unit.

前者のピロリ菌の例では、抗原抗体反応の前処理とフロースルーシステムが必要で、手間と装置が大きく複雑なものとなっている。後者の血液サンプルを直接扱う方法では、ｐＨ値の絶対値を測定しているので、ｐＨセンサ部の洗浄や標準液でのゼロ点構成などの操作が煩雑になるという課題が生じた。   In the former example of H. pylori, pretreatment of the antigen-antibody reaction and a flow-through system are necessary, and the labor and apparatus are large and complicated. In the latter method of directly handling a blood sample, since the absolute value of the pH value is measured, there arises a problem that operations such as washing of the pH sensor unit and a zero point configuration with a standard solution become complicated.

本発明は、上記問題に鑑みてなされたものであり、繰り返し測定におけるセンサの洗浄を容易にすることにより、複数のサンプルの化学的物質の濃度をより正確に測定することを可能にしたケミカルセンサ及びこれを用いた化学的物質の濃度の測定方法を提供する。 The present invention has been made in view of the above problems, and makes it possible to more accurately measure the concentration of chemical substances in a plurality of samples by facilitating cleaning of the sensor in repeated measurement. And a method for measuring the concentration of a chemical substance using the same.

上記課題を解決するために、本発明に係るケミカルセンサは、二つのセンサと参照電極を用いた回路構成において、前記センサ並びに参照電極を設けたセンサ部を覆うように交換可能な電解質膜を載せ、さらに、前記電解質膜上に片方の前記センサを覆うようにサンプル阻止膜を載せてあり、それらの上から測定サンプルを前記電解質膜に浸透若しくは透過させた際に、前記二つのセンサに測定サンプルが浸透若しくは透過する時間差から生じる検出値の差分を測定し、その差分の最大値又は前記センサから出力される信号の立ち上がり傾斜を用いて前記測定サンプルの化学的物質の濃度を測定するように構成してあることを特徴とする。 In order to solve the above-described problems, a chemical sensor according to the present invention has a replaceable electrolyte membrane so as to cover a sensor portion provided with the sensor and the reference electrode in a circuit configuration using two sensors and a reference electrode. Further, a sample blocking film is placed on the electrolyte membrane so as to cover one of the sensors, and when the measurement sample permeates or permeates the electrolyte membrane from above, the measurement sample is passed to the two sensors. Measures the difference in the detection value resulting from the time difference that permeates or permeates, and measures the concentration of the chemical substance in the measurement sample using the maximum value of the difference or the rising slope of the signal output from the sensor It is characterized by being.

前記センサ並びに参照電極を同一基板に配置してあることを特徴とする。
また、前記電解質膜をゲル状の物質で構成してあることを特徴とする。
さらに、前記電解質膜を多孔性の物質で構成してあることを特徴とする。 The sensor and the reference electrode are arranged on the same substrate.
Further, the electrolyte membrane is made of a gel substance.
Further, the electrolyte membrane is made of a porous material.

前記二つのセンサでｐＨを検出するようにしてあることを特徴とする。   The pH is detected by the two sensors.

前記二つのセンサをＩＳＦＥＴで構成してあることを特徴とする。
また、前記二つのＩＳＦＥＴのドレイン電極を共通にし、電源電圧を一定に印加するように構成してあることを特徴とする。
さらに、前記二つのＩＳＦＥＴのソース端子に同一の定電流源を設けてあり、二つのＩＳＦＥＴのソース電流を一定とする回路構成にし、ソースフォロア回路による差動ＦＥＴ動作になるように構成してあることを特徴とする。 The two sensors are composed of ISFETs .
Further, the drain electrodes of the two ISFETs are made common and the power supply voltage is applied to be constant.
Further, the same constant current source is provided at the source terminals of the two ISFETs, the circuit configuration is such that the source currents of the two ISFETs are constant, and the differential FET operation is performed by the source follower circuit. It is characterized by that.

