JP2004233294A - Electrochemical sensor measuring device and its measuring method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an electrochemical sensor measuring device and its measuring method for automatically detecting a calibration value in the electrochemical sensor measuring device only by a measuring sensor without using a calibration sensor, determining the sensor quality, and measuring glucose or the like in a solution. <P>SOLUTION: An electrochemical sensor 21 comprising two electrodes or three electrodes is mounted on this electrochemical sensor measuring device 20. A constant voltage is applied to a working electrode 22 and a reference electrode 24, and a current flowing between the working electrode 22 and a counter electrode 23 is detected. A transient response time until the current reaches the steady state is counted, and the sensor quality is determined on reference to the relation between the transient response time and the calibration value. <P>COPYRIGHT: (C)2004,JPO&NCIPI

Description

【００１１】
上述の簡易血糖装置１の血糖測定方法を以下図１０と共に図１１で説明する。
【００１２】
図１１に於いて、第１ステップＳ_１ では較正センサ１１の電極パット１３を簡易血糖装置１のコネクタ２に装着する。
【００１３】
次の第２ステップＳ_２ では簡易血糖装置（以下装置と記す）１内の内部処理に入り、電極挿入検知スイッチ４により、各センサの抵抗値の違いから電極パット１３の装着を検知する。この検知信号はＣＰＵ７に送信される。ＣＰＵ７はいづれのセンサが装着されたかをセンサに付加した夫々の抵抗値から認識する。
【００１４】
第３ステップＳ_３ に於いて、ＣＰＵ７は反応電圧設定回路５に信号を送り、反応電圧設定回路５はコネクタ２に嵌着された較正センサ１１の電極パット１３に所定電圧を供給する。
【００１５】
第４ステップＳ_４ では較正センサ１３の夫々の抵抗値に基づいた電流が発生する。この電流を電流／電圧変換器３に供給し、電圧に変換し、Ａ／Ｄ変換器６からＣＰＵ７にデジタルデータが供給される。
【００１６】
次の第５ステップＳ_５ ではＣＰＵ７が電流値変化により較正センサ１１であるか或は測定センサ１２であるかの判断を行なう。即ち、較正センサ１１であるか否かを判断し、ＮＯであれば第５ステップＳ_５ の頭に戻され、ＹＥＳであれば第６ステップＳ_６ に進められる。
【００１７】
次の第６ステップＳ_６ に於いて、ＣＰＵ７は予め、記憶されている表１の検量線ＮＯ表から抵抗値に対応する検量線ＮＯを識別選択する。
【００１８】
第７ステップＳ_７ では次は血糖値の測定段階に入る。即ち、図１０で示した較正センサ１１をコネクタから抜いて、測定センサ１２をコネクタ２に装着する。
【００１９】
第８ステップＳ_８ では測定用センサ１２の測定電極に例えば血糖値測定のために血液を接触させる。
【００２０】
第９ステップＳ_９ では装置１内の動作と成り、コネクタ２に挿着された測定センサ１２の装着状態を電流挿入検出スイッチ４で検出する。
【００２１】
第１０ステップＳ_１０では電源挿入検出スイッチの検知信号をＣＰＵ７に供給することで、ＣＰＵ７は反応電圧応答回路５に信号を送り、反応電圧設定回路５は電流／電圧変換器３を介してコネクタ２に所定の電圧を供給することでコネクタ２に挿入されている測定センサ１２の電極パット１３に所定電圧が供給される。
【００２２】
この電圧によって、測定センサ１２には所定の電流を発生するので、この電流を第１１ステップＳ_１１では電流／電圧変換器３で検出する。
【００２３】
次の第１２ステップＳ_１２では電流値変化を検出することで測定センサ１２であるか否かを判断する。ＮＯであれば第１２ステップＳ_１２の頭に戻され、ＹＥＳであれば第１３ステップＳ_１３に進められる。
【００２４】
第１３ステップＳ_１３では測定センサ１２と識別されると、ＣＰＵ７は予め不揮発性メモリに格納していた検量線の中から、表１の各抵抗値に対応する検量線を識別選択し、選択した検量線に基づいて試料の血糖値を設定する。
【００２５】
第１４ステップＳ_１４では、設定された血糖値をＬＣＤ等の表示器８に表示することでエンドに至る。
【００２６】
【特許文献１】特開平４−３５７４５２号公報（図３、図８）
【００２７】
【発明が解決しようとする課題】
然し、上記した様な簡易血糖装置の如き電気化学センサ測定装置では、測定センサ１２の特性にバラツキがあり、これを補正するためには測定センサ１２の他に較正センサ１１を使用するためユーザは測定センサでの血糖値測定以外に較正センサ１１による較正を行なう煩わしさを生ずる。
【００２８】
本発明は上述の課題を解消するために成されたもので測定センサのみで較正及び測定、分析可能で、較正値は電気化学センサに電圧印加した際の電流値変化を測定することで簡単に測定可能な電気化学センサ測定装置及びその測定方法を提供する。
【００２９】
【課題を解決するための手段】
第１の本発明の電気化学センサ測定装置は、少なくとも２個の電極２３及び２４を有する電気化学センサ素子２１と、この電気化学センサ素子２１を保存水溶液中に浸漬し、２個の電極２２と２４間に一定電圧を供給する電位制御手段２６と、電気化学センサ素子２１への電圧供給時に発生する過度応答電流を検出する電流検出手段２５と、この電流検出手段２５の過度応答出力の経過時間を計数し、経過時間と較正値の関係を参照して、電気化学センサ素子の較正値を決定する様に成したものである。
【００３０】
第２の本発明の電気化学センサ測定装置は、少なくとも２個の電極２２及び２３を有する電気化学センサ素子２１と、電気化学センサ素子２１を保存溶液中に浸漬し、作用極２０と参照極３１間に一定電圧を供給する電位制御手段２６と、電気化学センサ素子２１への電圧供給時に発生する過渡応答電流を検出する電流検出手段２５と、電流検出手段２５の過渡応答出力の経過時間を計数し、経過時間と較正値の関係から電気化学センサ素子２１の較正値を決定し、決定した較正値を基に電気化学センサ素子２１の良否を決定する情報処理手段３０とを具備して成るものである。
【００３１】
第１の本発明の電気化学センサの測定方法は少なくとも２個の電極２２及び２３を有する電気化学センサ素子２１を保存溶液中に浸漬し、２個の電極２２と２３間に一定電圧を供給する工程ＳＴ_３ と、電気化学センサ素子２１への電圧供給時に発生する過渡応答電流を検出する工程ＳＴ_４ と、電流検出時の過渡応答出力の経過時間を計数し、経過時間と較正値の関係を参照して、電気化学センサ素子２１の較正値を決定する工程ＳＴ_１２とより成るものである。
【００３２】
第２の本発明の電気化学センサの測定方法は、少なくとも２個の電極２２と２３を有する電気化学センサ素子２１を保存溶液中に浸漬し、２個の電極２２と２３間に一定電圧を供給する工程ＳＴ_３ と、電気化学センサ素子２１への電圧供給時に発生する過渡応答電流を検出する工程ＳＴ_４ と、検出電流の過渡応答出力の経過時間を計数する工程ＳＴ_５ と、経過時間と較正値の関係から電気化学センサ素子２１の較正値を決定する工程ＳＴ_６ と、決定した較正値を基に電気化学センサ素子２１の良否を決定する工程ＳＴ_１０とより成るものである。
【００３３】
斯かる、本発明の電気化学センサ測定装置及びその測定方法に依ると、較正センサを用いる必要がなく、測定センサを用いて電気化学センサ測定装置が自動的に較正値を測定するのでユーザが較正センサを用いて較正を行なう煩わしさを省くことが出来ると共に較正センサを必要としないものが得られる。
【００３４】
【発明の実施の形態】
以下、本発明の１形態例を図１乃至図６によって詳記する。
【００３５】
図１は本発明の電気化学センサ測定装置の系統図、図２は過渡応答時間と較正値の関係を示す曲線図、図３は本発明の電気化学センサ測定方法を示すフローチャート、図４は本発明に用いる電気化学センサの１形態例を示す平面図と側断面図、図５はプリント基板に配設した電気化学センサの平面図、図６はセンサカートリッジの平面及び側面並びに側断面図である。
