JP2005147990A - Method for measuring substrate concentration - Google Patents

Method for measuring substrate concentration Download PDF

Info

Publication number
JP2005147990A
JP2005147990A JP2003389128A JP2003389128A JP2005147990A JP 2005147990 A JP2005147990 A JP 2005147990A JP 2003389128 A JP2003389128 A JP 2003389128A JP 2003389128 A JP2003389128 A JP 2003389128A JP 2005147990 A JP2005147990 A JP 2005147990A
Authority
JP
Japan
Prior art keywords
voltage application
step
voltage
method
application step
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
JP2003389128A
Other languages
Japanese (ja)
Other versions
JP4449431B2 (en
Inventor
Hiroyuki Tokunaga
Eriko Yamanishi
永吏子 山西
博之 徳永
Original Assignee
Matsushita Electric Ind Co Ltd
松下電器産業株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Matsushita Electric Ind Co Ltd, 松下電器産業株式会社 filed Critical Matsushita Electric Ind Co Ltd
Priority to JP2003389128A priority Critical patent/JP4449431B2/en
Publication of JP2005147990A publication Critical patent/JP2005147990A/en
Application granted granted Critical
Publication of JP4449431B2 publication Critical patent/JP4449431B2/en
Application status is Active legal-status Critical
Anticipated expiration legal-status Critical

Links

Images

Abstract

<P>PROBLEM TO BE SOLVED: To provide a measuring method in order to reduce measurement errors due to Hct of blood, in the case of quantitatively determining a substrate included in the blood. <P>SOLUTION: The measuring method includes a voltage applying step (T0-T1) for preprocessing the blood; a voltage applying step (T2-T3) for compensating data; and a voltage applying step (T4-T5) for oxidizing a generated reduced electron carrier after a certain period of time. A parameter depending on hematocrit is calculated, based on a ratio of a peak current value (i2) which is obtained in the voltage applying step for compensating, to a peak current value (i4) which is obtained in the voltage applying step for oxidizing the generated reduced electron carrier after the certain period of time, and the amount of substrate is compensated by using the parameter. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

本発明は、血液中に含まれる基質を定量するために、バイオセンサ及びこのバイオセンサが装着される測定装置を用いる測定方法に関するものであり、特に血液中のヘマトクリットによる測定誤差を減少させる為の新規な定量方法を提供するものである。 The present invention, in order to quantify the substrate contained in the blood, relates measuring method using the measuring apparatus biosensor and the biosensor is attached, for in particular reduce the measurement error due to hematocrit in the blood it is intended to provide a novel quantitative method.

バイオセンサとは、微生物、酵素、抗体、DNA、RNA等の生物材料の分子認識能を利用し、生物材料を分子識別素子として応用した、試料液中の基質含有量を定量するセンサである。 The biosensor utilizing microorganisms, enzymes, antibodies, DNA, the molecule recognition ability of the biological material such as RNA, by applying the biological material as a molecular identification element, a sensor for quantifying the substrate content in the sample solution. 即ち、生物材料が目的の基質を認識したときに起こる反応、例えば微生物の呼吸による酸素の消費、酵素反応、発光等、を利用して試料液中に含まれる基質を定量するのである。 That is, the reaction that occurs when a biological material recognizes a substrate of interest, for example, respiratory oxygen consumption by the microorganisms, the enzymatic reaction, emission or the like, and to quantify the substrate contained in the sample solution by using a. そして各種バイオセンサの中でも酵素センサの実用化は進んでおり、例えば、グルコース、乳酸、コレステロール、アミノ酸用のバイオセンサである酵素センサは医療計測や食品工業に利用されている。 The practical use of enzyme sensors among the various biosensor is progressing, for example, glucose, lactate, cholesterol, enzymes sensor is biosensor for amino acids are used in medical measurement and food industry. この酵素センサは、例えば検体である試料液に含まれる基質と酵素などとの反応により生成する電子によって電子伝達体を還元し、測定装置がその電子伝達体の還元量を電気化学的に計測することにより、検体の定量分析を行うようになっている。 The enzyme sensor, for example by electrons produced by the reaction, such as substrate and the enzyme and contained in the sample solution is subject to reduced electron carrier, the measuring device measures the amount of reduction of the electron mediator electrochemically by, thereby performing quantitative analysis of analytes.

このようなバイオセンサを用いた測定方法について様々な形態のものが提案されている。 It has been proposed in various forms for the measuring method using such a biosensor. そこで従来の測定方法について説明する。 Therefore described conventional measuring methods. (例えば特許文献1参照。)試料液中の基質含有量を定量するには、バイオセンサを測定装置に挿入後、後述するバイオセンサの電極に測定装置によって一定電圧が印加された状態で、試料液を試料点着部に供給する。 (For example, see Patent Document 1.) To quantify the substrate content in the sample solution after inserting a biosensor into the measuring device, in a state where a constant voltage is applied by the measuring device to the electrodes of the biosensor will be described later, the sample supplying liquid to the sample adhering part. 点着された試料液がバイオセンサの内部に吸引されて試薬層の溶解が始まる。 Dissolution of spotted by the sample solution is sucked into the biosensor reagent layer begins. 測定装置はバイオセンサの電極間に生じる電気的変化を検知して定量動作を開始するようになっている。 Measuring device is adapted to initiate the quantification operation by detecting an electrical change that occurs between the electrodes of the biosensor.

試料液供給検知後のプロファイルを図5に示す。 The profile after the detection sample solution supply shown in FIG. 本プロファイルには三つの連続期間からなり、例えば時刻t0からt1の第1印加期間、時刻t1からt2の待機時間、時刻t2からt3の第2印加期間からなる。 This profile consists of three consecutive periods, for example, a first application period from time t0 t1, wait period from time t1 t2, and a second application period from time t2 t3. この第1印加期間を設けることでヘマトクリットによる測定誤差を抑制することができる。 It is possible to suppress the measurement error due to hematocrit by providing the first application period.

また、誤差影響を補正して分析対象物の濃度を求めるバイオセンサの測定方法について説明する。 Further, a description will be given of a measuring method of the biosensor for determining the concentration of the analyte by correcting the error effect. (例えば特許文献2参照。)バイオセンサに定められた電圧を2回印加して電気化学反応を促進させ、その結果得られる電流値から下記パラメータP1及びP2を算出し、これらのパラメータから統計的手法により誤差を補正して分析対象物濃度を算出する。 (For example, see Patent Document 2.) A voltage which is defined in the biosensor is applied twice to promote the electrochemical reaction, it calculates the following parameters P1 and P2 from the current values ​​obtained as a result of statistical these parameters by correcting the error to calculate the analyte concentration by the technique. P1:1回目励起における電流の最大値または最大値以降の電流値(If)と2回目励起の任意の時点における電流値(Ib)の比(If/Ib)。 P1: The ratio of the first maximum value or the maximum value after the current value of the current in the excitation and (If) current value at any point in the second excitation (Ib) (If / Ib). P2:2回目励起の任意の時点における電流値(Ib)。 P2: 2 time current value at any time of the excitation (Ib).
特開2003−156469号公報 JP 2003-156469 JP 国際公開第99/60391号パンフレット WO 99/60391 pamphlet

しかしながら従来の測定方法には、血液のヘマトクリットが測定感度に影響を及ぼすという問題があった。 However the conventional measuring method has a hematocrit of the blood is a problem that affects the measurement sensitivity. ヘマトクリットとは血液中に占める有形成分の体積比(%)である。 Hematocrit and is the volume ratio of the solid components accounted for in the blood (%). 一般的に貧血のない人では赤血球が40〜50%を占める。 Generally accounts for 40-50% red blood cells in people with no anemia. 慢性腎不全になり腎性貧血になるとヘマトクリットは下がり15%を下回る状態になる場合もあり、個人差、男女差も大きい。 It becomes renal anemia becomes chronic renal failure hematocrit sometimes in a state below the 15% down, individual differences, gender differences also large.

