JP2017111045A - Electrochemical measurement device and electrochemical measurement method - Google Patents
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本発明は、生体物質を含む測定対象液のなかで生体物質を分離する電気化学測定装置、および、電気化学測定方法に関する。 The present invention relates to an electrochemical measurement device and an electrochemical measurement method for separating a biological material in a measurement target liquid containing the biological material.
核酸やタンパク質などの生体高分子を測定対象液のなかで分離する方法として、無担体の電気泳動法であるフリーフロー電気泳動法が知られている。フリーフロー電気泳動法は、相互に対向する平板間に測定対象液の流れを形成し、測定対象液の流れと直交する方向である印加方向に直流電圧を印加する。測定対象液のなかの各荷電粒子は、荷電粒子が有する電荷量が大きいほど印加方向へ移動しやすく、また、電荷量が小さいほど印加方向へ移動しにくい。こうしたフリーフロー電気泳動法は、測定対象液に含まれる成分の解析において前処理に用いられ、キャピラリー電気泳動による後処理との組み合わせによって、生体高分子の分離、および、検出を可能としている（例えば、特許文献１を参照）。 As a method for separating biopolymers such as nucleic acids and proteins in a measurement target solution, a free-flow electrophoresis method which is a carrier-free electrophoresis method is known. In the free flow electrophoresis method, a flow of a measurement target liquid is formed between flat plates facing each other, and a DC voltage is applied in an application direction which is a direction orthogonal to the flow of the measurement target liquid. Each charged particle in the liquid to be measured is more likely to move in the application direction as the charge amount of the charged particle is larger, and less likely to move in the application direction as the charge amount is smaller. Such a free-flow electrophoresis method is used for pretreatment in analysis of components contained in a measurement target liquid, and enables separation and detection of biopolymers in combination with post-treatment by capillary electrophoresis (for example, , See Patent Document 1).
一方、フリーフロー電気泳動法によって分離された各検出対象は、それの後処理において、例えば、赤外活性や紫外活性などの光活性を有した標識と結合される。そして、検出対象ごとに行われるキャピラリー電気泳動法によって、各検出対象のなかで標識の位置が検出される。これらの工程を経る結果、測定対象液に対する前処理である分離では、生体高分子を分離するための泳動槽が用いられる一方で、測定対象液に対する後処理である検出では、生体高分子を検出するための別の装置が用いられる。測定対象液に含まれる成分の解析に時間的な制約を受ける臨床や、その解析が大規模となる開発では、こうした煩わしさを軽減させることが強く望まれている。 On the other hand, each detection target separated by free flow electrophoresis is combined with a label having photoactivity such as infrared activity or ultraviolet activity in the post-treatment thereof. Then, the position of the label is detected in each detection target by capillary electrophoresis performed for each detection target. As a result of these steps, the separation tank, which is a pretreatment for the measurement target liquid, uses an electrophoresis tank for separating the biopolymer, while the detection, which is a post-treatment for the measurement target liquid, detects the biopolymer. Another device is used to do this. It is strongly desired to alleviate such annoyance in clinical situations where time-constrained analysis of components contained in the measurement target solution and in development where the analysis is large-scale.
本発明は、上記課題を解決するためになされたものであり、その目的は、生体物質の分離、および、検出を共通する泳動槽で可能とした電気化学測定装置、および、電気化学測定方法を提供することにある。 The present invention has been made to solve the above-described problems, and an object of the present invention is to provide an electrochemical measurement apparatus and an electrochemical measurement method that enable separation and detection of biological substances in a common electrophoresis tank. It is to provide.
上記課題を解決するための電気化学測定装置は、生体物質を含む測定対象液を１つの方向である流動方向へ流すための泳動槽と、前記流動方向と交差する泳動方向に前記生体物質を泳動させるための泳動電極と、前記流動方向と前記泳動方向とを含む二次元方向に並び、前記測定対象液に関する電気化学的な特性値を前記二次元方向における各位置で測定するための複数の測定素子と、前記泳動電極と前記各測定素子とに接続し、前記泳動電極による泳動を開始させる信号を前記泳動電極に入力した後に、前記各測定素子による測定を開始する測定処理部とを備える。 An electrochemical measurement apparatus for solving the above-described problem includes a migration tank for flowing a measurement target liquid containing a biological material in a flow direction, which is one direction, and the biological material is migrated in a migration direction that intersects the flow direction. A plurality of measurements for measuring an electrochemical characteristic value relating to the measurement target liquid at each position in the two-dimensional direction, arranged in a two-dimensional direction including the migration electrode and the flow direction and the migration direction And a measurement processing unit connected to the migration electrode and each of the measurement elements, and starting measurement by each of the measurement elements after inputting a signal for starting migration by the migration electrode to the migration electrode.
上記課題を解決するための電気化学測定方法は、測定処理部が、生体物質を含む測定対象液が１つの方向である流動方向へ流れる泳動槽において、前記流動方向と交差する泳動方向に前記生体物質を泳動させる信号を泳動電極へ入力することと、前記信号を前記泳動電極へ入力した後に、前記流動方向と前記泳動方向とを含む二次元方向に並ぶ複数の測定素子を用い、前記測定対象液に関する電気化学的な特性値を前記二次元方向における各位置で測定することとを含む。 In the electrochemical measurement method for solving the above-described problem, the measurement processing unit is configured to move the living body in a migration direction intersecting the flow direction in a migration tank in which a measurement target liquid containing a biological substance flows in a flow direction that is one direction. Input a signal for migrating a substance to the electrophoresis electrode, and after inputting the signal to the electrophoresis electrode, using a plurality of measuring elements arranged in a two-dimensional direction including the flow direction and the migration direction, Measuring an electrochemical characteristic value of the liquid at each position in the two-dimensional direction.
上記装置、および、方法によれば、測定対象液中に含まれる生体物質が、その生体物質の大きさに基づく距離で流動方向へ泳動槽内を流動し、かつ、その生体物質が有する電荷量の大きさに基づく距離で泳動方向へ泳動槽内を泳動する。そして、流動方向へ移動する距離と、泳動方向へ泳動する距離との各々の差異に従って分離された生体物質は、二次元に並ぶ測定素子のなかで、その生体物質の近くに位置する測定素子によって、その存在を電気化学的な特性値として検出される。結果として、生体物質の分離、および、検出を、共通する泳動槽で行うことが可能となる。 According to the above apparatus and method, the biological material contained in the liquid to be measured flows in the migration tank in the flow direction at a distance based on the size of the biological material, and the amount of charge that the biological material has In the migration tank in the migration direction at a distance based on the size of The biological material separated according to the difference between the distance moving in the flow direction and the distance moving in the migration direction is measured by a measurement element located near the biological material in the two-dimensional measurement elements. The presence is detected as an electrochemical characteristic value. As a result, it is possible to perform separation and detection of biological substances in a common electrophoresis tank.
上記電気化学測定装置において、複数の前記測定素子は、前記流動方向、および、前記泳動方向にマトリックス状に並んでもよい。
上記構成によれば、流動方向、および、泳動方向にマトリックス状に測定素子が位置するため、流動方向、および、泳動方向に移動した生体物質は、複数の測定素子のなかのいずれか１つと対向しやすい。それゆえに、測定対象液に含まれる各生体物質に対してそれの存在がいずれか１つの測定素子によって検出されやすいため、生体物質の検出漏れを抑えることが可能となる。
In the electrochemical measurement device, the plurality of measurement elements may be arranged in a matrix in the flow direction and the migration direction.
According to the above configuration, since the measurement elements are arranged in a matrix in the flow direction and the migration direction, the biological material moved in the flow direction and the migration direction is opposed to any one of the plurality of measurement elements. It's easy to do. Therefore, since the presence of each biological material contained in the measurement target liquid is easily detected by any one measurement element, it is possible to suppress detection failure of the biological material.
上記電気化学測定装置において、前記泳動槽は、前記流動方向と前記泳動方向とを含む平面であって、相互に対向する一対の平面を備え、一方の前記平面に全ての前記測定素子が位置し、前記一対の平面間に前記測定対象液を流す隙間を備える構成であってもよい。 In the electrochemical measurement apparatus, the migration tank is a plane including the flow direction and the migration direction, and includes a pair of planes facing each other, and all the measurement elements are located on one of the planes. A configuration may be provided in which a gap for flowing the measurement target liquid is provided between the pair of planes.
泳動槽内に位置する生体物質と測定素子との間の距離は、一対の平面が広がる二次元方向と、一対の平面が対向する厚み方向との成分を有する。そして、特定の生体物質の電気化学的な特性値がいずれの測定素子によって測定されるかは、その生体物質と測定素子との間における二次元方向での距離の大きさと、その生体物質と測定素子との間における厚み方向での距離の大きさとに従う。そのため、例えば、相互に近接した測定素子の位置が、厚み方向において相互に異なるとき、厚み方向における生体物質の位置のばらつきによって、それを検出する測定素子の位置にもばらつきが生じる。結果として、厚み方向における生体物質の位置のばらつきが、検出の結果にばらつきを生じさせてしまう。 The distance between the biological substance located in the electrophoresis tank and the measurement element has a component of a two-dimensional direction in which the pair of planes spread and a thickness direction in which the pair of planes face each other. Then, which measurement element is used to measure the electrochemical characteristic value of a specific biological substance depends on the magnitude of the distance in the two-dimensional direction between the biological substance and the measurement element, and the biological substance and measurement. It follows the distance between the element in the thickness direction. Therefore, for example, when the positions of the measurement elements close to each other are different from each other in the thickness direction, the position of the measurement element that detects the variation also occurs due to the variation in the position of the biological material in the thickness direction. As a result, variations in the position of the biological material in the thickness direction cause variations in detection results.