【００３６】
図１の電気化学センサ測定装置２０を説明する前に図４乃至図６によって本発明に用いる電気化学センサについて説明する。
【００３７】
一般に電気化学センサを用いて溶液中の特定の物質を測定することは化学工業、臨床検査等で利用されている。例えば、臨床検査等での検体中の基質測定として尿中のグルコースの濃度測定等は広く行なわれている。
【００３８】
この様な基質の測定に利用する電気化学センサは一般には図４（Ａ）（Ｂ）に示す様に構成されている。図４（Ａ）は電気化学センサの平面図、図４（Ｂ）は図４（Ａ）のＡ−Ａ′断面矢視図である。図４（Ａ）（Ｂ）で絶縁性基板３６上には作用極２２、対極２３、参照極２４の３電極が構成されている。絶縁性基板３６はシリコン上に酸化シリコン膜を形成した基板、ガラス、石英、ポリイミド、ポリカーボネート、ガラスエポキシ基板等が用いられ、例えば、その大きさは６×９ｍｍの長方形状に形成される。
【００３９】
絶縁性基板３６上に形成する作用極２２及び対極２３はチタン層３８及び白金層４１で構成する。これらチタン層３８及び白金層４１は例えば、スパッタ法で膜厚０．０２〜０．２μｍ及び０．１〜１．０μｍに形成し、その大きさを例えば夫々作用極２２で１．２ｍｍ×２．０ｍｍ、対極２２で０．４ｍｍ×２．０ｍｍの長方形状に選択形成されている。
【００４０】
上述の作用極２２及び対極２３の電極材料は白金層４１の他にカーボン、金、イリジウム等のいづれか１つを選択することが出来る。又、電極の形成法はスパッタ法に限らず蒸着法、スクリーン印刷、鍍金等で形成可能である。
【００４１】
次に、参照極２４は絶縁性基板３６上に対極２３と対向した位置に銀層３７を形成し、次に銀層３７の表面を処理して塩化銀層３９を形成する。塩化銀層３９は塩化鉄（ＩＩＩ）若しくは塩化クロム（ＩＩＩ）水溶液で処理するか、塩化物水溶液中で電解する方法で製作される。参照極２４の下地として銀層３７の下に絶縁性基板３６との密着性を高めるために、例えばスパッタ法等でチタン層を０．１〜１．０μｍ厚に形成する様に成してもよい。参照極２４の大きさは例えば０．４ｍｍ×２．０ｍｍの長方形状と成されている。
【００４２】
作用極２２、対極２３、参照極２４に連通するリード（０．２ｍｍ×２．８ｍｍ）３４及びコンタクト電極（１．６ｍｍ×０．８ｍｍ）３５ｃ，３５ｂ，３５ａも絶縁性基板３６上に形成されている。この構成の３電極式では作用極２２と参照極２４間の電位差を一定に保ち、作用極２２と対極２３間の電流を測定する様に成される。
【００４３】
上述の構成では、３電極式の構成を説明したが、作用極２２と参照極２４とから構成される２電極式もあり、この場合は作用極２２と参照極２４の電位を一定に保ち、その時の作用極２２と参照極２４に流れる電流を測定する様に成されている。
【００４４】
次に絶縁性基板３６上に形成した作用極２２、対極２３、参照極２４上に選択透過膜４０が形成される。この選択透過膜は、過酸化水素を選択的に透過し、妨害物質を除去する機能を有し、例えばアセチルセルローズ膜或はイオン交換樹脂等から形成される。
【００４５】
選択透過膜４０上には膜中に酵素を担持する機能を有する酵素膜４２が形成される。この酵素膜４２は、例えば酵素とアルブミンの様な蛋白質をグルタルアルデヒドの様な架橋剤で固定化することで形成する。
【００４６】
酵素膜４２上には更に制限透過膜４３が形成される。制限透過膜４３はグルコースの透過を制限し汚染物質の吸着を防ぐ機能を有し例えば、フッ素系ポリマー膜、シリコーン膜、ポリカーボネート膜、ウレタンポリマー膜等から形成される。
【００４７】
上述の選択透過膜４０、酵素膜４２、制限透過膜４３からなる有機薄膜の各層の厚みは０．１〜数μｍ程度に選択されている。
【００４８】
制限透過膜４３は、汚染物質の吸着を防ぐと共に、グルコース等の透過を制限し測定範囲を拡大する機能がある。選択透過膜４０は例えば過酸化水素のみ透過し、妨害物質の透過を防ぐ機能がある。
制限透過膜４３及び選択透過膜４０には微小な孔が形成されており、この孔の大きさによって、物質の透過を制限している。
【００４９】
上述の電気化学センサ２１をスパッタ法を用いて製造するプロセスの概要は以下に記す通りとなる。
（１） 絶縁性基板（６０×７０ｍｍ）３６上にチタン層３８及び白金層４１をスパッタ法により成膜し、さらに銀層３７をスパッタ法により成膜する。
（２） フォトリソグラフィにより作用極２２、対極２３、参照極２４、リード３４、コンタクト電極３５ａ，３５ｂ，３５ｃを形成する。
（３） 塩化鉄（ＩＩＩ）水溶液で処理して銀層表面に塩化銀層３９を形成し、参照極２４を形成する。
（４） 選択透過膜４０、酵素膜４２、制限透過膜４３を形成する。
（５） 絶縁性基板３６を個々の電気化学センサ２１（６×９ｍｍ）に分割する。
【００５０】
次に、図５によって、図４（Ａ）（Ｂ）で説明した電気化学センサ２１をプリント基板に実装したセンサアッセンブルを説明する。
【００５１】
図５で長方形状のプリント基板４４の一端には電気化学センサ２１が実装され、プリント基板４４上に形成した配線部５３の一端と電気化学センサ２１のコンタクト部３５ａ，３５ｂ，３５ｃ間をワイヤボンディング、半田、異方性導電樹脂等で電気的に接続する。プリント基板４４にはセンサアッセンブル５２が電気化学センサ測定装置に挿入された時に電気化学センサ測定装置側が検出するためのセンサ検出コイル２７がパターニングされている。プリント基板４４の他端には電気化学センサ測定装置側のコネクタと嵌合して電気的に接続するプラグ５４と成されている。
【００５２】
図６（Ａ）（Ｂ）（Ｃ）は上述のセンサアッセンブル５２をカートリッジに実装した平面図、側面図、側断面図を示す。
【００５３】
カートリッジ４５は略直方体状に合成樹脂材料で成形した筐体内に図５で詳記したセンサアッセンブル５２を装着する。カートリッジ４５の一端には略円形状の開口部４８が形成され、この開口部４８から電気化学センサ２１の作用極２２、対極２３、参照極２４が露呈する様に成され、試料溶液と接し、それ以外の部分（コンタクト部３５ａ，３５ｂ，３５ｃ、リード３４）は溶液と接することがない様にＯリング状のゴム等で構成したシール部材４６を開口部周囲に設けている。カートリッジ４５の開口部４８側とは反対の開口端４７により、電気化学センサ測定装置２０のコネクタに嵌合して、電気的接続を可能にしている。
【００５４】
上述の電気化学センサ２１を含むカートリッジ４５を装着し、試料溶液中の例えば、グルコース濃度を測定するための電気化学センサ測定装置を図１によって説明する。
【００５５】
図１で４５は上述で説明した電気化学センサ２１やプリント基板４４上にパターニングされた検出コイル２７等を含むカートリッジであり、電気化学センサ測定装置２０の本体５５にコネクタを介して結合させた状態を示すブロック図であり、電気化学センサ２１の作用極２２は電流検出回路２５のオペアンプ２５ａの入力端に接続され、参照極２４は電位制御回路２６のオペアンプ２６ａの入力端に接続され、対極２３は電位制御回路２６内のオペアンプ２６ｂの出力端に接続されている。電圧供給源２６ｃはオペアンプ２６ｂの入力端とオペアンプ２６ａの出力端に接続されている。
【００５６】
カートリッジ４５側にパターニングされている一端がショートされたセンサ検出コイル２７のプラグ５４は一端に所定電圧が印加され他端が接地されたセンサ検出回路２８に接続されている。
【００５７】
電流検出回路２５の出力端はアナログ−デジタル（Ａ／Ｄ）変換器２９に接続され、Ａ／Ｄ変換器２９の出力端は情報処理装置等のマイクロコンピュータ（ＣＰＵ）３０に接続され、センサ検出回路２８の出力端もＣＰＵ３０に接続されている。
【００５８】
３１は液晶表示装置（ＬＣＤ）の如き表示手段、３２及び３３はＣＰＵ３０に一般に用いられるＲＯＭ及びＲＡＭの如きワーク用の不揮発性及び揮発性の記憶手段である。
【００５９】
上述の電気化学センサ測定装置２０の動作を図２の波形図及び図３のフローチャートに基づいて説明する。本例では、試料溶液中の過酸化水素（Ｈ_２ Ｏ_２ ）を測定する場合で説明を進める。
【００６０】
図１で説明した電気化学センサ２１が装着されたカートリッジ４５の開口部４８から露出している作用極２２、対極２３、参照極２４に図３の第１ステップＳＴ_１ で示す様に、保存液〔例えば電解質（塩化ナトリウム０．１５Ｍを含む水溶液）〕に浸漬させる。
【００６１】
次の第２ステップＳＴ_２ は電気化学センサ測定装置２０内の処理に入り、カートリッジ４５側のセンサ検出コイル２７によって、閉回路状態を検知したセンサ検出回路２８は電気化学センサ２１が本体５５に装着されたことを検出し、その検出データをＣＰＵ３０に伝送する。
【００６２】
センサ検出回路２８によって電気化学センサ２１の装着が検出されると、ＣＰＵ３０は電位制御回路２６を駆動し、第３ステップＳＴ_３ の様に電位制御回路２６の電圧供給源２６ｃを介して、電気化学センサ２１の作用極２２（＋）及び参照極（−）２４間に一定の電圧（４００〜７００ｍＶ）を印加する。
【００６３】