また、本発明に係る前記ケミカルセンサを用いた化学的物質の濃度の測定方法は、前記センサ並びに参照電極を設けたセンサ部を覆うように電解質膜を載せ、さらに、片方の前記センサを覆うように前記電解質膜上にサンプル阻止膜を載せ、その上から測定サンプルを前記電解質膜に浸透若しくは透過させて、前記二つのセンサに測定サンプルが浸透若しくは透過する時間差から生じる検出値の差分を測定し、その差分の最大値又は前記センサから出力される信号の立ち上がり傾斜を用いて前記測定サンプルの化学的物質の濃度を測定することを特徴とする。 Further, in the method for measuring the concentration of a chemical substance using the chemical sensor according to the present invention, an electrolyte membrane is placed so as to cover the sensor and a sensor portion provided with a reference electrode, and further, one of the sensors is covered. A sample blocking film is placed on the electrolyte membrane, and a measurement sample is allowed to permeate or permeate the electrolyte membrane from above, and a difference between detection values resulting from a time difference between the measurement sample permeating or permeating the two sensors is measured. , and measuring the concentration of a chemical substance in the measurement sample using a rising slope of the signal output from the maximum value or the sensor of the difference.

本発明によれば、ワンチップ上に、二つのセンサと参照電極を配置し、その上部にセンサ並びに参照電極を覆うように交換可能な電解質膜(シート)を載せ、さらにその膜上にサンプルを浸透若しくは透過させて、二つのセンサ信号の時間差から生じる検出値の差分を測定するようにしたことにより、サンプルのバクテリア感染の有無を判定することができるとともに、異なったサンプルを測定する場合、電解質膜を交換することにより、センサ部の洗浄が容易であるとともに、標準液でのゼロ点校正などの操作も不要になり、作業性が向上するという効果がある。   According to the present invention, two sensors and a reference electrode are arranged on a single chip, an exchangeable electrolyte membrane (sheet) is placed on the upper portion so as to cover the sensor and the reference electrode, and a sample is further placed on the membrane. By detecting the difference between the detected values resulting from the time difference between the two sensor signals by permeation or permeation, it is possible to determine the presence or absence of bacterial infection in the sample, and when measuring different samples, By exchanging the membrane, it is easy to clean the sensor part, and there is no need for an operation such as zero point calibration with a standard solution, thereby improving workability.

発明を実施するための最良の形態の説明図を図１及び図２に示す。このケミカルセンサは、図１に示すように、一つの基板１１の一部に参照電極１を設置し、その近傍に二つのセンサ１２，１３を設置して、センサ部１０を構成してある。センサ１２，１３及び参照電極１は測定回路に接続し、ｐＨを検出して、測定回路に検出結果を送信するものである。   An explanatory diagram of the best mode for carrying out the invention is shown in FIGS. In this chemical sensor, as shown in FIG. 1, a reference electrode 1 is installed on a part of one substrate 11 and two sensors 12 and 13 are installed in the vicinity thereof to constitute a sensor unit 10. The sensors 12 and 13 and the reference electrode 1 are connected to a measurement circuit, detect pH, and transmit a detection result to the measurement circuit.

図１に示すように、ケミカルセンサは交換可能な電解質膜２１を設けてある。なお、本実施例の電解質膜２１はゲル状の物質で構成してあるが、多孔性の物質でもよい。この電解質膜２１のほぼ半分の面上にサンプル阻止膜２２を載せてあり、図２に示すように、サンプル阻止膜２２を載せた電解質膜２１がセンサ部１０を覆うように載せ、サンプル阻止膜２２が他方のセンサ１３を覆うように載せてある。   As shown in FIG. 1, the chemical sensor is provided with a replaceable electrolyte membrane 21. In addition, although the electrolyte membrane 21 of a present Example is comprised with the gel-like substance, a porous substance may be sufficient. A sample blocking film 22 is placed on almost half of the surface of the electrolyte membrane 21. As shown in FIG. 2, the electrolyte blocking film 21 on which the sample blocking film 22 is placed is placed so as to cover the sensor unit 10, and the sample blocking film is placed. 22 is placed so as to cover the other sensor 13.

