JPWO2010024224A1 - Urea concentration measuring method and urea concentration measuring device - Google Patents

Urea concentration measuring method and urea concentration measuring device Download PDF

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JPWO2010024224A1
JPWO2010024224A1 JP2010526701A JP2010526701A JPWO2010024224A1 JP WO2010024224 A1 JPWO2010024224 A1 JP WO2010024224A1 JP 2010526701 A JP2010526701 A JP 2010526701A JP 2010526701 A JP2010526701 A JP 2010526701A JP WO2010024224 A1 JPWO2010024224 A1 JP WO2010024224A1
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urea
urea concentration
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益生 中川
益生 中川
哲平 石丸
哲平 石丸
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/76—Chemiluminescence; Bioluminescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/62—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving urea

Abstract

透析廃液試料の尿素濃度を測定する尿素濃度測定方法であって、塩素イオン及び尿素を含む透析廃液試料を反応領域に供給して、透析廃液試料で満たされた作用電極７及び対電極８の間に電流を流し、反応領域において作用電極７に接する試料溶液の厚さｔを２０ｍｍ以下とし、電気分解により作用電極７上で発生した酸化剤と尿素とが反応することにより生じた化学発光を計測して尿素濃度を定量することを特徴とする。このことにより、試薬を外部から供給する必要がなく、メンテナンスフリーで透析廃液試料の尿素濃度を精度良く測定することができる尿素濃度測定方法が提供される。A urea concentration measurement method for measuring a urea concentration of a dialysis waste liquid sample, wherein a dialysis waste liquid sample containing chloride ions and urea is supplied to a reaction region, and between a working electrode 7 and a counter electrode 8 filled with the dialysis waste liquid sample. In the reaction region, the thickness t of the sample solution in contact with the working electrode 7 is set to 20 mm or less, and the chemiluminescence generated by the reaction between the oxidant generated on the working electrode 7 by urea and urea is measured. Then, the urea concentration is quantified. Accordingly, there is provided a urea concentration measurement method that can accurately measure the urea concentration of the dialysis waste liquid sample without the need to supply a reagent from the outside and maintenance-free.

Description

本発明は、透析廃液試料中の尿素濃度を定量する尿素濃度測定方法、及びそれに用いられる尿素濃度測定装置に関する。   The present invention relates to a urea concentration measuring method for quantifying the urea concentration in a dialysis waste liquid sample, and a urea concentration measuring apparatus used therefor.

人工透析医療においては、ダイアライザと呼ばれる、内径１００μｍ程度の半透膜でできた管状の中空糸集合体を用いている。血中に存在する尿素等の溶質は、ダイアライザを通過する過程で透析液側に浸透することにより体外に除去される。従来、血中の尿素量は、採血することにより分析され、血中尿素窒素（Ｂｌｏｏｄ Ｕｒｅａ Ｎｉｔｒｏｇｅｎ、以下「ＢＵＮ」と略記することがある。）値として評価されていた。   In the artificial dialysis medical treatment, a tubular hollow fiber assembly called a dialyzer made of a semipermeable membrane having an inner diameter of about 100 μm is used. Solutes such as urea present in the blood are removed from the body by permeating into the dialysate side while passing through the dialyzer. Conventionally, the amount of urea in blood has been analyzed by collecting blood, and has been evaluated as a value of blood urea nitrogen (hereinafter sometimes abbreviated as “BUN”).

尿素を含む試料溶液中の尿素濃度を測定する方法として、尿素と反応して発色する試薬を用い、その試薬の標準色と比較することにより尿素濃度を測定する比色法、尿素に特異的に働く酵素であるウレアーゼをガラスビーズの周囲に固定化し、尿素の加水分解反応に伴う反応熱を測定することにより尿素濃度を測定する酵素サーミスタ法、尿素と反応して化学発光を生じる酸化剤、例えば、次亜ハロゲン酸塩を用い、その化学発光（Ｃｈｅｍｉｌｕｍｉｎｅｓｃｅｎｃｅ、以下「ＣＬ」と略記することがある。）の強度から尿素濃度を測定する化学発光法等が知られている。   As a method for measuring the urea concentration in a sample solution containing urea, a colorimetric method that measures the urea concentration by using a reagent that develops color by reacting with urea and comparing it with the standard color of the reagent, specific to urea An enzyme thermistor method that measures urea concentration by immobilizing urease, which is a working enzyme, around glass beads and measuring the heat of reaction accompanying the hydrolysis reaction of urea, an oxidizing agent that reacts with urea to produce chemiluminescence, for example A chemiluminescence method for measuring urea concentration based on the intensity of chemiluminescence (hereinafter sometimes abbreviated as “CL”) using hypohalite is known.

比色法では、尿素と反応して変色する試薬の調製に手間がかかり、測定誤差の原因の一つにもなるとともに、測定が終わるまでに時間がかかってしまう問題があった。また、経時的に濃度変化をモニタリングするには不向きであった。   In the colorimetric method, there is a problem in that it takes time to prepare a reagent that changes color by reacting with urea, which is one of the causes of measurement errors and that it takes time to complete the measurement. Moreover, it was not suitable for monitoring the change in concentration over time.

酵素サーミスタ法では、測定を繰り返すごとに酵素が劣化し、酵素の経時変化が大きく、長期間安定して測定することが困難であった。尿素濃度のモニタリングに用いることはできるが、複数回の測定に用いるには精度的に問題があった。   In the enzyme thermistor method, the enzyme deteriorates each time the measurement is repeated, the change with time of the enzyme is large, and it is difficult to measure stably for a long period of time. Although it can be used for monitoring the urea concentration, there is a problem in accuracy when used for multiple measurements.

