JP4894004B2 - Urea concentration measuring method and urea concentration measuring device - Google Patents

Urea concentration measuring method and urea concentration measuring device Download PDF

Info

Publication number
JP4894004B2
JP4894004B2 JP2007076513A JP2007076513A JP4894004B2 JP 4894004 B2 JP4894004 B2 JP 4894004B2 JP 2007076513 A JP2007076513 A JP 2007076513A JP 2007076513 A JP2007076513 A JP 2007076513A JP 4894004 B2 JP4894004 B2 JP 4894004B2
Authority
JP
Japan
Prior art keywords
urea
urea concentration
measuring
container
solution containing
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
JP2007076513A
Other languages
Japanese (ja)
Other versions
JP2008233005A (en
Inventor
益生 中川
徹 岡林
真啓 尾崎
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Okayama Prefecture Ind Promotion Foundation
Original Assignee
Okayama Prefecture Ind Promotion Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Okayama Prefecture Ind Promotion Foundation filed Critical Okayama Prefecture Ind Promotion Foundation
Priority to JP2007076513A priority Critical patent/JP4894004B2/en
Priority to DE112008000740T priority patent/DE112008000740B4/en
Priority to PCT/JP2008/054943 priority patent/WO2008117699A1/en
Publication of JP2008233005A publication Critical patent/JP2008233005A/en
Application granted granted Critical
Publication of JP4894004B2 publication Critical patent/JP4894004B2/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • 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

Landscapes

  • Physics & Mathematics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plasma & Fusion (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)

Description

本発明は、試料溶液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 sample solution, 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を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. In addition, it is not suitable for monitoring the concentration change 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、特に、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。しかしながら、次亜臭素酸ナトリウムのような酸化剤の安定性が良好ではなく、濃度が変化しやすいため改善が求められていた。   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, it can be used as a means for knowing the timing at which dialysis treatment should be terminated, particularly in artificial dialysis medical treatment. 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. However, the stability of an oxidizing agent such as sodium hypobromite is not good, and the concentration tends to change, so improvement has been demanded.

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

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、電気分解により系中で次亜ハロゲン酸イオンを生じさせることができるため、刺激性を有する次亜ハロゲン酸塩を直接ハンドリングする必要がなく、コスト的にメリットがあ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、そのような測定方法の好適な用途を提供することを目的とするものである。   The present invention has been made in order to solve the above-mentioned problems. Since hypohalite ions can be generated in the system by electrolysis, it is necessary to directly handle hypohalite having irritation. It is an object of the present invention to provide a urea concentration measurement method that is cost effective. Moreover, it aims at providing the suitable use of such a measuring method.

上記課題は、試料溶液の尿素濃度を測定する尿素濃度測定方法であって、作用電極及び対電極を配置した容器の中に、ハロゲンイオンを含む水溶液及び尿素を含む試料溶液を導入して、作用電極及び対電極の間に電流を流し、電気分解により系中で発生した次亜ハロゲン酸イオン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。 The above-described problem is a urea concentration measurement method for measuring the urea concentration of a sample solution. The method includes introducing an aqueous solution containing halogen ions and a sample solution containing urea into a container in which a working electrode and a counter electrode are arranged. It is characterized by measuring the chemiluminescence produced by the reaction of hypohalite ions and urea generated in the system by electrolysis by passing an electric current between the electrode and the counter electrode to quantify the urea concentration. This is solved by providing a method for measuring urea concentration.

また、上記課題は、試料溶液の尿素濃度を測定する尿素濃度測定方法であって、作用電極及び対電極を配置した容器の中に、ハロゲンイオンを含む水溶液を導入して、作用電極及び対電極の間に電流を流し、その後に尿素が含まれる試料溶液を導入し、電気分解により系中で発生した次亜ハロゲン酸イオン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。更に、上記課題は、試料溶液の尿素濃度を測定する尿素濃度測定方法であって、作用電極及び対電極を配置した容器の中に、ハロゲンイオン及び尿素を含む試料溶液を導入して、作用電極及び対電極の間に電流を流し、電気分解により系中で発生した次亜ハロゲン酸イオン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。また、上記測定方法において、次亜ハロゲン酸イオンが、次亜臭素酸イオン又は次亜塩素酸イオンから選択される少なくとも１種であることが好適であり、試料溶液が透析廃液であることが好適であり、電気分解の際に攪拌することも好適である。 Another object of the present invention is to provide a urea concentration measuring method for measuring the urea concentration of a sample solution, wherein an aqueous solution containing halogen ions is introduced into a container in which the working electrode and the counter electrode are arranged, and the working electrode and the counter electrode A sample solution containing urea was introduced after that, and the concentration of urea was measured by measuring the chemiluminescence produced by the reaction of hypohalite ions and urea generated in the system by electrolysis. It is solved by providing a method for measuring urea concentration , characterized by quantifying Furthermore, the above-mentioned problem is a urea concentration measurement method for measuring the urea concentration of a sample solution, wherein a sample solution containing halogen ions and urea is introduced into a container in which a working electrode and a counter electrode are arranged, and the working electrode And measuring the chemiluminescence produced by the reaction of hypohalite ions and urea generated in the system by electrolysis by passing an electric current between the counter electrode and the urea, to determine the urea concentration This is solved by providing a concentration measurement method . In the above measurement method, the hypohalite ion is preferably at least one selected from hypobromite ion or hypochlorite ion, and the sample solution is preferably a dialysis waste liquid. It is also preferable to stir during electrolysis.