作用極２２と参照極２４間に一定電圧を印加すると保存液に依存する電流が作用極２２と対極２３間に流れて、定常状態になると殆ど流れなくなる。この現象については電気化学及び工業物理化学Ｖｏｌ６８，Ｎｏ１．ｐ６３〜６８に詳しく記載されている。作用極２２と参照極２４の間に電圧を印加した場合、今までこれら電極と静電気的につりあって分布していた電極近傍の陽イオンや陰イオンが、電極電位の急激な変化にともなって、新しい平衡状態を達成するため移動を開始する。作用極２２の電位がこれまでよりも正になるように電位を印加すると、陽イオンは作用極２２から遠ざかり、逆に陰イオンは近づき、平衡分布に落ち着いたところで新しい電気二重層が形成される。電荷を持った粒子が動くので、この動きは外部回路を流れる電流として観測される。この現象は、電気二重層という一種のコンデンサに溶液という抵抗体を通して電流を流し、電荷を充電（あるいは放電）する過程と似ている。
【００６４】
この様な電流値を第４ステップＳＴ_４ では電流検出回路２５で検出する様にする。図１では電流検出回路２５を作用極２２側に接続させたが、一定電圧印加後に流れる電流は作用極２２と対極２３間に流れるので電流検出回路２５は対極２３側に接続させる様にしてもよい。
【００６５】
電流検出回路２５で検出された電流はＲＯＭ３２に保存したファームウェアに従って、ＣＰＵ３０へＡ／Ｄ変換器２９を介して取り込み、第５ステップＳＴ_５ の様にＲＡＭ３３に格納する。
【００６６】
このＲＡＭ３３に格納された電流値は第３ステップＳＴ_３ での電圧印加直後は図２に示す様に約１０μＡとなり、経時的に前記した様に減少し、約１０μＡ以下になって定常状態となる。図２の横軸は経過時間を示し、縦軸は電流検出回路２５の出力電流を示すものであり、第６ステップＳＴ_６ では、この経過時間をカウントし、このカウント値を第７ステップＳＴ_７ に示す様にＲＡＭ３３に格納する。
【００６７】
このＲＡＭ３３に格納された過渡応答時間と較正値との関係を図２に示す。この図から解る様に電気化学センサ２１は過渡応答時間が１分未満の場合は、曲線５６の様に配線部５３の断線、電極２２〜２４の不活性あるいは制限透過膜４３の欠陥などの原因で不良である。一方、過渡応答時間が１０分より大きい曲線５７の場合は、制限透過膜４３及び選択透過膜４０が緻密であり不良と成り、過渡応答時間が２分、４分、５分の曲線５８，５９，６０では較正値が４０ｎＡ、２０ｎＡ、１０ｎＡと成されている。作用極２２、対極２３及び参照極２４から構成される測定電極上に機能性有機薄膜を形成した場合、イオンの流れは有機薄膜中の拡散によって制限される。したがって、この電流が流れる時間（過渡応答時間）は、有機薄膜の膜質に依存する。
【００６８】
第８ステップＳＴ_８ では電流値が定常状態に達するまでの過渡応答時間を決定して、第９ステップＳＴ_９ では、この決定した過渡応答時間をＲＡＭ３３に格納する。
【００６９】
第１０ステップＳＴ_１０では決定した過渡応答時間と上記した較正値（保存液に対する電流出力値）の関係を参照し、電気化学センサ２１の良否を判定する。即ち、電気化学センサ２１は良品か否かをみて不良品であれば第１１ステップＳＴ_１１に進んでＬＣＤ３１の画面上に不良品表示を行なう。良品の場合は第１２ステップＳＴ_１２に於いて、図２の曲線５８〜６０に示す過渡応答時間が２分では較正値４０ｎＡ、４分では較正値２０ｎＡ、５分では較正値１０ｎＡの様に、過渡応答時間と較正値の関係から較正値を決定する。
【００７０】
決定された較正値から装置本体５５に装着されたカートリッジ４５内の電気化学センサ２１が正常であれば測定が可能で、試料溶液内の例えばＨ_２ Ｏ_２ を測定する第１３乃至第１８ステップＳＴ_１３〜ＳＴ_１８に進められる。
【００７１】
第１３ステップＳＴ_１３ではカートリッジ４５内の電気化学センサ２１を測定しようとする試料溶液に浸漬させる。
【００７２】
電気化学センサ２１の酵素膜４２がグルコースオキシターゼで、試料溶液中に含有するグルコース（ブドウ糖）を測定する場合は、試料溶液中のグルコースは酵素グルコースオキシターゼの作用により、グルコノラクトンと過酸化水素（Ｈ_２ Ｏ_２ ）は下式１の如く変換される。
【００７３】
〔式１〕
グルコース＋Ｏ_２ ＋Ｈ_２ Ｏ→グラコノクラトン＋Ｈ_２ Ｏ_２ ‥‥（１）
【００７４】
（１）式で生成されたＨ_２ Ｏ_２ は下式２の反応に基づいて電流に変換されＨ_２ Ｏ_２ を定量できるため、グルコース濃度を算出することができる。
【００７５】
〔式２〕
Ｈ_２ Ｏ_２ →２Ｈ^＋ ＋Ｏ_２ ＋２ｅ⁻ ‥‥（２）
（２）式で試料溶液中のＨ_２ Ｏ_２ は作用極２２上で陽極酸化され、作用極２２と対極２３間に酸化電流が発生するので電流検出回路２５で電流値を第１４ステップＳＴ_１４の様に検出する。
【００７６】
酵素はグルコースオキシダーゼのほかに、アルコールオキシダーゼ、乳酸オキシダーゼ、アスコルビン酸オキシダーゼを使用すれば、アルコール、乳酸、アルコルビン酸をそれぞれ測定することができることは明らかである。
【００７７】
次の第１５ステップＳＴ_１５では、検出した電流値をＡ／Ｄ変換器２９でデジタルデータに変換し、ＣＰＵ３０に取り込み、ＲＡＭ３３に格納する。
【００７８】
次の第１６ステップＳＴ_１６に於いては、ＣＰＵ３０はＲＯＭ３２に格納されている較正値より試料溶液のグルコース濃度を計算し、再びＲＡＭ３３に格納する（第１７ステップＳＴ_１７）。その後、ＣＰＵ３０はＲＡＭ３３に格納されたグルコース濃度をＬＣＤ３１に表示する（第１８ステップＳＴ_１８）ことでエンドに至る。
【００７９】
上述の本例の実施形態によれば以下の効果が得られる。
（１） 作用極２２等の測定電極と酵素膜４２等の機能性有機薄膜から成る電気化学センサ２１は機能性有機薄膜の膜質のバラツキが大きいため、個々の電気化学センサ２１での出力のバラツキが大きくなるが基準液となる保存液に浸漬することで例えばグルコース濃度と出力値との関係を知るための較正値を、ＣＰＵが電気化学センサの装着を認識し、電圧印加後に発生する電流が定常状態になるまでの過渡応答時間をカウントすることで機能性有機薄膜の膜質（厚みや透孔状態）に依存するファクタをカウント時間から簡単に決定することが可能と成って電気化学センサの較正値を自動的に決定することが出来る。
（２） （１）と同様に電気化学センサの良否判定も簡単に行なうことが可能と成る。
【００８０】
次に図７乃至図９を用いて、本発明の他の形態例を説明する。
【００８１】
図７は本発明の電気化学センサ測定装置の他の形態例を示す系統図、図８はウェーハ上に複数の電気化学センサを一体形成した場合の模式的な平面図及び断面図、図９は本発明の電気化学センサの他の形態例を示すフローチャートである。尚、図１乃至図７との対応部分には同一符号を付して重複説明を省略する。
【００８２】
図７に於いて、図１の構成との相違点のみを以下で説明する。電気化学センサ測定装置の本体５５側にはセンサ検出回路２８を必要としない。又、電流検出回路２５の入力端子Ｔ_１ 及び電位制御回路２６の入出力端子Ｔ_２ 及びＴ_３ にはプローバ４９が接続されている。
【００８３】
このプローバ４９はウェーハ５０の電気化学センサ２１のコンタクト電極３５ａ，３５ｂ，３５ｃに接触可能に成されている。
【００８４】
図４（Ａ）（Ｂ）では単一の電気化学センサを示したが、図８（Ａ）（Ｂ）ではウェーハ５０等に複数の電気化学センサ２１を形成させた場合の平面図〔図８（Ａ）〕及び図８（Ａ）のＢ−Ｂ′断面矢視図〔図８（Ｂ）〕であり、大面積のガラス等の絶縁性基板３６上に作用極２２、対極２３、参照極２４及びコンタクト電極３５ａ，３５ｂ，３５ｃから成る複数の電気化学センサ２１上に選択透過膜４０及び酵素膜４２並びに制限透過膜４３から成る機能性有機薄膜が順次形成された状態で複数の電気化学センサ２１を一体に形成する。コンタクト３５ａ，３５ｂ，３５ｃ上の機能性有機薄膜をエッチング等で除去することによりプローバを接触させる位置が明確化され、プローバ４９、コンタクト電極３５ａ，３５ｂ，３５ｃとの導通が可能と成る。ウェーハ５０は五目盤状に切断し、図４（Ａ）（Ｂ）に示す如き単一の電気化学センサ２１を得る様に成されている。
【００８５】
以下、図７の電気化学センサ測定装置２０の動作を図９のフローチャートによって説明する。
【００８６】
図９に於いて、第１ステップＳＴＥ_１ ではウェーハ５０上に形成された複数の電気化学センサ素子２１の単一の電気化学センサ素子の作用極２２、対極２３、参照極２４のコンタクト電極３５ｃ，３５ｂ，３５ａにプローバ４９をコンタクトさせて接触させる。
【００８７】
第２ステップＳＴＥ_２ では電気化学センサ素子の作用極２２、対極２３、参照極２４上に例えば、電解質である塩化ナトリウム０．１５モルを含む水溶液からなる保存液を滴下する。
【００８８】
第３ステップＳＴＥ_３ では電気化学センサ測定装置２０内の電位制御回路２６によって作用極２２と参照極２４間に一定の電圧（４００〜７００ｍＶ）を印加する。
【００８９】
第４ステップＳＴＥ_４ では作用極２２と対極２３間に発生する電流を電流検出回路２５で検出する。
【００９０】
第５ステップＳＴＥ_５ では検出した電流値をＡ／Ｄ変換器２９でデジタル変換し、ＣＰＵ３０に取り込みＲＡＭ３３に格納させる。
【００９１】
第６ステップＳＴＥ_６ では第３ステップで電気化学センサ２１に電圧を印加した直後には電流検出回路２５の電流値はおよそ１０μＡとなり、経時的に減少しおよそ１０ｎＡ以下になり定常状態となる。発生する電流が定常状態になるまでの時間である過渡応答時間をＣＰＵ３０によりカウントする。