この点、上記構成によれば、１つの平面上に全ての測定素子が位置するため、特定の生体物質と各測定素子との間における厚み方向での距離は、測定素子間においてほぼ等しい。それゆえに、特定の生体物質の電気化学的な特性値がいずれの測定素子によって測定されるかは、上記二次元方向における生体物質と測定素子との間の距離によって定まるため、特定の生体物質の存在を特定の測定素子で検出できる確率を高めることが可能となる。 In this regard, according to the above configuration, since all the measurement elements are located on one plane, the distance in the thickness direction between the specific biological material and each measurement element is substantially equal between the measurement elements. Therefore, the measurement element that determines the electrochemical characteristic value of a specific biological material is determined by the distance between the biological material and the measurement element in the two-dimensional direction. It is possible to increase the probability that the presence can be detected by a specific measuring element.
上記電気化学測定装置は、複数の前記測定素子のなかでの測定結果の分布から前記測定対象液の属性を判定する判定部をさらに備えてもよい。
測定対象液における全生体物質の濃度や、測定対象液が有する酸性度などのようなパラメータは、各測定素子の測定結果に対して共通に影響を及ぼし、各測定素子の測定結果の絶対値に対しては、共通する誤差の要因ともなる。この点、上記構成によれば、複数の測定素子のなかでの測定結果の分布に基づいて１つの液の属性が特定されるため、例えば、１つの測定素子における特性値に基づいて液の属性が特定される構成と比べて、上述した誤差の要因による影響を軽減することが可能である。
The electrochemical measurement apparatus may further include a determination unit that determines an attribute of the measurement target liquid from a distribution of measurement results among the plurality of measurement elements.
Parameters such as the concentration of all biological substances in the liquid to be measured and the acidity of the liquid to be measured have a common influence on the measurement results of each measurement element, resulting in an absolute value of the measurement result of each measurement element. On the other hand, it becomes a cause of a common error. In this regard, according to the above configuration, since the attribute of one liquid is specified based on the distribution of measurement results among the plurality of measuring elements, for example, the attribute of the liquid is determined based on the characteristic value in one measuring element. As compared with the configuration in which is specified, it is possible to reduce the influence of the error factors described above.
上記電気化学測定装置は、前記流動方向において最も下流に位置する前記測定素子である最下素子に前記測定対象液が到達したことを検出する検出部をさらに備えてもよい。
上記構成によれば、全ての測定素子に測定対象液が行きわたったか否かを検出することが可能である。
The electrochemical measurement apparatus may further include a detection unit that detects that the liquid to be measured has reached the lowest element, which is the measurement element located most downstream in the flow direction.
According to the above configuration, it is possible to detect whether or not the measurement target liquid has spread over all the measurement elements.
上記電気化学測定装置において、前記測定処理部は、前記最下素子に前記測定対象液が到達したことを前記検出部が検出したとき、前記各測定素子による測定を開始してもよい。 In the electrochemical measurement device, the measurement processing unit may start measurement by each measurement element when the detection unit detects that the measurement target liquid has reached the lowermost element.
上記構成によれば、全ての測定素子に測定対象液が行きわたった状態で測定を開始させることが可能であるため、生体物質の検出に関わる再現性を高めることが可能である。 According to the above configuration, since measurement can be started in a state in which the measurement target solution is distributed to all the measurement elements, it is possible to improve reproducibility related to detection of a biological substance.
本発明によれば、生体物質の分離、および、検出を、共通する泳動槽で行うことが可能となる。 According to the present invention, it is possible to perform separation and detection of biological substances in a common electrophoresis tank.
図１から図７を参照して一実施形態における電気化学測定装置、および、電気化学測定方法を説明する。 An electrochemical measurement apparatus and an electrochemical measurement method according to an embodiment will be described with reference to FIGS.
［電気化学セル］
図１が示すように、電気化学測定装置が備える電気化学セルは、相互に対向する２つの基板である第１基板１１と第２基板１２とを備える。電気化学セルは、第１基板１１と第２基板１２との間に、第１基板１１の全体にわたりほぼ均一な幅を有した隙間を備える。
[Electrochemical cell]
As shown in FIG. 1, the electrochemical cell included in the electrochemical measurement device includes a first substrate 11 and a second substrate 12 which are two substrates facing each other. The electrochemical cell includes a gap having a substantially uniform width across the entire first substrate 11 between the first substrate 11 and the second substrate 12.
第１基板１１と第２基板１２との間の隙間は、１つの方向である行方向の両端において封止され、それによって、行方向と直交する列方向を流動方向として、生体物質を含む測定対象液を流動方向へ流す流路として機能する。第１基板１１と第２基板１２との間の隙間は、例えば、１００μｍ以下の厚みを有する。また、第１基板１１、第２基板１２、および、これらの隙間の両端を封止する部材は、上記流路を備える泳動槽の一例を構成する。 The gap between the first substrate 11 and the second substrate 12 is sealed at both ends in the row direction, which is one direction, and thereby includes a biological material with the column direction orthogonal to the row direction as the flow direction. It functions as a flow path for flowing the target liquid in the flow direction. The gap between the first substrate 11 and the second substrate 12 has a thickness of 100 μm or less, for example. Moreover, the member which seals the both ends of the 1st board | substrate 11, the 2nd board | substrate 12, and these clearance gaps comprises an example of the electrophoresis tank provided with the said flow path.
泳動槽に流れる液は、例えば、生体物質と緩衝液とを含む測定対象液や、緩衝液である。生体物質は、例えば、核酸、タンパク質、酵素、多糖、脂質などの生体高分子や、アミノ酸、各種の糖、ミネラルなどの無機質を含む生体低分子である。 The liquid flowing in the electrophoresis tank is, for example, a measurement target liquid including a biological material and a buffer solution, or a buffer solution. Biological substances are, for example, biological macromolecules such as nucleic acids, proteins, enzymes, polysaccharides, and lipids, and small biological molecules including inorganic substances such as amino acids, various sugars, and minerals.
電気化学セルは、第１基板１１と第２基板１２との隙間である流路内に、泳動電極と、複数の測定素子とを備える。本実施形態における泳動電極は、第１泳動電極１６Ａ、および、第２泳動電極１６Ｂである。本実施形態における複数の測定素子は、酸化還元電流を測定するための測定素子であって、対極群１３、作用電極群１４、および、参照電極群１５を備える。 The electrochemical cell includes a migration electrode and a plurality of measurement elements in a flow path that is a gap between the first substrate 11 and the second substrate 12. The migration electrodes in this embodiment are the first migration electrode 16A and the second migration electrode 16B. The plurality of measurement elements in the present embodiment are measurement elements for measuring an oxidation-reduction current, and include a counter electrode group 13, a working electrode group 14, and a reference electrode group 15.
対極群１３は、第１基板１１が備える面のなかで第２基板１２と対向する対向面１１Ａに位置すると共に、複数の対極１３Ａと、複数の対極配線１３Ｂとを備える。対極群１３において、行方向に並ぶ３つの対極１３Ａが対極行であって、対極群１３は、列方向に並ぶ３行の対極行を備える。また、対極群１３は、各対極行に１つずつ対極配線１３Ｂを備え、各対極配線１３Ｂは、対極行を構成する３つの対極１３Ａに並列に接続される。すなわち、対極群１３は、３行×３列の対極１３Ａを備え、１行ずつの対極１３Ａが、１つの対極配線１３Ｂによって並列に接続される。 The counter electrode group 13 is located on the facing surface 11A facing the second substrate 12 among the surfaces of the first substrate 11, and includes a plurality of counter electrodes 13A and a plurality of counter electrode wirings 13B. In the counter electrode group 13, three counter electrodes 13A arranged in the row direction are counter electrode rows, and the counter electrode group 13 includes three counter electrode rows arranged in the column direction. The counter electrode group 13 includes one counter electrode line 13B for each counter electrode row, and each counter electrode wire 13B is connected in parallel to three counter electrodes 13A constituting the counter electrode row. That is, the counter electrode group 13 includes counter electrodes 13A of 3 rows × 3 columns, and the counter electrodes 13A of each row are connected in parallel by one counter electrode wiring 13B.
作用電極群１４は、第１基板１１が備える対向面１１Ａに位置すると共に、複数の作用電極１４Ａと、複数の作用電極配線１４Ｂとを備える。作用電極群１４において、列方向に並ぶ３つの作用電極１４Ａが作用電極列であって、作用電極群１４は、行方向に並ぶ３列の作用電極列を備える。また、作用電極群１４は、各作用電極列に１つずつ作用電極配線１４Ｂを備え、各作用電極配線１４Ｂは、作用電極列を構成する３つの作用電極１４Ａに並列に接続される。すなわち、作用電極群１４は、３行×３列の作用電極１４Ａを備え、１列ずつの作用電極１４Ａが、１つの作用電極配線１４Ｂによって並列に接続される。なお、対極群１３のうちで作用電極群１４と重なる部位には、対極群１３と作用電極群１４とを相互に絶縁する絶縁膜が位置する。 The working electrode group 14 includes a plurality of working electrodes 14A and a plurality of working electrode wirings 14B, as well as being positioned on the facing surface 11A of the first substrate 11. In the working electrode group 14, three working electrodes 14A arranged in the column direction are working electrode columns, and the working electrode group 14 includes three working electrode columns arranged in the row direction. Further, the working electrode group 14 includes one working electrode wiring 14B for each working electrode row, and each working electrode wiring 14B is connected in parallel to the three working electrodes 14A constituting the working electrode row. That is, the working electrode group 14 includes working electrodes 14A of 3 rows × 3 columns, and the working electrodes 14A for each column are connected in parallel by one working electrode wiring 14B. Note that an insulating film that insulates the counter electrode group 13 and the working electrode group 14 from each other is located in a portion of the counter electrode group 13 that overlaps the working electrode group 14.