一方、近年のバイオセンサに要求されるスペックとして測定時間の短縮化が望まれている。 On the other hand, shortening the measurement time is desired as a specification required for recent biosensor. バイオセンサを用いて迅速に基質の測定を行う場合、試料の粘性がその測定精度に大きな影響を与える。 When performing fast measurements of the substrate by using a biosensor, the viscosity of the sample has a great influence on the measurement accuracy. 特に、人体の血液を試料液とする場合、粘性の高い(Hctが高い:以下、高Hct)血液の場合は応答レベルが相対的に低下し、粘性の低い(Hctが低い:以下、低Hct)血液の場合は応答レベルが相対的に高くなり、この傾向は測定時間の短縮化が進むにつれ顕著になる場合がある。 In particular, when the human blood as the sample liquid, viscous (high Hct hereinafter, high Hct) in the case of blood relatively reduced response levels, low viscosity (Hct low: less, low Hct ) If blood becomes relatively high response level, this tendency may become remarkable as the shortening of the measurement time progresses. この現象は、試薬層の血液への溶解性、および溶存種の拡散速度がHctの影響を受けていることを示唆する。 This phenomenon suggests that solubility in blood reagent layer, and the diffusion rate of dissolved species is affected by Hct.

図6は測定時間とヘマトクリットの関係を示す図である。 6 is a diagram showing the relationship between measurement time and hematocrit. これは、図5で示した特許文献1の測定手法に準じて測定を行った結果である。 This is a result of measurement according to the measurement technique of Patent Document 1 shown in FIG. 測定時間とは図5で示したt3であり、低Hctおよび高Hctの血液を用いて測定した時のt3における電流値をそれぞれプロットしたものである。 Measurement time is t3 shown in FIG. 5, is a current value at t3 when measured using a low Hct and high Hct of blood a plot, respectively. 図6から明らかなように、測定時間が短くなるとヘマトクリットの差異による電流値の差が大きくなることが分かる。 As apparent from FIG. 6, the difference between the current value due to the difference in hematocrit When the measurement time is shortened is can be seen that large. とりわけ、測定時間が5秒程度の場合にはヘマトクリットの影響を大きく受ける。 Especially, greatly affected by hematocrit when the measured time is about 5 seconds. その為、特許文献1の測定法で時間短縮を行うことはヘマトクリットによる測定誤差が顕著となり、非常に困難であった。 Therefore, by performing a time reduction in the measurement method of Patent Document 1 is the measurement error due to hematocrit becomes remarkable has been very difficult.

特許文献2に示される従来の測定方法は、1回目励起における電流の最大値または最大値以降の電流値と、2回目励起の任意の時点における電流値の比を試料物性による影響をより大きく受けるパラメータとして使用している。 Conventional measuring method shown in Patent Document 2 receives larger and the maximum value or the current value of the maximum value after the current, the ratio of the current value at any point in the second excitation effects due to the sample properties at the first excitation It is used as a parameter. 1回目励起は溶解初期の段階であることから、試薬層の血液への溶解性および溶存種の拡散速度が律速になり、ヘマトクリットに依存した電流値が得られやすいが、血液の供給速度、手技の差によって電流値がばらつきやすい。 Since the first excitation is dissolved early stage, the diffusion rate of solubility and dissolved species into the blood of the reagent layer becomes rate-limiting, hematocrit current value is easily obtained which is dependent, blood feed rate of, procedure It tends to vary the current value by the difference. さらに血液中に含まれる易酸化性物質が1回目励起の際に電流値として検出されやすく、血中易酸化性物質の個人差により1回目励起の電流値は誤差が生じやすい。 Easily further detected as a current value when the oxidizable material is first excitation contained in the blood, the current value of the first excited by individual differences of the oxidizable substances in the blood are likely error occurs. また、1回目励起の電流の最大値または最大値以降の電流を補正に用いるためには、ある程度の印加時間が必要である。 In order to use the maximum value or the maximum value after the current first excitation current to the correction requires a certain amount of the application time. しかし初期段階(1回目励起)で長時間電位をかけると、還元性電子伝達体が過剰量酸化されるため、待機時間を長くして還元性電子伝達体を再び蓄積しなければ2回目励起期間で検知される応答値の基質依存性が悪くなる可能性がある。 However, applying a long potential at the initial stage (first excitation), reducing the electron mediator is excess oxidizing, second excitation period unless the reducing electron mediator again accumulated long standby time in which may substrate dependency deteriorates sensed the response values. その為特許文献2の測定方法では、ばらつきを抑えた測定を行うこと、測定時間の短縮を行うことが非常に困難であった。 In Therefore measuring method of Patent Document 2, by performing a measurement with reduced variations, it is very difficult to shorten the measurement time.

前記従来の課題を解決するために、本発明の基質濃度の測定方法は、絶縁基板上の少なくとも一部に形成された対電極、測定電極を含む電極部、当該電極部上または周辺に少なくとも酵素、電子伝達体を含む試薬層を有するバイオセンサと、当該電極部の各電極に電位を印加する為の接続端子及び駆動電源を有する測定装置を用い、当該駆動電源によって前記電極部に電位を印加させて出力される電流を検知し、血液中に含まれる基質を定量する測定方法であって、断続的な3回以上の電圧印加工程を包含する。 In order to solve the conventional problems, method of measuring the concentration of the substrate of the present invention is at least an enzyme at least some the formed counter electrode on the insulating substrate, the electrode unit comprising a measuring electrode, on or near the electrode portions , applied a biosensor, the measurement device used with the connection terminals and the drive power source for applying a potential to each electrode of the electrode unit, the potential to the electrode portion by the drive power supply having a reagent layer containing an electron mediator is allowed to detect a current outputted by the substrate contained in the blood there is provided a measuring method for quantifying comprises an intermittent three or more voltage applying step.

また、前記断続的な電圧印加工程が、少なくとも血液前処理のための電圧印加工程、データ補正のための電圧印加工程、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程を包含してもよい。 Further, the intermittent voltage application step, at least the voltage application step for the blood preprocessing, the data voltage application step for the correction, the voltage application step for oxidizing the resulting reduced electron mediator after a predetermined time has elapsed it may encompass.

また、前記電圧印加工程において、血液前処理のための電圧印加工程の後に、データ補正のための電圧印加工程が実施され、当該データ補正のための電圧印加工程の後に、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程が実施されてもよい。 Further, in the voltage applying step, after the voltage application step for the blood pretreatment, the voltage application step for the data correction is performed, after the voltage application step for the data correction, was produced after a predetermined time has elapsed voltage application step for oxidizing the reduced form electron mediator may be performed.

また、前記データ補正のための電圧印加工程より得られたピーク電流値と、前記一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程より得られたピーク電流値との比に基づいてヘマトクリットに依存したパラメータを算出し、前記パラメータにより基質量を補正してもよい。 The ratio of the peak current value obtained from the voltage applying step for oxidizing the peak current value obtained from the voltage applying step, the predetermined time is generated after lapse of the reduced form electron carrier for the data correction calculating a parameter that depends on the hematocrit based on the amount of substrate may be corrected by the parameter.

また前記パラメータを判別係数とする判別関数を用いてヘマトクリットを補正してもよい。 Or it may be corrected hematocrit using discriminant function to determine coefficients of the parameters.

また、前記血液前処理のための電圧印加工程およびデータ補正のための電圧印加工程における印加電圧が、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程における印加電圧よりも大きいことを特徴とする測定方法としてもよい。 Further, the applied voltage in the voltage application step for the voltage application step and the data correction for the blood preprocessing, than the voltage applied in the voltage application step for oxidizing the reduced form electron mediator generated after a predetermined time has elapsed it may be measured wherein the larger.

また、前記血液前処理のための電圧印加工程における電圧印加時間が0.2秒〜2秒であることを特徴とする測定方法としてもよい。 The present invention may also be measured and wherein the voltage application time in the voltage application step for the blood before treatment is 0.2 to 2 seconds.

