JPS59187249A - Analyzing device of urea nitrogen - Google Patents

Abstract

PURPOSE:To measure a whole blood sample rapidly, simply and accurately by a system wherein enzyme urease and a liquid to be analyzed which contains urea are introduced into a prescribed conductivity-measuring cell provided with a porous membrane, and a variation in the conductivity is thereby detected. CONSTITUTION:A conductivity-measuring electrode 1 is composed of a platinum electrode 11, an insulating layer 12 and a porous membrane 10 closely fitted on the platinum electrode 11 through the intermediary of an O ring 9. A urea nitrogen detecting element comprises two conductivity-measuring electrodes 1, lead wires 2, a measuring cell 3, a measuring cell chamber 4 filled up with a buffer solution, and a silicon diaphragm 5 for agitation which can be vibrated. Prescribed quantities of enzyme urease and a liquid to be analyzed which contains urea are injected from an injection port 6, and the conductivity of the solution is measured under the impression of an AC power through the intermediary of the electrodes 1. The urea nitrogen contained in said liquid is determined easily from measured values of the variation of the conductivity in a prescribed time difference by using working curves. Accordingly, a complete blood sample can be measured rapidly, simply and accurately.

Description

【発明の詳細な説明】 〔発明の属する分野〕 この発明は、酵素ウレアーゼを用いて被検液中の尿素に
含まれる窒素量いわゆる尿素窒素を電導度測定法により
定量する装置に関する。DETAILED DESCRIPTION OF THE INVENTION [Field to which the invention pertains] The present invention relates to an apparatus for quantifying the amount of nitrogen contained in urea in a test liquid, so-called urea nitrogen, by a conductivity measurement method using the enzyme urease.

臨床検査分野における生体液中の尿素窒素濃度は腎機能
の指標として重要視されている。さらに近年、腎疾患の
治療法に人工透析が広く行われ、透析中の腎機能のモニ
タリングに尿素窒素量が利用されてきた。In the field of clinical testing, urea nitrogen concentration in biological fluids is considered important as an indicator of renal function. Furthermore, in recent years, artificial dialysis has become widely used as a treatment for kidney diseases, and the amount of urea nitrogen has been used to monitor kidney function during dialysis.

この種の尿素窒素定量法は、一般に正確、Ｎｉ１便かつ
迅速であることが要請される。特に、血液の場合、遠心
分Ｍ操作を必要としない全血のままの測定が強く望まれ
ている。This type of urea nitrogen determination method is generally required to be accurate, efficient, and rapid. In particular, in the case of blood, there is a strong desire to measure whole blood without the need for centrifugation M operation.

〔従来技術とその問題点〕[Prior art and its problems]

この種の尿素窒素定量法として、いくうかの比色法が知
られているが、これらには、ｆｌ）体液のような着色試
料をそのまま使うことができない、（２）操作が煩雑で
時間がかがる、（３）試薬を使い捨てにするため経済的
でない、といった欠点がある。Several colorimetric methods are known for this type of urea nitrogen determination method, but these methods have problems such as (1) inability to use colored samples such as body fluids, and (2) complicated and time-consuming operations. (3) It is not economical because the reagents are disposable.

また、酵素を固定化された膜、ビーズなどをガラス電極
、ｐＨ電極、などのイオン選択性電極と組み合わせて尿
素窒素を定量する方法も知られているが、ガラス電極の
場合は、体液中のＮａ、にイオンの影響を受けるという
欠点があり、ｐＨ′１！極の場合は、ガス状のアンモニ
アを測定するため被検液のｐＨを１１以上にする必要が
あり、これが酵素反応の至適ｐＨと大きく異なり、反応
部分と検出部分を分離しなければならなくなるという欠
点がある。また、ｐＨ電極を用いるものＩ−ｉ揮発性ア
ミンの妨害を受けやすいという欠点もあり、広く実用化
されるには至っていない。It is also known to quantify urea nitrogen by combining enzyme-immobilized membranes, beads, etc. with ion-selective electrodes such as glass electrodes and pH electrodes. Na has the disadvantage of being affected by ions, and pH'1! In the polar case, in order to measure gaseous ammonia, it is necessary to raise the pH of the sample solution to 11 or higher, which is significantly different from the optimal pH for enzyme reactions, and the reaction part and detection part must be separated. There is a drawback. In addition, those using pH electrodes have the disadvantage of being easily interfered with by volatile amines (I-i), so they have not been widely put into practical use.