化学発光は、尿素と次亜ハロゲン酸イオンが反応する過程で生成される励起窒素が基底状態に戻る際に生じるとされている（非特許文献１）。化学発光法は、尿素濃度をリアルタイムで測定することが可能であるため、試料溶液が尿素を含む試料溶液である場合には、人工透析医療において透析治療の終了すべきタイミングを知る手段として用いることができる。例えば、非特許文献２では、ＢＵＮ値を知る目安として、透析廃液中の尿素濃度を測定することが記載されている。具体的には、透析廃液中の尿素と、次亜臭素酸ナトリウムとが反応することにより生じた化学発光を測定することで、尿素濃度の測定を行う方法について記載されている。また、非特許文献３には、ＮａＢｒとＮａＯＨとを含む水溶液を反応容器内に注入して電気分解することにより次亜臭素酸を生じさせ、これと尿素とが反応して生じた化学発光を測定することで、尿素濃度の測定を行う方法が記載されている。しかしながら、次亜臭素酸ナトリウム等の試薬を供給する機械装置が必要であるため複雑となり改善が望まれていた。   Chemiluminescence is said to occur when excited nitrogen generated in the process of urea and hypohalite ion reaction returns to the ground state (Non-patent Document 1). Since the chemiluminescence method can measure the urea concentration in real time, if the sample solution is a sample solution containing urea, it should be used as a means of knowing when to end dialysis treatment in artificial dialysis medicine. Can do. For example, Non-Patent Document 2 describes measuring the urea concentration in the dialysis waste liquid as a guide for knowing the BUN value. Specifically, it describes a method for measuring urea concentration by measuring chemiluminescence generated by the reaction of urea in dialysis waste liquid with sodium hypobromite. In Non-Patent Document 3, hypochlorous acid is generated by injecting an aqueous solution containing NaBr and NaOH into a reaction vessel and electrolyzing it, and the chemiluminescence generated by the reaction of this with urea. A method for measuring the urea concentration by measurement is described. However, since a mechanical device for supplying a reagent such as sodium hypobromite is necessary, it has become complicated and an improvement has been desired.

Xincheng Hu他，「Bull. Chem. Soc. Jpn.」，1996年，第69巻，第5号，p.1179-1185Xincheng Hu et al., “Bull. Chem. Soc. Jpn.”, 1996, Vol.69, No.5, p.1179-1185 岡林徹他，「臨牀透析」，2006年，第22巻，第8号，p.1199-1204Toru Okabayashi et al., “Imperial Dialysis”, 2006, Vol. 22, No. 8, p.1199-1204 中川益生他，「電気学会研究会資料；センサ・マイクロマシン部門総合研究会」，2007年，ケミカルセンサ研究会，CHS-07-42，p.87-90Nakagawa, M. et al., “The Society of Electrical Engineers, Japan; Sensor and Micromachine Division Research Group”, 2007, Chemical Sensor Society, CHS-07-42, p.87-90

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、試薬を外部から供給する必要がなく、メンテナンスフリーで透析廃液試料の尿素濃度を精度良く測定することができる尿素濃度測定方法を提供することを目的とするものである。また、リアルタイムで透析時間の終了を知ることのできる人工透析装置を提供することを目的とするものである。   The present invention has been made to solve the above-described problems, and provides a urea concentration measurement method capable of accurately measuring the urea concentration of a dialysis waste liquid sample without the need to supply a reagent from the outside and maintenance-free. It is for the purpose. It is another object of the present invention to provide an artificial dialysis apparatus that can know the end of the dialysis time in real time.

上記課題は、透析廃液試料の尿素濃度を測定する尿素濃度測定方法であって、塩素イオン及び尿素を含む透析廃液試料を反応領域に供給して、透析廃液試料で満たされた作用電極及び対電極の間に電流を流し、反応領域において作用電極に接する試料溶液の厚さを２０ｍｍ以下とし、電気分解により作用電極上で発生した酸化剤と尿素とが反応することにより生じた化学発光を計測して尿素濃度を定量することを特徴とする尿素濃度測定方法を提供することによって解決される。このとき、電気分解の際に作用電極に接する試料溶液を攪拌しないことが好適な実施態様である。   The above-described problem is a urea concentration measurement method for measuring the urea concentration of a dialysis waste liquid sample, which supplies a dialysis waste liquid sample containing chloride ions and urea to a reaction region, and is filled with the dialysis waste liquid sample and a counter electrode In the reaction region, the thickness of the sample solution in contact with the working electrode is set to 20 mm or less, and the chemiluminescence generated by the reaction between the oxidant generated on the working electrode by electrolysis and urea is measured. This is solved by providing a method for measuring urea concentration, characterized by quantifying the urea concentration. At this time, it is a preferred embodiment that the sample solution in contact with the working electrode is not stirred during electrolysis.

更に上記課題は、塩素イオン及び尿素を含む透析廃液試料を供給する手段と、作用電極及び対電極を有しその間に電流を流す手段と、電気分解により作用電極上で発生した酸化剤と尿素とが反応することにより生じる化学発光を計測する手段とを備え、作用電極に接する試料溶液の厚さが２０ｍｍ以下である反応領域を備えたことを特徴とする尿素濃度測定装置を提供することによっても解決される。このとき、反応領域の上流及び／又は下流に整流板を備えてなる尿素濃度測定装置が本発明の好適な実施態様であり、上記尿素濃度測定装置を備えた人工透析装置が本発明の好適な実施態様である。   Further, the above-mentioned problems include means for supplying a dialysis waste liquid sample containing chlorine ions and urea, means for passing a current between the working electrode and the counter electrode, and an oxidizing agent and urea generated on the working electrode by electrolysis. And a means for measuring chemiluminescence generated by the reaction of the sample, and a reaction region in which the thickness of the sample solution in contact with the working electrode is 20 mm or less is provided. Solved. At this time, a urea concentration measuring device provided with a current plate upstream and / or downstream of the reaction region is a preferred embodiment of the present invention, and an artificial dialysis device equipped with the urea concentration measuring device is suitable for the present invention. This is an embodiment.

本発明の尿素濃度測定方法によれば、試薬を外部から供給する必要がなく、メンテナンスフリーで透析廃液試料の尿素濃度を精度良く測定することができる。また、リアルタイムで透析廃液試料の尿素濃度を測定することができるため、透析時間の終了を知ることのできる人工透析装置として好適に用いることができる。   According to the urea concentration measuring method of the present invention, it is not necessary to supply a reagent from the outside, and the urea concentration of the dialysis waste liquid sample can be accurately measured without maintenance. Further, since the urea concentration of the dialysis waste liquid sample can be measured in real time, it can be suitably used as an artificial dialysis apparatus that can know the end of the dialysis time.