参照電極群１５は、第１基板１１が備える対向面１１Ａに位置すると共に、複数の参照電極１５Ａと、複数の参照電極配線１５Ｂとを備える。参照電極群１５において、行方向に並ぶ３つの参照電極１５Ａが参照電極行であって、参照電極群１５は、列方向に並ぶ３行の参照電極行を備える。また、参照電極群１５は、各参照電極行に１つずつ参照電極配線１５Ｂを備え、各参照電極配線１５Ｂは、参照電極行を構成する３つの参照電極１５Ａに並列に接続される。すなわち、参照電極群１５は、３行×３列の参照電極１５Ａを備え、１行ずつの参照電極１５Ａが、１つの参照電極配線１５Ｂによって並列に接続される。なお、対極群１３、および、作用電極群１４のうちで参照電極群１５と重なる部位には、対極群１３や作用電極群１４と、参照電極群１５とを相互に絶縁する絶縁膜が位置する。 The reference electrode group 15 includes a plurality of reference electrodes 15A and a plurality of reference electrode wirings 15B, as well as being positioned on the facing surface 11A included in the first substrate 11. In the reference electrode group 15, three reference electrodes 15A arranged in the row direction are reference electrode rows, and the reference electrode group 15 includes three reference electrode rows arranged in the column direction. The reference electrode group 15 includes one reference electrode wiring 15B for each reference electrode row, and each reference electrode wiring 15B is connected in parallel to the three reference electrodes 15A constituting the reference electrode row. That is, the reference electrode group 15 includes reference electrodes 15A of 3 rows × 3 columns, and the reference electrodes 15A for each row are connected in parallel by one reference electrode wiring 15B. In the counter electrode group 13 and the working electrode group 14, an insulating film that insulates the counter electrode group 13, the working electrode group 14, and the reference electrode group 15 from each other is located in a portion overlapping the reference electrode group 15. .
第１泳動電極１６Ａ、および、第２泳動電極１６Ｂは、いずれも列方向に沿って、第１基板１１のほぼ全体にわたり延びる形状を有すると共に、第１基板１１が備える対向面１１Ａに位置する。第１泳動電極１６Ａ、および、第２泳動電極１６Ｂは、行方向において相互に対向し、かつ、第１基板１１のほぼ両端に位置する。 The first migration electrode 16 </ b> A and the second migration electrode 16 </ b> B both have a shape extending over the entire first substrate 11 along the column direction, and are positioned on the facing surface 11 </ b> A provided in the first substrate 11. The first migration electrode 16 </ b> A and the second migration electrode 16 </ b> B are opposed to each other in the row direction and are located at substantially both ends of the first substrate 11.
図２が示すように、電気化学セルは、第１泳動電極１６Ａと第２泳動電極１６Ｂとに挟まれた領域として測定流路１６Ｃを備える。測定流路１６Ｃは、行方向、および、列方向を含む二次元方向へ広がる領域である。測定流路１６Ｃは、上述した測定対象液Ｌが流れる流路である。測定流路１６Ｃは、電気化学セルの外部に位置するポンプＰに接続され、ポンプＰは、測定対象液Ｌを連続的に測定流路１６Ｃへ入れる。測定流路１６Ｃの内部には、行方向、および、列方向に沿って３行×３列のマトリックス状に位置する９つの測定素子２０が収納されている。 As shown in FIG. 2, the electrochemical cell includes a measurement channel 16C as a region sandwiched between the first migration electrode 16A and the second migration electrode 16B. The measurement flow channel 16C is a region extending in a two-dimensional direction including a row direction and a column direction. The measurement channel 16C is a channel through which the measurement target liquid L described above flows. The measurement flow path 16C is connected to a pump P located outside the electrochemical cell, and the pump P continuously puts the measurement target liquid L into the measurement flow path 16C. Nine measuring elements 20 positioned in a matrix of 3 rows × 3 columns along the row direction and the column direction are housed inside the measurement flow channel 16C.
各測定素子２０は、測定対象液Ｌに関する電気化学的な特性値を測定する素子であって、特性値の一例である酸化還元電流を測定する。各測定素子２０は、１つの対極１３Ａ、１つの作用電極１４Ａ、および、１つの参照電極１５Ａから構成される。 Each measuring element 20 is an element that measures an electrochemical characteristic value related to the measurement target liquid L, and measures an oxidation-reduction current that is an example of the characteristic value. Each measuring element 20 includes one counter electrode 13A, one working electrode 14A, and one reference electrode 15A.
第２基板１２と対向する方向から見て、対極１３Ａは逆Ｌ字状を有し、作用電極１４Ａは円形状を有し、参照電極１５ＡはＴ字状を有する。作用電極１４Ａは、対極１３Ａと参照電極１５Ａとに挟まれ、これらが相互に重ならないように、各電極は位置する。対極１３Ａ、および、作用電極１４Ａを形成する材料は、例えば、酸化インジウム錫（ＩＴＯ）であり、参照電極１５Ａは、例えば、ＩＴＯ膜に銀と塩化銀インクとが塗布された電極である。 When viewed from the direction facing the second substrate 12, the counter electrode 13A has an inverted L shape, the working electrode 14A has a circular shape, and the reference electrode 15A has a T shape. The working electrode 14A is sandwiched between the counter electrode 13A and the reference electrode 15A, and each electrode is positioned so that they do not overlap each other. The material forming the counter electrode 13A and the working electrode 14A is, for example, indium tin oxide (ITO), and the reference electrode 15A is, for example, an electrode in which silver and silver chloride ink are applied to an ITO film.
［生体物質の分布］
次に、測定流路１６Ｃの内部における生体物質の分布についてその推移を説明する。なお、以下では、生体物質の流動と生体物質の泳動とを説明する便宜上、測定対象液Ｌが、生体物質のなかで大きい分子である高分子ＭＬＡ，ＭＬＢと、生体物質のなかで高分子よりも小さい低分子ＭＳＡ，ＭＳＢと、これら高分子ＭＬＡ，ＭＬＢの大きさと、低分子ＭＳＡ，ＭＳＢの大きさとの間の大きさを有する分子とを含む例を説明する。
[Biomaterial distribution]
Next, the transition of the distribution of the biological material in the measurement channel 16C will be described. In the following, for convenience of explaining the flow of the biological material and the migration of the biological material, the measurement target liquid L is larger than the polymers MLA and MLB, which are large molecules in the biological material, and the polymer in the biological material. An example including small molecules MSA and MSB having a smaller size and molecules having a size between the size of the high molecules MLA and MLB and the size of the low molecule MSA and MSB will be described.
図３（ａ）が示すように、まず、測定流路１６Ｃに緩衝液のみが流れる状態で、第１泳動電極１６Ａから第２泳動電極１６Ｂへの電位勾配を形成するための直流定電圧信号が、第１泳動電極１６Ａと第２泳動電極１６Ｂとに印加される。次いで、緩衝液に生体物質が加えられ、生体物質が液中でほぼ均一に分布する状態で、測定流路１６Ｃの行方向の全体にわたり測定対象液Ｌが測定流路１６Ｃへ流される。 As shown in FIG. 3A, first, a DC constant voltage signal for forming a potential gradient from the first migration electrode 16A to the second migration electrode 16B in a state where only the buffer solution flows through the measurement channel 16C. , Applied to the first migration electrode 16A and the second migration electrode 16B. Next, the biological material is added to the buffer solution, and the measurement target liquid L is caused to flow to the measurement flow channel 16C over the entire row direction of the measurement flow channel 16C in a state where the biological material is substantially uniformly distributed in the liquid.
図３（ｂ）が示すように、測定対象液Ｌの流動が進むことに伴い、列方向である流動方向には、生体物質の大きさに応じた生体物質の分布が形成されはじめる。すなわち、低分子ＭＳＡ，ＭＳＢが流動方向へ流動した距離は、高分子ＭＬＡ，ＭＬＢが流動方向へ移動した距離よりも大きくなる。そして、こうした流動距離の差異に追従した分布が、生体物質の分布として形成されはじめる。 As shown in FIG. 3B, as the flow of the measurement target liquid L progresses, a biological material distribution corresponding to the size of the biological material begins to be formed in the flow direction that is the column direction. That is, the distance that the low molecular weight MSA and MSB flow in the flow direction is larger than the distance that the high molecular weight MLA and MLB move in the flow direction. And the distribution which followed the difference of such a flow distance begins to be formed as distribution of a biological material.
また、測定対象液Ｌの流動が進むことに伴い、行方向である泳動方向には、生体物質の電荷量に応じた分布が形成されはじめる。すなわち、中性である緩衝液のなかで生体物質は通常負電荷を有するため、低電荷量を有する低分子ＭＳＡは、高電荷量を有する低分子ＭＳＢよりも第１泳動電極１６Ａの近くへ泳動しはじめ、高電荷量を有する低分子ＭＳＢは、低電荷量を有する低分子ＭＳＡよりも第２泳動電極１６Ｂの近くへ泳動しはじめる。また、低電荷量を有する高分子ＭＬＡは、高電荷量を有する高分子ＭＬＢよりも第１泳動電極１６Ａの近くへ泳動しはじめ、高電荷量を有する高分子ＭＬＢは、低電荷量を有する高分子ＭＬＡよりも第２泳動電極１６Ｂの近くへ泳動しはじめる。 Further, as the flow of the measurement target liquid L proceeds, a distribution corresponding to the charge amount of the biological material starts to be formed in the migration direction, which is the row direction. That is, since a biological substance usually has a negative charge in a neutral buffer solution, a low molecular weight MSA having a low charge amount migrates closer to the first migration electrode 16A than a low molecular MSB having a high charge amount. The low molecular MSB having a high charge amount starts to move closer to the second migration electrode 16B than the low molecular MSA having a low charge amount. In addition, the polymer MLA having a low charge amount starts to migrate closer to the first migration electrode 16A than the polymer MLB having a high charge amount, and the polymer MLB having a high charge amount has a high charge amount having a low charge amount. The migration starts closer to the second migration electrode 16B than the molecular MLA.
なお、低電荷量を有する低分子ＭＳＡや高分子ＭＬＡであって第１泳動電極１６Ａの近くに位置する低分子ＭＳＡや高分子ＭＬＡは、それの行方向における位置をおよそ保つ。また、高電荷量を有する低分子ＭＳＢや高分子ＭＬＢであって第２泳動電極１６Ｂの近くに位置する低分子ＭＳＢや高分子ＭＬＢは、それの行方向における位置をおよそ保つ。そして、この泳動傾向に準じた分布が、生体物質の分布として形成されはじめる。 Note that the low molecular MSA and the high molecular MLA having a low charge amount, which are located in the vicinity of the first migration electrode 16A, keep their positions in the row direction. Further, the low molecular MSB and the high molecular MLB having a high charge amount, which are located near the second migration electrode 16B, keep their positions in the row direction. A distribution according to this migration tendency begins to be formed as a distribution of biological material.