作用電極及び対電極を配置した容器と、ハロゲンイオンを含む水溶液を容器に導入する手段と、尿素を含む試料溶液を容器に導入する手段と、該ハロゲンイオンを含む水溶液と該尿素を含む試料溶液とを容器に導入した後に作用電極及び対電極の間に電流を流す手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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たことを特徴とする尿素濃度測定装置が本発明の好適な実施態様である。作用電極及び対電極を配置した容器と、ハロゲンイオンを含む水溶液を容器に導入する手段と、該ハロゲンイオンを含む水溶液を容器に導入した後に作用電極及び対電極の間に電流を流す手段と、該電流を流した後に尿素を含む試料溶液を容器に導入する手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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たことを特徴とする尿素濃度測定装置が本発明の好適な実施態様である。また、作用電極及び対電極を配置した容器と、ハロゲンイオン及び尿素を含む試料溶液を容器に導入する手段と、該ハロゲンイオン及び尿素を含む試料溶液を容器に導入した後に作用電極及び対電極の間に電流を流す手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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たことを特徴とする尿素濃度測定装置も本発明の好適な実施態様である。 Sample solution containing a container placing the working electrode and the counter electrode, means for introducing an aqueous solution containing halogen ions to the vessel, means for introducing a sample solution containing urea in a container, and an aqueous urea containing said halogen ions Means for passing an electric current between the working electrode and the counter electrode after being introduced into the container, and means for measuring chemiluminescence generated by the reaction of hypohalite ions and urea generated in the system by electrolysis A urea concentration measuring device characterized by comprising: is a preferred embodiment of the present invention. A container in which a working electrode and a counter electrode are arranged; means for introducing an aqueous solution containing halogen ions into the container; and means for passing an electric current between the working electrode and the counter electrode after introducing the aqueous solution containing halogen ions into the container; A means for introducing a sample solution containing urea into the container after passing the current; and a means for measuring chemiluminescence generated by the reaction of hypohalite ions generated in the system by electrolysis with urea. The urea concentration measuring apparatus characterized by the above is a preferred embodiment of the present invention. In addition, a container in which the working electrode and the counter electrode are arranged, means for introducing a sample solution containing halogen ions and urea into the container, and after the sample solution containing the halogen ions and urea is introduced into the container, the working electrode and the counter electrode There is also provided a urea concentration measuring device comprising means for passing an electric current between them and means for measuring chemiluminescence generated by reaction of hypohalite ions generated in the system by electrolysis with urea This is a preferred embodiment of the present invention.

また、上記尿素濃度測定装置により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が本発明の好適な実施態様である。   Moreover, an artificial dialysis apparatus characterized in that the urea concentration in the dialysis waste liquid is measured by the urea concentration measuring apparatus is a preferred embodiment of the present invention.

本発明の尿素濃度測定方法は、電気分解により必要に応じて次亜ハロゲン酸イオンを生じさせることができるため、刺激性を有する次亜ハロゲン酸塩を直接ハンドリングする必要がなく、コスト的にメリットがある。また、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。   The urea concentration measurement method of the present invention can generate hypohalite ions as required by electrolysis, so there is no need to directly handle hypohalite having irritation, and it is cost-effective. There is. Further, since the urea concentration 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.

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の一例を示した模式図であり、作用電極９及び対電極８を配置した容器７と、尿素を含む試料溶液を容器７に導入する手段と、作用電極９及び対電極８の間に電流を流す手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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 diagram showing an example of a urea concentration measuring apparatus 1 used in the present invention, a container 7 in which a working electrode 9 and a counter electrode 8 are arranged, and means for introducing a sample solution containing urea into the container 7. And means for passing a current between the working electrode 9 and the counter electrode 8, and means for measuring chemiluminescence generated by the reaction of hypohalite ions and urea generated in the system by electrolysis. Is.

本発明の尿素濃度測定装置１には、尿素を含む試料溶液を容器７（以下、「反応セル」と呼ぶことがある。）に導入する手段が備えられており、図１に示されるように、尿素を含む試料溶液は、尿素を含む試料溶液導入口２からチュービングポンプ３を経由して導入されるようになっている。また、ハロゲンイオンを含む水溶液４を反応セル７に導入する場合には、本発明の尿素濃度測定装置１がハロゲンイオンを含む水溶液４を導入する手段を備えていることが好ましく、図１に示されるように、ハロゲンイオンを含む水溶液４は、バルブ６を経由して反応セル７に導入されるようになっている。   The urea concentration measuring apparatus 1 of the present invention is provided with means for introducing a sample solution containing urea into a container 7 (hereinafter sometimes referred to as “reaction cell”), as shown in FIG. The sample solution containing urea is introduced from the sample solution introduction port 2 containing urea via the tubing pump 3. In addition, when the aqueous solution 4 containing halogen ions is introduced into the reaction cell 7, it is preferable that the urea concentration measuring apparatus 1 of the present invention includes means for introducing the aqueous solution 4 containing halogen ions, as shown in FIG. As described above, the aqueous solution 4 containing halogen ions is introduced into the reaction cell 7 via the valve 6.