実施例１〜６及び比較例１で用いた尿素濃度測定装置の概略図である。It is the schematic of the urea concentration measuring apparatus used in Examples 1-6 and Comparative Example 1. FIG. 実施例１で得られた化学発光応答波形図である。2 is a chemiluminescence response waveform diagram obtained in Example 1. FIG. 実施例２で得られた化学発光応答波形図である。6 is a chemiluminescence response waveform diagram obtained in Example 2. FIG. 実施例３で得られた化学発光応答波形図である。6 is a chemiluminescence response waveform diagram obtained in Example 3. FIG. 実施例４で得られた化学発光応答波形図である。6 is a chemiluminescence response waveform diagram obtained in Example 4. FIG. 実施例５で得られた化学発光応答波形図である。6 is a chemiluminescence response waveform diagram obtained in Example 5. FIG. 実施例６で得られた化学発光応答波形図である。FIG. 6 is a chemiluminescence response waveform diagram obtained in Example 6. 比較例１で得られた化学発光応答波形図である。6 is a chemiluminescence response waveform diagram obtained in Comparative Example 1. FIG. 実施例１で得られた尿素濃度と化学発光強度との相関図である。FIG. 3 is a correlation diagram between the urea concentration obtained in Example 1 and the chemiluminescence intensity. 実施例６で得られた尿素濃度と化学発光強度との相関図である。FIG. 6 is a correlation diagram between the urea concentration obtained in Example 6 and chemiluminescence intensity. 比較例１で得られた尿素濃度と化学発光強度との相関図である。6 is a correlation diagram between urea concentration and chemiluminescence intensity obtained in Comparative Example 1. FIG. 実施例７で用いられた尿素濃度測定装置の概略図である。FIG. 10 is a schematic view of a urea concentration measuring device used in Example 7. 実施例７で用いられた反応セルのＡ−Ａ拡大断面図である。7 is an AA enlarged cross-sectional view of a reaction cell used in Example 7. FIG. 実施例７で得られた化学発光応答波形図である。7 is a chemiluminescence response waveform diagram obtained in Example 7. FIG.

以下、図面を参照しながら本発明をより具体的に説明する。図１は、本発明で用いられる尿素濃度測定装置１の一例を示した概略図であり、塩素イオン及び尿素を含む透析廃液試料を供給する手段と、作用電極７及び対電極８を有し、その間に電流を流す手段と、電気分解により作用電極７上で発生した酸化剤と尿素とが反応することにより生じる化学発光を計測する手段とを備え、作用電極７に接する試料溶液の厚さｔが２０ｍｍ以下である反応領域を備えたものである。   Hereinafter, the present invention will be described more specifically with reference to the drawings. FIG. 1 is a schematic view showing an example of a urea concentration measuring apparatus 1 used in the present invention, which has means for supplying a dialysis waste liquid sample containing chloride ions and urea, a working electrode 7 and a counter electrode 8. Means for passing an electric current in the meantime, and means for measuring chemiluminescence generated by the reaction between the oxidant generated on the working electrode 7 by electrolysis and urea, and the thickness t of the sample solution in contact with the working electrode 7 Is provided with a reaction region of 20 mm or less.

本発明の尿素濃度測定装置１には、透析廃液試料を容器４内に供給する手段が備えられており、図１に示されるように、透析廃液試料供給口２からバルブ３を経由して容器４内部に透析廃液試料が供給されるようになっている。供給後にはバルブ３及びバルブ１７を閉じて新たに透析廃液試料が容器４内に入らないようにすることが尿素濃度の定量を精度良く行う観点から好ましい。供給された透析廃液試料は、後述する反応領域において電気分解により化学発光を生じ、生じた化学発光がガラス窓６の上部に配置された光ファイバーロッド１３を介して光電子増倍管モジュール１４に導かれその発光量が計測される。   The urea concentration measuring apparatus 1 according to the present invention is provided with means for supplying a dialysis waste liquid sample into the container 4 and, as shown in FIG. The dialysis waste liquid sample is supplied inside 4. It is preferable from the viewpoint of accurately quantifying the urea concentration that the valve 3 and the valve 17 are closed after the supply so that a new dialysis waste liquid sample does not enter the container 4. The supplied dialysis waste liquid sample generates chemiluminescence by electrolysis in a reaction region described later, and the generated chemiluminescence is guided to the photomultiplier tube module 14 via the optical fiber rod 13 disposed on the upper part of the glass window 6. The amount of light emission is measured.

本発明の尿素濃度測定装置１における容器４の内部には、作用電極７及び対電極８が配置されており、透析廃液試料で満たされた作用電極７及び対電極８の間に電流を流す手段が備えられている。このように、作用電極７及び対電極８の間に電流を流すことにより、透析廃液試料に含まれる塩素イオン（Ｃｌ−）から酸化剤を生じさせることができる。透析廃液試料中に含まれる塩素イオンの濃度は、通常、０．１〜０．４ｗｔ％であり、臭素イオンは実質的に含まない。酸化剤としては、特に限定されないが、次亜塩素酸イオン（ＣｌＯ−）及び塩素ガス（Ｃｌ２）からなる群から選択される少なくとも１種であることが好ましい。ここで、本発明で用いられる透析廃液試料のｐＨは、通常、中性であることから、電気分解により次亜塩素酸イオンだけではなく、塩素ガスが生じやすくなることを本発明者らは確認している。電気分解により塩素ガスではなく次亜塩素酸イオンを生じさせる観点からは、例えば、ＮａＯＨやＫＯＨ等のアルカリ性化合物を加えて透析廃液試料をアルカリ性に調製するｐＨ調製手段を備えていてもよい。A working electrode 7 and a counter electrode 8 are arranged inside the container 4 in the urea concentration measuring apparatus 1 of the present invention, and a means for passing a current between the working electrode 7 and the counter electrode 8 filled with the dialysis waste liquid sample. Is provided. In this way, an oxidant can be generated from chlorine ions (Cl − ) contained in the dialysis waste liquid sample by passing a current between the working electrode 7 and the counter electrode 8. The concentration of chlorine ions contained in the dialysis waste liquid sample is usually 0.1 to 0.4 wt%, and does not substantially contain bromine ions. The oxidizing agent is not particularly limited, but is preferably at least one selected from the group consisting of hypochlorite ions (ClO − ) and chlorine gas (Cl 2 ). Here, since the pH of the dialysis waste liquid sample used in the present invention is usually neutral, the present inventors confirmed that not only hypochlorite ions but also chlorine gas is likely to be generated by electrolysis. is doing. From the viewpoint of generating hypochlorite ions instead of chlorine gas by electrolysis, for example, a pH adjusting means for preparing an alkaline dialysis waste solution sample by adding an alkaline compound such as NaOH or KOH may be provided.