【００９２】
第７ステップＳＴＥ_７ では、このカウント値をＣＰＵ３０を介してＲＡＭ３３に格納する。
【００９３】
第８ステップＳＴＥ_８ では、ＲＡＭ３３に保存されているカウント値に基づいて過渡応答時間を決定する。
【００９４】
第９ステップＳＴＥ_９ では、この過渡応答時間をＲＡＭ３３に格納する。
【００９５】
第１０ステップＳＴＥ_１０ではＲＡＭ３３に格納された過渡応答時間と較正値の関係から較正値を決定し、決定した較正値からウェーハ５０上で単一の電気化学センサ２１が正常か否かを判断する。第１１ステップＳＴＥ_１１ではＬＣＤ３１に判断結果を表示することでエンドに至る。ここで図２に示す様に過渡応答時間が１分未満の場合は、リード３４や配線部の断線、電極の不活性あるいは制限透過膜４０の欠陥などの原因で不良である。一方、過渡応答時間が１０分より大の場合は、制限透過膜４３及び選択透過膜４０が緻密であり不良である。
【００９６】
上述の構成ではウェーハ上の複数の電気化学センサ２１を１個づつ測定したが複数個の電気化学センサ２１を同時に測定したり、２極型の電気化学センサに適用したりすることも勿論可能である。
【００９７】
上述の図７乃至図９に示す構成及び動作によれば、複数の電気化学センサ２１がウェーハ５０上に形成された状態で、複数の電気化学センサ素子２１の較正値を決定し、正常か否かのチェックをカートリッジ装着前に行うことが出来て、サブアッセンブル５２した後で生じた際の不良品の様にプリント基板４４やカートリッジ４５を廃棄しなくても済み、組立工数等も節約することができる。
【００９８】
【発明の効果】
本発明の電気化学センサ測定装置及びその測定方法によれば較正センサを必要とせず、測定用の電気化学センサのみで較正値を自動的に決定することが出来て、電気化学センサが正常か否かを自動的に判定することが出来る。又、複数の電気化学センサ素子はウェーハ上で較正値を決定すると共に正常か否かを判断可能で組立工数後のチェックに比べて組立工数の軽減、不良廃棄部分の節減を図ることが出来る効果を有する。
【図面の簡単な説明】
【図１】本発明の電気化学センサ測定装置の系統図である。
【図２】本発明の過渡応答時間較正値と出力の関係を示す曲線図である。
【図３】本発明の電気化学センサ測定方法を示すフローチャートである。
【図４】本発明に用いる電気化学センサの１形態例を示す平面図及び側断面図である。
【図５】本発明に用いるプリント基板に配設した電気化学センサの平面図である。
【図６】本発明に用いるセンサ用カートリッジの平面及び側面並びに側断面図である。
【図７】本発明の電気化学センサ測定装置の他の形態例を示す系統図である。
【図８】ウェーハ上に複数の電気化学センサを一体形成した場合の模式的な平面図及び断面図である。
【図９】本発明の電気化学センサの他の形態例を示すフローチャートである。
【図１０】従来の電気化学センサ測定装置の系統図である。
【図１１】従来の電気化学センサ測定方法のフローチャートである。
【符号の説明】
２０‥‥電気化学センサ測定装置、２１‥‥電気化学センサ、２２‥‥作用極、２３‥‥対極、２４‥‥参照極、２５‥‥電流検出回路、２６‥‥電位制御回路、２８‥‥センサ検出回路、３０‥‥ＣＰＵ、４５‥‥カートリッジ、５５‥‥本体、４９‥‥プローバ[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an electrochemical sensor measuring apparatus for analyzing and measuring glucose, alcohol, and the like contained in blood and the like by an amperometry method using an electrochemical sensor, and a measuring method thereof.
[0002]
[Prior art]
Conventionally, a quantitative analysis method for blood and the like and a device for measuring the current of an electrochemical sensor such as a biosensor with a simple blood glucose meter and displaying the glucose concentration using the current value and a calibration curve are disclosed in Patent Document 1. Is disclosed.
[0003]
FIG. 10 is a system diagram of the simple blood glucose device disclosed in Patent Document 1 described above, and FIG. 11 is a flowchart for explaining the operation.
[0004]
In FIG. 10, reference numeral 1 denotes a simple blood sugar device, 2 denotes a connector into which an electrode pad 13 such as a calibration sensor 11 can be inserted, and the connector 2 includes a current / voltage converter 3 and an electrode pad 13. And the like.
[0005]
The output of the current / voltage converter 3 supplies digitized data to an information processing device 7 (hereinafter, referred to as a CPU) such as a computer via an analog / digital converter 6, and the output of the electrode insertion detection switch 4 is also a CPU 7. Supplied to
[0006]
Reference numeral 5 denotes a reaction voltage setting circuit which applies a voltage to the connector 2 via the current / voltage converter 3 based on the electrode insertion / attachment data of the electrode insertion switch 4 sent to the CPU 7, and applies the voltage to the electrode pad 13 of the sensor. Supply voltage.
[0007]
Reference numeral 8 denotes a display such as a liquid crystal display (LCD), 9 denotes a non-volatile memory such as an electrically erasable / writable read-only memory (EEPROM) widely used in the CPU 7, and 10 denotes a volatile memory such as a RAM.
[0008]
At least the calibration sensor 11 and the measurement sensor 12 are required at the time of measuring blood glucose by the simple blood sugar device 1 described above, and these sensors are attached to the simple blood sugar device 1. These sensors have their own resistance values, and the simple blood glucose device 1 detects the resistance values of the respective sensors at the time of mounting to set the operation state, and detects that the electrodes are mounted based on the resistance values. Then, a function corresponding to the attached sensor is executed.