以上のように構成してあるケミカルセンサによるｐＨ測定方法について図２及び図３を用いて説明する。先ず、参照電極１及びセンサ部１０を洗浄した状態で、サンプル阻止膜２２を載置した電解質膜２１をセンサ部１０に載せる。この際、センサ部１０を覆うように電解質膜２１を載せ、さらに、他方のセンサ１３を覆う電解質膜２１上にサンプル阻止膜２２を載せる。その上から測定サンプル溶液３０を滴下して、二つのセンサ１２，１３のｐＨ値の差で測定サンプル溶液３０のｐＨ変化を測定する。センサ１２，１３で測定したｐＨ値は信号として測定部に出力される。   The pH measurement method using the chemical sensor configured as described above will be described with reference to FIGS. First, in a state where the reference electrode 1 and the sensor unit 10 are washed, the electrolyte membrane 21 on which the sample blocking film 22 is placed is placed on the sensor unit 10. At this time, the electrolyte membrane 21 is placed so as to cover the sensor unit 10, and the sample blocking film 22 is placed on the electrolyte membrane 21 covering the other sensor 13. The measurement sample solution 30 is dropped from above, and the pH change of the measurement sample solution 30 is measured by the difference in pH value between the two sensors 12 and 13. The pH value measured by the sensors 12 and 13 is output as a signal to the measurement unit.

測定サンプル溶液３０は電解質膜２１の上面にサンプル阻止膜２２を載せていない部分から先に浸透する。そのため、先ず一方のセンサ１２でｐＨ変化が起こる。このｐＨ変化が起こっている間、変化するｐＨ値を信号に変換して測定部に出力する。しばらくすると、サンプル阻止膜２２により、測定サンプル溶液３０が電解質膜２１に横方向に拡散し浸透すると、他方のセンサ１２でもｐＨ変化が起こり、双方のセンサ１２，１３でｐＨ値が同一になる。従って、双方のセンサ信号の差分はゼロになる。センサ１２，１３による測定サンプル溶液３０のｐＨ値判定は、双方の信号の差分を測定することにより求めるために、その差分の最大値を測定する。差分が最大に達した値を用いて測定サンプル溶液３０のｐＨ値を判定する。なお、差分の最大値の代わりに信号の立ち上がり傾斜から測定サンプル溶液３０のｐＨ値を判定することも可能である。   The measurement sample solution 30 permeates first from the portion where the sample blocking film 22 is not placed on the upper surface of the electrolyte membrane 21. Therefore, first, the pH change occurs in one of the sensors 12. While this pH change occurs, the changing pH value is converted into a signal and output to the measurement unit. After a while, when the measurement sample solution 30 is laterally diffused and penetrated into the electrolyte membrane 21 by the sample blocking membrane 22, the pH change occurs in the other sensor 12, and the pH values of both the sensors 12 and 13 become the same. Therefore, the difference between the two sensor signals is zero. The determination of the pH value of the measurement sample solution 30 by the sensors 12 and 13 is performed by measuring the maximum value of the difference in order to obtain the difference by measuring the difference between both signals. The pH value of the measurement sample solution 30 is determined using the value at which the difference reaches the maximum. In addition, it is also possible to determine the pH value of the measurement sample solution 30 from the rising slope of the signal instead of the maximum difference value.

なお、この実施形態においては、ｐＨのみに限定せず、グルコース濃度その他の化学的変化量も測定することができる。例えば、グルコール濃度を測定して血糖値や尿糖値を判定する場合は、電解質膜２１に酵素を含めて酵素反応を利用して測定する手段を用いるとよい。   In this embodiment, not only the pH but also the chemical concentration such as glucose concentration can be measured. For example, when measuring the glucose concentration to determine the blood glucose level or the urine sugar level, it is preferable to use a means for measuring by using an enzyme reaction including an enzyme in the electrolyte membrane 21.