本発明の尿素濃度測定装置１における容器７には、作用電極９及び対電極８が配置されており、前記作用電極９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９及び対電極８の間に電流を流すことにより、ハロゲンイオンから次亜ハロゲン酸イオンを生じさせることができる。具体的には、ＮａＦ、ＫＦ、ＮａＣｌ、ＫＣｌ、ＮａＢｒ、ＫＢｒ、ＮａＩ、ＫＩ等の塩が溶解し、Ｆ−、Ｃｌ−、Ｂｒ−、Ｉ−等のハロゲンイオンを含む水溶液４を反応セル７に導入して、作用電極９及び対電極８の間に電流を流すことによりＦＯ−、ＣｌＯ−、ＢｒＯ−、ＩＯ−等の次亜ハロゲン酸イオンを生じさせることができる。本発明で用いられる次亜ハロゲン酸イオンとしては特に限定されないが、次亜臭素酸イオン又は次亜塩素酸イオンから選択される少なくとも１種であることが好ましい。本発明の尿素濃度測定方法において、反応性の観点からはハロゲンイオンとし臭素イオンを用いることが好ましく、扱いやすさやコスト面からは塩素イオンを用いることが好ましい。本明細書の実施例では臭素イオンを用いた例のみを示しているが、塩素イオンを用いても電気分解によって次亜塩素酸イオンが発生し、化学発光による尿素の定量が可能であることを本発明者らは確認している。 A working electrode 9 and a counter electrode 8 are arranged in the container 7 of the urea concentration measuring apparatus 1 of the present invention, and means for flowing a current between the working electrode 9 and the counter electrode 8 is provided. In this way, by passing a current between the working electrode 9 and the counter electrode 8, hypohalite ions can be generated from the halogen ions. Specifically, an aqueous solution 4 in which a salt such as NaF, KF, NaCl, KCl, NaBr, KBr, NaI, KI or the like is dissolved and a halogen ion such as F − , Cl − , Br − , or I − is dissolved in the reaction cell 7. And a hypohalite ion such as FO − , ClO − , BrO − , IO −, etc. can be generated by passing a current between the working electrode 9 and the counter electrode 8. The hypohalite ion used in the present invention is not particularly limited, but is preferably at least one selected from hypobromite ion or hypochlorite ion. In the urea concentration measurement method of the present invention, it is preferable to use bromine ions as halogen ions from the viewpoint of reactivity, and chlorine ions are preferably used from the viewpoint of ease of handling and cost. In the examples of this specification, only examples using bromine ions are shown. However, even if chlorine ions are used, hypochlorite ions are generated by electrolysis, and urea can be quantified by chemiluminescence. The inventors have confirmed.

本発明の尿素濃度測定方法において、電気分解する際にハロゲンイオンを含む水溶液４がアルカリ性ではない場合には、次亜ハロゲン酸イオンではなく、Ｃｌ２やＢｒ２等が生じやすいため、ＮａＯＨやＫＯＨ等を加えて水溶液をアルカリ性にすることが好ましい。 In the urea concentration measuring method according to the present invention, when the aqueous solution 4 containing halogen ions is not alkaline during electrolysis, Cl 2 , Br 2, etc. are likely to be generated instead of hypohalite ions, so NaOH or KOH Etc. are preferably added to make the aqueous solution alkaline.

本発明で用いられる作用電極９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。また、電極の電位を一定にコントロールするために、参照電極を用いてもよい。   The working electrode 9 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, but 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. Further, a reference electrode may be used in order to control the potential of the electrode to be constant.

本発明の尿素濃度測定方法においては、電気分解することにより系中で次亜ハロゲン酸イオンを生じさせることができるため、刺激性を有する次亜ハロゲン酸塩を直接ハンドリングする必要がなく、コスト的にメリットがある。   In the method for measuring urea concentration of the present invention, hypohalite ions can be generated in the system by electrolysis, so there is no need to handle hypohalite having irritancy directly, which is costly. There are merits.