図３（ｃ）が示すように、低分子ＭＳＡ，ＭＳＢの流動が最下流の測定素子２０まで進むと、列方向である流動方向には、さらに、生体物質の大きさに応じた広い分布が形成される。すなわち、低分子ＭＳＡ，ＭＳＢは、ほぼ最下流の測定素子２０と対向し、高分子ＭＬＡ，ＭＬＢは、ほぼ最上流の測定素子２０と対向し、低分子ＭＳＡ，ＭＳＢの大きさと、高分子ＭＬＡ，ＭＬＢの大きさとの間の大きさを有する生体物質は、中間の測定素子２０と対向する。 As shown in FIG. 3C, when the flow of the low molecular weight MSA and MSB proceeds to the most downstream measuring element 20, the flow direction which is the column direction further has a wide distribution according to the size of the biological material. It is formed. That is, the low molecular weight MSA and MSB are substantially opposed to the most downstream measuring element 20, and the high molecular weight MLA and MLB are substantially opposed to the most upstream measuring element 20, and the size of the low molecular weight MSA and MSB and the high molecular weight MLA are measured. , The biological material having a size between MLBs is opposed to the intermediate measuring element 20.
また、低分子ＭＳＡ，ＭＳＢの流動が最下流の測定素子２０まで進むと、行方向である泳動方向には、さらに、生体物質の電荷量に応じた広い分布が形成される。すなわち、低電荷量を有する低分子ＭＳＡは、第１泳動電極１６Ａの近くに位置し、高電荷量を有する低分子ＭＳＢは、第２泳動電極１６Ｂの近くに位置する。また、低電荷量を有する高分子ＭＬＡは、第１泳動電極１６Ａの近くに位置し、高電荷量を有する高分子ＭＬＢは、第２泳動電極１６Ｂの近くに位置する。 Further, when the flow of the low molecular weight MSA and MSB proceeds to the measurement element 20 at the most downstream side, a broad distribution corresponding to the charge amount of the biological substance is further formed in the migration direction which is the row direction. That is, the low-molecular MSA having a low charge amount is located near the first migration electrode 16A, and the low-molecular MSB having a high charge amount is located near the second migration electrode 16B. The polymer MLA having a low charge amount is located near the first migration electrode 16A, and the polymer MLB having a high charge amount is located near the second migration electrode 16B.
そして、低分子ＭＳＡ，ＭＳＢが最下流の測定素子２０に到達したとき、高分子ＭＬＡ，ＭＬＢは、それの有する電荷量に応じた行方向の位置で、例えば、最上流の測定素子２０と対向する。また、低分子ＭＳＡ，ＭＳＢは、それの有する電荷量に応じた行方向の位置で、最下流の測定素子２０と対向する。高分子ＭＬＡ，ＭＬＢの大きさと、低分子ＭＳＡ，ＭＳＢの大きさとの間の大きさを有した分子は、それの有する電荷量に応じた行方向の位置で、例えば、中間の測定素子２０と対向する。このように、測定流路１６Ｃを流れる生体物質は、それが有する大きさと電荷量とに基づいて、生体物質の種類ごとに分離される。 When the low molecular weight MSA and MSB reach the most downstream measuring element 20, the macromolecules MLA and MLB are opposed to the measuring element 20 at the most upstream position, for example, at a position in the row direction corresponding to the charge amount of the high molecular weight MLA and MLB. To do. Further, the low molecular weight MSA and MSB are opposed to the most downstream measuring element 20 at a position in the row direction corresponding to the charge amount possessed by them. Molecules having a size between the size of the high molecular weight MLA, MLB and the size of the low molecular weight MSA, MSB are arranged at the position in the row direction according to the charge amount of the molecule, for example, the intermediate measuring element 20 opposite. In this way, the biological material flowing through the measurement channel 16C is separated for each type of biological material based on the size and charge amount of the biological material.
ここで、測定流路１６Ｃの内部に位置する生体物質と、測定素子２０との間の距離は、第１基板１１や第２基板１２が広がる二次元方向と、測定流路１６Ｃが有する厚み方向との成分を有する。そして、特定の生体物質の電気化学的な特性値がいずれの測定素子２０によって測定されるかは、生体物質と測定素子２０との間における二次元方向での距離の大きさと、生体物質と測定素子２０との間における厚み方向での距離の大きさとに従う。特に、相互に近接した測定素子２０の間に位置する生体物質においては、いずれの測定素子２０においてそれの存在が検出されるかが、こうした距離の大小によって変わる。言い換えれば、相互に近接した測定素子２０の位置が、厚み方向において相互に異なるとき、厚み方向における生体物質の位置のばらつきによって、それを検出する測定素子２０の位置にもばらつきが生じる。 Here, the distance between the biological material located inside the measurement channel 16C and the measurement element 20 is determined in the two-dimensional direction in which the first substrate 11 and the second substrate 12 are spread and the thickness direction of the measurement channel 16C. And have ingredients. Then, which measurement element 20 measures the electrochemical characteristic value of a specific biological substance depends on the magnitude of the distance between the biological substance and the measurement element 20 in the two-dimensional direction, the biological substance and the measurement. The distance between the element 20 and the element 20 in the thickness direction is obeyed. In particular, in a biological substance located between measurement elements 20 that are close to each other, which measurement element 20 the presence of which is detected varies depending on the magnitude of the distance. In other words, when the positions of the measurement elements 20 close to each other are different from each other in the thickness direction, the position of the measurement element 20 that detects the variation also occurs due to the variation in the position of the biological material in the thickness direction.
一方で、上述した電気化学セルでは、第１基板１１の一側面に全ての測定素子２０が位置するため、特定の生体物質と各測定素子２０との間における厚み方向での距離は、各測定素子２０においてほぼ等しい。それゆえに、特定の生体物質の電気化学的な特性値がいずれの測定素子２０によって測定されるかは、第１基板１１や第２基板１２が広がる二次元方向における生体物質と測定素子２０との間の距離によって、およそ定まる。すなわち、二次元方向において生体物質と最も近い測定素子２０が、その生体物質の存在を検出する。そのため、特定の生体物質の存在を予め設定された特定の測定素子２０で検出できる確率を高めることが可能となる。 On the other hand, in the electrochemical cell described above, since all the measuring elements 20 are located on one side surface of the first substrate 11, the distance in the thickness direction between the specific biological material and each measuring element 20 is determined by each measurement. In element 20, they are approximately equal. Therefore, which measurement element 20 is used to measure the electrochemical characteristic value of a specific biological material is determined between the biological material and the measurement element 20 in the two-dimensional direction in which the first substrate 11 and the second substrate 12 spread. It is determined by the distance between them. That is, the measuring element 20 closest to the biological material in the two-dimensional direction detects the presence of the biological material. Therefore, it is possible to increase the probability that the presence of a specific biological material can be detected by a specific measurement element 20 set in advance.
なお、流動方向、および、泳動方向を含む二次元方向においてマトリックス状に測定素子２０が位置するため、流動方向や泳動方向へ移動した生体物質は、９つの測定素子２０のなかのいずれか１つと対向しやすい。それゆえに、生体物質の存在はいずれか１つの測定素子２０によって検出されやすいため、生体物質の検出が漏れることを抑えることが可能ともなる。 Since the measurement elements 20 are located in a matrix in the flow direction and the two-dimensional direction including the migration direction, the biological material that has moved in the flow direction or the migration direction is any one of the nine measurement elements 20. Easy to face each other. Therefore, since the presence of the biological material is easily detected by any one of the measurement elements 20, it is possible to suppress leakage of the detection of the biological material.
［測定処理部］
図４が示すように、電気化学測定装置は、測定処理部３０を備え、測定処理部３０は、第１泳動電極１６Ａ、第２泳動電極１６Ｂ、および、各測定素子２０を駆動させると共に、各測定素子２０から測定結果を取得して生体物質の存在を検出する。測定処理部３０は、３行×３列の測定素子２０の駆動に際して、各測定素子２０を別々に取り扱う。
[Measurement processing section]
As shown in FIG. 4, the electrochemical measurement apparatus includes a measurement processing unit 30. The measurement processing unit 30 drives the first migration electrode 16A, the second migration electrode 16B, and each measurement element 20, and each The measurement result is acquired from the measurement element 20 to detect the presence of the biological material. The measurement processing unit 30 handles each measurement element 20 separately when driving the measurement elements 20 in 3 rows × 3 columns.
測定処理部３０は、最上流に位置する１行目の測定素子２０を、第１泳動電極１６Ａに近い測定素子２０から順に、第１測定素子２０ａ、第２測定素子２０ｂ、第３測定素子２０ｃとして取り扱う。測定処理部３０は、２行目に位置する３つの測定素子２０を、第１泳動電極１６Ａに近い測定素子２０から順に、第４測定素子２０ｄ、第５測定素子２０ｅ、第６測定素子２０ｆとして取り扱う。測定処理部３０は、最下流に位置する３行目の測定素子２０を、第１泳動電極１６Ａに近い測定素子２０から順に、第７測定素子２０ｇ、第８測定素子２０ｈ、第９測定素子２０ｉとして取り扱う。 The measurement processing unit 30 sets the first row of measurement elements 20 located in the uppermost stream in order from the measurement element 20 close to the first migration electrode 16A, in order of the first measurement element 20a, the second measurement element 20b, and the third measurement element 20c. Treat as. The measurement processing unit 30 sets the three measurement elements 20 located in the second row as the fourth measurement element 20d, the fifth measurement element 20e, and the sixth measurement element 20f in order from the measurement element 20 close to the first migration electrode 16A. handle. The measurement processing unit 30 sets the measurement elements 20 in the third row located on the most downstream side in order from the measurement element 20 close to the first migration electrode 16A, the seventh measurement element 20g, the eighth measurement element 20h, and the ninth measurement element 20i. Treat as.