実施例１の説明図を図４及び図５に示す。このケミカルセンサは、図４に示すように、センサ部をＩＳＦＥＴ４０で構成してある。ＩＳＦＥＴ４０はシリコン基板４１の表面に絶縁膜４２を覆って構成してあり、その一部に金属で構成した参照電極１を設置してある。ＩＳＦＥＴ４０の表面には参照電極１で相対するようにゲート領域４３，４４を二つ設けてある。このゲート領域４３，４４で測定サンプルのｐＨを検出し、測定回路に検出結果を送信するものである。そのため、シリコン基板４１上に２つのゲート領域４３，４４を設け、これらゲート領域４３，４４間に絶縁膜４２を設けてある。一部の絶縁膜４２上に参照電極１を載せ、全ての絶縁膜４２の下面にはチャネルストッパ４５を設けてある。参照電極１を載せた絶縁膜４２に接するチャネルストッパ４５の周縁にドレイン領域４６を設けてあり、その他の絶縁膜４２に接するチャネルストッパ４５の周縁にはソース領域４７を設けてあり、ＩＳＦＥＴを２つ設ける構成にしてある。   An explanatory diagram of Example 1 is shown in FIGS. In this chemical sensor, as shown in FIG. The ISFET 40 is configured by covering the surface of a silicon substrate 41 with an insulating film 42, and a reference electrode 1 made of metal is provided on a part of the ISFET 40. Two gate regions 43 and 44 are provided on the surface of the ISFET 40 so as to face each other at the reference electrode 1. The gate regions 43 and 44 detect the pH of the measurement sample and transmit the detection result to the measurement circuit. Therefore, two gate regions 43 and 44 are provided on the silicon substrate 41, and an insulating film 42 is provided between the gate regions 43 and 44. The reference electrode 1 is placed on a part of the insulating film 42, and a channel stopper 45 is provided on the lower surface of all the insulating films 42. A drain region 46 is provided at the periphery of the channel stopper 45 in contact with the insulating film 42 on which the reference electrode 1 is placed, and a source region 47 is provided at the periphery of the channel stopper 45 in contact with the other insulating film 42, so that the ISFET is 2 One is provided.

図４に示すように、ケミカルセンサは交換可能な電解質膜２１を設けてある。なお、本実施例の電解質膜２１はゲル状の物質で構成してあるが、多孔性の物質でもよい。この電解質膜２１のほぼ半分の面上にサンプル阻止膜２２を載せてあり、図５に示すように、サンプル阻止膜２２を載せた電解質膜２１がＩＳＦＥＴ４０を覆うように載せ、サンプル阻止膜２２が他方のゲート領域４４を覆うように載せてある。   As shown in FIG. 4, the chemical sensor is provided with a replaceable electrolyte membrane 21. In addition, although the electrolyte membrane 21 of a present Example is comprised with the gel-like substance, a porous substance may be sufficient. A sample blocking film 22 is placed on almost half of the surface of the electrolyte membrane 21. As shown in FIG. 5, the electrolyte blocking film 21 on which the sample blocking film 22 is placed covers the ISFET 40. The other gate region 44 is covered.

以上のように構成してあるケミカルセンサは図６に示すような回路構成を有する。具体的には、２つのＩＳＦＥＴ５１，５２間に参照電極１を設け、ＩＳＦＥＴ５１，５２のドレイン電極を共通にし、電源電圧を一定に印加するように構成してある。また、２つのＩＳＦＥＴ５１，５２のソース端子に同一の定電流源５３，５４を設けてあり、２つのＩＳＦＥＴ５１，５２のソース電流を一定とする回路構成にし、ソースフォロア回路による差動ＦＥＴ動作になるように構成してある。   The chemical sensor configured as described above has a circuit configuration as shown in FIG. Specifically, the reference electrode 1 is provided between the two ISFETs 51 and 52, the drain electrodes of the ISFETs 51 and 52 are made common, and the power supply voltage is applied constantly. Further, the same constant current sources 53 and 54 are provided at the source terminals of the two ISFETs 51 and 52, the circuit configuration is such that the source currents of the two ISFETs 51 and 52 are constant, and the differential FET operation is performed by the source follower circuit. It is constituted as follows.