また、前記データ補正のための電圧印加工程直前の開回路時間が0.2秒〜1秒であることを特徴とする測定方法としてもよい。 The present invention may also be measured and wherein the open-circuit time of the voltage application step immediately prior to the data correction is 0.2 to 1 second.

また、前記データ補正のための電圧印加工程における電圧印加時間が0.2秒〜2秒であることを特徴とする測定方法としてもよい。 The present invention may also be measured and wherein the voltage application time in the voltage application step for the data correction is 0.2 to 2 seconds.

また、前記一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程直前の開回路時間が1秒〜6秒であることを特徴とする測定方法としてもよい。 The present invention may also be measured and wherein the open-circuit time of the voltage application step just prior to oxidizing said predetermined time is generated after lapse of the reduced form electron mediator is 6 seconds 1 second.

本発明の基質濃度の測定方法によれば、絶縁基板上の少なくとも一部に形成された対電極、測定電極を含む電極部、当該電極部上または周辺に少なくとも酵素、電子伝達体を含む試薬層を有するバイオセンサと、当該電極部の各電極に電位を印加する為の接続端子及び駆動電源を有する測定装置を用い、当該駆動電源によって前記電極部に電位を印加させて出力される電流を検知し、血液中に含まれる基質を定量する測定方法であって、血液前処理のための電圧印加工程、データ補正のための電圧印加工程、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程を包含し、前記補正のための電圧印加工程より得られたピーク電流値と、前記一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程より According to the measuring method of concentration of the substrate of the present invention, at least a part formed counter electrode on the insulating substrate, the electrode unit comprising a measuring electrode, a reagent layer containing at least an enzyme, an electron mediator on or near the electrode portions detecting a biosensor, the measurement device used with the connection terminals and the drive power source for applying a potential to each electrode of the electrode unit, a current output by applying a potential to the electrode portion by the drive power supply having a and, a substrate contained in the blood there is provided a measuring method for quantitatively oxidizes voltage application step for the blood pretreatment, the voltage application step for the data correction, the reduced form electron mediator generated after a predetermined time has elapsed includes a voltage application step for the peak current value obtained from the voltage applying step for correcting, from the voltage applying step for oxidizing the reduced form electron mediator which is generated after lapse of said predetermined time られたピーク電流値との比に基づいてヘマトクリットに依存したパラメータを算出し、前記パラメータにより基質量を補正することで、測定精度の良好な測定方法を提供することができる。 Calculating a parameter that depends on the hematocrit based on the ratio of the peak current value that is, by correcting the amount of substrate by the parameter, it is possible to provide a good method for measuring the measurement accuracy.

以下に、本発明の基質濃度の測定方法の実施の形態を図面とともに詳細に説明する。 Hereinafter, detailed description of the embodiments of the method of measuring the concentration of the substrate of the present invention in conjunction with the accompanying drawings.

(実施の形態1) (Embodiment 1)
図1は、本発明の第1の実施例における基質濃度の測定方法のプロファイル図を示す。 Figure 1 shows a profile view of a method for determining a substrate concentration in the first embodiment of the present invention.

図1におけるプロファイルにおいて、血液が供給されたことを検知した時刻をT0とする。 In the profile in FIG. 1, the time it is detected that the blood has been supplied to T0. 図1のプロファイルにおいては、5つの工程からなり、T0からT1を第1工程(血液前処理の為の電圧印加工程)、T1からT2を第2工程(開回路)、T2からT3を第3工程(データ補正のための電圧印加工程)、T3からT4を第4工程(開回路)、T4からT5を第5工程(一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程)とする。 In the profile of FIG. 1, consists of five steps, the first step of the T1 from T0 (voltage application step for the blood pretreatment), a T2 from T1 second step (open circuit), from T2 T3 3 step (a voltage application step for data correction) from T3 T4 fourth step (open circuit), the voltage applied for oxidation of reduced form electron mediator which the T5 generated after the elapse of a fifth step (fixed time T4 process) to.

血液前処理のための第1工程では、溶解初期の段階で酵素反応の結果生成した還元型電子伝達体が酸化されると同時に、血液中に含まれる易酸化性物質が最初の電圧印加工程である第1工程で酸化される。 In the first step for blood pretreatment, simultaneously with the generation result of the enzymatic reaction in dissolution initial stage reduced electron mediator is oxidized, oxidizable substances contained in the blood in the first voltage application step It is oxidized at a certain first step.

次に第2工程を開回路にすることで、酵素反応により生成した還元型電子伝達体が蓄積されていく。 Then by the second step an open circuit, reduced electron mediator generated by the enzymatic reaction is accumulated.

データ補正のための第3工程では、第2工程の開回路時間を十分に持たせずに印加を開始するので、特に高Hctの血液になるほど、還元型電子伝達体を十分に蓄積できず、ピーク電流i2はヘマトクリットの影響を大きく受けた値となる。 In a third step for data compensation, since starting the application without fully having an open circuit time of the second step, more particularly to a high Hct of blood, it can not be sufficiently accumulated reduced electron mediator, peak current i2 becomes larger received values ​​the influence of the hematocrit.

本発明においては、データ補正に使用する第3工程以外に血液前処理として第1工程を設けることで、血液の供給速度、手技の差によるばらつきや血中の還元性物質の影響を除去することができ、ヘマトクリットの影響のみを受けたパラメータが第3工程で得られる。 In the present invention, by providing the first step in addition to the third step using the data correction as a blood pretreatment, removing the influence of the reducing substance variation and blood by the supply rate, the difference between the procedure of the blood It can be a parameter that received only the hematocrit effect can be obtained in the third step. 更にこの第1工程の存在により、血中の易酸化性物質の影響を軽減させた最終応答値を得ることが同時に可能となる。 Furthermore the presence of the first step, it is possible simultaneously to obtain a final response value and reduce the effects of oxidizable substances in the blood.

次に第4工程で再び開回路にし、再度、還元型電子伝達体を蓄積する。 Then open circuit again in the fourth step, again, accumulating the reduced form electron mediator. このとき、一定時間以上時間をとることで、高Hctの血液においても十分量の還元型電子伝達体が蓄積される。 In this case, by taking more than a certain time period, a sufficient amount of the reduced form electron mediator is also accumulated in the blood of high Hct.

第5工程で電位V3を印加した際に得られるピーク電流i4は、見かけ上ヘマトクリットの影響が小さい値となる。 Peak current i4 obtained upon applying a potential V3 at the fifth step, a value is less affected apparently hematocrit. その後基質濃度との最も依存性が高い電流値を示すi5の電流値を測定する。 Thereafter most dependence and substrate concentration and the current value of i5 showing high current value. このi5を最終応答値とする。 This i5 and final response value. そして、ヘマトクリットの最終応答値に与える影響を低減させるため、データ補正のための第3工程で求めたi2を利用して、i4/i2のパラメータを算出し、応答値i5にこのパラメータを基に予め決めておいた補正を加える。 Then, in order to reduce the influence on the final response value of hematocrit, using the i2 determined in the third step for data correction, to calculate the parameters of i4 / i2, the response value i5 based on this parameter Add a predetermined that had been corrected.

本測定方法では、データ補正のための電圧印加工程の前の開回路時間T1〜T2は使用する酵素の能力によって異なるが、0.2秒から1秒が好ましい。 In this measurement method, the open-circuit time T1~T2 before the voltage application step for the data correction is different from the ability of the enzyme to be used, but is preferably 1 second 0.2 seconds. また、血液前処理のための電圧印加工程の時間T0〜T1及びデータ補正のための電圧印加工程の時間T2〜T3は使用する酵素の能力によって異なるが、0.2秒から2秒が好ましい。 Although time T2~T3 voltage application step for the time T0~T1 and data correction of the voltage application step for the blood before treatment varies by the ability of the enzyme to be used, preferably 2 seconds 0.2 seconds. また、前記血液前処理のための電圧印加工程およびデータ補正のための電圧印加工程における印加電圧が、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程における印加電圧よりも大きいことが好ましい。 Further, the applied voltage in the voltage application step for the voltage application step and the data correction for the blood preprocessing, than the voltage applied in the voltage application step for oxidizing the reduced form electron mediator generated after a predetermined time has elapsed greater is preferable. さらに、電圧V2は0.1V〜0.8Vが好ましい。 Further, the voltage V2 0.1V~0.8V are preferred. また一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程直前の開回路時間は1秒〜6秒であることが好ましい。 It is preferable open-circuit time of the voltage application step just prior to oxidizing the reduced form electron mediator generated after a certain period of time is 6 seconds 1 second.