[0009]
For example, resistors having different resistance values as shown in Table 1 are mounted on the calibration sensor 11 or the measurement sensor 12.
[0010]
[Table 1]

[0011]
The blood glucose measuring method of the above-described simple blood glucose device 1 will be described below with reference to FIG.
[0012]
In FIG. 11, the first step S ₁ Then, the electrode pad 13 of the calibration sensor 11 is attached to the connector 2 of the simple blood sugar device 1.
[0013]
Next second step S ₂ Then, the internal processing in the simple blood glucose device (hereinafter referred to as the device) 1 is started, and the electrode pad detection switch 4 detects the mounting of the electrode pad 13 from the difference in the resistance value of each sensor. This detection signal is transmitted to the CPU 7. The CPU 7 recognizes which sensor is attached from each resistance value added to the sensor.
[0014]
Third step S ₃ The CPU 7 sends a signal to the reaction voltage setting circuit 5, and the reaction voltage setting circuit 5 supplies a predetermined voltage to the electrode pad 13 of the calibration sensor 11 fitted to the connector 2.
[0015]
4th step S ₄ Then, a current is generated based on each resistance value of the calibration sensor 13. This current is supplied to the current / voltage converter 3, converted into a voltage, and digital data is supplied from the A / D converter 6 to the CPU 7.
[0016]
Next fifth step S ₅ Then, the CPU 7 determines whether the sensor is the calibration sensor 11 or the measurement sensor 12 based on a change in the current value. That is, whether or not the sensor is the calibration sensor 11 is determined. ₅ And if YES, the sixth step S ₆ Proceed to
[0017]
Next sixth step S ₆ The CPU 7 identifies and selects the calibration curve NO corresponding to the resistance value from the calibration curve NO table of Table 1 stored in advance.
[0018]
7th step S ₇ The next step is to measure the blood sugar level. That is, the calibration sensor 11 shown in FIG. 10 is disconnected from the connector, and the measurement sensor 12 is attached to the connector 2.
[0019]
8th step S ₈ Then, the blood is brought into contact with the measurement electrode of the measurement sensor 12 for measuring, for example, a blood glucose level.
[0020]
9th step S ₉ Then, the operation inside the device 1 is performed, and the mounting state of the measurement sensor 12 inserted into the connector 2 is detected by the current insertion detection switch 4.
[0021]
Tenth step S ₁₀ By supplying a detection signal of the power insertion detection switch to the CPU 7, the CPU 7 sends a signal to the reaction voltage response circuit 5, and the reaction voltage setting circuit 5 applies a predetermined voltage to the connector 2 via the current / voltage converter 3. By the supply, a predetermined voltage is supplied to the electrode pad 13 of the measurement sensor 12 inserted in the connector 2.
[0022]
A predetermined current is generated in the measurement sensor 12 by this voltage, and this current is supplied to the eleventh step S ₁₁ Then, the current / voltage converter 3 detects the current.
[0023]
Next twelfth step S ₁₂ Then, it is determined whether or not the sensor 12 is the measurement sensor 12 by detecting a change in the current value. If NO, twelfth step S ₁₂ And if YES, the thirteenth step S _Thirteen Proceed to
[0024]
13th step S _Thirteen When the CPU 7 is identified as the measurement sensor 12, the CPU 7 identifies and selects a calibration curve corresponding to each of the resistance values in Table 1 from among the calibration curves stored in the nonvolatile memory in advance, and based on the selected calibration curve. Set the blood glucose level of the sample.
[0025]
14th step S ₁₄ Then, the set blood sugar level is displayed on the display 8 such as an LCD, and the process ends.
[0026]
[Patent Document 1] Japanese Patent Application Laid-Open No. 4-357452 (FIGS. 3 and 8)
[0027]
[Problems to be solved by the invention]
However, in an electrochemical sensor measuring device such as a simple blood glucose device as described above, there are variations in the characteristics of the measuring sensor 12, and in order to correct this, the user uses the calibration sensor 11 in addition to the measuring sensor 12. In addition to the measurement of the blood sugar level by the measurement sensor, the trouble of performing the calibration by the calibration sensor 11 occurs.
[0028]
The present invention has been made to solve the above-mentioned problem, and can be calibrated, measured, and analyzed only with a measurement sensor, and the calibration value can be easily obtained by measuring a change in a current value when a voltage is applied to an electrochemical sensor. Provided is an electrochemical sensor measurement device and a measurement method thereof that can be measured.
[0029]
[Means for Solving the Problems]
The electrochemical sensor measurement device according to the first aspect of the present invention includes an electrochemical sensor element 21 having at least two electrodes 23 and 24, and immersing the electrochemical sensor element 21 in a storage aqueous solution to form two electrodes 22. A potential control means 26 for supplying a constant voltage between the current sensors 24, a current detection means 25 for detecting a transient response current generated when a voltage is supplied to the electrochemical sensor element 21, and an elapsed time of the transient response output of the current detection means 25 Is counted, and the calibration value of the electrochemical sensor element is determined with reference to the relationship between the elapsed time and the calibration value.
[0030]
The electrochemical sensor measurement device according to the second aspect of the present invention comprises an electrochemical sensor element 21 having at least two electrodes 22 and 23, an electrochemical sensor element 21 immersed in a storage solution, and a working electrode 20 and a reference electrode 31. A potential control means 26 for supplying a constant voltage during the operation, a current detection means 25 for detecting a transient response current generated when a voltage is supplied to the electrochemical sensor element 21, and counting of an elapsed time of a transient response output of the current detection means 25. And information processing means 30 for determining the calibration value of the electrochemical sensor element 21 from the relationship between the elapsed time and the calibration value, and determining the quality of the electrochemical sensor element 21 based on the determined calibration value. It is.
[0031]
According to the first method for measuring an electrochemical sensor of the present invention, an electrochemical sensor element 21 having at least two electrodes 22 and 23 is immersed in a storage solution, and a constant voltage is supplied between the two electrodes 22 and 23. Process ST ₃ And a step ST for detecting a transient response current generated when a voltage is supplied to the electrochemical sensor element 21. ₄ And a step ST in which the elapsed time of the transient response output at the time of current detection is counted, and the calibration value of the electrochemical sensor element 21 is determined with reference to the relationship between the elapsed time and the calibration value. ₁₂ It consists of:
[0032]
According to a second method for measuring an electrochemical sensor of the present invention, an electrochemical sensor element 21 having at least two electrodes 22 and 23 is immersed in a storage solution and a constant voltage is supplied between the two electrodes 22 and 23. Step ST ₃ And a step ST for detecting a transient response current generated when a voltage is supplied to the electrochemical sensor element 21. ₄ And a step ST for counting the elapsed time of the transient response output of the detected current. ₅ Determining the calibration value of the electrochemical sensor element 21 from the relationship between the elapsed time and the calibration value ST ₆ Determining the quality of the electrochemical sensor element 21 based on the determined calibration value ST ₁₀ It consists of:
[0033]
According to the electrochemical sensor measuring device and the measuring method thereof of the present invention, it is not necessary to use a calibration sensor, and the electrochemical sensor measuring device automatically measures a calibration value using the measuring sensor, so that the user can perform calibration. It is possible to eliminate the trouble of performing calibration using a sensor and obtain a sensor that does not require a calibration sensor.
[0034]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, one embodiment of the present invention will be described in detail with reference to FIGS.
[0035]
FIG. 1 is a system diagram of the electrochemical sensor measuring device of the present invention, FIG. 2 is a curve diagram showing the relationship between the transient response time and the calibration value, FIG. 3 is a flowchart showing the electrochemical sensor measuring method of the present invention, and FIG. FIG. 5 is a plan view and a side sectional view showing an embodiment of an electrochemical sensor used in the present invention, FIG. 5 is a plan view of an electrochemical sensor disposed on a printed circuit board, and FIG. .
[0036]
Before describing the electrochemical sensor measurement device 20 of FIG. 1, the electrochemical sensor used in the present invention will be described with reference to FIGS.
[0037]
Generally, measurement of a specific substance in a solution using an electrochemical sensor is used in a chemical industry, a clinical test, or the like. For example, measurement of glucose concentration in urine and the like are widely performed as substrate measurement in a specimen in a clinical test or the like.
[0038]
An electrochemical sensor used for measuring such a substrate is generally configured as shown in FIGS. 4A is a plan view of the electrochemical sensor, and FIG. 4B is a cross-sectional view taken along the line AA ′ of FIG. 4A. In FIGS. 4A and 4B, three electrodes of a working electrode 22, a counter electrode 23, and a reference electrode 24 are formed on an insulating substrate 36. As the insulating substrate 36, a substrate in which a silicon oxide film is formed on silicon, glass, quartz, polyimide, polycarbonate, a glass epoxy substrate, or the like is used. For example, the insulating substrate 36 is formed in a rectangular shape of 6 × 9 mm.