以上のように構成してあるケミカルセンサによるｐＨ測定方法について図５、図６並びに図７を用いて説明する。先ず、ＩＳＦＥＴ４０を洗浄した状態で、サンプル阻止膜２２を載置した電解質膜２１をＩＳＦＥＴ４０に載せる。この際、ＩＳＦＥＴ４０を覆うように電解質膜２１を載せ、さらに、電解質膜２１上に他方のゲート領域４５を覆うようにサンプル阻止膜２２を載せる。その上からｐＨ変化に時間差が生じるように、測定サンプル溶液３０を滴下して、二つのゲート領域４４，４５のｐＨ値の差で測定サンプル溶液３０のｐＨ変化を測定する。ゲート領域４４，４５で測定したｐＨ値は信号として測定部に出力される。   The pH measurement method using the chemical sensor configured as described above will be described with reference to FIGS. First, with the ISFET 40 being cleaned, the electrolyte membrane 21 on which the sample blocking film 22 is placed is placed on the ISFET 40. At this time, the electrolyte membrane 21 is placed so as to cover the ISFET 40, and the sample blocking film 22 is placed on the electrolyte membrane 21 so as to cover the other gate region 45. Then, the measurement sample solution 30 is dropped so that a time difference occurs in the pH change, and the pH change of the measurement sample solution 30 is measured by the difference in pH value between the two gate regions 44 and 45. The pH value measured in the gate regions 44 and 45 is output as a signal to the measurement unit.

測定サンプル溶液３０は電解質膜２１の上面にサンプル阻止膜２２を載せていない部分から先に浸透する。そのため、図８に示すように、先ず、一方のゲート領域４４でｐＨ変化が起こる。このｐＨ変化が起こっている間、変化するｐＨ値を信号に変換して測定部に出力する。しばらくすると、図８に示すように、サンプル阻止膜２２により、その後他方のゲート領域４５でｐＨ変化が起こり、このｐＨ変化が起こっている間、変化するｐＨ値をｐＨセンサにて電気信号に変換して測定部に出力する。その後測定サンプル溶液３０が電解質膜２１に浸透すると、双方のゲート領域４４，４５でｐＨ値が同一になり、ｐＨ差はゼロになる。そこで、ｐＨ値の測定では双方の信号の差分を測定し、その差分の最大値で判定する。差分が最大に達した値を用いて測定サンプル溶液３０のｐＨ値を測定する。 The measurement sample solution 30 permeates first from the portion where the sample blocking film 22 is not placed on the upper surface of the electrolyte membrane 21. Therefore, as shown in FIG. 8, first, pH change occurs in one gate region 44. While this pH change occurs, the changing pH value is converted into a signal and output to the measurement unit. After a while, as shown in FIG. 8, the sample blocking film 22 causes a pH change in the other gate region 45, and while this pH change occurs, the changing pH value is converted into an electrical signal by the pH sensor. And output to the measurement unit. Thereafter, when the measurement sample solution 30 penetrates into the electrolyte membrane 21, the pH value becomes the same in both gate regions 44 and 45, and the pH difference becomes zero. Therefore, in the measurement of the pH value, the difference between both signals is measured, and the determination is made based on the maximum value of the difference. The pH value of the measurement sample solution 30 is measured using the value at which the difference reaches the maximum.

電気的には、以下の作用をする。先ず、上記に示したソースフォロア回路では、２つのＦＥＴ５１，５２はゲート電極の電位変化に追従してソース電極電位が変化し、増幅率は１となるので、ソース電位を測定することにより直接にＦＥＴ５１，５２のゲート膜電位より界面電位を測定することができる。測定サンプル溶液３０・ゲート膜界面の電位はｐＨに比例するので、この構成でｐＨ測定ができる。   Electrically, it operates as follows. First, in the source follower circuit shown above, since the source electrode potential of the two FETs 51 and 52 changes following the potential change of the gate electrode and the amplification factor becomes 1, it is directly measured by measuring the source potential. The interface potential can be measured from the gate film potential of the FETs 51 and 52. Since the potential at the interface between the measurement sample solution 30 and the gate film is proportional to the pH, the pH can be measured with this configuration.