更に、尿素にウレアーゼを作用させ、生成したアンモニ
アと二酸化炭素を心２４度法で検出する尿素定縫（特開
昭４８−３７９６号公報）も知られているが、この定量
法は（１）屯導度測定セルが２組必要である、（２）尿
素濃度が低い場合は酵素液の電４度を補正しなければな
らない、（３）全血を被検液に用いると長期の使用に伴
い電極表面が汚染され、汚染が著しい場合は測定できな
い、などの欠点がある。電導夏法による定力１．法（特
公昭５６−４７４９７号公報）も知られているが、この
場合も上述した（３）の欠点があり、長期間にわたり迅
速、簡便、正確な測定を要求される尿素窒素検出部とし
ては不十分なものと判断せざるを得ない。Furthermore, urea fixed stitching (Japanese Unexamined Patent Publication No. 1983-3796) is known, in which urease is applied to urea and the generated ammonia and carbon dioxide are detected using the 24 degrees centigrade method. Two sets of tonic conductivity measurement cells are required. (2) If the urea concentration is low, it is necessary to correct the electrical conductivity of the enzyme solution. (3) If whole blood is used as the test solution, long-term use is possible. This has the disadvantage that the electrode surface is contaminated, and measurements cannot be made if the contamination is significant. Constant force by conduction summer method 1. Although the method (Japanese Patent Publication No. 56-47497) is also known, this method also has the drawback (3) mentioned above, and is not suitable for a urea nitrogen detection unit that requires quick, simple, and accurate measurement over a long period of time. I have to judge that it is insufficient.

〔発明の目的〕 この発明は、上述の欠点を除去して、長期間にわたｐ全
血試料を迅速、簡便、正確に測定できる尿素窒素分析装
置を提供することを目的とする。[Object of the Invention] It is an object of the present invention to provide a urea nitrogen analyzer that eliminates the above-mentioned drawbacks and can quickly, simply, and accurately measure p-whole blood samples over a long period of time.

〔発明の要点〕[Key points of the invention]

このような目的は、本発明によれば、尿素を分解しアン
モニアと二酸化炭素を生成することのできる酵素ウレア
ーゼを、多孔性膜ｆ：板覆した２個の電導７度測定電極
を備え、緩衝液を満たされた電導度測定セル室内に導き
、更にこの測定セル室内に尿素を含む被検液を導入し、
この被検液を含む緩衝液の導′屯率の変化量または変化
率を測定することにより達成される。According to the present invention, the enzyme urease, which can decompose urea and produce ammonia and carbon dioxide, is provided with two conductivity measuring electrodes covered with a porous membrane f: a buffered membrane. Introducing the liquid into the conductivity measurement cell chamber filled with the liquid, further introducing the test liquid containing urea into the measurement cell chamber,
This is achieved by measuring the amount or rate of change in conductivity of a buffer solution containing this test solution.

ここで特徴的なことは、本発明では、主導朋画定電橙の
先端を多孔性膜で被覆し、緩衝液中のイオンはこれを透
過して検知部に達するが蛋白質や血球などの被検液中の
高分子はこれを通過しないという選択透過性のある構造
にしたことである。What is unique here is that in the present invention, the tip of the leading electrode is coated with a porous membrane, and ions in the buffer solution pass through this and reach the detection part, but proteins and blood cells are detected. It has a selectively permeable structure that does not allow polymers in the liquid to pass through it.

これは、一般に、電導度測定電極の劣化は、長期使用に
伴い商液中の蛋白質や血球が電極検知部表面に付着し、
′低極検知部の実効表面積を減少させるためと考えられ
るので、多孔性膜を電極検知部表面に一装着すれば表面
は汚染されず、長期にわたる全血測定が可能となるとい
う考え方に基づいている。This is because the conductivity measurement electrode generally deteriorates due to proteins and blood cells in the commercial solution adhering to the surface of the electrode detection part due to long-term use.
'This is thought to be to reduce the effective surface area of the low-polarity detection part, and is based on the idea that if a porous membrane is attached to the surface of the electrode detection part, the surface will not be contaminated and long-term whole blood measurement will be possible. There is.