[0039]
The working electrode 22 and the counter electrode 23 formed on the insulating substrate 36 are composed of a titanium layer 38 and a platinum layer 41. The titanium layer 38 and the platinum layer 41 are formed, for example, in a thickness of 0.02 to 0.2 μm and 0.1 to 1.0 μm by a sputtering method. 0.0 mm, and the counter electrode 22 is selectively formed in a rectangular shape of 0.4 mm × 2.0 mm.
[0040]
As the electrode material of the working electrode 22 and the counter electrode 23, any one of carbon, gold, iridium and the like can be selected in addition to the platinum layer 41. Further, the method of forming the electrode is not limited to the sputtering method, and the electrode can be formed by vapor deposition, screen printing, plating, or the like.
[0041]
Next, the reference electrode 24 forms a silver layer 37 on the insulating substrate 36 at a position facing the counter electrode 23, and then treats the surface of the silver layer 37 to form a silver chloride layer 39. The silver chloride layer 39 is manufactured by treating with an aqueous solution of iron (III) chloride or chromium (III) chloride, or by electrolyzing in an aqueous solution of chloride. In order to enhance the adhesion to the insulating substrate 36 under the silver layer 37 as a base of the reference electrode 24, for example, a titanium layer may be formed to a thickness of 0.1 to 1.0 μm by a sputtering method or the like. Good. The size of the reference electrode 24 is, for example, a rectangular shape of 0.4 mm × 2.0 mm.
[0042]
Leads (0.2 mm × 2.8 mm) 34 and contact electrodes (1.6 mm × 0.8 mm) 35 c, 35 b, 35 a communicating with the working electrode 22, the counter electrode 23, and the reference electrode 24 are also formed on the insulating substrate 36. ing. In the three-electrode system having this configuration, the potential difference between the working electrode 22 and the reference electrode 24 is kept constant, and the current between the working electrode 22 and the counter electrode 23 is measured.
[0043]
In the above-described configuration, the three-electrode configuration has been described. However, there is also a two-electrode configuration including the working electrode 22 and the reference electrode 24. In this case, the potentials of the working electrode 22 and the reference electrode 24 are kept constant. The current flowing through the working electrode 22 and the reference electrode 24 at that time is measured.
[0044]
Next, a permselective film 40 is formed on the working electrode 22, the counter electrode 23, and the reference electrode 24 formed on the insulating substrate 36. The permselective membrane has a function of selectively permeating hydrogen peroxide and removing interfering substances, and is formed of, for example, an acetyl cellulose membrane or an ion exchange resin.
[0045]
On the permselective membrane 40, an enzyme membrane 42 having a function of supporting an enzyme in the membrane is formed. The enzyme film 42 is formed by, for example, immobilizing an enzyme and a protein such as albumin with a cross-linking agent such as glutaraldehyde.
[0046]
On the enzyme membrane 42, a restricted permeation membrane 43 is further formed. The restricted permeation membrane 43 has a function of restricting permeation of glucose and preventing adsorption of contaminants, and is formed of, for example, a fluoropolymer film, a silicone film, a polycarbonate film, a urethane polymer film, or the like.
[0047]
The thickness of each layer of the organic thin film including the above-described permselective membrane 40, enzyme membrane 42, and restricted permeation membrane 43 is selected to be about 0.1 to several μm.
[0048]
The restricted permeation membrane 43 has a function of preventing adsorption of contaminants, restricting permeation of glucose and the like, and expanding a measurement range. The permselective membrane 40 has a function of transmitting only hydrogen peroxide, for example, and preventing transmission of interfering substances.
Fine pores are formed in the limiting permeable membrane 43 and the permselective membrane 40, and the size of the pores restricts the permeation of a substance.
[0049]
An outline of a process of manufacturing the above-described electrochemical sensor 21 by using the sputtering method is as described below.
(1) A titanium layer 38 and a platinum layer 41 are formed on an insulating substrate (60 × 70 mm) 36 by a sputtering method, and a silver layer 37 is formed by a sputtering method.
(2) The working electrode 22, the counter electrode 23, the reference electrode 24, the lead 34, and the contact electrodes 35a, 35b, 35c are formed by photolithography.
(3) A silver chloride layer 39 is formed on the surface of the silver layer by treatment with an aqueous solution of iron (III) chloride, and the reference electrode 24 is formed.
(4) The permselective membrane 40, the enzyme membrane 42, and the restricted permeation membrane 43 are formed.
(5) The insulating substrate 36 is divided into individual electrochemical sensors 21 (6 × 9 mm).
[0050]
Next, a sensor assembly in which the electrochemical sensor 21 described in FIGS. 4A and 4B is mounted on a printed circuit board will be described with reference to FIG.
[0051]
In FIG. 5, the electrochemical sensor 21 is mounted on one end of a rectangular printed board 44, and wire bonding is performed between one end of the wiring portion 53 formed on the printed board 44 and the contact portions 35a, 35b, 35c of the electrochemical sensor 21. , Solder, anisotropic conductive resin and the like. On the printed circuit board 44, a sensor detection coil 27 for detecting the sensor assembly 52 when the sensor assembly 52 is inserted into the electrochemical sensor measuring device is detected. The other end of the printed circuit board 44 is provided with a plug 54 which is fitted and electrically connected to a connector on the electrochemical sensor measuring device side.
[0052]
FIGS. 6A, 6B, and 6C show a plan view, a side view, and a side sectional view in which the above-described sensor assembly 52 is mounted on a cartridge.
[0053]
In the cartridge 45, a sensor assembly 52 described in detail in FIG. 5 is mounted in a casing formed of a synthetic resin material into a substantially rectangular parallelepiped shape. A substantially circular opening 48 is formed at one end of the cartridge 45, and the working electrode 22, the counter electrode 23, and the reference electrode 24 of the electrochemical sensor 21 are formed through the opening 48 so as to be in contact with the sample solution. The other portions (contact portions 35a, 35b, 35c, and leads 34) are provided with seal members 46 made of O-ring rubber or the like around the openings so as not to come into contact with the solution. An opening end 47 of the cartridge 45 opposite to the opening 48 side is fitted to a connector of the electrochemical sensor measurement device 20 to enable electrical connection.
[0054]
An electrochemical sensor measuring device for mounting a cartridge 45 including the above-described electrochemical sensor 21 and measuring, for example, glucose concentration in a sample solution will be described with reference to FIG.
[0055]
In FIG. 1, reference numeral 45 denotes a cartridge including the electrochemical sensor 21 described above and the detection coil 27 patterned on the printed circuit board 44 and the like, which is connected to the main body 55 of the electrochemical sensor measuring device 20 via a connector. The working electrode 22 of the electrochemical sensor 21 is connected to the input terminal of an operational amplifier 25a of a current detection circuit 25, the reference electrode 24 is connected to the input terminal of an operational amplifier 26a of a potential control circuit 26, and the counter electrode 23 Is connected to the output terminal of an operational amplifier 26b in the potential control circuit 26. The voltage supply source 26c is connected to the input terminal of the operational amplifier 26b and the output terminal of the operational amplifier 26a.
[0056]
The plug 54 of the sensor detection coil 27 having one end short-circuited to the cartridge 45 side is connected to the sensor detection circuit 28 to which a predetermined voltage is applied to one end and the other end is grounded.
[0057]
The output terminal of the current detection circuit 25 is connected to an analog-to-digital (A / D) converter 29, and the output terminal of the A / D converter 29 is connected to a microcomputer (CPU) 30 such as an information processing device. The output terminal of the circuit 28 is also connected to the CPU 30.
[0058]
31 is a display means such as a liquid crystal display (LCD), and 32 and 33 are non-volatile and volatile storage means for work such as ROM and RAM generally used for the CPU 30.
[0059]
The operation of the above-described electrochemical sensor measurement device 20 will be described based on the waveform diagram of FIG. 2 and the flowchart of FIG. In this example, hydrogen peroxide (H ₂ O ₂ ) Will be described.
[0060]
The working electrode 22, counter electrode 23 and reference electrode 24 exposed from the opening 48 of the cartridge 45 in which the electrochemical sensor 21 described in FIG. ₁ As shown by, the sample is immersed in a storage solution [for example, an electrolyte (aqueous solution containing 0.15 M sodium chloride)].
[0061]
Next second step ST ₂ Enters the process in the electrochemical sensor measuring device 20, and the sensor detection coil 27 on the cartridge 45 side detects the closed circuit state. The sensor detection circuit 28 detects that the electrochemical sensor 21 is mounted on the main body 55, The detection data is transmitted to the CPU 30.