本発明の尿素濃度測定方法では、ハロゲンイオンを含む水溶液４及び尿素を含む試料溶液を反応セル７に導入してから電気分解してもよく、ハロゲンイオンを含む水溶液４を反応セル７に導入して電気分解してから、その後に尿素を含む水溶液を導入してもよく、ハロゲンイオン及び尿素を含む試料溶液のみを反応セル７に導入して電気分解してもよい。いずれの方法によっても次亜ハロゲン酸イオンを生じさせることができるが、ハロゲンイオンを含む水溶液４及び尿素を含む試料溶液を反応セル７に導入してから電気分解する場合には、含窒素成分の種類によっては、尿素以外の透析廃液成分の存在を確認することができる場合があり好ましい。本発明者らは、尿素以外の透析廃液成分による化学発光と尿素による化学発光のタイミングが異なることを確認している。次亜ハロゲン酸イオンと尿素との反応による化学発光の迅速な測定が可能である観点からは、ハロゲンイオンを含む水溶液４を反応セル７に導入して電気分解してから、その後に尿素を含む水溶液を導入する方法を用いることが好ましい。また、試料溶液がハロゲンイオンを含んでいる場合には、試料溶液のみを反応セル７に導入して電気分解することにより、次亜ハロゲン酸イオンを生じさせることができるため、操作が簡便であり好ましい。特に、後述のように、試料溶液として透析廃液を用いた場合には、透析廃液にはＣｌ−のようなハロゲンイオンが多く含まれているため、別途、ハロゲンイオンを含む水溶液４を導入する手段を設けなくてもよい利点があり好ましい。また、電気分解により生じた次亜ハロゲン酸イオンと尿素との反応を均一にさせる観点からは、反応セル７内の水溶液を攪拌する手段を備えていることが好ましい。 In the urea concentration measurement method of the present invention, the aqueous solution 4 containing halogen ions and the sample solution containing urea may be introduced into the reaction cell 7 and then electrolyzed, or the aqueous solution 4 containing halogen ions may be introduced into the reaction cell 7. Then, after electrolysis, an aqueous solution containing urea may be introduced, or only a sample solution containing halogen ions and urea may be introduced into the reaction cell 7 for electrolysis. Hypohalite ions can be generated by either method. However, when the aqueous solution 4 containing halogen ions and the sample solution containing urea are introduced into the reaction cell 7 and then electrolyzed, Depending on the type, the presence of dialysis waste liquid components other than urea may be confirmed, which is preferable. The present inventors have confirmed that the timing of chemiluminescence due to dialysis waste liquid components other than urea and chemiluminescence due to urea are different. From the viewpoint that rapid measurement of chemiluminescence by reaction of hypohalite ions and urea is possible, an aqueous solution 4 containing halogen ions is introduced into the reaction cell 7 and electrolyzed, and thereafter urea is contained. It is preferable to use a method of introducing an aqueous solution. In addition, when the sample solution contains halogen ions, hypohalite ions can be generated by introducing only the sample solution into the reaction cell 7 and electrolyzing, so that the operation is simple. preferable. In particular, as described later, when a dialysis waste liquid is used as a sample solution, since the dialysis waste liquid contains a lot of halogen ions such as Cl − , a means for separately introducing an aqueous solution 4 containing halogen ions. There is an advantage in that it is not necessary to provide this. Moreover, it is preferable to provide a means for stirring the aqueous solution in the reaction cell 7 from the viewpoint of uniforming the reaction between hypohalite ions generated by electrolysis and urea.

本発明の尿素濃度測定装置１には、発生した次亜ハロゲン酸イオンと尿素とから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（ＣＬ強度）を測定することにより、間接的に試料溶液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、次亜ハロゲン酸イオンと尿素とが反応することにより反応セル７内で生じた化学発光は、光電子増倍管１３を通じてフォトンカウンティングされる。本発明の尿素濃度測定方法において、化学発光を測定する際の発光強度の揺らぎを減少してＳ／Ｎ比を向上させる観点からは、反応セル７内の水溶液を攪拌する手段を備えていることが好ましく、作用電極９近傍に攪拌手段を配置することがより好ましい。これにより尿素濃度の定量を精度良く行うことができる。定量後の反応セル７内の水溶液は、バルブ１５を通じて排出口１６から排出される。   The urea concentration measuring apparatus 1 according to the present invention includes means for measuring chemiluminescence generated from the generated hypohalite ions and urea. Thus, the urea concentration of the sample solution can be quantified indirectly by measuring chemiluminescence (CL intensity). As shown in FIG. 1, chemiluminescence generated in the reaction cell 7 due to the reaction between hypohalite ions and urea is photon-counted through a photomultiplier tube 13. In the urea concentration measurement method of the present invention, a means for stirring the aqueous solution in the reaction cell 7 is provided from the viewpoint of improving the S / N ratio by reducing fluctuations in emission intensity when measuring chemiluminescence. Is preferable, and it is more preferable to dispose the stirring means in the vicinity of the working electrode 9. Thereby, the urea concentration can be accurately determined. The aqueous solution in the reaction cell 7 after quantification is discharged from the discharge port 16 through the valve 15.