この発明による尿素窒素分析装置は以下の原−理に基づ
くものである。尿素はｐＨ付近では酵素ウレアーゼによ
り加水分解され、（１）式に示すように、アンモニアと
二酸化炭素を生成する。The urea nitrogen analyzer according to the present invention is based on the following principle. Urea is hydrolyzed by the enzyme urease near pH, producing ammonia and carbon dioxide as shown in equation (1).

＋ＯＨ−・・・・・・・・・・・・・・・・・・・・・
　（１）ここで用いる酵素ウレアーゼは尿素に特−異的
に作用するため、被検液中の他の物質からアンモニアや
二酸化炭素が生成されることはない。生成されたＮＨ，
”　、　ＨＣｏ３−は、それぞれ緩衝溶液もしくは溶媒
の導電率を増加させるため、２個の電導度測定電極を配
置してこれらの間でのコンダクタンス増加分を検出し、
これの一定時間後の変化量もしくは変化量の速度論理的
彦解析により、被検液中の尿素望素量を計迎［する。一
定時間後の導電率増加量は尿素窒素濃度に比例するので
、尿素窒素を定量することができるのである。+OH-・・・・・・・・・・・・・・・・・・・・・
(1) Since the enzyme urease used here specifically acts on urea, ammonia and carbon dioxide are not generated from other substances in the test solution. generated NH,
”, HCo3− increases the conductivity of the buffer solution or solvent, respectively, by arranging two conductivity measurement electrodes and detecting the increase in conductance between them.
The amount of urea and rea in the test liquid is measured by the amount of change after a certain period of time or by a kinetic analysis of the amount of change. Since the amount of increase in conductivity after a certain period of time is proportional to the urea nitrogen concentration, urea nitrogen can be quantified.

〔発明の実施例〕[Embodiments of the invention]

以下、この発明に基づ〈実施例を図面を参照しながら説
明する。Hereinafter, embodiments based on the present invention will be described with reference to the drawings.

第１図に尿素窒素検出部の構成を示す。こ＼で１は電導
度測定電極、２はそのリード線、３は測定セル、４は緩
衝溶液で満たされた測定セル室である。この測定セル室
４内の溶液は、シリコンダイヤフラム５などを介し、図
示しない駆動装置で振動させることにより、攪拌されて
いる。被検液は注入口６から一定量注入する。測定セル
３は一定の容積゛（０，４ｍｔ）があり、図示されてい
ない温度調整手段によって２０〜４０℃の範囲の一定温
度°に調整されている。なお、７は緩衝溶液導入８は緩
衝溶液排出管である。FIG. 1 shows the configuration of the urea nitrogen detection section. Here, 1 is a conductivity measuring electrode, 2 is its lead wire, 3 is a measuring cell, and 4 is a measuring cell chamber filled with a buffer solution. The solution in the measurement cell chamber 4 is agitated by being vibrated by a drive device (not shown) via a silicon diaphragm 5 or the like. A fixed amount of the test liquid is injected from the injection port 6. The measuring cell 3 has a constant volume (0.4 mt) and is adjusted to a constant temperature in the range of 20 to 40 DEG C. by temperature regulating means (not shown). Note that 7 is a buffer solution introduction pipe and 8 is a buffer solution discharge pipe.