[0062]
When the sensor detection circuit 28 detects that the electrochemical sensor 21 is mounted, the CPU 30 drives the potential control circuit 26 to execute the third step ST ₃ As described above, a constant voltage (400 to 700 mV) is applied between the working electrode 22 (+) and the reference electrode (-) 24 of the electrochemical sensor 21 via the voltage supply source 26c of the potential control circuit 26.
[0063]
When a constant voltage is applied between the working electrode 22 and the reference electrode 24, a current depending on the preservation solution flows between the working electrode 22 and the counter electrode 23, and hardly flows in a steady state. This phenomenon is described in Electrochemistry and Industrial Physical Chemistry Vol 68, No. 1. It is described in detail on pages 63-68. When a voltage is applied between the working electrode 22 and the reference electrode 24, cations and anions in the vicinity of the electrodes, which have been electrostatically balanced with these electrodes until now, are distributed along with the rapid change of the electrode potential. Begin moving to achieve a new equilibrium. When a potential is applied so that the potential of the working electrode 22 becomes more positive than before, the cations move away from the working electrode 22, and conversely, the anions approach, and a new electric double layer is formed when the equilibrium distribution is settled. . As the charged particles move, this movement is observed as a current flowing through an external circuit. This phenomenon is similar to the process of passing a current through a kind of capacitor called an electric double layer through a resistor called a solution to charge (or discharge) electric charges.
[0064]
Such a current value is set in the fourth step ST. ₄ Then, the current detection circuit 25 detects the current. In FIG. 1, the current detection circuit 25 is connected to the working electrode 22 side. However, since the current flowing after the application of a constant voltage flows between the working electrode 22 and the counter electrode 23, the current detection circuit 25 may be connected to the counter electrode 23 side. Good.
[0065]
The current detected by the current detection circuit 25 is taken into the CPU 30 via the A / D converter 29 in accordance with the firmware stored in the ROM 32, and the fifth step ST ₅ Is stored in the RAM 33 as shown in FIG.
[0066]
The current value stored in the RAM 33 is stored in the third step ST. ₃ Immediately after the voltage is applied, the current becomes about 10 μA as shown in FIG. 2, decreases with time as described above, and becomes a steady state at about 10 μA or less. The horizontal axis in FIG. 2 shows the elapsed time, and the vertical axis shows the output current of the current detection circuit 25. The sixth step ST ₆ Then, the elapsed time is counted, and this count value is set in the seventh step ST. ₇ Is stored in the RAM 33 as shown in FIG.
[0067]
FIG. 2 shows the relationship between the transient response time stored in the RAM 33 and the calibration value. As can be seen from the figure, when the transient response time of the electrochemical sensor 21 is less than 1 minute, the cause such as the disconnection of the wiring portion 53, the inactivation of the electrodes 22 to 24, or the defect of the restricted permeable film 43 as shown by the curve 56. Is bad. On the other hand, in the case of the curve 57 in which the transient response time is longer than 10 minutes, the limiting permeable membrane 43 and the permselective membrane 40 are dense and defective, and the curves 58, 59 in which the transient response time is 2 minutes, 4 minutes and 5 minutes. , 60, the calibration values are 40 nA, 20 nA, and 10 nA. When a functional organic thin film is formed on the measurement electrode including the working electrode 22, the counter electrode 23, and the reference electrode 24, the flow of ions is restricted by diffusion in the organic thin film. Therefore, the time during which this current flows (transient response time) depends on the quality of the organic thin film.
[0068]
8th step ST ₈ Determines the transient response time until the current value reaches the steady state, and determines the ninth step ST ₉ Then, the determined transient response time is stored in the RAM 33.
[0069]
10th step ST ₁₀ Then, the quality of the electrochemical sensor 21 is determined by referring to the relationship between the determined transient response time and the above-described calibration value (current output value with respect to the storage solution). That is, if the electrochemical sensor 21 is defective, it is determined whether the electrochemical sensor 21 is non-defective or not. ₁₁ To display a defective product on the screen of the LCD 31. 12th step ST for non-defective products ₁₂ In FIG. 2, the transient response time shown by the curves 58 to 60 in FIG. 2 is a calibration value of 40 nA for 2 minutes, a calibration value of 20 nA for 4 minutes, a calibration value of 10 nA for 5 minutes, and the relationship between the transient response time and the calibration value. Determine the calibration value.
[0070]
If the electrochemical sensor 21 in the cartridge 45 attached to the apparatus main body 55 is normal from the determined calibration value, measurement is possible, and for example, H in the sample solution can be measured. ₂ O ₂ 13th to 18th steps ST for measuring _Thirteen ~ ST ₁₈ Proceed to
[0071]
13th step ST _Thirteen Then, the electrochemical sensor 21 in the cartridge 45 is immersed in the sample solution to be measured.
[0072]
When the enzyme film 42 of the electrochemical sensor 21 is glucose oxidase and the glucose (glucose) contained in the sample solution is measured, the glucose in the sample solution is converted into gluconolactone and hydrogen peroxide by the action of the enzyme glucose oxidase. H ₂ O ₂ ) Is converted as in the following equation 1.
[0073]
[Equation 1]
Glucose + O ₂ + H ₂ O → Gracono Kraton + H ₂ O ₂ ‥‥ (1)
[0074]
H generated by equation (1) ₂ O ₂ Is converted into a current based on the reaction of the following equation 2 and H ₂ O ₂ Can be determined, so that the glucose concentration can be calculated.
[0075]
[Equation 2]
H ₂ O ₂ → 2H ⁺ + O ₂ + 2e ⁻ ‥‥ (2)
In formula (2), H in the sample solution ₂ O ₂ Is anodized on the working electrode 22, and an oxidation current is generated between the working electrode 22 and the counter electrode 23. ₁₄ Detect like.
[0076]
It is clear that the use of alcohol oxidase, lactate oxidase, and ascorbate oxidase in addition to glucose oxidase can measure alcohol, lactic acid, and ascorbic acid, respectively.
[0077]
Next 15th step ST _Fifteen Then, the detected current value is converted into digital data by the A / D converter 29, taken into the CPU 30, and stored in the RAM 33.
[0078]
Next 16th step ST ₁₆ In the above, the CPU 30 calculates the glucose concentration of the sample solution from the calibration value stored in the ROM 32, and stores it in the RAM 33 again (step ST17). ₁₇ ). Thereafter, the CPU 30 displays the glucose concentration stored in the RAM 33 on the LCD 31 (step ST18). ₁₈ ) By the end.
[0079]
According to the above-described embodiment of the present example, the following effects can be obtained.
(1) The electrochemical sensor 21 composed of the measurement electrode such as the working electrode 22 and the functional organic thin film such as the enzyme film 42 has a large variation in the film quality of the functional organic thin film, and therefore the output of each electrochemical sensor 21 varies. However, by immersing in a storage solution serving as a reference solution, for example, a calibration value for knowing a relationship between a glucose concentration and an output value is obtained. By counting the transient response time up to the steady state, it is possible to easily determine the factor depending on the film quality (thickness and pore state) of the functional organic thin film from the count time, and calibrate the electrochemical sensor The value can be determined automatically.
(2) As in (1), the quality of the electrochemical sensor can be easily determined.
[0080]
Next, another embodiment of the present invention will be described with reference to FIGS.
[0081]
FIG. 7 is a system diagram showing another embodiment of the electrochemical sensor measuring apparatus of the present invention, FIG. 8 is a schematic plan view and a sectional view when a plurality of electrochemical sensors are integrally formed on a wafer, and FIG. 5 is a flowchart showing another embodiment of the electrochemical sensor of the present invention. 1 to 7 are denoted by the same reference numerals, and redundant description will be omitted.
[0082]
In FIG. 7, only differences from the configuration of FIG. 1 will be described below. The sensor detection circuit 28 is not required on the main body 55 side of the electrochemical sensor measurement device. Also, the input terminal T of the current detection circuit 25 ₁ And the input / output terminal T of the potential control circuit 26 ₂ And T ₃ Is connected to a prober 49.
[0083]
The prober 49 can contact the contact electrodes 35a, 35b, and 35c of the electrochemical sensor 21 on the wafer 50.