本発明によれば、ワンチップ上に、二つのセンサと参照電極を配置し、その上部にセンサ並びに参照電極を覆うように交換可能な電解質膜(シート)を載せ、さらにその膜上にサンプルを浸透若しくは透過させて、二つのセンサ信号の時間差から生じる検出値の差分を測定するようにしたことにより、サンプルのバクテリア感染の有無を判定することができるとともに、異なったサンプルを繰り返し測定する場合、電解質膜を交換することにより、センサ部の洗浄が容易であるとともに、標準液でのゼロ点校正などの操作も不要になり、作業性が向上する。   According to the present invention, two sensors and a reference electrode are arranged on a single chip, an exchangeable electrolyte membrane (sheet) is placed on the upper portion so as to cover the sensor and the reference electrode, and a sample is further placed on the membrane. By penetrating or penetrating and measuring the difference in detection value resulting from the time difference between the two sensor signals, it is possible to determine the presence or absence of bacterial infection of the sample, and when repeatedly measuring different samples, By exchanging the electrolyte membrane, the sensor part can be easily cleaned, and operations such as zero point calibration with a standard solution are no longer necessary, thereby improving workability.

本発明に係るケミカルセンサにおける発明を実施するための最良の形態の説明図である。It is explanatory drawing of the best form for implementing invention in the chemical sensor which concerns on this invention. 図１図示ケミカルセンサにおけるセンサ部と電解質膜とを一体化した状態を示す説明図である。It is explanatory drawing which shows the state which integrated the sensor part and electrolyte membrane in the chemical sensor shown in FIG. 図１図示ケミカルセンサに測定サンプルを滴下した状態を示す説明図である。It is explanatory drawing which shows the state which dripped the measurement sample to the chemical sensor shown in FIG. 図１とは別のケミカルセンサの実施例を示す説明図である。It is explanatory drawing which shows the Example of the chemical sensor different from FIG. 図４図示ケミカルセンサにおけるＩＳＦＥＴと電解質膜とを一体化した状態を示す説明図である。It is explanatory drawing which shows the state which integrated ISFET and electrolyte membrane in the chemical sensor shown in FIG. 図４図示ケミカルセンサの回路説明図である。It is circuit explanatory drawing of the chemical sensor shown in FIG. 図４図示ケミカルセンサに測定サンプルを滴下した状態を示す説明図である。It is explanatory drawing which shows the state which dripped the measurement sample to the chemical sensor shown in FIG. 図４図示実施例におけるセンサの応答信号と差動信号の時間変化を表した図である。4 is a diagram showing the time change of the response signal and the differential signal of the sensor in the embodiment shown in FIG.

符号の説明Explanation of symbols

１ 参照電極
１０ センサ部
１１ 基板
１２，１３ センサ
２１ 電解質膜
２２ サンプル阻止膜
３０ 測定サンプル溶液
４０ ＩＳＦＥＴ
４１ シリコン基板
４２ 絶縁膜
４３，４４ ゲート領域
４５ チャネルストッパ
４６ ドレイン領域
４７ ソース領域
５１，５２ ＩＳＦＥＴ
５３，５４ 定電流源 DESCRIPTION OF SYMBOLS 1 Reference electrode 10 Sensor part 11 Board | substrate 12, 13 Sensor 21 Electrolyte film 22 Sample blocking film 30 Measurement sample solution 40 ISFET
41 Silicon substrate 42 Insulating film 43, 44 Gate region 45 Channel stopper 46 Drain region 47 Source region 51, 52 ISFET
53, 54 Constant current source

Claims (9)