本発明で用いられる作用電極７としては、特に限定されず、白金、金、銀、パラジウム、銅等の金属、又はカーボン電極等が用いられるが、電極の耐久性と電解電位の安定性等の観点から白金電極が好適に用いられる。本発明で用いられる対電極８としては、特に限定されず、白金、金、銀、パラジウム、鉛等の金属、又はカーボン電極等が用いられるが、分極抵抗の減少と電極電位の安定性等の観点から銀電極が好適に用いられる。対電極８の位置は、作用電極７との間に電流を流すことのできる場所であればよく、特に限定されない。作用電極７付近での化学発光を計測する妨げにならないように作用電極７と対抗する位置に配置しない方がよい。例えば、塩橋を用いて電気的に連結された位置に配置されていても構わない。また、電極の電位を一定にコントロールするために、参照電極２２を用いてもよい。ここで、参照電極２２を用いる場合、作用電極７と対電極８との間に電圧を印加して電解電流を流しながら作用電極７と参照電極２２との間の電位差を測定する。これにより、作用電極７の電位を一定にコントロールすることができる。作用電極７と対電極８との間の電解電流及び電解電圧を決定した後は、参照電極２２を除去して定電流により測定を行ってもよい。   The working electrode 7 used in the present invention is not particularly limited, and a metal such as platinum, gold, silver, palladium, copper, or a carbon electrode is used. However, the durability of the electrode and the stability of the electrolytic potential, etc. From the viewpoint, a platinum electrode is preferably used. The counter electrode 8 used in the present invention is not particularly limited, and a metal such as platinum, gold, silver, palladium, lead, or a carbon electrode is used. However, the polarization resistance is decreased and the electrode potential is stable. From the viewpoint, a silver electrode is preferably used. The position of the counter electrode 8 is not particularly limited as long as the current can flow between the counter electrode 8 and the working electrode 7. It is better not to arrange it at a position facing the working electrode 7 so as not to hinder measurement of chemiluminescence in the vicinity of the working electrode 7. For example, you may arrange | position in the position electrically connected using the salt bridge. Further, the reference electrode 22 may be used in order to control the potential of the electrode constant. Here, when the reference electrode 22 is used, a voltage is applied between the working electrode 7 and the counter electrode 8 to measure the potential difference between the working electrode 7 and the reference electrode 22 while flowing an electrolytic current. Thereby, the electric potential of the working electrode 7 can be controlled to be constant. After the electrolysis current and electrolysis voltage between the working electrode 7 and the counter electrode 8 are determined, the reference electrode 22 may be removed and measurement may be performed with a constant current.

本発明の尿素濃度測定装置１には、電気分解により作用電極７上で発生した酸化剤と尿素とが反応することにより生じる化学発光を計測する手段が備えられている。このように、化学発光強度（ＣＬ強度）を測定することにより、間接的に透析廃液試料の尿素濃度を定量することができる。図１に示されるように、ガラス窓６と作用電極７との間に存在する反応領域において、作用電極７上で生じた酸化剤と尿素とが反応することにより化学発光が生じ、生じた化学発光がガラス窓６の上部に配置された光ファイバーロッド１３を介して光電子増倍管モジュール１４においてフォトンカウンティングされる。また、透析廃液試料に色素等の増感剤を供給できる手段を設けて、増感された化学発光を計測することもできる。   The urea concentration measuring apparatus 1 of the present invention is provided with means for measuring chemiluminescence generated by the reaction between the oxidant generated on the working electrode 7 by electrolysis and urea. Thus, by measuring the chemiluminescence intensity (CL intensity), the urea concentration of the dialysis waste liquid sample can be quantified indirectly. As shown in FIG. 1, in the reaction region existing between the glass window 6 and the working electrode 7, chemiluminescence is generated by the reaction between the oxidant generated on the working electrode 7 and urea, and the generated chemistry. Light emission is photon counted in the photomultiplier tube module 14 via an optical fiber rod 13 disposed on the upper part of the glass window 6. Further, a means capable of supplying a sensitizer such as a dye to the dialysis waste liquid sample can be provided to measure the sensitized chemiluminescence.

本発明の尿素濃度測定装置１は、作用電極７に接する試料溶液の厚さｔが２０ｍｍ以下である反応領域を備えたものである。作用電極７に接する試料溶液の厚さｔとは、図１に示されるように、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔのことであり、本発明の尿素濃度測定装置１が、厚さｔが２０ｍｍ以下の反応領域を備えていることにより、精度良く透析廃液試料の尿素濃度を測定することができ、しかも再現性が良好である。このように、本発明の尿素濃度測定装置１が、厚さｔが２０ｍｍ以下の反応領域を備えていることにより尿素濃度の定量が良好となる理由については、反応領域に存在する尿素の全てと作用電極７上で生じた酸化剤とが反応して化学発光が生じ、この生じた化学発光の全量を計測するためであると本発明者らは推測している。また、本発明の尿素濃度測定装置１が、厚さｔが２０ｍｍ以下である反応領域を備えていることにより、反応領域に対して外側からの物質輸送がほとんどないため、安定した化学発光応答波形図が得られ、その結果、尿素濃度の定量が良好であるとともに再現性が良好となる。   The urea concentration measuring apparatus 1 of the present invention includes a reaction region in which the thickness t of the sample solution in contact with the working electrode 7 is 20 mm or less. The thickness t of the sample solution in contact with the working electrode 7 is the thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 as shown in FIG. Since the measuring device 1 includes a reaction region having a thickness t of 20 mm or less, the urea concentration of the dialysis waste liquid sample can be accurately measured, and the reproducibility is good. As described above, the reason why the urea concentration measuring apparatus 1 of the present invention has a favorable determination of the urea concentration by including the reaction region having a thickness t of 20 mm or less is that all the urea present in the reaction region is The present inventors presume that it is for measuring the total amount of the chemiluminescence generated by the reaction with the oxidant generated on the working electrode 7 and generating chemiluminescence. In addition, since the urea concentration measuring apparatus 1 of the present invention includes a reaction region having a thickness t of 20 mm or less, there is almost no substance transport from the outside to the reaction region, so that a stable chemiluminescence response waveform is obtained. As a result, the urea concentration is well quantified and the reproducibility is good.