また、データ補正のための電圧印加を数回行い、数回のデータ補正のための電圧印加で得られた複数の電流値を補正に用いることでさらに精度が向上する。 Also conducted several times voltage application for data correction, further accuracy by using the corrected multiple current value obtained by the voltage applied for several data correction is improved. その際の電圧は違う電圧を印加してもよい。 Voltage of that case may be applied to different voltage.

また、前記データ補正の為の電圧印加工程、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程で得られた電流値を、上記特許文献2に示されたような方法で、判別係数とする判別関数を用いてヘマトクリットを補正してもよい。 The voltage application step for the data correction, the current value obtained by the voltage applying step for oxidizing the reduced form electron mediator generated after a predetermined time has elapsed, as shown in Patent Document 2 METHOD in may correct the hematocrit using discriminant function to determine coefficients.

データ補正のための電圧印加工程ではヘマトクリットの影響を大きく受けた値が得られればどのポイントの電流値を用いても可能であるが、誤差の少ない補正を行う為にはその影響が顕著に出やすいピーク電流を用いることが、好ましい。 Although the voltage application step for the data correction is possible by using the current value of any point as long obtain greater received values ​​the influence of the hematocrit, in order to perform error less correction output significantly its influence it is preferable to use a cheap peak current.

本発明のより具体的な実施の形態について図面とともに詳細に説明する。 It will be described in detail with reference to the drawings for a more specific embodiment of the present invention. 以下の構成からなるバイオセンサをセンサの一例として用いた。 Using a biosensor comprising the following structure as an example of a sensor.

図2(a)はバイオセンサの分解斜視図であり、図2(b)はバイオセンサの上面から見た電極部の構成を示す図である。 2 (a) is an exploded perspective view of the biosensor, FIG. 2 (b) is a diagram showing a structure of an electrode portion as viewed from the upper surface of the biosensor. 19はポリエチレンテレフタレート等からなる絶縁性の基板(以下、「基板」とする。)であって、基板19の表面にはパラジウムからなる導体層がスパッタリングによって形成されている。 19 an insulating substrate made of polyethylene terephthalate (hereinafter referred to. As "substrate") a, is the surface of the substrate 19 conductive layer made of palladium is formed by sputtering. 26は中央部に空気孔27が設けられた絶縁性の基板であって、切欠部25を有するスペーサ24を基板19との間に挟みこんで基板19と一体に配置される。 26 is an insulating substrate which air holes 27 are provided in the central portion are arranged crowded in together with the substrate 19 sandwiched between the spacer 24 substrate 19 having a notch 25.

基板19上には、複数のスリットによって導体層が分割されて対電極21、測定電極20および検知極22が形成されている。 On the substrate 19, the counter electrode 21 the conductive layer is divided, the measurement electrode 20 and detection electrode 22 is formed by a plurality of slits.

スペーサ24は基板19上の対電極21、測定電極20および検知電極22を覆うように配置され、検体供給路25aが形成される。 The spacer 24 is disposed so as to cover the counter electrode 21, measuring electrode 20 and sensing electrode 22 on the substrate 19, the sample supply channel 25a is formed. スペーサ24の切欠部25から露出している対電極21、測定電極20および検知電極22上に、酵素としてグルコースデヒドロゲナーゼ、電子伝達体としてフェリシアン化カリウム等を含有する試薬を塗布し試薬層23を形成させる。 Notch 25 counter electrode 21 exposed from the spacer 24, on the measuring electrode 20 and sensing electrode 22, the glucose dehydrogenase as the enzyme to form a coating a reagent containing potassium ferricyanide or the like as an electron mediator reagent layer 23 .

この酵素と電子伝達体が含まれる試薬層が検体供給路に吸引された血液に溶解し、血液中の基質であるグルコースとの間で酵素反応が進行し電子伝達体が還元されて還元型電子伝達体が生成される。 The reagent layer enzyme and the electron mediator is included is dissolved in the blood that is sucked into the sample supply path, the enzyme reaction proceeds are reduced electron mediator reduced electron between the glucose is a substrate for the blood the transmission member is produced. この還元型電子伝達体を電気化学的に酸化し、このとき得られる電流値から血液中のグルコース濃度が測定される。 The reduced form electrochemically oxidizing the electron mediator, the glucose concentration in the blood is measured from the current value obtained at this time. このような一連の反応は、対電極21、測定電極20及び検知電極22によって電気化学的変化に伴う電流値を読み取る。 Such a series of reactions, the counter electrode 21, the measuring electrode 20 and detecting electrode 22 reads the current value due to electrochemical changes.

図3はHctが25%(低Hct)、45%、65%(高Hct)の血液を用いて、本測定方法において算出したパラメータである。 3 Hct 25% (low Hct), 45%, with 65% (high Hct) of blood is a parameter calculated in this measuring method. 第1工程(血液前処理のための電圧印加)が0.5V印加で0.5秒、第2工程(開回路)が0.5秒、第3工程(データ補正のための印加)が0.5V印加で0.5秒、第4工程(開回路)が1.5秒、第5工程(一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加)が0.2V印加で2秒となっている。 The first step 0.5 seconds is 0.5V applied (voltage application for blood pretreatment), a second step (open circuit) is 0.5 seconds, the third step (applied for data correction) 0 0.5 seconds .5V applied, the fourth step (open circuit) is 1.5 seconds, (voltage applied for the oxidation of reduced form electron mediator generated after a certain time) the fifth step is 0.2V applied in and it has a 2 seconds. そして第3工程での電圧印加開始より0.1秒後の電流値i2と第5工程での電圧印加開始より0.1秒後の電流値i4を測定して算出したi4/i2が図3のパラメータとなる。 The third current value after 0.1 seconds from the start of voltage application in step i2 and i4 / i2 calculated by measuring the current value i4 of 0.1 seconds after the start of voltage application in the fifth step in FIG. 3 the parameters. 横軸が第5工程での電圧印加開始より2秒後の最終応答値i5、縦軸がi4/i2である。 The final response value i5 of 2 seconds after the horizontal axis than the voltage application start at the fifth step, the vertical axis represents the i4 / i2. ヘマトクリット値を判別することの困難な点は、低Hctの低基質濃度の血液と、高Hctの高基質濃度の血液とi5において、同じ電流値が得られる場合があることである。 Difficulty of having to determine the hematocrit value, the blood of a low substrate concentration in the low Hct, in blood and i5 high substrate concentration high Hct, is that in some cases the same current value is obtained. 図5のパラメータを用いることによって、i5が同じ電流値を示す場合でもヘマトクリットごとに分別することができることが明らかである。 By using the parameters in FIG. 5, it is clear that it can be fractionated into each hematocrit even when i5 indicates the same current value.

図3で得られたパラメータの各数値に対する補正値を下記のテーブル1に示す。 A correction value for each value of the parameters obtained in FIG. 3 shown in Table 1 below.

このテーブルに従い、補正値を最終応答値i5に掛ける。 In accordance with this table, multiplied by the correction value to the final response value i5.