二つのセンサと参照電極を用いた回路構成において、前記センサ並びに参照電極を設けたセンサ部を覆うように交換可能な電解質膜を載せ、さらに、前記電解質膜上に片方の前記センサを覆うようにサンプル阻止膜を載せてあり、それらの上から測定サンプルを前記電解質膜に浸透若しくは透過させた際に、前記二つのセンサに測定サンプルが浸透若しくは透過する時間差から生じる検出値の差分を測定し、その差分の最大値又は前記センサから出力される信号の立ち上がり傾斜を用いて前記測定サンプルの化学的物質の濃度を測定するように構成してあることを特徴とするケミカルセンサ。 In a circuit configuration using two sensors and a reference electrode, an exchangeable electrolyte membrane is placed so as to cover the sensor and the sensor portion provided with the reference electrode, and one of the sensors is covered on the electrolyte membrane. When a sample blocking membrane is placed and a measurement sample permeates or permeates the electrolyte membrane from above, a difference between detection values resulting from a time difference between the measurement sample permeating or permeating the two sensors is measured, A chemical sensor configured to measure a chemical substance concentration of the measurement sample using a maximum value of the difference or a rising slope of a signal output from the sensor. 前記センサ並びに参照電極を同一基板に配置してあることを特徴とする請求項１記載のケミカルセンサ。 The chemical sensor according to claim 1, wherein the sensor and the reference electrode are arranged on the same substrate. 前記電解質膜をゲル状の物質で構成してあることを特徴とする請求項１又は２記載のケミカルセンサ。 3. The chemical sensor according to claim 1, wherein the electrolyte membrane is made of a gel substance. 前記電解質膜を多孔性の物質で構成してあることを特徴とする請求項１乃至３のいずれかに記載のケミカルセンサ。 The chemical sensor according to claim 1, wherein the electrolyte membrane is made of a porous material. 前記二つのセンサで水素イオン濃度（以下「ｐＨ」という。）を検出するようにしてあることを特徴とする請求項１乃至４のいずれかに記載のケミカルセンサ。 The chemical sensor according to any one of claims 1 to 4, wherein a hydrogen ion concentration (hereinafter referred to as "pH") is detected by the two sensors. 前記二つのセンサをＩＳＦＥＴで構成してあることを特徴とする請求項５記載のケミカルセンサ。 6. The chemical sensor according to claim 5, wherein the two sensors are ISFETs . 前記二つのＩＳＦＥＴのドレイン電極を共通にし、電源電圧を一定に印加するように構成してあることを特徴とする請求項６記載のケミカルセンサ。 7. The chemical sensor according to claim 6, wherein drain electrodes of the two ISFETs are made common and a power supply voltage is applied constant. 前記二つのＩＳＦＥＴのソース端子に同一の定電流源を設けてあり、二つのＩＳＦＥＴのソース電流を一定とする回路構成にし、ソースフォロア回路による差動ＦＥＴ動作になるように構成してあることを特徴とする請求項６又は７記載のケミカルセンサ。 The same constant current source is provided at the source terminals of the two ISFETs, the circuit configuration is such that the source currents of the two ISFETs are constant, and the differential FET operation is performed by the source follower circuit. The chemical sensor according to claim 6 or 7, characterized in that 請求項１乃至８のいずれかに記載のケミカルセンサを用いた化学的物質の濃度の測定方法において、前記センサ並びに参照電極を設けたセンサ部を覆うように電解質膜を載せ、さらに、片方の前記センサを覆うように前記電解質膜上にサンプル阻止膜を載せ、その上から測定サンプルを前記電解質膜に浸透若しくは透過させて、前記二つのセンサに測定サンプルが浸透若しくは透過する時間差から生じる検出値の差分を測定し、その差分の最大値又は前記センサから出力される信号の立ち上がり傾斜を用いて前記測定サンプルの化学的物質の濃度を測定することを特徴とする化学的物質の濃度の測定方法。 The method for measuring the concentration of a chemical substance using the chemical sensor according to any one of claims 1 to 8 , wherein an electrolyte membrane is placed so as to cover the sensor and a sensor portion provided with a reference electrode, A sample blocking film is placed on the electrolyte membrane so as to cover the sensor, and a measurement sample is permeated or permeated into the electrolyte membrane from above, and a detection value generated from a time difference between the measurement sample permeating or permeating the two sensors. the difference is measured, the measurement method of the concentration of chemical substances, characterized in that for measuring the concentration of chemical substances of the measurement sample using a rising slope of the signal output from the maximum value or the sensor of the difference.
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