作用電極７に接する試料溶液の厚さｔが２０ｍｍを超える場合、化学発光応答波形図が複雑で再現性が悪くなるともに、尿素濃度と化学発光強度との相関が得られないため、尿素濃度の定量が困難となるおそれがあり、厚さｔは１６ｍｍ以下であることが好ましく、１２ｍｍ以下であることがより好ましく、８ｍｍ以下であることが更に好ましく、４ｍｍ以下であることが特に好ましい。厚さｔが０．１ｍｍ未満である場合、化学発光強度が低くなりすぎ、測定される尿素濃度の精度が低下するおそれがあり、厚さｔは０．１ｍｍ以上であることが好ましい。   When the thickness t of the sample solution in contact with the working electrode 7 exceeds 20 mm, the chemiluminescence response waveform diagram is complicated and the reproducibility is deteriorated, and the correlation between the urea concentration and the chemiluminescence intensity cannot be obtained. Quantification may be difficult, and the thickness t is preferably 16 mm or less, more preferably 12 mm or less, still more preferably 8 mm or less, and particularly preferably 4 mm or less. When the thickness t is less than 0.1 mm, the chemiluminescence intensity becomes too low, and the accuracy of the measured urea concentration may be lowered, and the thickness t is preferably 0.1 mm or more.

本発明の尿素濃度測定方法において、透析廃液試料で満たされた容器４内をクリーニングする観点からは、攪拌する手段を備えていることが好ましく、特に反応領域をクリーニングする観点から作用電極７上に攪拌する手段を配置することがより好ましい。しかしながら、透析廃液試料の尿素濃度を精度良く測定する観点からは、電気分解の際に作用電極７に接する試料溶液を攪拌しないことが好ましい。このことにより、反応領域近傍に存在する未反応の尿素が反応領域に移動してこないため、反応領域のみに存在する尿素に由来する化学発光を計測することが可能となる。また、攪拌装置が不要となるために、装置が簡便となり故障が少なくなる利点を有する。また、透析廃液試料で満たされた容器４内は、本発明の尿素濃度測定装置１に逆電圧をかけてクリーニングしてもよいし、次亜塩素酸水溶液等を流通させてクリーニングしてもよい。定量後の透析廃液試料は、バルブ１７を通じて排出口１８から排出される。   In the urea concentration measuring method of the present invention, it is preferable to provide a stirring means from the viewpoint of cleaning the inside of the container 4 filled with the dialysis waste liquid sample, and particularly on the working electrode 7 from the viewpoint of cleaning the reaction region. More preferably, a means for stirring is arranged. However, from the viewpoint of accurately measuring the urea concentration of the dialysis waste liquid sample, it is preferable not to stir the sample solution in contact with the working electrode 7 during electrolysis. As a result, unreacted urea existing in the vicinity of the reaction region does not move to the reaction region, so that chemiluminescence derived from urea existing only in the reaction region can be measured. In addition, since a stirring device is not required, the device is simple and has the advantage of less failure. Further, the inside of the container 4 filled with the dialysis waste liquid sample may be cleaned by applying a reverse voltage to the urea concentration measuring apparatus 1 of the present invention, or may be cleaned by circulating a hypochlorous acid aqueous solution or the like. . The dialysis waste liquid sample after quantification is discharged from the discharge port 18 through the valve 17.

また、本発明の尿素濃度測定装置１は、測定精度をより向上させる観点から整流板２３を反応領域付近に設置することが好ましい。すなわち、反応領域の上流及び／又は下流に整流板２３を備えてなる尿素濃度測定装置１が本発明の好適な実施態様である。具体的には、図１２で示される尿素濃度測定装置１からも分かるように、作用電極７の上流及び下流に整流板２３を設置する実施態様が好適に採用される。   Moreover, it is preferable that the urea concentration measuring apparatus 1 of this invention installs the baffle plate 23 in the reaction region vicinity from a viewpoint of improving a measurement precision more. That is, the urea concentration measuring apparatus 1 including the rectifying plate 23 upstream and / or downstream of the reaction region is a preferred embodiment of the present invention. Specifically, as can be seen from the urea concentration measuring apparatus 1 shown in FIG. 12, an embodiment in which the rectifying plates 23 are installed upstream and downstream of the working electrode 7 is suitably employed.

本発明の尿素濃度測定装置１は、透析廃液中の尿素濃度を測定することを特徴とする人工透析装置として用いることが好ましく、特に、リアルタイムで尿素濃度を測定することができるため、透析治療の終了すべきタイミングを知ることのできる人工透析装置として好適に用いることができる。   The urea concentration measuring device 1 of the present invention is preferably used as an artificial dialysis device characterized by measuring the urea concentration in the dialysis waste liquid. In particular, since the urea concentration can be measured in real time, It can be suitably used as an artificial dialysis apparatus that can know the timing to be terminated.

以下、実施例を用いて本発明を更に具体的に説明する。   Hereinafter, the present invention will be described more specifically with reference to examples.