本発明の尿素濃度測定装置１は種々の用途に用いることができるが、好適に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できる。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。   Although the urea concentration measuring apparatus 1 of the present invention can be used for various applications, it can be preferably used as an artificial dialysis apparatus 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 at which dialysis treatment should 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を用いて、反応セル７として、５ｍｌの円筒形の筒（塩化ビニル製）を用いた。作用電極９として、白金電極（直径１４ｍｍ）を反応セル７の底に設置した。また、対電極８として銀電極を反応セル７の内側の壁面に巻きつけるように配置した。臭化ナトリウム（ＮａＢｒ）及び水酸化ナトリウム（ＮａＯＨ）を含む電解溶液（ＮａＢｒ濃度４７．３ｇ／ｄｌ、ＮａＯＨ濃度０．８ｇ／ｄｌ）２ｍｌを尿素を含む試料溶液導入口２からテフロン（登録商標）チューブ（内径２ｍｍ）を通して反応セル７に導入した。一方、濃度をそれぞれ調整した尿素水溶液（ＵＮ値：２、５、１０、２０、５０、１００ｍｇ／ｄｌ）０．１ｍｌを、チュービングポンプ３を使って一定流量で反応セル７に注入した。本実施例において、尿素水溶液の濃度は、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。長さ１５ｍｍの攪拌子１０（ＰＴＦ製）をＰｔ電極上で回転させながら、白金電極と銀電極の間に６００ｍＡで３０秒間一定電流を流すと、ＮａＢｒの電解により化学発光が生じた。生じたＣＬ強度を、光電子増倍管１３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ＣＬ応答波形図を図２に、尿素濃度とＣＬ強度との相関図を図５に示す。 Example 1
Using the urea concentration measuring apparatus 1 shown in FIG. 1, a 5 ml cylindrical tube (made of vinyl chloride) was used as the reaction cell 7. As the working electrode 9, a platinum electrode (diameter 14 mm) was installed at the bottom of the reaction cell 7. Further, a silver electrode was disposed as the counter electrode 8 so as to be wound around the inner wall surface of the reaction cell 7. 2 ml of an electrolytic solution (NaBr concentration 47.3 g / dl, NaOH concentration 0.8 g / dl) containing sodium bromide (NaBr) and sodium hydroxide (NaOH) is supplied from the sample solution inlet 2 containing urea to Teflon (registered trademark) The reaction cell 7 was introduced through a tube (inner diameter 2 mm). On the other hand, 0.1 ml of urea aqueous solution (UN value: 2, 5, 10, 20, 50, 100 mg / dl) adjusted in concentration was injected into the reaction cell 7 at a constant flow rate using the tubing pump 3. In this example, the concentration of the urea aqueous solution is converted to a urea nitrogen (Urea Nitrogen, sometimes abbreviated as “UN”) value. When a constant current was passed between the platinum electrode and the silver electrode at 600 mA for 30 seconds while rotating the stirrer 10 (made of PTF) having a length of 15 mm on the Pt electrode, chemiluminescence was generated by electrolysis of NaBr. The generated CL intensity was measured by the photon counting method using the photomultiplier tube 13. The obtained CL response waveform diagram is shown in FIG. 2, and the correlation diagram between urea concentration and CL intensity is shown in FIG.

実施例２
実施例１において、攪拌せずに６００ｍＡで３３０秒間、続いて４０秒間一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ＣＬ応答波形図を図３に示す。 Example 2
In Example 1, chemiluminescence measurement was performed in the same manner as in Example 1 except that a constant current was passed at 600 mA for 330 seconds without stirring and then for 40 seconds. The obtained CL response waveform diagram is shown in FIG.

実施例３
実施例１において、攪拌しながら電気分解した後に尿素を含む試料溶液を導入した以外は実施例１と同様にして化学発光の計測を行った。得られたＣＬ応答波形図を図４に、尿素濃度とＣＬ強度との相関図を図６に示す。 Example 3
In Example 1, chemiluminescence was measured in the same manner as in Example 1 except that the sample solution containing urea was introduced after electrolysis while stirring. The obtained CL response waveform diagram is shown in FIG. 4, and the correlation diagram between urea concentration and CL intensity is shown in FIG.

比較例１
次亜臭素酸ナトリウムと水酸化ナトリウムの混合水溶液（次亜ハロゲン酸ナトリウム濃度１．０×１０−３Ｍ、水酸化ナトリウム濃度０．２Ｍ）３０ｍｌ及び濃度をそれぞれ調整した尿素水溶液（ＵＮ値：０．２８、０．５６、１．４、２．８、５．６、１４、２８、５６、１４０ｍｇ／ｄｌ）７ｍｌを反応容器内で互いに回転流をつくるように２０秒間攪拌させ、その際に生じたＣＬ強度をフォトンカウンティング法により計測した。得られた尿素濃度とＣＬ強度との相関図を図７に示す。 Comparative Example 1
30 ml of a mixed aqueous solution of sodium hypobromite and sodium hydroxide (sodium hypohalite concentration 1.0 × 10 −3 M, sodium hydroxide concentration 0.2 M) and an aqueous urea solution adjusted in concentration (UN value: 0) .28, 0.56, 1.4, 2.8, 5.6, 14, 28, 56, 140 mg / dl) 7 ml were stirred for 20 seconds so as to create a rotating flow with each other in the reaction vessel. The resulting CL intensity was measured by the photon counting method. FIG. 7 shows a correlation diagram between the obtained urea concentration and CL intensity.