第２図に、電導度測定電極１を説明するための断面図を
示す。１１は材料として白金を用いた白金極であるが、
白金黒−白金、ステンレスなどの材料を用いることもで
きる。１２は絶縁層、１３はＱ　＋）フグ保持用ガイド
であり、多孔性膜１０がＱ　ＩＪング９により白金極１
１の先端表面に密’ＡＮされた状態となっている。多孔
性膜１０は孔径０．０３μｍの孔が多数おいている厚さ
７μｍのポリカーボネート膜である。以上のように構成
された電導度測定電極１は２個配置され、これを介して
、こノ間の溶液の電導度がコンダクタンスとして交ｍ電
源（好ましくは、電圧ＩＶｉ度、周波数０．５ｋＨｚ以
上）印加の下に測定される。なお、２個の独立した電導
度測定電極１を用いる代りに、絶縁体に２本の白金電極
を一緒に埋込んだ電極構成を１個用いてもよい。FIG. 2 shows a cross-sectional view for explaining the conductivity measuring electrode 1. As shown in FIG. 11 is a platinum electrode using platinum as the material,
Materials such as platinum black-platinum and stainless steel can also be used. 12 is an insulating layer, 13 is a guide for holding a Q+) blowfish, and a porous film 10 is connected to a platinum electrode 1 by a Q IJ ring 9.
It is in a state where it is densely ANd on the tip surface of 1. The porous membrane 10 is a polycarbonate membrane with a thickness of 7 μm and has many pores with a pore diameter of 0.03 μm. Two electrical conductivity measurement electrodes 1 configured as described above are arranged, and the electrical conductivity of the solution between these electrodes is measured as a conductance through an AC power source (preferably at a voltage of IVi degrees and a frequency of 0.5 kHz or higher). ) is measured under an applied voltage. Note that instead of using two independent conductivity measuring electrodes 1, one electrode configuration in which two platinum electrodes are embedded together in an insulator may be used.

使用した溶液は、０．　ＯＩ　Ｍ　！Ｊン酸塩緩衝溶液
（ｐＨ７，０）にＱ、１Ｍ＠ＮａｃＡとウレアーゼ２５
０ｍｇ／ｄｉとを含み、これにそれぞれ尿素窒素２５，
５０゜１００　、２００ｍｇ／ｄ４を加えたものである
。用いられたウレアーゼ（ＥＣ３・５・１・５）は市販
で得られるものである。測定は２５℃で行った。The solution used was 0. OIM! Q, 1M@NacA and urease 25 in J phosphate buffer solution (pH 7,0)
0mg/di, each containing urea nitrogen 25,
50°100, 200mg/d4 was added. The urease (EC3.5.1.5) used was commercially available. Measurements were performed at 25°C.

第３図は、測定の進行につれ、測定セル室４内の溶液の
電導率が変化していく状況を説明するための線図である
。捷ず、測定セル室４を緩衝溶液で十分洗浄（６ｍｔ／
分、３０秒間）した後、ウレアーゼ溶液２０μｔを測定
セル室４内にＡ時点で注入する。注入直後、ウレアーゼ
溶液中の電解質などの影響により導電率が増加するが、
攪拌が十分に行なわれているので、注入後５秒程度で一
定値となった。導電率が一定値に々つた後、Ｂ時点で０
、１　Ｍ−Ｎ　ａ　Ｃｔを含む尿素窒素溶液を測定セル
室４内に２０μを注入する注入直後、尿素窒素溶液中の
電解質の影響により導電率は急激に増加し、その後はゆ
るやかな増加に変わシ、１〜２分後にはほぼ一定値が得
られている。第３図は尿素窒素濃度１００ｍｇ／ｄＡの
溶液を用いた場合の導電率変化であり、Ｂ時点から３０
秒後のＣ時点で洗浄が行われている。第３図の例では酵
素ウレアーゼを測定セル室４内に２０μＬ注入したが、
あらかじめ緩衝溶液に１２　ｍ　ｇ　／　ｄ　Ｌ　のａ
度に溶解しておくこともでき、この場合は測定セル室４
内の洗浄後、ただちに尿素窒素溶液を注４し、洗浄を含
めて１分間＼ で測定を完了させることができる。FIG. 3 is a diagram for explaining how the conductivity of the solution in the measurement cell chamber 4 changes as the measurement progresses. Wash the measurement cell chamber 4 thoroughly with a buffer solution (6 mt/
30 seconds), 20 μt of urease solution is injected into the measurement cell chamber 4 at time A. Immediately after injection, the conductivity increases due to the influence of electrolytes in the urease solution, but
Since the stirring was sufficient, the value reached a constant value about 5 seconds after injection. After the conductivity reaches a constant value, it becomes 0 at time B.
, 20μ of urea nitrogen solution containing 1M-N a Ct is injected into the measurement cell chamber 4. Immediately after injection, the conductivity increases rapidly due to the influence of the electrolyte in the urea nitrogen solution, and then changes to a gradual increase. After 1 to 2 minutes, a nearly constant value is obtained. Figure 3 shows the change in conductivity when using a solution with a urea nitrogen concentration of 100 mg/dA.
Cleaning is being performed at time C seconds later. In the example shown in Fig. 3, 20 μL of the enzyme urease was injected into the measurement cell chamber 4.
12 mg/d L of a in buffer solution in advance
It is also possible to dissolve it at the same time, in which case the measurement cell chamber 4
Immediately after cleaning the chamber, pour in urea nitrogen solution and complete the measurement in 1 minute including cleaning.