実施例１
図１に示される尿素濃度測定装置１から透析廃液試料供給口２、バルブ３、バルブ１７、排出口１８とそれらをつなぐ配管を省いた装置を用いて、透析廃液試料の尿素濃度測定を行った。容器４内部に設けられたガラス窓６と対抗する位置に作用電極７として円盤状の白金電極（直径４０ｍｍ）を配置した。ガラス窓６と作用電極７との間の領域は、透析廃液試料の流通経路であるとともに反応領域でもあり、ガラス窓下面１０及び作用電極表面１１は透析廃液試料と接するようになっている。ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔを２ｍｍに設定し、作用電極表面１１上に、攪拌子９（断面積：１ｍｍ２、長さ：１５ｍｍ）を設置した。また、対電極８として銀電極を反応領域から離れた位置である容器４内側の壁面に巻きつけるように配置した。濃度をそれぞれ調整した透析廃液試料（ＵＮ値：１０、５、２．５ｍｇ／ｄｌ）を容器４内部に供給した。本実施例において、透析廃液試料の濃度は、尿素窒素（Ｕｒｅａ Ｎｉｔｒｏｇｅｎ、「ＵＮ」と略記することがある。）値に換算したものである。磁気攪拌器５により攪拌子９を回転させて反応領域の流れを定常的にした状態で、白金電極と銀電極の間に定電流電源１２により２３０ｍＡの定電流を流すと化学発光が生じた。ここで、化学発光は、白金電極上における塩素イオンの電気分解により、次亜塩素酸イオンや比較的高濃度の塩素ガスが生じ、次いで反応領域で透析廃液試料に含まれる尿素イオンと反応することにより生じると考えられる。生じた化学発光を、ガラス窓６の上部に設置された光ファイバーロッド１３を介して電源１５が接続された光電子増倍管モジュール１４及びパルスカウンター１６を用いてフォトンカウンティング法により計測した。得られた化学発光応答波形図を図２に、尿素濃度と化学発光強度との相関図を図９に示す。Example 1
The urea concentration measurement of the dialysis waste liquid sample was performed using the apparatus in which the dialysis waste liquid sample supply port 2, the valve 3, the valve 17, the discharge port 18 and the piping connecting them were omitted from the urea concentration measurement apparatus 1 shown in FIG. . A disc-shaped platinum electrode (diameter 40 mm) was disposed as the working electrode 7 at a position facing the glass window 6 provided inside the container 4. The area between the glass window 6 and the working electrode 7 is a flow path for the dialysis waste liquid sample as well as a reaction area, and the glass window lower surface 10 and the working electrode surface 11 are in contact with the dialysis waste liquid sample. The thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 was set to 2 mm, and a stirrer 9 (cross-sectional area: 1 mm 2 , length: 15 mm) was placed on the working electrode surface 11. Moreover, the silver electrode was arrange | positioned as the counter electrode 8 so that it might wind around the wall surface inside the container 4 which is a position away from the reaction area. Dialysis waste liquid samples (UN values: 10, 5, and 2.5 mg / dl) each having a adjusted concentration were supplied into the container 4. In this example, the concentration of the dialysis waste liquid sample is converted to urea nitrogen (may be abbreviated as “UNa”). Chemoluminescence was generated when a constant current of 230 mA was passed between the platinum electrode and the silver electrode with a constant current power supply 12 in a state where the stirrer 9 was rotated by the magnetic stirrer 5 and the flow of the reaction region was made steady. Here, chemiluminescence generates hypochlorite ions and a relatively high concentration of chlorine gas by electrolysis of chlorine ions on the platinum electrode, and then reacts with urea ions contained in the dialysis waste liquid sample in the reaction region. This is thought to be caused by The generated chemiluminescence was measured by a photon counting method using a photomultiplier tube module 14 and a pulse counter 16 connected to a power source 15 via an optical fiber rod 13 installed on the upper part of the glass window 6. The obtained chemiluminescence response waveform diagram is shown in FIG. 2, and the correlation between urea concentration and chemiluminescence intensity is shown in FIG.

実施例２
実施例１において、用いた透析廃液試料のＵＮ値を１１ｍｇ／ｄｌとし、攪拌せずに２３０ｍＡで定電流を流した以外は実施例１と同様にして化学発光の計測を行った。得られた化学発光応答波形図を図３に示す。Example 2
In Example 1, chemiluminescence was measured in the same manner as in Example 1 except that the UN value of the used dialysis waste liquid sample was 11 mg / dl, and a constant current was passed at 230 mA without stirring. The obtained chemiluminescence response waveform diagram is shown in FIG.

実施例３
実施例１において、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔを５ｍｍに設定し、ＵＮ値が１１ｍｇ／ｄｌの透析廃液試料を用い、攪拌せずに２３０ｍＡで定電流を流した以外は実施例１と同様にして化学発光の計測を行った。得られた化学発光応答波形図を図４に示す。Example 3
In Example 1, the thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 was set to 5 mm, and a dialysis waste liquid sample having a UN value of 11 mg / dl was used. Chemiluminescence was measured in the same manner as in Example 1 except that The obtained chemiluminescence response waveform diagram is shown in FIG.

実施例４
実施例１において、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔを１０ｍｍに設定し、ＵＮ値が１１ｍｇ／ｄｌの透析廃液試料を用い、攪拌せずに２３０ｍＡで定電流を流した以外は実施例１と同様にして化学発光の計測を行った。得られた化学発光応答波形図を図５に示す。Example 4
In Example 1, the thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 is set to 10 mm, a dialysis waste liquid sample having a UN value of 11 mg / dl is used, and constant current is maintained at 230 mA without stirring. Chemiluminescence was measured in the same manner as in Example 1 except that The obtained chemiluminescence response waveform diagram is shown in FIG.

実施例５
実施例１において、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔを１５ｍｍに設定し、ＵＮ値が１１ｍｇ／ｄｌの透析廃液試料を用い、攪拌せずに２３０ｍＡで定電流を流した以外は実施例１と同様にして化学発光の計測を行った。得られた化学発光応答波形図を図６に示す。Example 5
In Example 1, the thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 is set to 15 mm, and a dialysis waste liquid sample having a UN value of 11 mg / dl is used. Chemiluminescence was measured in the same manner as in Example 1 except that The obtained chemiluminescence response waveform diagram is shown in FIG.

実施例６
実施例１において、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔを１ｍｍに設定し、ＵＮ値がそれぞれ１５、７及び３．９ｍｇ／ｄｌの透析廃液試料を用い、攪拌せずに２３０ｍＡで定電流を流した以外は実施例１と同様にして化学発光の計測を行った。得られた化学発光応答波形図を図７に、尿素濃度と化学発光強度との相関図を図１０に示す。Example 6
In Example 1, the thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 was set to 1 mm, and dialysis waste liquid samples having UN values of 15, 7 and 3.9 mg / dl were used, respectively. The chemiluminescence was measured in the same manner as in Example 1 except that a constant current was passed at 230 mA. FIG. 7 shows the chemiluminescence response waveform obtained, and FIG. 10 shows the correlation between the urea concentration and the chemiluminescence intensity.