上述したように、測定流路１６Ｃの内部に位置する生体物質は、それの大きさと電荷量とに基づいて、生体物質の種類ごとに、いずれか１つの測定素子２０の測定範囲へ分離される。測定処理部３０は、９つの測定素子２０を別々に取り扱うため、測定素子２０ごとの生体物質の種類もまた別々に取り扱う。 As described above, the biological material positioned inside the measurement channel 16C is separated into the measurement range of any one measurement element 20 for each type of biological material based on the size and the amount of charge. . Since the measurement processing unit 30 handles the nine measurement elements 20 separately, the type of biological material for each measurement element 20 is also handled separately.
例えば、測定処理部３０は、第１測定素子２０ａの測定結果に基づいて、第１測定素子２０ａに対応する生体物質が存在するか否かを検出する。また、例えば、測定処理部３０は、第９測定素子２０ｉの測定結果に基づいて、第９測定素子２０ｉに対応する別の生体物質が存在するか否かを検出する。さらに、例えば、測定処理部３０は、第１測定素子２０ａの測定結果と、第９測定素子２０ｉの測定結果との比較に基づいて、第１測定素子２０ａに対応する生体物質が、第９測定素子２０ｉに対応する生体物質よりも多いか否かを検出する。 For example, the measurement processing unit 30 detects whether or not a biological material corresponding to the first measurement element 20a exists based on the measurement result of the first measurement element 20a. For example, the measurement processing unit 30 detects whether another biological material corresponding to the ninth measurement element 20i exists based on the measurement result of the ninth measurement element 20i. Further, for example, the measurement processing unit 30 determines that the biological material corresponding to the first measurement element 20a is the ninth measurement based on the comparison between the measurement result of the first measurement element 20a and the measurement result of the ninth measurement element 20i. It is detected whether there is more than the biological material corresponding to the element 20i.
図５が示すように、測定処理部３０は、制御部３１、記憶部３２、駆動部３３、および、出力部３４を備える。測定処理部３０は、各対極配線１３Ｂ、各作用電極配線１４Ｂ、各参照電極配線１５Ｂ、第１泳動電極１６Ａ、および、第２泳動電極１６Ｂに接続される。制御部３１は、記憶部３２が記憶するデータなどを用い、駆動部３３、および、出力部３４の駆動を制御する。 As shown in FIG. 5, the measurement processing unit 30 includes a control unit 31, a storage unit 32, a drive unit 33, and an output unit 34. The measurement processing unit 30 is connected to each counter electrode wiring 13B, each working electrode wiring 14B, each reference electrode wiring 15B, the first migration electrode 16A, and the second migration electrode 16B. The control unit 31 controls driving of the drive unit 33 and the output unit 34 using data stored in the storage unit 32.
制御部３１は、緩衝液が最下流の測定素子２０に到達するまで駆動部３３を待機させると共に、緩衝液が最下流の測定素子２０に到達して以降に、第１泳動電極１６Ａと第２泳動電極１６Ｂとを駆動するための信号を、駆動部３３へ入力する。駆動部３３は、制御部３１から入力される信号に従い、緩衝液が最下流の測定素子２０に到達して以降に、生体物質を泳動させる電位勾配を、第１泳動電極１６Ａと第２泳動電極１６Ｂとの間に形成させる。 The control unit 31 causes the drive unit 33 to stand by until the buffer solution reaches the most downstream measurement element 20, and after the buffer solution reaches the most downstream measurement element 20, A signal for driving the electrophoresis electrode 16B is input to the drive unit 33. In accordance with a signal input from the control unit 31, the drive unit 33 generates a potential gradient for migrating a biological substance after the buffer solution reaches the most downstream measurement element 20. The first migration electrode 16 </ b> A and the second migration electrode 16B.
制御部３１は、測定対象液Ｌが最下流の測定素子２０に到達したタイミングで、第１泳動電極１６Ａと第２泳動電極１６Ｂとの駆動を停止するための信号を、駆動部３３へ入力する。駆動部３３は、制御部３１から入力される信号に従い、測定対象液Ｌが最下流の測定素子２０に到達したタイミングで、第１泳動電極１６Ａと第２泳動電極１６Ｂとに、電位勾配の形成を停止させる。 The control unit 31 inputs a signal for stopping the driving of the first migration electrode 16A and the second migration electrode 16B to the drive unit 33 at the timing when the measurement target liquid L reaches the most downstream measurement element 20. . The drive unit 33 forms a potential gradient on the first migration electrode 16A and the second migration electrode 16B at the timing when the measurement target liquid L reaches the measurement element 20 on the most downstream side in accordance with a signal input from the control unit 31. Stop.
制御部３１は、測定対象液Ｌが最下流の測定素子２０に到達したか否かを検出する検出部３１Ａを備える。検出部３１Ａは、例えば、第１泳動電極１６Ａと第２泳動電極１６Ｂとが駆動されて以降に、第１泳動電極１６Ａや第２泳動電極１６Ｂに流れる電流を監視し、その電流値が所定値よりも小さくなったとき、生体物質の泳動がほぼ終了し、測定対象液Ｌが最下流の測定素子２０に到達したものとみなしてそれを検出する。また、例えば、最下流に位置する測定素子２０の近傍に、生体物質を検出するための検出素子を電気化学セルが別途備えてもよい。そして、検出部３１Ａは、例えば、第１泳動電極１６Ａと第２泳動電極１６Ｂとが駆動されて以降に、検出素子の検出結果を監視し、検出素子が生体物質を検出したとき、測定対象液Ｌが最下流の測定素子２０に到達したものとみなしてそれを検出してもよい。 The control unit 31 includes a detection unit 31A that detects whether or not the measurement target liquid L has reached the most downstream measurement element 20. For example, the detection unit 31A monitors the current flowing through the first migration electrode 16A and the second migration electrode 16B after the first migration electrode 16A and the second migration electrode 16B are driven, and the current value is a predetermined value. When it becomes smaller than that, the migration of the biological substance is almost finished, and it is assumed that the measurement target liquid L has reached the most downstream measurement element 20 and is detected. Further, for example, an electrochemical cell may be separately provided with a detection element for detecting a biological substance in the vicinity of the measurement element 20 located on the most downstream side. For example, the detection unit 31A monitors the detection result of the detection element after the first migration electrode 16A and the second migration electrode 16B are driven, and when the detection element detects a biological substance, the measurement target liquid It may be detected that L has reached the most downstream measuring element 20.
制御部３１は、測定対象液Ｌが最下流の測定素子２０に到達したタイミングで、各測定素子２０による測定を順に開始させるためのタイミング信号を、駆動部３３へ入力する。駆動部３３は、制御部３１から入力されるタイミング信号に従い、測定対象液Ｌが最下流の測定素子２０に到達したタイミングで、各対極配線１３Ｂ、および、各参照電極配線１５Ｂを、１行目から順に線順次走査する。 The control unit 31 inputs a timing signal for sequentially starting the measurement by each measurement element 20 to the drive unit 33 at the timing when the measurement target liquid L reaches the most downstream measurement element 20. The drive unit 33 connects each counter electrode wiring 13B and each reference electrode wiring 15B to the first row at the timing when the measurement target liquid L reaches the most downstream measurement element 20 according to the timing signal input from the control unit 31. Line sequential scanning is performed in order.
すなわち、各測定素子２０の近傍に分布する生体物質の種類は、上述した流動距離と泳動傾向とに従って、言い換えれば、生体物質の大きさとそれが有する電荷量とに従って予め定められる。駆動部３３は、まず、１行目の測定素子２０の近傍に位置すると推定される生体物質に対し、それの酸化還元電流を測定するための電圧信号を、１行目の対極配線１３Ｂ、および、１行目の参照電極配線１５Ｂに入力する。そして、駆動部３３は、全ての作用電極配線１４Ｂを通じて、１行目の各作用電極１４Ａに流れる酸化還元電流を別々に測定する。次いで、駆動部３３は、２行目の測定素子２０の近傍に位置すると推定される生体物質に対し、それの酸化還元電流を測定するための電圧信号を、２行目の対極配線１３Ｂ、および、２行目の参照電極配線１５Ｂに入力する。そして、駆動部３３は、全ての作用電極配線１４Ｂを通じて、２行目の各作用電極１４Ａに流れる酸化還元電流を別々に測定する。最後に、駆動部３３は、３行目の測定素子２０の近傍に位置すると推定される生体物質に対し、それの酸化還元電流を測定するための電圧信号を、３行目の対極配線１３Ｂ、および、３行目の参照電極配線１５Ｂに入力する。そして、駆動部３３は、全ての作用電極配線１４Ｂを通じて、３行目の各作用電極１４Ａに流れる酸化還元電流を別々に測定する。 That is, the type of biological material distributed in the vicinity of each measuring element 20 is determined in advance according to the above-described flow distance and migration tendency, in other words, according to the size of the biological material and the amount of charge it has. The drive unit 33 first outputs a voltage signal for measuring the oxidation-reduction current of a biological material estimated to be located in the vicinity of the measurement element 20 in the first row, to the counter electrode wiring 13B in the first row, and Input to the reference electrode wiring 15B in the first row. And the drive part 33 measures separately the oxidation reduction current which flows into each working electrode 14A of the 1st row through all the working electrode wiring 14B. Next, the drive unit 33 sends a voltage signal for measuring the oxidation-reduction current of the biological material estimated to be located in the vicinity of the measurement element 20 in the second row to the counter electrode wiring 13B in the second row, and Input to the second-row reference electrode wiring 15B. Then, the drive unit 33 separately measures the oxidation-reduction current flowing through each working electrode 14A in the second row through all the working electrode wirings 14B. Finally, the drive unit 33 outputs a voltage signal for measuring the oxidation-reduction current of a biological substance estimated to be located in the vicinity of the measurement element 20 in the third row to the counter electrode wiring 13B in the third row, And it inputs into the reference electrode wiring 15B of the 3rd row. And the drive part 33 measures separately the oxidation reduction current which flows into each working electrode 14A of the 3rd row through all the working electrode wiring 14B.