図4は本発明の測定手法、従来の手法を用いて測定した際のヘマトクリットの影響を示す図である。 Figure 4 is a measurement technique, shows the influence of hematocrit when measured using a conventional technique of the present invention. 従来の測定方法は、第1印加として0.5Vを6秒、待機時間を6秒、第2印加として0.2Vを3秒のトータル測定時間が15秒の場合と、第1印加として0.5Vを2秒、待機時間を2秒、第2印加として0.2Vを1秒のトータル測定時間を5秒に短縮した場合を示す。 0 conventional measuring methods, 0.5V 6 seconds as the first application, 6 seconds waiting time, and if the total measurement time of 3 seconds 0.2V is 15 seconds as a second application, the first application. 5V 2 seconds, shows the case of reducing the waiting time of 2 seconds, the total measurement time of 1 second 0.2V as the second applied to 5 seconds. 従来の測定方法は15秒から5秒に時間短縮を行うことによって、Hct25%の低Hct血液は測定結果が基準のHct45%比べて相対的に高く、Hct65%の高Hct血液は相対的に低くなる。 By conventional measuring method of performing shortening time to 5 seconds to 15 seconds, Hct25% low Hct blood is relatively high measurement results compared Hct45% of the reference, Hct65% of high Hct blood is relatively low Become.

本測定方法を用いることによって、トータルの測定時間は等しいにも関わらず、ヘマトクリットのバラツキを低減することが可能になる。 By using this measurement method, the total measurement time despite equal, it is possible to reduce variations in hematocrit.

本発明にかかるバイオセンサの測定方法は、絶縁基板上の少なくとも一部に形成された対電極、測定電極を含む電極部、当該電極部上または周辺に少なくとも酵素、電子伝達体を含む試薬層を有するバイオセンサと、当該電極部の各電極に電位を印加する為の接続端子及び駆動電源を有する測定装置を用い、当該駆動電源によって前記電極部に電位を印加させて出力される電流を検知し、血液中に含まれる基質を定量する測定方法であって、血液前処理のための電圧印加工程、データ補正のための電圧印加工程、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程を包含し、前記補正のための電圧印加工程より得られたピーク電流値と、前記一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程 Measuring method of the biosensor according to the present invention, at least a part formed counter electrode on the insulating substrate, the electrode unit comprising a measuring electrode, at least an enzyme on or near the electrode portions, a reagent layer containing an electron mediator a biosensor having a measuring device used with a connection terminal and the driving power source for applying a potential to each electrode of the electrode unit, and detects a current outputted by applying a potential to the electrode portion by the drive power source , there is provided a measuring method for quantifying a substrate contained in blood, to oxidize the voltage application step for the blood pretreatment, the voltage application step for the data correction, the reduced form electron mediator generated after a predetermined time has elapsed encompasses the voltage applying step, the voltage and the peak current value obtained from application process, voltage application step for oxidizing the reduced form electron mediator which is generated after lapse of said predetermined time for correction り得られたピーク電流値との比に基づいてヘマトクリットに依存したパラメータを算出し、前記パラメータにより基質量を補正することで、血液中に含まれる基質濃度を定量するバイオセンサの測定精度の良好な測定方法等として有用である。 Calculating a parameter that depends on the hematocrit based on the ratio between the obtained peak current values ​​Ri, by correcting the amount of substrate by the parameter, good measurement accuracy of the biosensor to quantify substrate concentration in the blood it is useful as a Do measuring method and the like.

本発明の測定方法のプロファイルを示す図 It shows the profile of the measurement method of the present invention 本発明に関わるバイオセンサの分解斜視図 Exploded perspective view of the biosensor according to the present invention 本発明の測定方法をより算出されたパラメータと測定感度の関係を示す図 Diagram showing the relationship of a more calculated parameters and measurement sensitivity measuring method of the present invention 本発明の測定方法、従来の手法を用いて測定した場合のHctの影響を示す図 Measuring method, it shows the effect of Hct as measured using a conventional technique of the present invention 従来の測定方法のプロファイルを示す図 It shows the profile of a conventional measuring method Hct、測定時間および測定感度の関係を示す図 Hct, diagram showing the relationship between measurement time and measurement sensitivity

符号の説明 DESCRIPTION OF SYMBOLS

1 t0 従来の測定方法における血液が供給された時間 2 t1 従来の測定方法における第1印加期間が終了し開回路が開始される時間 3 t2 従来の測定方法における第2印加期間が開始される時間 4 t3 従来の測定方法における最終応答値として電流値を読み取る時間 5 v1 従来の測定方法における第1印加期間の電圧 6 v2 従来の測定方法における第2印加期間の電圧 7 T0 本発明の測定方法における血液が供給された時間 8 T1 本発明の測定方法における血液前処理のための電圧印加工程が終了する 1 t0 time second application period in the conventional measurement methods Time 3 t2 conventional measuring method first application period ends and open circuit is started in the blood of time 2 t1 conventional supply measuring method in is started in 4 t3 method of measuring voltage 7 T0 present invention of the second application period of the voltage 6 v2 conventional measuring method of the first application period at time 5 v1 conventional measuring method of reading the current value as the final response value in the conventional measurement methods voltage application step for the blood before processing is completed in the measuring method of the time 8 T1 present invention blood is supplied
時間 9 T2 本発明の測定方法におけるデータ補正のための電圧印加工程が開始する Voltage applying step is started for data correction in the method of measuring time 9 T2 invention
時間 10 T3 本発明の測定方法におけるデータ補正のための電圧印加工程が終了する Voltage application step for the data correction is completed in a method of measuring time 10 T3 invention
時間11 T4 本発明の測定方法における一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程が開始する時間 12 T5 本発明の測定方法における最終応答値として電流値を読み取る時間 13 V1 本発明の測定方法における血液前処理のための印加電圧 14 V2 本発明の測定方法におけるデータ補正のための印加電圧 15 V3 本発明の測定方法における一定時間経過後に生成した還元型電子伝達体 Time 11 T4 present time read the current value as the final response value in the measuring method of the time 12 T5 present invention the voltage application step for oxidizing the reduced form electron mediator generated after a predetermined time has elapsed is started in the measurement method of the invention 13 V1 this reduced form electron mediator which is generated after a certain period of time at an applied voltage of 15 V3 measuring method of the present invention for data correction in the measurement method of the applied voltage 14 V2 present invention for blood pretreatment in the measurement method of the invention
を酸化するための印加電圧 16 i2 本発明の測定方法における血液前処理のための電圧印加工程で得られる Obtained in the voltage application step for the blood pretreatment in the measurement method of the applied voltage 16 i2 present invention for the oxidation of
ピーク電流 17 i4 本発明の測定方法における一定時間経過後に生成した還元型電子伝達体 Reduced form electron mediator which is generated after a certain period of time in the measurement method of peak current 17 i4 present invention
を酸化するための電圧印加工程で得られるピーク電流 18 i5 本発明の測定方法における最終応答値 19 絶縁性の基板 20 測定電極 21 対極 22 検知電極 23 試薬層 24 スペーサ 25 切欠部 25a 検体供給路 26 絶縁性の基板 27 空気孔 The final response value 19 insulating substrate 20 measuring electrode 21 counter electrode 22 sensing electrode 23 in the voltage application method of measuring process peak current 18 i5 present invention obtained in for oxidizing a reagent layer 24 spacer 25 notch 25a specimen supply path 26 insulating substrate 27 air hole

Claims (10)