比較例１
実施例１において、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔを３５ｍｍに設定し、ＵＮ値がそれぞれ１５、７及び３．９ｍｇ／ｄｌの透析廃液試料を用い、攪拌せずに２３０ｍＡで定電流を流した以外は実施例１と同様にして化学発光の計測を行った。得られた化学発光応答波形図を図８に、尿素濃度と化学発光強度との相関図を図１１に示す。Comparative Example 1
In Example 1, the thickness t of the space sandwiched between the glass window lower surface 10 and the working electrode surface 11 was set to 35 mm, and dialysis waste liquid samples having UN values of 15, 7, and 3.9 mg / dl were used, respectively. The chemiluminescence was measured in the same manner as in Example 1 except that a constant current was passed at 230 mA. The obtained chemiluminescence response waveform diagram is shown in FIG. 8, and the correlation diagram between urea concentration and chemiluminescence intensity is shown in FIG.

作用電極７に接する試料溶液の厚さ、すなわち、ガラス窓下面１０と作用電極表面１１とに挟まれる空間の厚さｔが２０ｍｍ以下である実施例１〜６では、図２〜７から分かるように安定した化学発光応答波形図が得られた。特に、図２及び図７の化学発光応答波形図では、ＵＮ値が小さくなるにつれて、化学発光のピークが経過時間軸の左方向へシフトしている。このことから、反応領域に存在する尿素が全て反応し尽くされていることが推察され、測定精度が向上するとともに測定時間の短縮も可能である。また、実施例１及び実施例６で得られた尿素濃度と化学発光強度との相関図である図９及び図１０から分かるように、尿素濃度と化学発光量との間に一定の関係があるので、化学発光量を測定することにより透析廃液試料中の尿素濃度を知ることができ、再現性も良好であった。したがって、本発明の尿素濃度測定方法により、試薬を外部から供給する必要がなく、メンテナンスフリーで透析廃液試料の尿素濃度を精度良く測定できることが分かる。   In Examples 1 to 6 in which the thickness of the sample solution in contact with the working electrode 7, that is, the thickness t of the space between the glass window lower surface 10 and the working electrode surface 11 is 20 mm or less, as can be seen from FIGS. A stable chemiluminescence response waveform diagram was obtained. In particular, in the chemiluminescence response waveform diagrams of FIGS. 2 and 7, the peak of chemiluminescence shifts to the left of the elapsed time axis as the UN value decreases. From this, it is inferred that all the urea present in the reaction region has been completely reacted, so that the measurement accuracy can be improved and the measurement time can be shortened. Further, as can be seen from FIGS. 9 and 10 which are correlation diagrams between the urea concentration and the chemiluminescence intensity obtained in Example 1 and Example 6, there is a certain relationship between the urea concentration and the chemiluminescence amount. Therefore, by measuring the amount of chemiluminescence, the urea concentration in the dialysis waste liquid sample could be known, and the reproducibility was also good. Therefore, it can be seen that the urea concentration measurement method of the present invention does not need to supply a reagent from the outside, and can accurately measure the urea concentration of the dialysis waste liquid sample without maintenance.

実施例７
本発明の尿素濃度測定装置１の他の実施態様として、図１２に示される尿素濃度測定装置１を用い、透析廃液試料の一例として０．２ｍｏｌ／ｌの尿素を含む電解質溶液を用いて尿素濃度測定を行った。透明アクリル樹脂製の反応セル１９（流路の断面積０．８ｃｍ２）内に、作用電極７として平板状の白金電極（幅１６ｍｍ、長さ２０ｍｍ、厚さ０．１ｍｍ）を前記白金電極の裏面が反応セル内壁表面２０と接するように配置した。図１３で示される反応セルのＡ−Ａ拡大断面図からも分かるように、反応セル１９内において、反応セル内壁表面２１と作用電極表面１１との間の領域は、透析廃液試料の流通経路であるとともに反応領域でもあり、反応セル内壁表面２１及び作用電極表面１１は透析廃液試料と接するようになっている。反応セル内壁表面２１と作用電極表面１１とに挟まれる空間の厚さｔを５ｍｍに設定した。また、白金電極の下流に対電極８として、一対の銀電極（幅１６ｍｍ、長さ４０ｍｍ、厚さ０．５ｍｍ）を前記銀電極の裏面が反応セル内壁表面２０と反応セル内壁表面２１とにそれぞれ接するように配置した。また、前記白金電極の上流、及び白金電極と銀電極の間に整流板２３を設けた。更に、作用電極表面１１と対抗する位置に光電子増倍管モジュール１４（浜松ホトニクス株式会社製「Ｈ７１５５」）を設置した。続いて、定流量ポンプ２４により２．５ｍｌ／ｍｉｎで電解質溶液を流通させた。このとき、透析廃液試料が作用電極表面１１を層流で流れるように保った。白金電極と銀電極の間に１００ｍＡの定電流を５００秒間、断続的に３回流すと化学発光が生じた。生じた化学発光を、光電子増倍管モジュール１４を用いてフォトンカウンティング法により計測した。電解電流を流している間は、ほぼ一定の化学発光が観測できた。この化学発光強度は試料溶液中の尿素濃度に依存して変化し、試料内の尿素濃度を連続的に測定することができた。得られた化学発光応答波形図を図１４に示す。図１４の化学発光応答波形図からも分かるように、整流板２３を反応セル１９内に設けることにより測定精度を向上させることができた。なお、０．２ｍｏｌ／ｌの尿酸やクレアニチンを添加した試料溶液を用いて同様に測定を行ったところ、化学発光が得られなかった。したがって、本発明の尿素濃度測定装置１を用いることにより尿素濃度を精度良く選択的に測定できることが分かる。Example 7
As another embodiment of the urea concentration measuring apparatus 1 of the present invention, the urea concentration measuring apparatus 1 shown in FIG. 12 is used, and an urea solution is used by using an electrolyte solution containing 0.2 mol / l urea as an example of a dialysis waste liquid sample. Measurements were made. A flat platinum electrode (width 16 mm, length 20 mm, thickness 0.1 mm) as a working electrode 7 is placed in a reaction cell 19 (transparent cross-sectional area 0.8 cm 2 ) made of transparent acrylic resin. It arrange | positioned so that a back surface may contact | connect the reaction cell inner wall surface 20. FIG. As can be seen from the AA enlarged sectional view of the reaction cell shown in FIG. 13, the region between the reaction cell inner wall surface 21 and the working electrode surface 11 in the reaction cell 19 is a flow path of the dialysis waste liquid sample. The reaction cell inner wall surface 21 and the working electrode surface 11 are in contact with the dialysis waste liquid sample. The thickness t of the space between the reaction cell inner wall surface 21 and the working electrode surface 11 was set to 5 mm. In addition, as a counter electrode 8 downstream of the platinum electrode, a pair of silver electrodes (width 16 mm, length 40 mm, thickness 0.5 mm) are connected to the reaction cell inner wall surface 20 and the reaction cell inner wall surface 21 on the back surface of the silver electrode. They were placed in contact with each other. Further, a rectifying plate 23 was provided upstream of the platinum electrode and between the platinum electrode and the silver electrode. Further, a photomultiplier tube module 14 (“H7155” manufactured by Hamamatsu Photonics Co., Ltd.) was installed at a position facing the working electrode surface 11. Subsequently, the electrolyte solution was circulated by the constant flow pump 24 at 2.5 ml / min. At this time, the dialysis waste liquid sample was kept flowing on the working electrode surface 11 in a laminar flow. When a constant current of 100 mA was intermittently passed 3 times for 500 seconds between the platinum electrode and the silver electrode, chemiluminescence occurred. The generated chemiluminescence was measured by the photon counting method using the photomultiplier tube module 14. While the electrolysis current was passed, almost constant chemiluminescence was observed. The chemiluminescence intensity varied depending on the urea concentration in the sample solution, and the urea concentration in the sample could be continuously measured. The obtained chemiluminescence response waveform diagram is shown in FIG. As can be seen from the chemiluminescence response waveform diagram of FIG. 14, the measurement accuracy could be improved by providing the rectifying plate 23 in the reaction cell 19. When the same measurement was performed using a sample solution to which 0.2 mol / l uric acid or creanitine was added, chemiluminescence was not obtained. Therefore, it can be seen that the urea concentration can be selectively measured with high accuracy by using the urea concentration measuring apparatus 1 of the present invention.