このように、測定処理部３０は、最下流の測定素子２０に測定対象液Ｌが行きわたった状態、ひいては、最下流の測定素子２０にその存在を検出させるための生体物質が、最下流の測定素子２０に到達したタイミングで、それの測定を開始させることが可能である。そのため、生体物質の検出に関わる再現性を高めることが可能である。 In this way, the measurement processing unit 30 is in a state in which the measurement target liquid L has spread over the most downstream measurement element 20, and thus the biological material for causing the most downstream measurement element 20 to detect its presence is the most downstream. The measurement can be started at the timing when the measurement element 20 is reached. Therefore, it is possible to improve the reproducibility related to the detection of the biological material.
制御部３１は、測定対象液の属性を判定する判定部３１Ｂを備える。記憶部３２は、９つの測定素子２０のなかでの特性値の分布から測定対象液Ｌの属性を判定するための演算式を記憶する。本実施形態において９つの測定素子２０における特性値は、９つの測定素子２０の各々における酸化還元電流である。本実施形態における液の属性は、例えば、測定対象液Ｌに基づく健康の度合い、特定の生体物質の量が低いことなどによる疾患の度合いなどである。 The control unit 31 includes a determination unit 31B that determines the attribute of the measurement target liquid. The storage unit 32 stores an arithmetic expression for determining the attribute of the measurement target liquid L from the distribution of characteristic values among the nine measurement elements 20. In the present embodiment, the characteristic value in the nine measuring elements 20 is an oxidation-reduction current in each of the nine measuring elements 20. The attributes of the liquid in the present embodiment are, for example, the degree of health based on the measurement target liquid L, the degree of disease due to a low amount of a specific biological material, and the like.
上述したように、各測定素子２０によって測定される酸化還元電流は、測定素子２０の測定範囲に存在する生体物質の種類と濃度とに従う値である。各測定素子２０の測定範囲に存在する生体物質の種類は、生体物質の大きさとそれが有する電荷量とによって予め定められるため、各測定素子２０によって測定される酸化還元電流は、結局のところ、その測定素子２０に対応する生体物質が存在するか否か、存在するとすればその濃度はどの程度かを示す値である。判定部３１Ｂは、記憶部３２が記憶するデータとこうした測定結果とを用い、例えば、９つの測定素子２０の測定結果による多変量解析から、健康の度合いや疾患の度合いを判定する。 As described above, the oxidation-reduction current measured by each measurement element 20 is a value according to the type and concentration of the biological substance existing in the measurement range of the measurement element 20. Since the type of the biological substance existing in the measurement range of each measuring element 20 is determined in advance by the size of the biological substance and the amount of charge that it has, the oxidation-reduction current measured by each measuring element 20 is, after all, This is a value indicating whether or not a biological substance corresponding to the measuring element 20 exists, and if so, what is its concentration. The determination unit 31B uses the data stored in the storage unit 32 and such measurement results to determine the degree of health and the degree of disease from, for example, multivariate analysis based on the measurement results of the nine measurement elements 20.
ここで、測定対象液Ｌにおける全生体物質の濃度や、測定対象液Ｌが有する酸性度などのようなパラメータは、各測定素子２０の測定結果に対して共通に影響を及ぼし、各測定素子２０の測定結果の絶対値に対しては、共通する誤差の要因ともなる。この点、判定部３１Ｂは、各測定素子２０のなかでの測定結果の分布に基づいて、測定対象液Ｌの属性を特定する、すなわち、１つ以上の測定素子２０の測定結果に対する他の測定素子２０の相対値に基づいて測定対象液Ｌの属性を特定する。そのため、例えば、１つの測定素子２０から得られた特性値に基づいて測定対象液Ｌの属性が特定される構成と比べて、上述した誤差の要因による影響を軽減することが可能となる。なお、９つの測定素子２０のなかでの特性値の分布の一例を図６に示す。 Here, parameters such as the concentration of all biological substances in the measurement target liquid L and the acidity of the measurement target liquid L have a common influence on the measurement result of each measurement element 20. The absolute value of the measurement result is also a common error factor. In this regard, the determination unit 31B specifies the attribute of the measurement target liquid L based on the distribution of the measurement results in each measurement element 20, that is, other measurement for the measurement results of one or more measurement elements 20. The attribute of the measurement target liquid L is specified based on the relative value of the element 20. Therefore, for example, compared to a configuration in which the attribute of the measurement target liquid L is specified based on a characteristic value obtained from one measurement element 20, it is possible to reduce the influence due to the error factor described above. An example of the distribution of characteristic values among the nine measuring elements 20 is shown in FIG.
［電気化学測定方法］
図７が示すように、電気化学測定装置が実行する電気化学測定方法は、測定処理部３０が以下の順に各工程を行うことを含む。
まず、測定処理部３０は、緩衝液が流れている電気化学セルに対して、第１泳動電極１６Ａと第２泳動電極１６Ｂとを駆動し、生体物質を泳動させるための電位勾配を第１基板１１と第２基板１２との隙間に形成する（ステップＳ１１）。次いで、測定処理部３０は、測定対象液Ｌの注入を開始すると共に（ステップＳ１２）、最下流の測定素子２０に測定対象液Ｌが到達するまで、最下流の測定素子２０に測定対象液Ｌが到達したかを判断する（ステップＳ１３，Ｓ１４）。
[Electrochemical measurement method]
As shown in FIG. 7, the electrochemical measurement method executed by the electrochemical measurement device includes the measurement processing unit 30 performing each step in the following order.
First, the measurement processing unit 30 drives the first migration electrode 16A and the second migration electrode 16B to the electrochemical cell in which the buffer solution flows, and generates a potential gradient for migrating the biological material on the first substrate. 11 and the second substrate 12 (step S11). Next, the measurement processing unit 30 starts injecting the measurement target liquid L (step S12), and until the measurement target liquid L reaches the most downstream measurement element 20, the measurement target liquid L reaches the most downstream measurement element 20. Is reached (steps S13 and S14).
最下流の測定素子２０に測定対象液Ｌが到達すると、測定処理部３０は、測定流路１６Ｃの内部における各部位の酸化還元電流を測定するために、各測定素子２０を駆動する（ステップＳ１５）。すなわち、測定処理部３０は、測定対象液Ｌが最下流の測定素子２０に到達したタイミングで、酸化還元電流を測定するための電圧信号の印加と、酸化還元電流の測定とを、１行目の測定素子２０から順に、３行目の測定素子２０までを用いて実行する。 When the measurement target liquid L reaches the most downstream measurement element 20, the measurement processing unit 30 drives each measurement element 20 in order to measure the oxidation-reduction current of each part in the measurement flow path 16C (step S15). ). That is, the measurement processing unit 30 applies the voltage signal for measuring the oxidation-reduction current and the measurement of the oxidation-reduction current at the timing when the measurement target liquid L reaches the most downstream measurement element 20 in the first row. The measurement elements 20 are sequentially executed using the measurement elements 20 in the third row.
測定処理部３０は、全ての測定素子２０から特性値である酸化還元電流を取得すると、全ての測定素子２０のなかでの特性値の分布に基づいて測定対象液Ｌの属性を特定し、その特定された結果を出力部３４から出力する（ステップＳ１６）。 When the measurement processing unit 30 acquires the oxidation-reduction current that is the characteristic value from all the measurement elements 20, the measurement processing unit 30 identifies the attribute of the measurement target liquid L based on the distribution of the characteristic values among all the measurement elements 20, The identified result is output from the output unit 34 (step S16).
本実施形態によれば、以下のような効果を得ることができる。
（１）生体物質の分離、および、検出を、共通する泳動槽で行うことが可能である。
（２）測定対象液Ｌに含まれる各生体物質に対してそれの存在がいずれか１つの測定素子２０によって検出されやすいため、生体物質の検出漏れを抑えることが可能となる。
According to this embodiment, the following effects can be obtained.
(1) Separation and detection of biological materials can be performed in a common electrophoresis tank.
(2) Since the presence of each biological substance contained in the measurement target liquid L is easily detected by any one of the measurement elements 20, it is possible to suppress detection failure of the biological substance.
（３）第１基板１１が有する１つの側面に全ての測定素子が位置するため、特定の生体物質の存在を特定の測定素子２０で検出できる確率を高めることが可能となる。 (3) Since all the measurement elements are located on one side surface of the first substrate 11, it is possible to increase the probability that the presence of the specific biological material can be detected by the specific measurement element 20.
（４）複数の測定素子のなかでの測定結果の相対値に基づいて測定対象液の属性が特定されるため、特定された属性に対する信頼性を高めることが可能でもある。
（５）全ての測定素子２０に測定対象液Ｌが行きわたったか否かを検出できる。
(4) Since the attribute of the liquid to be measured is specified based on the relative value of the measurement results among the plurality of measurement elements, it is possible to increase the reliability of the specified attribute.
(5) It is possible to detect whether or not the measurement target liquid L has spread over all the measurement elements 20.
（６）全ての測定素子２０に測定対象液Ｌが行きわたった状態で測定を開始させることが可能であるため、生体物質の検出に関わる再現性を高めることが可能である。 (6) Since the measurement can be started in a state where the measurement target liquid L is distributed to all the measuring elements 20, it is possible to improve the reproducibility related to the detection of the biological material.
上記実施形態は、以下のように変更して実施することができる。
［特性値の取得］
・測定処理部３０は、測定対象液Ｌが最下流の測定素子２０に到達する前に測定を開始してもよいし、測定対象液Ｌが最下流の測定素子２０に到達する前に、全ての測定素子２０で測定を繰り返してもよい。
The above embodiment can be implemented with the following modifications.
[Get characteristic value]
The measurement processing unit 30 may start measurement before the measurement target liquid L reaches the most downstream measurement element 20, or before the measurement target liquid L reaches the most downstream measurement element 20, Measurement may be repeated with the measuring element 20.