  1. 絶縁基板上の少なくとも一部に形成された対電極、測定電極を含む電極部、当該電極部上または周辺に少なくとも酵素、電子伝達体を含む試薬層を有するバイオセンサと、当該電極部の各電極に電位を印加する為の接続端子及び駆動電源を有する測定装置を用い、当該駆動電源によって前記電極部に電位を印加させて出力される電流を検知し、血液中に含まれる基質を定量する測定方法であって、断続的な3回以上の電圧印加工程を包含することを特徴とする基質濃度の測定方法。 At least a portion formed counter electrode on the insulating substrate, the electrode unit comprising a measuring electrode, a biosensor having at least an enzyme, a reagent layer containing an electron mediator on or near the electrode portions, the electrodes of the electrode portions using a measuring device having a connection terminal and the driving power source for applying a potential to, for sensing the current output by applying a potential to the electrode portion by the drive power source, to quantify the substrate contained in the blood measurement a method, method of measuring the substrate concentration which is characterized in that it comprises an intermittent three or more voltage applying step.
  2. 前記断続的な電圧印加工程が、少なくとも血液前処理のための電圧印加工程、データ補正のための電圧印加工程、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程を包含することを特徴とする、請求項1記載の基質濃度の測定方法。 The intermittent voltage application step is included at least the voltage applying step for blood pretreatment, the voltage application step for the data correction, the voltage application step for oxidizing the reduced form electron mediator generated after a predetermined time has elapsed the method for determining a substrate concentration of the feature to claim 1, wherein that.
  3. 前記電圧印加工程において、血液前処理のための電圧印加工程の後に、データ補正のための電圧印加工程が実施され、当該データ補正のための電圧印加工程の後に、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程が実施されることを特徴とする、請求項2記載の基質濃度の測定方法。 In the voltage applying step, after the voltage application step for the blood pretreatment, the voltage application step for the data correction been performed, after the voltage application step for the data correction, reduction generated after a predetermined time has elapsed and a voltage application step for the oxidation of electron mediator is carried out, method for determining a substrate concentration according to claim 2, wherein.
  4. 前記データ補正のための電圧印加工程より得られたピーク電流値と、前記一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程より得られたピーク電流値との比に基づいてヘマトクリットに依存したパラメータを算出し、前記パラメータにより基質量を補正することを特徴とする請求項2〜3記載の基質濃度の測定方法。 Based on the ratio of the peak current value obtained from the voltage applying step, the peak current value obtained from the voltage applying step for oxidizing the reduced form electron mediator which is generated after lapse of said predetermined time for said data corrected calculating a parameter that depends on the hematocrit Te, method for determining a substrate concentration according to claim 2-3, wherein the correcting the amount of substrate by the parameter.
  5. 前記パラメータを判別係数とする判別関数を用いてヘマトクリットを補正することを特徴とする請求項4記載の基質濃度の測定方法。 The method for determining a substrate concentration according to claim 4, wherein the correcting the hematocrit using discriminant function to determine coefficients of the parameters.
  6. 前記血液前処理のための電圧印加工程およびデータ補正のための電圧印加工程における印加電圧が、一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程における印加電圧よりも大きいことを特徴とする請求項1〜5記載の基質濃度の測定方法。 Applied voltage in the voltage application step for voltage application step and the data correction for the blood pretreatment is greater than the voltage applied in the voltage application step for oxidizing the reduced form electron mediator generated after a predetermined time has elapsed the method for determining a substrate concentration of claims 1 to 5, wherein.
  7. 前記血液前処理のための電圧印加工程における電圧印加時間が0.2秒〜2秒であることを特徴とする請求項1〜6記載の基質濃度の測定方法。 The method for determining a substrate concentration of claims 1 to 6, wherein the voltage application time in the voltage application step for the blood before treatment is characterized by a 0.2 to 2 seconds.
  8. 前記データ補正のための電圧印加工程直前の開回路時間が0.2秒〜1秒であることを特徴とする請求項1〜7記載の基質濃度の測定方法。 The method for determining a substrate concentration of claims 1-7, wherein the open circuit time of the voltage application step just prior to being a 0.2 to 1 second for the data correction.
  9. 前記データ補正のための電圧印加工程における電圧印加時間が0.2秒〜2秒であることを特徴とする請求項1〜8記載の基質濃度の測定方法。 The method for determining a substrate concentration according to claim 8, wherein the voltage application time in the voltage application step for the data correction is characterized in that 0.2 to 2 seconds.
  10. 前記一定時間経過後に生成した還元型電子伝達体を酸化するための電圧印加工程直前の開回路時間が1秒〜6秒であることを特徴とする請求項1〜9記載の基質濃度の測定方法。 The method for determining a substrate concentration of claims 1-9, wherein the open-circuit time of the voltage application step just prior to oxidizing said predetermined time is generated after lapse of the reduced form electron mediator is 6 seconds 1 second .
JP2003389128A 2003-11-19 2003-11-19 The method for determining a substrate concentration Active JP4449431B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2003389128A JP4449431B2 (en) 2003-11-19 2003-11-19 The method for determining a substrate concentration

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2003389128A JP4449431B2 (en) 2003-11-19 2003-11-19 The method for determining a substrate concentration

Publications (2)

Publication Number Publication Date
JP2005147990A true JP2005147990A (en) 2005-06-09
JP4449431B2 JP4449431B2 (en) 2010-04-14

Family

ID=34695972

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2003389128A Active JP4449431B2 (en) 2003-11-19 2003-11-19 The method for determining a substrate concentration

Country Status (1)

Country Link
JP (1) JP4449431B2 (en)

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007108171A (en) * 2005-09-30 2007-04-26 Lifescan Inc Method and instrument for quick electrochemical analysis
JPWO2005054839A1 (en) * 2003-12-04 2007-06-28 松下電器産業株式会社 Measurement methods and sensors and measuring equipment used therefor hematocrit (Hct)
JPWO2005054840A1 (en) * 2003-12-04 2007-06-28 松下電器産業株式会社 Measurement methods and sensors and measuring equipment used therefor blood components
JP2007271623A (en) * 2006-03-31 2007-10-18 Lifescan Inc System and method for discriminating control solution from physiological sample
JP2009085950A (en) * 2007-09-28 2009-04-23 Lifescan Inc Systems and methods of determining control solution from physiological sample
JP2009168815A (en) * 2008-01-17 2009-07-30 Lifescan Inc System and method for measuring analyte in sample
JP2009535651A (en) * 2006-05-03 2009-10-01 バイエル・ヘルスケア・エルエルシー Underfill detection system for a biosensor
KR101001902B1 (en) 2007-09-27 2010-12-17 주식회사 필로시스 Method for correcting Erroneous Results of Measurement in biosensors and Apparatus using the same
US7955492B2 (en) 2004-04-19 2011-06-07 Panasonic Corporation Method for measuring blood components and biosensor and measuring instrument for use therein
JP2011137816A (en) * 2009-12-30 2011-07-14 Lifescan Inc System, device and method for measuring whole blood hematocrit value based on initial filling speed
US8026104B2 (en) 2006-10-24 2011-09-27 Bayer Healthcare Llc Transient decay amperometry
US8147674B2 (en) 2007-12-10 2012-04-03 Bayer Healthcare Llc Rapid-read gated amperometry
US8317988B2 (en) 2004-10-12 2012-11-27 Bayer Healthcare Llc Concentration determination in a diffusion barrier layer
JP2013504053A (en) * 2009-09-04 2013-02-04 ライフスキャン・スコットランド・リミテッド Glucose measurement method and system
JP2013053925A (en) * 2011-09-05 2013-03-21 Funai Electric Advanced Applied Technology Research Institute Inc Detector for detecting detection target substance
US8404100B2 (en) 2005-09-30 2013-03-26 Bayer Healthcare Llc Gated voltammetry
US8425757B2 (en) 2005-07-20 2013-04-23 Bayer Healthcare Llc Gated amperometry
US8551320B2 (en) 2008-06-09 2013-10-08 Lifescan, Inc. System and method for measuring an analyte in a sample
WO2013157263A1 (en) * 2012-04-19 2013-10-24 パナソニック株式会社 Biological information measurement device, and biological information measurement method using same
WO2013168390A1 (en) 2012-05-07 2013-11-14 パナソニック株式会社 Biological information measurement device and biological information measurement method using same
WO2013183215A1 (en) * 2012-06-06 2013-12-12 パナソニック株式会社 Biometric information measurement device and biometric information measurement method using same
US8744776B2 (en) 2008-12-08 2014-06-03 Bayer Healthcare Llc Method for determining analyte concentration based on complex index functions
CN104132991A (en) * 2013-05-02 2014-11-05 爱科来株式会社 Measuring apparatus and measuring method
JP2014224828A (en) * 2008-12-08 2014-12-04 バイエル・ヘルスケア・エルエルシーBayer HealthCareLLC Low total salt reagent composition and system for biosensor
US9164076B2 (en) 2010-06-07 2015-10-20 Bayer Healthcare Llc Slope-based compensation including secondary output signals
US9410917B2 (en) 2004-02-06 2016-08-09 Ascensia Diabetes Care Holdings Ag Method of using a biosensor
EP3156790A1 (en) 2015-10-15 2017-04-19 ARKRAY, Inc. Biosensor and manufacturing method of biosensor
US9775806B2 (en) 2011-09-21 2017-10-03 Ascensia Diabetes Care Holdings Ag Analysis compensation including segmented signals
US9933385B2 (en) 2007-12-10 2018-04-03 Ascensia Diabetes Care Holdings Ag Method of using an electrochemical test sensor
EP3444602A1 (en) 2017-08-17 2019-02-20 ARKRAY, Inc. Measuring method and measuring apparatus
EP3454057A1 (en) 2017-08-17 2019-03-13 ARKRAY, Inc. Measuring method and measuring apparatus