図７に示される電気分解せずに次亜ハロゲン酸イオンと尿素とが反応した際の尿素濃度とＣＬ強度との相関図と、本発明の尿素濃度測定方法により得られた尿素濃度とＣＬ強度との相関図である図５及び図６との対比から分かるように、本発明の尿素濃度測定方法では、尿素濃度とＣＬ強度とがリニアに相関している。また、図２及び図４との対比から分かるように、攪拌しながら電気分解した後に尿素を含む試料溶液を導入した実施例３では、波形がシャープであり、応答時間が早いことが分かる。   FIG. 7 shows a correlation diagram between urea concentration and CL intensity when hypohalite ion and urea react without electrolysis, and urea concentration and CL intensity obtained by the urea concentration measuring method of the present invention. As can be seen from the comparison with FIGS. 5 and 6 which are correlation diagrams, the urea concentration and the CL intensity are linearly correlated in the urea concentration measuring method of the present invention. Further, as can be seen from the comparison with FIGS. 2 and 4, in Example 3 in which the sample solution containing urea was introduced after electrolysis while stirring, the waveform was sharp and the response time was quick.

本発明の尿素濃度測定装置の実施態様を示す説明図である。It is explanatory drawing which shows the embodiment of the urea concentration measuring apparatus of this invention. 尿素を含む試料溶液を導入後に攪拌しながら電気分解した際のＣＬ応答波形図である。It is a CL response waveform figure at the time of carrying out electrolysis, stirring a sample solution containing urea after introduction. 尿素を含む試料溶液を導入後に攪拌せずに電気分解した際のＣＬ応答波形図である。FIG. 6 is a CL response waveform diagram when a sample solution containing urea is electrolyzed without being stirred after being introduced. 攪拌しながら電気分解した後に尿素を含む試料溶液を導入した際のＣＬ応答波形図である。FIG. 6 is a CL response waveform diagram when a sample solution containing urea is introduced after electrolysis while stirring. 尿素を含む試料溶液を導入後に攪拌しながら電気分解した際の尿素濃度とＣＬ強度との相関図である。図中の数値は電解電流の値を表す。FIG. 6 is a correlation diagram between urea concentration and CL intensity when a sample solution containing urea is electrolyzed while being stirred after being introduced. The numerical value in the figure represents the value of the electrolysis current. 攪拌しながら電気分解した後に尿素を含む試料溶液を導入した際の尿素濃度とＣＬ強度との相関図である。FIG. 5 is a correlation diagram between urea concentration and CL intensity when a sample solution containing urea is introduced after electrolysis while stirring. 電気分解せずに次亜ハロゲン酸イオンと尿素とが反応した際の尿素濃度とＣＬ強度との相関図である。FIG. 6 is a correlation diagram between urea concentration and CL intensity when hypohalite ions react with urea without electrolysis.

符号の説明Explanation of symbols

１ 尿素濃度測定装置
２ 尿素を含む試料溶液導入口
３ チュービングポンプ
４ ハロゲンイオンを含む水溶液
５ 容器
６ バルブ
７ 容器（反応セル）
８ 対電極
９ 作用電極
１０ 攪拌子
１１ 磁気攪拌器
１２ 定電流電源
１３ 光電子増倍管
１４ ＰＣ
１５ バルブ
１６ 排出口 DESCRIPTION OF SYMBOLS 1 Urea density | concentration measuring apparatus 2 Sample solution inlet containing urea 3 Tubing pump 4 Aqueous solution containing halogen ion 5 Container 6 Valve 7 Container (reaction cell)
8 Counter electrode 9 Working electrode 10 Stirrer 11 Magnetic stirrer 12 Constant current power supply 13 Photomultiplier tube 14 PC
15 Valve 16 Discharge port

Claims (10)