例えば、図８が示すように、測定処理部３０が実行する電気化学測定方法は、測定対象液Ｌの注入を開始してから、最下流の測定素子２０に測定対象液Ｌが到達するまで、測定処理部３０は、測定流路１６Ｃの内部における各部位の酸化還元電流を測定するために、各測定素子２０を繰り返し駆動する（ステップＳ２３，２４）。すなわち、測定処理部３０は、測定対象液Ｌの注入を開始してから、最下流の測定素子２０に測定対象液Ｌが到達するまでの間に、測定素子２０に到達するべき生体物質の到達量の推移を、各測定素子２０から取得する。そして、最下流の測定素子２０に測定対象液Ｌが到達したときに、各測定素子２０の駆動を停止し、各測定範囲における生体物質の到達量の推移から、測定対象液Ｌの属性を特定する。 For example, as shown in FIG. 8, the electrochemical measurement method executed by the measurement processing unit 30 starts the injection of the measurement target liquid L until the measurement target liquid L reaches the most downstream measurement element 20. The measurement processing unit 30 repeatedly drives each measurement element 20 in order to measure the oxidation-reduction current at each site in the measurement flow path 16C (steps S23 and S24). That is, the measurement processing unit 30 starts the injection of the measurement target liquid L and arrives at the biological material that should reach the measurement element 20 after the measurement target liquid L arrives at the most downstream measurement element 20. The transition of the quantity is acquired from each measuring element 20. Then, when the measurement target liquid L reaches the most downstream measurement element 20, the driving of each measurement element 20 is stopped, and the attribute of the measurement target liquid L is specified from the transition of the arrival amount of the biological substance in each measurement range. To do.
こうした装置、および、方法によれば、測定対象液Ｌの属性を特定するための情報量が、測定素子２０による測定が繰り返されるごとに増える。そのため、特定された属性の精度を高めることが可能でもある。なお、測定対象液Ｌの注入を開始してから、所定の時間が経過するまでの間に、測定素子２０に到達するべき生体物質の到達量の推移を、各測定素子２０から取得する構成であってもよい。こうした装置、および、方法であれば、最下流の測定素子２０である最下素子に測定対象液が到達したことを検出する構成を省略でき、電気化学測定装置や電気化学セルの構成について、それの簡素化を図ることが可能である。 According to such an apparatus and method, the amount of information for specifying the attribute of the measurement target liquid L increases each time the measurement by the measurement element 20 is repeated. Therefore, it is possible to increase the accuracy of the identified attribute. In addition, it is the structure which acquires transition of the arrival amount of the biological material which should arrive at the measurement element 20 from each measurement element 20 after starting injection | pouring of the measurement object liquid L until predetermined time passes. There may be. With such an apparatus and method, it is possible to omit the configuration for detecting that the liquid to be measured has reached the lowermost element, which is the most downstream measuring element 20, and for the configurations of the electrochemical measuring apparatus and the electrochemical cell, It is possible to simplify.
・測定素子２０が測定する電気化学的な特性値は、酸化還元電流に限らず、例えば、酵素反応によって流れる電流、液中における交流インピーダンス、および、測定対象液と電極との界面電位であってもよく、これらのなかの組み合わせであってもよい。 The electrochemical characteristic value measured by the measuring element 20 is not limited to the oxidation-reduction current. Or a combination of these.
電気化学的な特性値が、酵素反応によって流れる電流の測定であるとき、作用電極１４Ａは、その表面に酵素が固定化された酵素電極である。こうした構成であれば、酵素反応によってその存在を検出できる生体物質の分離、および、検出に、上記電気化学測定装置を適用することが可能である。 When the electrochemical characteristic value is measurement of a current flowing through an enzyme reaction, the working electrode 14A is an enzyme electrode having an enzyme immobilized on its surface. With such a configuration, the electrochemical measurement apparatus can be applied to separation and detection of a biological substance whose presence can be detected by an enzymatic reaction.
電機化学的な特性値が、液中における交流インピーダンスであるとき、上述した作用電極１４Ａを、液中に交流電圧を印加することを可能に構成された一対の交流印加電極に変更した構成であればよい。こうした構成であれば、交流インピーダンスによってその存在を検出できる生体物質の分離、および、検出に、上記電気化学測定装置を適用することが可能であって、また、上述した参照電極１５Ａを省略することもできる。 When the electrochemical characteristic value is an alternating current impedance in the liquid, the working electrode 14A described above may be changed to a pair of alternating current application electrodes configured to be able to apply an alternating voltage to the liquid. That's fine. With such a configuration, the electrochemical measurement device can be applied to the separation and detection of a biological substance whose presence can be detected by AC impedance, and the above-described reference electrode 15A is omitted. You can also.
電気化学的な特性値が、測定対象液Ｌと電極との界面電位であるとき、上述した作用電極は、電界効果型トランジスタ（ＦＥＴ）である。こうした構成であれば、界面電位によってその存在を検出できる生体物質の分離、および、検出に、上記電気化学測定装置を適用することが可能であって、また、上述した対極１３Ａを省略することもできる。 When the electrochemical characteristic value is the interface potential between the liquid L to be measured and the electrode, the working electrode described above is a field effect transistor (FET). With such a configuration, it is possible to apply the electrochemical measurement device to the separation and detection of a biological substance whose presence can be detected by the interface potential, and the counter electrode 13A described above may be omitted. it can.
・測定処理部３０は、泳動電極による泳動を開始させる信号を泳動電極に入力した後に、各測定素子２０による測定を開始する構成であればよく、例えば、泳動電極による泳動を開始させる信号を泳動電極に入力した状態で、各測定素子２０による測定を開始してもよい。こうした測定の形態では、電位勾配が形成された状態での特性値の測定となるため、電位勾配が形成されていない状態での特性値の測定とは測定結果が異なる場合がある。一方で、電位勾配が形成された状態での測定結果同士の比較に基づく生体物質の検出は可能であるから、生体物質の分離、および、検出を、単一の泳動槽において行うことは可能である。 The measurement processing unit 30 may be configured to start measurement by each measurement element 20 after inputting a signal for starting migration by the migration electrode to the migration electrode. For example, the measurement processing unit 30 migrates a signal for starting migration by the migration electrode. You may start the measurement by each measuring element 20 in the state input into the electrode. In such a measurement mode, the characteristic value is measured in a state where a potential gradient is formed. Therefore, the measurement result may be different from the measurement of the characteristic value in a state where no potential gradient is formed. On the other hand, since it is possible to detect biological materials based on comparison between measurement results in a state where a potential gradient is formed, it is possible to separate and detect biological materials in a single electrophoresis tank. is there.
［判定部］
・測定対象液Ｌのなかに既知の濃度で内標準物質が添加される使用の形態では、例えば、電気化学セルは、内標準物質の濃度を測定するための測定素子を備え、判定部３１Ｂは、内標準物質の測定結果に対する、各測定素子２０での測定結果の相対値を出力したり、その相対値に基づいて測定対象液Ｌの属性を判定したりしてもよい。こうした測定の形態によっても、電気化学測定装置による検出の精度を高めることは可能であって、また、電気化学測定装置によって特定された属性の信頼性を高めることも可能である。
[Determining part]
In the form of use in which the internal standard substance is added at a known concentration in the measurement target liquid L, for example, the electrochemical cell includes a measuring element for measuring the concentration of the internal standard substance, and the determination unit 31B The relative value of the measurement result of each measuring element 20 with respect to the measurement result of the internal standard substance may be output, or the attribute of the measurement target liquid L may be determined based on the relative value. Even with such a measurement form, it is possible to increase the accuracy of detection by the electrochemical measurement device, and it is also possible to increase the reliability of the attribute specified by the electrochemical measurement device.
・測定処理部３０は、各測定素子２０から特性値を取得し、取得された各特性値を検出値として出力部３４に出力させる構成であってもよい。こうした測定処理部３０であれば、判定部３１Ｂの省略によって、測定処理部３０における構成の簡素化を図ることが可能でもある。 The measurement processing unit 30 may be configured to acquire characteristic values from each measurement element 20 and output the acquired characteristic values to the output unit 34 as detection values. With such a measurement processing unit 30, it is possible to simplify the configuration of the measurement processing unit 30 by omitting the determination unit 31B.
［検出部］
・最下流の測定素子２０に測定対象液Ｌが到達したことを検出する機能を、電気化学測定装置から割愛し、最下流の測定素子２０に測定対象液Ｌが到達したことは、測定対象液Ｌの注入から所定時間が経過したことに基づいて、制御部３１が推定してもよい。
[Detection unit]
The function of detecting that the measurement target liquid L has arrived at the most downstream measurement element 20 is omitted from the electrochemical measurement device, and the fact that the measurement target liquid L has reached the most downstream measurement element 20 is The control unit 31 may estimate based on the fact that a predetermined time has elapsed since the injection of L.
・測定処理部３０は、最下流の測定素子２０に測定対象液Ｌが到達した後に、各測定素子２０を駆動して、各測定素子２０に特性値の測定を開始させてもよい。また、測定処理部３０は、最下流の測定素子２０に測定対象液Ｌが到達する前に、各測定素子２０を駆動して、各測定素子２０に特性値の測定を開始させてもよい。これらの測定の開始タイミングによっても、最下流の測定素子２０に測定対象液Ｌが到達したことを検出する機能を、電気化学測定装置から割愛し、それの構成の簡素化を図ることが可能である。 The measurement processing unit 30 may drive each measurement element 20 after the measurement target liquid L has arrived at the most downstream measurement element 20 and cause each measurement element 20 to start measuring the characteristic value. In addition, the measurement processing unit 30 may drive each measurement element 20 and start measurement of the characteristic value before each measurement target liquid L reaches the most downstream measurement element 20. Even with the start timing of these measurements, it is possible to omit the function of detecting that the measurement target liquid L has reached the most downstream measurement element 20 from the electrochemical measurement device, and to simplify the configuration thereof. is there.