Cited By (82)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2011141301A (en) * 2003-12-04 2011-07-21 Panasonic Corp HEMATOCRIT (Hct) MEASURING METHOD, SENSOR USED FOR SAME, AND MEASURING INSTRUMENT
JPWO2005054839A1 (en) * 2003-12-04 2007-06-28 松下電器産業株式会社 Measurement methods and sensors and measuring equipment used therefor hematocrit (Hct)
JPWO2005054840A1 (en) * 2003-12-04 2007-06-28 松下電器産業株式会社 Measurement methods and sensors and measuring equipment used therefor blood components
US8535497B2 (en) 2003-12-04 2013-09-17 Panasonic Corporation Method of measuring blood component, sensor used in the method, and measuring device
US8540864B2 (en) 2003-12-04 2013-09-24 Panasonic Corporation Method of measuring blood component, sensor used in the method, and measuring device
JP2011047964A (en) * 2003-12-04 2011-03-10 Panasonic Corp Method of measuring hematocrit (hct), sensor used therefor, and measuring instrument
US9719956B2 (en) 2003-12-04 2017-08-01 Panasonic Healthcare Holdings Co., Ltd. Method of measuring blood component, sensor used in the method, and measuring device
US9213012B2 (en) 2003-12-04 2015-12-15 Panasonic Healthcare Holdings Co., Ltd. Method of measuring blood component, sensor used in the method, and measuring device
JP2011047962A (en) * 2003-12-04 2011-03-10 Panasonic Corp Method of measuring hematocrit (hct), sensor used therefor, and measuring instrument
JP2011047963A (en) * 2003-12-04 2011-03-10 Panasonic Corp Method of measuring hematocrit (hct), sensor used therefor, and measuring instrument
US8088271B2 (en) 2003-12-04 2012-01-03 Panasonic Corporation Method of measuring hematocrit (Hct), sensor used in the method, and measuring device
JP2011141300A (en) * 2003-12-04 2011-07-21 Panasonic Corp HEMATOCRIT (Hct) MEASURING METHOD, SENSOR USED FOR SAME, AND MEASURING INSTRUMENT
JP4717636B2 (en) * 2003-12-04 2011-07-06 パナソニック株式会社 Measurement methods and sensors and measuring equipment used therefor hematocrit (Hct)
JP2011141302A (en) * 2003-12-04 2011-07-21 Panasonic Corp HEMATOCRIT (Hct) MEASURING METHOD, SENSOR USED FOR SAME, AND MEASURING INSTRUMENT
US8480869B2 (en) 2003-12-04 2013-07-09 Panasonic Corporation Method of measuring hematocrit (Hct), sensor used in the method, and measuring device
US9410917B2 (en) 2004-02-06 2016-08-09 Ascensia Diabetes Care Holdings Ag Method of using a biosensor
US10067082B2 (en) 2004-02-06 2018-09-04 Ascensia Diabetes Care Holdings Ag Biosensor for determining an analyte concentration
US9285335B2 (en) 2004-04-19 2016-03-15 Panasonic Healthcare Holdings Co., Ltd. Method for measuring blood components and biosensor and measuring instrument for use therein
US7955492B2 (en) 2004-04-19 2011-06-07 Panasonic Corporation Method for measuring blood components and biosensor and measuring instrument for use therein
US8524055B2 (en) 2004-04-19 2013-09-03 Panasonic Corporation Method for measuring blood components and biosensor and measuring instrument for use therein
US9546974B2 (en) 2004-10-12 2017-01-17 Ascensia Diabetes Care Holdings Ag Concentration determination in a diffusion barrier layer
US8317988B2 (en) 2004-10-12 2012-11-27 Bayer Healthcare Llc Concentration determination in a diffusion barrier layer
US9206460B2 (en) 2004-10-12 2015-12-08 Bayer Healthcare Llc Concentration determination in a diffusion barrier layer
US8852422B2 (en) 2004-10-12 2014-10-07 Bayer Healthcare Llc Concentration determination in a diffusion barrier layer
US8877035B2 (en) 2005-07-20 2014-11-04 Bayer Healthcare Llc Gated amperometry methods
US8425757B2 (en) 2005-07-20 2013-04-23 Bayer Healthcare Llc Gated amperometry
JP2007108171A (en) * 2005-09-30 2007-04-26 Lifescan Inc Method and instrument for quick electrochemical analysis
US8404100B2 (en) 2005-09-30 2013-03-26 Bayer Healthcare Llc Gated voltammetry
US8647489B2 (en) 2005-09-30 2014-02-11 Bayer Healthcare Llc Gated voltammetry devices
US9835582B2 (en) 2005-09-30 2017-12-05 Ascensia Diabetes Care Holdings Ag Devices using gated voltammetry methods
US9110013B2 (en) 2005-09-30 2015-08-18 Bayer Healthcare Llc Gated voltammetry methods
US8529751B2 (en) 2006-03-31 2013-09-10 Lifescan, Inc. Systems and methods for discriminating control solution from a physiological sample
US8449740B2 (en) 2006-03-31 2013-05-28 Lifescan, Inc. Systems and methods for discriminating control solution from a physiological sample
JP2007271623A (en) * 2006-03-31 2007-10-18 Lifescan Inc System and method for discriminating control solution from physiological sample
US9274078B2 (en) 2006-03-31 2016-03-01 Lifescan, Inc. Systems and methods of discriminating control solution from a physiological sample
JP2009535651A (en) * 2006-05-03 2009-10-01 バイエル・ヘルスケア・エルエルシー Underfill detection system for a biosensor
US8470604B2 (en) 2006-10-24 2013-06-25 Bayer Healthcare Llc Transient decay amperometry
US9005527B2 (en) 2006-10-24 2015-04-14 Bayer Healthcare Llc Transient decay amperometry biosensors
US8026104B2 (en) 2006-10-24 2011-09-27 Bayer Healthcare Llc Transient decay amperometry
US10190150B2 (en) 2006-10-24 2019-01-29 Ascensia Diabetes Care Holdings Ag Determining analyte concentration from variant concentration distribution in measurable species
KR101001902B1 (en) 2007-09-27 2010-12-17 주식회사 필로시스 Method for correcting Erroneous Results of Measurement in biosensors and Apparatus using the same
US9157110B2 (en) 2007-09-28 2015-10-13 Lifescan, Inc. Systems and methods of discriminating control solution from a physiological sample
US8778168B2 (en) 2007-09-28 2014-07-15 Lifescan, Inc. Systems and methods of discriminating control solution from a physiological sample
JP2009085950A (en) * 2007-09-28 2009-04-23 Lifescan Inc Systems and methods of determining control solution from physiological sample
US9933385B2 (en) 2007-12-10 2018-04-03 Ascensia Diabetes Care Holdings Ag Method of using an electrochemical test sensor
US8147674B2 (en) 2007-12-10 2012-04-03 Bayer Healthcare Llc Rapid-read gated amperometry
US9034160B2 (en) 2007-12-10 2015-05-19 Bayer Healthcare Llc Rapid-read gated amperometry devices
US10345255B2 (en) 2007-12-10 2019-07-09 Ascensia Diabetes Care Holdings Ag Rapid-read gated amperometry devices
US8916040B2 (en) 2008-01-17 2014-12-23 Lifescan, Inc. System and method for measuring an analyte in a sample
US9739749B2 (en) 2008-01-17 2017-08-22 Lifescan, Inc. System and method for measuring an analyte in a sample
JP2015092194A (en) * 2008-01-17 2015-05-14 ライフスキャン・インコーポレイテッドLifescan,Inc. Method of identifying defects in test pieces
US8603768B2 (en) 2008-01-17 2013-12-10 Lifescan, Inc. System and method for measuring an analyte in a sample
JP2009168815A (en) * 2008-01-17 2009-07-30 Lifescan Inc System and method for measuring analyte in sample
US8709739B2 (en) 2008-01-17 2014-04-29 Lifescan, Inc. System and method for measuring an analyte in a sample
JP2013040967A (en) * 2008-01-17 2013-02-28 Lifescan Inc System and method for measuring analyte within sample
JP2012123021A (en) * 2008-01-17 2012-06-28 Lifescan Inc System and method for measuring analyte within sample
US8551320B2 (en) 2008-06-09 2013-10-08 Lifescan, Inc. System and method for measuring an analyte in a sample
US9784707B2 (en) 2008-06-09 2017-10-10 Lifescan, Inc. System and method for measuring an analyte in a sample
US8744776B2 (en) 2008-12-08 2014-06-03 Bayer Healthcare Llc Method for determining analyte concentration based on complex index functions
JP2014224828A (en) * 2008-12-08 2014-12-04 バイエル・ヘルスケア・エルエルシーBayer HealthCareLLC Low total salt reagent composition and system for biosensor
JP2013504053A (en) * 2009-09-04 2013-02-04 ライフスキャン・スコットランド・リミテッド Glucose measurement method and system
JP2011137816A (en) * 2009-12-30 2011-07-14 Lifescan Inc System, device and method for measuring whole blood hematocrit value based on initial filling speed
US9164076B2 (en) 2010-06-07 2015-10-20 Bayer Healthcare Llc Slope-based compensation including secondary output signals
US9995702B2 (en) 2010-06-07 2018-06-12 Ascensia Diabetes Care Holdsings AG Slope-base compensation including secondary output signals
JP2013053925A (en) * 2011-09-05 2013-03-21 Funai Electric Advanced Applied Technology Research Institute Inc Detector for detecting detection target substance
US9775806B2 (en) 2011-09-21 2017-10-03 Ascensia Diabetes Care Holdings Ag Analysis compensation including segmented signals
US9804115B2 (en) 2012-04-19 2017-10-31 Panasonic Healthcare Holdings Co., Ltd. Biological information measurement device, and biological information measurement method using same
WO2013157263A1 (en) * 2012-04-19 2013-10-24 パナソニック株式会社 Biological information measurement device, and biological information measurement method using same
US10012610B2 (en) 2012-04-19 2018-07-03 Phc Holdings Corporation Biological information measurement device, and biological information measurement method using same
US9625442B2 (en) 2012-04-19 2017-04-18 Panasonic Healthcare Holdings Co., Ltd. Biological information measurement device, and biological information measurement method using same
US9629577B2 (en) 2012-05-07 2017-04-25 Panasonic Healthcare Holdings Co., Ltd. Biological information measurement device and biological information measurement method using same
WO2013168390A1 (en) 2012-05-07 2013-11-14 パナソニック株式会社 Biological information measurement device and biological information measurement method using same
JP5801479B2 (en) * 2012-05-07 2015-10-28 パナソニックヘルスケアホールディングス株式会社 Biological information measurement method using the biological information measuring device
US10107777B2 (en) 2012-06-06 2018-10-23 Phc Holdings Corporation Biological information measurement device and biological information measurement method using same
US9410916B2 (en) 2012-06-06 2016-08-09 Panasonic Healthcare Holdings Co., Ltd. Biological information measurement device and biological information measurement method using same
JP5842059B2 (en) * 2012-06-06 2016-01-13 パナソニックヘルスケアホールディングス株式会社 Biological information measurement method using the biological information measuring device
WO2013183215A1 (en) * 2012-06-06 2013-12-12 パナソニック株式会社 Biometric information measurement device and biometric information measurement method using same
CN104132991A (en) * 2013-05-02 2014-11-05 爱科来株式会社 Measuring apparatus and measuring method
JP2014232102A (en) * 2013-05-02 2014-12-11 アークレイ株式会社 Measurement device and measurement method
EP3156790A1 (en) 2015-10-15 2017-04-19 ARKRAY, Inc. Biosensor and manufacturing method of biosensor
EP3444602A1 (en) 2017-08-17 2019-02-20 ARKRAY, Inc. Measuring method and measuring apparatus
EP3454057A1 (en) 2017-08-17 2019-03-13 ARKRAY, Inc. Measuring method and measuring apparatus