試料溶液の尿素濃度を測定する尿素濃度測定方法であって、作用電極及び対電極を配置した容器の中に、ハロゲンイオンを含む水溶液及び尿素を含む試料溶液を導入して、作用電極及び対電極の間に電流を流し、電気分解により系中で発生した次亜ハロゲン酸イオン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 the urea concentration of a sample solution, wherein a working electrode and a counter electrode are introduced by introducing an aqueous solution containing halogen ions and a sample solution containing urea into a container in which the working electrode and the counter electrode are arranged. A method for measuring urea concentration , characterized by measuring chemiluminescence generated by the reaction of hypohalite ions and urea generated in the system by electrolysis by passing an electric current between them and quantifying the urea concentration . 試料溶液の尿素濃度を測定する尿素濃度測定方法であって、作用電極及び対電極を配置した容器の中に、ハロゲンイオンを含む水溶液を導入して、作用電極及び対電極の間に電流を流し、その後に尿素が含まれる試料溶液を導入し、電気分解により系中で発生した次亜ハロゲン酸イオン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 the urea concentration of a sample solution, wherein an aqueous solution containing halogen ions is introduced into a container in which a working electrode and a counter electrode are arranged, and a current is passed between the working electrode and the counter electrode. Then, a sample solution containing urea is introduced, and the urea concentration is quantified by measuring the chemiluminescence produced by the reaction of hypohalite ions and urea generated in the system by electrolysis. And urea concentration measurement method. 試料溶液の尿素濃度を測定する尿素濃度測定方法であって、作用電極及び対電極を配置した容器の中に、ハロゲンイオン及び尿素を含む試料溶液を導入して、作用電極及び対電極の間に電流を流し、電気分解により系中で発生した次亜ハロゲン酸イオン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 sample solution, wherein a sample solution containing a halogen ion and urea is introduced into a container in which a working electrode and a counter electrode are arranged, and between the working electrode and the counter electrode. A method for measuring urea concentration , characterized by measuring chemiluminescence generated by reacting hypohalite ions and urea generated in the system by electrolysis and quantifying urea concentration. 次亜ハロゲン酸イオンが、次亜臭素酸イオン又は次亜塩素酸イオンから選択される少なくとも１種である請求項１〜３のいずれか記載の尿素濃度測定方法。 The urea concentration measuring method according to any one of claims 1 to 3 , wherein the hypohalite ion is at least one selected from hypobromite ion or hypochlorite ion. 試料溶液が透析廃液である請求項１〜４のいずれか記載の尿素濃度測定方法。 The urea concentration measuring method according to any one of claims 1 to 4 , wherein the sample solution is a dialysis waste liquid. 電気分解の際に攪拌する請求項１〜５のいずれか記載の尿素濃度測定方法。 The urea concentration measuring method according to any one of claims 1 to 5 , wherein stirring is performed during electrolysis. 請求項１記載の尿素濃度測定方法に用いられる尿素濃度測定装置であって、作用電極及び対電極を配置した容器と、ハロゲンイオンを含む水溶液を容器に導入する手段と、尿素を含む試料溶液を容器に導入する手段と、該ハロゲンイオンを含む水溶液と該尿素を含む試料溶液とを容器に導入した後に作用電極及び対電極の間に電流を流す手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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たことを特徴とする尿素濃度測定装置。 A urea concentration measuring device used in the urea concentration measuring method according to claim 1, wherein a container having a working electrode and a counter electrode disposed therein, means for introducing an aqueous solution containing halogen ions into the container, and a sample solution containing urea Means for introducing into the container; means for passing an electric current between the working electrode and the counter electrode after introducing the aqueous solution containing the halogen ions and the sample solution containing urea into the container; An apparatus for measuring urea concentration, comprising: means for measuring chemiluminescence generated by a reaction between halohalide ions and urea. 請求項２記載の尿素濃度測定方法に用いられる尿素濃度測定装置であって、作用電極及び対電極を配置した容器と、ハロゲンイオンを含む水溶液を容器に導入する手段と、該ハロゲンイオンを含む水溶液を容器に導入した後に作用電極及び対電極の間に電流を流す手段と、該電流を流した後に尿素を含む試料溶液を容器に導入する手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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たことを特徴とする尿素濃度測定装置。A urea concentration measuring device used in the urea concentration measuring method according to claim 2, wherein a container in which a working electrode and a counter electrode are arranged, means for introducing an aqueous solution containing halogen ions into the container, and an aqueous solution containing the halogen ions Means for flowing a current between the working electrode and the counter electrode after introducing the liquid into the container, means for introducing a sample solution containing urea into the container after flowing the current, and hypohalogen generated in the system by electrolysis A urea concentration measuring apparatus comprising: means for measuring chemiluminescence generated by a reaction between acid ions and urea. 請求項３記載の尿素濃度測定方法に用いられる尿素濃度測定装置であって、作用電極及び対電極を配置した容器と、ハロゲンイオン及び尿素を含む試料溶液を容器に導入する手段と、該ハロゲンイオン及び尿素を含む試料溶液を容器に導入した後に作用電極及び対電極の間に電流を流す手段と、電気分解により系中で発生した次亜ハロゲン酸イオン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たことを特徴とする尿素濃度測定装置。A urea concentration measuring device used in the urea concentration measuring method according to claim 3, wherein a container in which a working electrode and a counter electrode are arranged, means for introducing a sample solution containing halogen ions and urea into the container, and the halogen ions Chemiluminescence produced by the reaction of urea with hypohalite ions generated in the system by means of flowing current between the working electrode and the counter electrode after introducing a sample solution containing urea and urea into the container And a urea concentration measuring device. 請求項７〜９のいずれか記載の尿素濃度測定装置により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。 An artificial dialysis apparatus, wherein the urea concentration in the dialysis waste liquid is measured by the urea concentration measuring apparatus according to any one of claims 7 to 9 .
JP2007076513A 2007-03-23 2007-03-23 Urea concentration measuring method and urea concentration measuring device Expired - Fee Related JP4894004B2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP2007076513A JP4894004B2 (en) 2007-03-23 2007-03-23 Urea concentration measuring method and urea concentration measuring device
DE112008000740T DE112008000740B4 (en) 2007-03-23 2008-03-18 Method for measuring urea concentration and device for measuring urea concentration
PCT/JP2008/054943 WO2008117699A1 (en) 2007-03-23 2008-03-18 Method of measuring urea concentration and apparatus for measuring urea concentration

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2007076513A JP4894004B2 (en) 2007-03-23 2007-03-23 Urea concentration measuring method and urea concentration measuring device

Publications (2)

Publication Number Publication Date
JP2008233005A JP2008233005A (en) 2008-10-02
JP4894004B2 true JP4894004B2 (en) 2012-03-07

Family

ID=39788435

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2007076513A Expired - Fee Related JP4894004B2 (en) 2007-03-23 2007-03-23 Urea concentration measuring method and urea concentration measuring device