[0084]
4 (A) and 4 (B) show a single electrochemical sensor, but FIGS. 8 (A) and 8 (B) are plan views showing a case where a plurality of electrochemical sensors 21 are formed on a wafer 50 or the like [FIG. (A)] and a sectional view taken along the line BB ′ in FIG. 8 (A) [FIG. 8 (B)], showing a working electrode 22, a counter electrode 23 and a reference electrode on an insulating substrate 36 made of glass or the like having a large area. A plurality of electrochemical sensors are formed in such a state that a functional organic thin film composed of a permselective membrane 40, an enzyme membrane 42, and a restricted permeation membrane 43 is sequentially formed on a plurality of electrochemical sensors 21 composed of 24 and contact electrodes 35a, 35b, 35c. 21 are integrally formed. By removing the functional organic thin film on the contacts 35a, 35b, 35c by etching or the like, the position for contacting the prober is clarified, and conduction with the prober 49 and the contact electrodes 35a, 35b, 35c becomes possible. The wafer 50 is cut into a fifth-meshed shape, and a single electrochemical sensor 21 as shown in FIGS. 4A and 4B is obtained.
[0085]
Hereinafter, the operation of the electrochemical sensor measurement device 20 of FIG. 7 will be described with reference to the flowchart of FIG.
[0086]
In FIG. 9, the first step STE ₁ Then, the prober 49 is brought into contact with the contact electrodes 35c, 35b and 35a of the working electrode 22, the counter electrode 23 and the reference electrode 24 of the single electrochemical sensor element 21 of the plurality of electrochemical sensor elements 21 formed on the wafer 50. Let it.
[0087]
Second step STE ₂ Then, for example, a storage solution composed of an aqueous solution containing 0.15 mol of sodium chloride as an electrolyte is dropped on the working electrode 22, the counter electrode 23, and the reference electrode 24 of the electrochemical sensor element.
[0088]
Third step STE ₃ In the method, a constant voltage (400 to 700 mV) is applied between the working electrode 22 and the reference electrode 24 by the potential control circuit 26 in the electrochemical sensor measurement device 20.
[0089]
4th step STE ₄ Then, the current generated between the working electrode 22 and the counter electrode 23 is detected by the current detection circuit 25.
[0090]
Fifth step STE ₅ Then, the detected current value is converted into a digital signal by the A / D converter 29, taken into the CPU 30, and stored in the RAM 33.
[0091]
6th step STE ₆ Immediately after the voltage is applied to the electrochemical sensor 21 in the third step, the current value of the current detection circuit 25 becomes about 10 μA, decreases with time, becomes about 10 nA or less, and becomes a steady state. The CPU 30 counts a transient response time, which is a time required for the generated current to reach a steady state.
[0092]
Seventh step STE ₇ Then, the count value is stored in the RAM 33 via the CPU 30.
[0093]
8th step STE ₈ Then, the transient response time is determined based on the count value stored in the RAM 33.
[0094]
Ninth step STE ₉ Then, the transient response time is stored in the RAM 33.
[0095]
Tenth step STE ₁₀ Then, the calibration value is determined from the relationship between the transient response time and the calibration value stored in the RAM 33, and it is determined whether the single electrochemical sensor 21 is normal on the wafer 50 from the determined calibration value. Eleventh step STE ₁₁ Then, the end is reached by displaying the judgment result on the LCD 31. Here, if the transient response time is less than 1 minute as shown in FIG. 2, the failure is due to disconnection of the lead 34 or the wiring portion, inactivation of the electrode, or a defect of the restricted transmission film 40. On the other hand, when the transient response time is longer than 10 minutes, the limiting permeable film 43 and the selective permeable film 40 are dense and defective.
[0096]
In the above configuration, the plurality of electrochemical sensors 21 on the wafer were measured one by one. However, it is of course possible to measure a plurality of electrochemical sensors 21 at the same time or to apply the present invention to a bipolar electrochemical sensor. is there.
[0097]
According to the configuration and operation shown in FIGS. 7 to 9 described above, in a state where the plurality of electrochemical sensors 21 are formed on the wafer 50, the calibration values of the plurality of electrochemical sensor elements 21 are determined, and whether or not they are normal is determined. Can be checked before the cartridge is mounted, and the printed circuit board 44 and the cartridge 45 need not be discarded as in the case of a defective product that occurs after the sub-assembly 52, and the number of assembly steps can be reduced. Can be.
[0098]
【The invention's effect】
ADVANTAGE OF THE INVENTION According to the electrochemical sensor measuring apparatus and its measuring method of this invention, a calibration sensor is not required, a calibration value can be automatically determined only by the electrochemical sensor for measurement, and whether the electrochemical sensor is normal Can be automatically determined. In addition, a plurality of electrochemical sensor elements can determine a calibration value on a wafer and determine whether the sensor is normal or not, so that the number of assembling steps can be reduced compared to a check after the number of assembling steps, and a defective discarded portion can be saved. Having.
[Brief description of the drawings]
FIG. 1 is a system diagram of an electrochemical sensor measurement device of the present invention.
FIG. 2 is a curve diagram showing a relationship between a transient response time calibration value and an output according to the present invention.
FIG. 3 is a flowchart showing the electrochemical sensor measurement method of the present invention.
FIG. 4 is a plan view and a side sectional view showing one embodiment of an electrochemical sensor used in the present invention.
FIG. 5 is a plan view of an electrochemical sensor provided on a printed circuit board used in the present invention.
FIG. 6 is a plan view, a side view, and a side sectional view of a sensor cartridge used in the present invention.
FIG. 7 is a system diagram showing another embodiment of the electrochemical sensor measurement device of the present invention.
FIG. 8 is a schematic plan view and a cross-sectional view when a plurality of electrochemical sensors are integrally formed on a wafer.
FIG. 9 is a flowchart showing another embodiment of the electrochemical sensor of the present invention.
FIG. 10 is a system diagram of a conventional electrochemical sensor measuring device.
FIG. 11 is a flowchart of a conventional electrochemical sensor measurement method.
[Explanation of symbols]
20 ‥‥ electrochemical sensor measuring device, 21 ‥‥ electrochemical sensor, 22 ‥‥ working electrode, 23 ‥‥ counter electrode, 24 ‥‥ reference electrode, 25 ‥‥ current detection circuit, 26 ‥‥ potential control circuit, 28 ‥‥ Sensor detection circuit, 30 CPU, 45 cartridge, 55 body, 49 prober

Claims (8)

An electrochemical sensor element having at least two electrodes;
Potential control means for immersing the electrochemical sensor element in a storage aqueous solution and supplying a constant voltage between the two electrodes;
Current detection means for detecting a transient response current generated when the voltage is supplied to the electrochemical sensor element,
Information processing means for counting the elapsed time of the transient response output of the current detecting means and referring to the relationship between the elapsed time and the calibration value to determine the calibration value of the electrochemical sensor element. Characteristic electrochemical sensor measurement device. The electrochemical sensor element having the determined calibration value is immersed in a sample solution, and the calibration value is used to calculate the concentration of the sample solution from the current value of the current detection means using the information processing means. The electrochemical sensor measurement device according to claim 1, wherein the measurement is performed. 3. The electrochemical sensor measurement device according to claim 1, wherein a plurality of the electrochemical sensor elements are formed on an insulating substrate. An electrochemical sensor element having at least two electrodes;
Potential control means for immersing the electrochemical sensor element in a storage solution and supplying a constant voltage between the two electrodes;
Current detection means for detecting a transient response current generated when the voltage is supplied to the electrochemical sensor element,
The elapsed time of the transient response output of the current detection means is counted, the calibration value of the electrochemical sensor element is determined from the relationship between the elapsed time and the calibration value, and the electrochemical sensor element is determined based on the determined calibration value. An electrochemical sensor measurement device comprising: information processing means for determining pass / fail. Dipping an electrochemical sensor element having at least two electrodes in a storage solution and supplying a constant voltage between the two electrodes;
Detecting a transient response current generated when the voltage is supplied to the electrochemical sensor element,
Counting the elapsed time of the transient response output at the time of the current detection, and determining the calibration value of the electrochemical sensor element with reference to the relationship between the elapsed time and the calibration value. How to measure the sensor. Immersing the electrochemical sensor element in which the calibration value is determined in a sample solution;
6. The method according to claim 5, further comprising calculating the sample solution concentration from a current value obtained by detecting the transient response current using the calibration value. Forming a plurality of the electrochemical sensor elements on an insulating substrate, and bringing a probe into contact with electrode contact portions respectively connected to the at least two electrodes of the electrochemical sensor elements to perform measurement. The method for measuring an electrochemical sensor according to claim 5, wherein the method comprises: Dipping an electrochemical sensor element having at least two electrodes in a storage solution and supplying a constant voltage between the two electrodes;
Detecting a transient response current generated when the voltage is supplied to the electrochemical sensor element,
Counting the elapsed time of the transient response output of the detection current;
Determining a calibration value of the electrochemical sensor element from the relationship between the elapsed time and the calibration value,
Determining a pass / fail of the electrochemical sensor element based on the determined calibration value.

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