［測定素子］
・対極群１３、作用電極群１４、参照電極群１５、第１泳動電極１６Ａ、および、第２泳動電極１６Ｂの少なくとも１つは、第２基板１２が備える面のなかで第１基板１１と対向する面に位置してもよい。こうした電極や配線の配置であれば、全ての電極や配線が第１基板１１に位置する構成と比べて、電極や配線の位置に関わる制約を軽減することが可能である。
[Measuring element]
At least one of the counter electrode group 13, the working electrode group 14, the reference electrode group 15, the first migration electrode 16 </ b> A, and the second migration electrode 16 </ b> B is opposed to the first substrate 11 in the surface of the second substrate 12. It may be located on the surface to be. With such an arrangement of electrodes and wirings, it is possible to reduce restrictions on the positions of the electrodes and wirings, compared to a configuration in which all the electrodes and wirings are located on the first substrate 11.
・複数の測定素子２０は、３行×３列に限らず、２行×２列であってもよいし、４行以上であってもよいし、４列以上であってもよく、さらには、マトリックス状の配置に限らず、例えば、ペンタイル状の配置や多重環状の配置であってもよく、二次元方向に並ぶ構成であればよい。 The plurality of measuring elements 20 is not limited to 3 rows × 3 columns, may be 2 rows × 2 columns, 4 rows or more, 4 columns or more, and The arrangement is not limited to a matrix shape, and may be, for example, a pen tile-like arrangement or a multi-annular arrangement, as long as the arrangement is two-dimensional.
・複数の測定素子２０の一部は、第２基板１２が備える面のなかで第１基板１１と対向する面に位置してもよい。こうした測定素子２０の配置であれば、全ての測定素子２０が第１基板１１に位置する構成と比べて、測定素子２０の位置に関わる制約を軽減することが可能である。 A part of the plurality of measurement elements 20 may be located on a surface facing the first substrate 11 among the surfaces of the second substrate 12. With such an arrangement of the measurement elements 20, it is possible to reduce restrictions on the positions of the measurement elements 20 compared to a configuration in which all the measurement elements 20 are located on the first substrate 11.
［泳動電極］
・電気化学セルが備える泳動電極の数は、３つ以上であってもよく、例えば、３つ以上の泳動電極に対して、泳動電極ごとに位相が異なる進行波電圧を測定処理部３０が印加し、それによって、測定流路１６Ｃの内部に位置する生体物質を泳動させてもよい。
［その他の構成］
[Electrophoresis electrode]
The number of electrophoretic electrodes provided in the electrochemical cell may be three or more. For example, the measurement processing unit 30 applies traveling wave voltages having different phases for each electrophoretic electrode to three or more electrophoretic electrodes. Thereby, the biological material located inside the measurement channel 16C may be migrated.
[Other configurations]
・電気化学測定装置は、酸性の測定対象液Ｌに関しても、また、アルカリ性の測定対象液Ｌに関しても、生体物質の分離、および、検出を、共通する泳動槽で行うことは可能である。 The electrochemical measurement apparatus can perform separation and detection of biological substances in a common electrophoresis tank for both the acidic measurement target liquid L and the alkaline measurement target liquid L.
・測定処理部が電気化学セルに実行させる生体物質の泳動は、測定処理部が形成させる電位勾配による電気泳動に限らず、例えば、測定処理部が形成させる不均一な電界による誘電泳動であってもよい。この際、電気化学セルが備える泳動電極は、相互に異なる大きさを有する泳動電極であってもよいし、他の泳動電極との距離が泳動電極内において異なる泳動電極であってもよい。 The migration of the biological material that the measurement processing unit performs on the electrochemical cell is not limited to the electrophoresis based on the potential gradient formed by the measurement processing unit, for example, the dielectrophoresis by the non-uniform electric field formed by the measurement processing unit. Also good. In this case, the migration electrodes provided in the electrochemical cell may be migration electrodes having different sizes from each other, or may be migration electrodes having different distances from other migration electrodes within the migration electrode.
・電気化学セルにおける測定対象液Ｌの流動は、測定対象液Ｌの自重による泳動であってもよいし、測定流路１６Ｃの一端に接続される吸引部を電気化学測定装置が備え、吸引部による測定対象液Ｌの吸引によって実現してもよい。 The flow of the measurement target liquid L in the electrochemical cell may be migration due to its own weight, or the electrochemical measurement device includes a suction part connected to one end of the measurement flow path 16C, and the suction part This may be realized by suction of the liquid L to be measured.
・測定流路１６Ｃのなかで測定対象液Ｌが注入される位置は、測定流路１６Ｃにおける行方向の全体に限らず、測定流路１６Ｃにおける行方向の一端であってもよいし、行方向における中央であってもよい。 The position into which the measurement target liquid L is injected in the measurement channel 16C is not limited to the entire row direction in the measurement channel 16C, but may be one end in the row direction in the measurement channel 16C. May be the center.
Ｌ…測定対象液、Ｐ…ポンプ、ＭＬＡ，ＭＬＢ…高分子、ＭＳＡ，ＭＳＢ…低分子、１１…第１基板、１１Ａ…対向面、１２…第２基板、１３…対極群、１３Ａ…対極、１３Ｂ…対極配線、１４…作用電極群、１４Ａ…作用電極、１４Ｂ…作用電極配線、１５…参照電極群、１５Ａ…参照電極、１５Ｂ…参照電極配線、１６Ａ…第１泳動電極、１６Ｂ…第２泳動電極、１６Ｃ…測定流路、２０…測定素子、２０ａ…第１測定素子、２０ｂ…第２測定素子、２０ｃ…第３測定素子、２０ｄ…第４測定素子、２０ｅ…第５測定素子、２０ｆ…第６測定素子、２０ｇ…第７測定素子、２０ｈ…第８測定素子、２０ｉ…第９測定素子、３０…測定処理部、３１…制御部、３１Ａ…検出部、３１Ｂ…判定部、３２…記憶部、３３…駆動部、３４…出力部。 L: liquid to be measured, P: pump, MLA, MLB ... polymer, MSA, MSB ... low molecule, 11 ... first substrate, 11A ... opposite surface, 12 ... second substrate, 13 ... counter electrode group, 13A ... counter electrode, 13B ... Counter electrode wiring, 14 ... Working electrode group, 14A ... Working electrode, 14B ... Working electrode wiring, 15 ... Reference electrode group, 15A ... Reference electrode, 15B ... Reference electrode wiring, 16A ... First migration electrode, 16B ... Second Electrophoresis electrode, 16C ... measurement channel, 20 ... measurement element, 20a ... first measurement element, 20b ... second measurement element, 20c ... third measurement element, 20d ... fourth measurement element, 20e ... fifth measurement element, 20f ... 6th measurement element, 20g ... 7th measurement element, 20h ... 8th measurement element, 20i ... 9th measurement element, 30 ... Measurement processing part, 31 ... Control part, 31A ... Detection part, 31B ... Determination part, 32 ... Storage unit 33 ... Drive unit 34 ... Output unit
Claims (7)
前記流動方向と交差する泳動方向に前記生体物質を泳動させるための泳動電極と、
前記流動方向と前記泳動方向とを含む二次元方向に並び、前記測定対象液に関する電気化学的な特性値を前記二次元方向における各位置で測定するための複数の測定素子と、
前記泳動電極と前記各測定素子とに接続し、前記泳動電極による泳動を開始させる信号を前記泳動電極に入力した後に、前記各測定素子による測定を開始する測定処理部とを備える
電気化学測定装置。 An electrophoresis tank for flowing a liquid to be measured containing a biological substance in one direction of flow;
A migration electrode for migrating the biological material in a migration direction that intersects the flow direction;
A plurality of measuring elements arranged in a two-dimensional direction including the flow direction and the migration direction, and for measuring an electrochemical characteristic value related to the measurement target liquid at each position in the two-dimensional direction,
An electrochemical measurement apparatus comprising: a measurement processing unit that is connected to the migration electrode and each of the measurement elements and starts measurement by the measurement elements after inputting a signal for starting migration by the migration electrode to the migration electrode .
請求項１に記載の電気化学測定装置。 The electrochemical measurement device according to claim 1, wherein the plurality of measurement elements are arranged in a matrix in the flow direction and the migration direction.
請求項１または２に記載の電気化学測定装置。 The migration tank is a plane including the flow direction and the migration direction, and includes a pair of planes facing each other, all the measurement elements are located on one of the planes, and between the pair of planes. The electrochemical measurement device according to claim 1, further comprising a gap through which the measurement target liquid flows.
請求項１から３のいずれか一項に記載の電気化学測定装置。 The electrochemical measurement device according to any one of claims 1 to 3, further comprising a determination unit that determines an attribute of the measurement target liquid from a distribution of measurement results among the plurality of measurement elements.
請求項１から４のいずれか一項に記載の電気化学測定装置。 The electrochemical measurement according to any one of claims 1 to 4, further comprising a detection unit that detects that the measurement target liquid has reached the lowest element, which is the measurement element located most downstream in the flow direction. apparatus.
請求項５に記載の電気化学測定装置。 The electrochemical measurement device according to claim 5, wherein the measurement processing unit starts measurement by each measurement element when the detection unit detects that the measurement target liquid has reached the lowermost element.
生体物質を含む測定対象液が１つの方向である流動方向へ流れる泳動槽において、
前記流動方向と交差する泳動方向に前記生体物質を泳動させる信号を泳動電極へ入力することと、
前記信号を前記泳動電極へ入力した後に、前記流動方向と前記泳動方向とを含む二次元方向に並ぶ複数の測定素子を用い、前記測定対象液に関する電気化学的な特性値を前記二次元方向における各位置で測定することとを含む
電気化学測定方法。 The measurement processor
In a migration tank in which a liquid to be measured containing a biological substance flows in a flow direction that is one direction,
Inputting a signal for migrating the biological material in the migration direction intersecting the flow direction to the migration electrode;
After inputting the signal to the migration electrode, a plurality of measurement elements arranged in a two-dimensional direction including the flow direction and the migration direction are used, and an electrochemical characteristic value related to the measurement target liquid is measured in the two-dimensional direction. An electrochemical measurement method comprising measuring at each position.
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