１ 尿素濃度測定装置
２ 透析廃液試料供給口
３ バルブ
４ 容器
５ 磁気攪拌器
６ ガラス窓
７ 作用電極
８ 対電極
９ 攪拌子
１０ ガラス窓下面
１１ 作用電極表面
１２ 定電流電源
１３ 光ファイバーロッド
１４ 光電子増倍管モジュール
１５ 電源
１６ パルスカウンター
１７ バルブ
１８ 排出口
１９ 反応セル
２０ 反応セル内壁表面
２１ 反応セル内壁表面
２２ 参照電極
２３ 整流板
２４ 定流量ポンプ
ｔ ガラス窓下面と作用電極表面とに挟まれる空間の厚さDESCRIPTION OF SYMBOLS 1 Urea concentration measuring device 2 Dialysis waste liquid sample supply port 3 Valve 4 Container 5 Magnetic stirrer 6 Glass window 7 Working electrode 8 Counter electrode 9 Stirrer 10 Glass window lower surface 11 Working electrode surface 12 Constant current power supply 13 Optical fiber rod 14 Photomultiplier Tube module 15 Power source 16 Pulse counter 17 Valve 18 Discharge port 19 Reaction cell 20 Reaction cell inner wall surface 21 Reaction cell inner wall surface 22 Reference electrode 23 Rectifier plate 24 Constant flow pump t Thickness of the space sandwiched between the glass window lower surface and the working electrode surface The

Claims (5)

透析廃液試料の尿素濃度を測定する尿素濃度測定方法であって、塩素イオン及び尿素を含む透析廃液試料を反応領域に供給して、透析廃液試料で満たされた作用電極及び対電極の間に電流を流し、反応領域において作用電極に接する試料溶液の厚さを２０ｍｍ以下とし、電気分解により作用電極上で発生した酸化剤と尿素とが反応することにより生じた化学発光を計測して尿素濃度を定量することを特徴とする尿素濃度測定方法。   A urea concentration measurement method for measuring a urea concentration of a dialysis waste liquid sample, comprising supplying a dialysis waste liquid sample containing chloride ions and urea to a reaction region and passing a current between a working electrode and a counter electrode filled with the dialysis waste liquid sample. The thickness of the sample solution in contact with the working electrode in the reaction region is set to 20 mm or less, and the chemiluminescence generated by the reaction between the oxidant generated on the working electrode and urea by electrolysis is measured to determine the urea concentration. A method for measuring urea concentration, characterized by quantifying. 電気分解の際に作用電極に接する試料溶液を攪拌しない請求項１記載の尿素濃度測定方法。   The method for measuring urea concentration according to claim 1, wherein the sample solution in contact with the working electrode is not stirred during electrolysis. 塩素イオン及び尿素を含む透析廃液試料を供給する手段と、作用電極及び対電極を有しその間に電流を流す手段と、電気分解により作用電極上で発生した酸化剤と尿素とが反応することにより生じる化学発光を計測する手段とを備え、作用電極に接する試料溶液の厚さが２０ｍｍ以下である反応領域を備えたことを特徴とする尿素濃度測定装置。   A means for supplying a dialysis waste liquid sample containing chlorine ions and urea, a means for passing a current between the working electrode and the counter electrode, and the reaction between the oxidant generated on the working electrode by electrolysis and urea And a means for measuring the chemiluminescence produced, and a reaction region in which the thickness of the sample solution in contact with the working electrode is 20 mm or less. 反応領域の上流及び／又は下流に整流板を備えてなる請求項３記載の尿素濃度測定装置。   4. The urea concentration measuring device according to claim 3, further comprising a rectifying plate upstream and / or downstream of the reaction region. 請求項３又は４記載の尿素濃度測定装置を備えた人工透析装置。   An artificial dialysis apparatus comprising the urea concentration measuring apparatus according to claim 3 or 4.
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