Country Status (3)

Country Link
JP (1) JP4894004B2 (en)
DE (1) DE112008000740B4 (en)
WO (1) WO2008117699A1 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010024224A1 (en) * 2008-08-26 2010-03-04 財団法人岡山県産業振興財団 Urea concentration measurement method and urea concentration measurement apparatus
DE112012001473B4 (en) * 2011-03-28 2016-08-25 Kake Educational Institution A method for measuring a sample solution concentration and apparatus for measuring a sample solution concentration
DE102012109026A1 (en) * 2012-09-25 2014-03-27 Eads Deutschland Gmbh Detection device and detection method for the automatic determination of biomass
EP3376212B1 (en) 2017-03-17 2020-01-29 Ricoh Company Ltd. Chemiluminescence analyzer, blood purification apparatus, and blood purification system
DE102020112570A1 (en) 2020-05-08 2021-11-11 Analytik Jena Gmbh Device for chemiluminescence analysis

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2812745B2 (en) * 1989-11-08 1998-10-22 株式会社日本触媒 Chemiluminescence determination of ammonia and its device
JPH0579986A (en) * 1991-09-24 1993-03-30 Kansai Electric Power Co Inc:The Ammonium quantification using chemical luminescence
JP3206985B2 (en) * 1992-10-02 2001-09-10 東亜ディーケーケー株式会社 Chemiluminescence analyzer
JPH09155358A (en) * 1995-10-06 1997-06-17 Kinousui Kenkyusho:Kk Sterilized water, method and apparatus for preparing the same, and apparatus for measuring concentration of hypochlorous acid of sterilized water
JP4855854B2 (en) * 2006-07-10 2012-01-18 川澄化学工業株式会社 Chemiluminescent urea sensor for hemodialysis and urea measurement method in hemodialysis
WO2010024224A1 (en) * 2008-08-26 2010-03-04 財団法人岡山県産業振興財団 Urea concentration measurement method and urea concentration measurement apparatus

Also Published As

Publication number Publication date
JP2008233005A (en) 2008-10-02
DE112008000740B4 (en) 2011-03-17
WO2008117699A1 (en) 2008-10-02
DE112008000740T5 (en) 2010-02-04

Similar Documents

Publication Publication Date Title
JP4894004B2 (en) Urea concentration measuring method and urea concentration measuring device
CN101788522B (en) Chemical oxygen demand (COD) on-line monitoring device and method based on boron-doped diamond membrane electrode
WO2010024224A1 (en) Urea concentration measurement method and urea concentration measurement apparatus
JP6609489B2 (en) Electrolyte analyzer
JP2018124130A (en) Device and method for measuring residual chlorine
JP5770491B2 (en) Method for measuring total concentration of oxidizing substance, concentration meter for measuring total concentration of oxidizing substance, and sulfuric acid electrolysis apparatus using the same
EP0992792A2 (en) Fluid analyte measurement system
US20160061791A1 (en) Automatic Ammonium Analyzer
JP6022040B2 (en) Method and apparatus for measuring and controlling the concentration of electroactive species in an aqueous solution
EP3056232A1 (en) Method and apparatus for measuring urea concentration
JP4779911B2 (en) Analysis equipment
JP4463382B2 (en) Residual chlorine measuring device
Oliveira et al. A coulometric flow cell for in-line generation of reagent, titrant or standard solutions
JP7177341B2 (en) Reagentless residual chlorine measuring device and reagentless residual chlorine measuring method
JP2004251833A (en) Total nitrogen measuring method and instrument
JPWO2014174818A1 (en) Oxidizing substance determination method and oxidizing substance determination apparatus
JP3813606B2 (en) Combined electrode of electrolysis electrode and redox potential measurement electrode
JP4826778B2 (en) Method and apparatus for measuring chlorine dioxide and chlorite ion concentrations in aqueous solution
JP2020003382A (en) Total effective chlorine measurement device, method for correction of the same, and method for measuring total effective chlorine
JP2006242629A (en) Discriminated potentiometric titration device of hydrogen peroxide and acetyl hydroperoxide
JP2017015669A (en) Residual chlorine measurement method and residual chlorine measurement device
JP5714433B2 (en) Electrolytic cell
Ozaki et al. Urea monitor based on chemiluminescence and electrolysis as a marker for dialysis efficiency
JPS623898B2 (en)
JPH11201936A (en) Method and mechanism for evaluation of concentration of residual halogens

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20100205

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20110830

A521 Written amendment

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20111031

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

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20111129

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

Free format text: JAPANESE INTERMEDIATE CODE: A01

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20111208

R150 Certificate of patent or registration of utility model

Ref document number: 4894004

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

Free format text: JAPANESE INTERMEDIATE CODE: R150

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

Free format text: PAYMENT UNTIL: 20150106

Year of fee payment: 3

S111 Request for change of ownership or part of ownership

Free format text: JAPANESE INTERMEDIATE CODE: R313113

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

Free format text: PAYMENT UNTIL: 20150106

Year of fee payment: 3

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

LAPS Cancellation because of no payment of annual fees