Also Published As

Publication number Publication date
JP4449431B2 (en) 2010-04-14

Similar Documents

Publication Publication Date Title
AU2006233772B2 (en) Analyte determination method and analyte meter
US8512546B2 (en) Method and apparatus for assay of electrochemical properties
EP1252514B1 (en) Electrochemical methods and devices for use in the determination of hematocrit corrected analyte concentrations
JP5185044B2 (en) System and method for determining the control solution from the physiological sample
US9234873B2 (en) Method for determination of analyte concentrations and related apparatus
AU2008279274B2 (en) Electrochemical test strip
JP4018748B2 (en) Electrochemical cell
US8163162B2 (en) Methods and apparatus for analyzing a sample in the presence of interferents
JP4260017B2 (en) Fail determination method and the analyzer of the analysis process
KR101477948B1 (en) Gated voltammetry analysis duration determination
US8404102B2 (en) Method and apparatus for rapid electrochemical analysis
CA2838176C (en) Compensating for inadequate sample volume in biosensor devices
JP5702661B2 (en) Voltammetry system for analyzing examining biological analytes
US20030159945A1 (en) Biosensor, measuring instrument for biosensor, and method of quantifying substrate
EP1443322A1 (en) Concentration measuring method and concentration measuring device
ES2717135T3 (en) Method to signal the user to add an additional sample to a test strip, method to measure the temperature of a sample and methods to determine the concentration of an analyte based on controlled amperometry
CN102012389B (en) Quantitative analyzing method and quantitative analyzer using sensor
US9244078B2 (en) Oxidizable species as an internal reference in control solutions for biosensors
US7638033B2 (en) Biosensor system
EP2223104B1 (en) Slope-based compensation
US8287718B2 (en) Liquid sample measurement method and apparatus
EP1688742B1 (en) Electrochemical biosensor
JP5373948B2 (en) Abnormal output detection system for a biosensor
AU4086800A (en) Sample detection to initiate timing of an electrochemical assay
EP2360477B1 (en) Systems, devices and methods for improving accuracy of biosensors using fill time

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20061110

RD01 Notification of change of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7421

Effective date: 20061213

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20090225

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20091027

RD01 Notification of change of attorney

Free format text: JAPANESE INTERMEDIATE CODE: A7421

Effective date: 20091120

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20091208

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20100105

A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20100118

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20130205

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20130205

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20140205

Year of fee payment: 4

S111 Request for change of ownership or part of ownership

Free format text: JAPANESE INTERMEDIATE CODE: R313113

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

S111 Request for change of ownership or part of ownership

Free format text: JAPANESE INTERMEDIATE CODE: R313113

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

S111 Request for change of ownership or part of ownership

Free format text: JAPANESE INTERMEDIATE CODE: R313113

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

S533 Written request for registration of change of name

Free format text: JAPANESE INTERMEDIATE CODE: R313533

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250