第３図で見られる尿素窒素溶液注入後の導電率のゆるや
かな変化は、尿素とウレアーゼの反応によシアンモニア
と二酸化炭素が生成しているためである。第３図中に示
した尿素窒素溶液注入後５砂目と３０秒口の時間差△ｔ
の間の電導率の変化量ΔＳと尿素窒素濃度との関係を第
４図に示す。The gradual change in electrical conductivity after injection of the urea nitrogen solution seen in FIG. 3 is due to the generation of cyanmonia and carbon dioxide due to the reaction between urea and urease. Time difference △t between the 5th grain and 30 seconds after injection of urea nitrogen solution shown in Figure 3
FIG. 4 shows the relationship between the amount of change ΔS in electrical conductivity during the period and the urea nitrogen concentration.

第４図かられかるように、導電率の変化量は尿素窒素濃
度に対して良好な直線関係を示す。したがって、あらか
じめ尿素窒素濃度と導電率の変化量との検量線を作成し
ておけば、未知濃度の被検液の尿素窒素を簡単に決定す
ることができる。更には導電率変化量を電圧に変換し、
所定濃度の尿素窒素標準液で校正し、未知試料中の尿素
窒素を迎１定することができる。すなわちウレアーゼを
緩衝溶液中に溶解１〜、かつ反応時間を３０秒に設定す
ることにより、洗浄を含めて１被検液１分以内で尿素窒
素濃度を定量できることになる。As can be seen from FIG. 4, the amount of change in electrical conductivity shows a good linear relationship with the urea nitrogen concentration. Therefore, by creating a calibration curve between the urea nitrogen concentration and the amount of change in conductivity in advance, it is possible to easily determine the urea nitrogen in a test liquid with an unknown concentration. Furthermore, the amount of change in conductivity is converted into voltage,
By calibrating with a urea nitrogen standard solution of a predetermined concentration, the urea nitrogen in an unknown sample can be determined. That is, by dissolving urease in a buffer solution for 1 to 30 seconds and setting the reaction time to 30 seconds, the urea nitrogen concentration can be determined within 1 minute for each test solution, including washing.

なお、第３図では一定時間△を後の導電率増加量ΔＳを
検出しているが、同図は一定時間後の導電率の変化率を
検出してもよいことをも示している。更に、導電率変化
量が一定値に達するまでの時間を計測し、尿素窒素量に
換算できることも明らかである。In FIG. 3, the conductivity increase amount ΔS is detected after a certain period of time Δ, but the same figure also shows that the rate of change in conductivity after a certain period of time may be detected. Furthermore, it is clear that the time required for the amount of change in conductivity to reach a certain value can be measured and converted into the amount of urea nitrogen.

次に、全血試料を用いて不法の同時再現性を検討した結
果を示す。なお、全血試料の抗凝固、剤はに２・ＥＤＴ
Ａ　（エチレンジアミン四ｔｅ＝・２Ｋｍ）を用いた。Next, we will show the results of examining illegal simultaneous reproducibility using whole blood samples. In addition, for anticoagulation of whole blood samples, anticoagulant 2・EDT
A (ethylene diamine tetrate=·2Km) was used.

表　　１　　表 ２種の全、＋ｒｕともに同時再現性は良好である。Table 1 Table Simultaneous reproducibility is good for both total and +ru.

また、同一血液から、全血試料と血清試料を調製し、全
血と血清とについての尿素窒素濃度の相関を検討した。In addition, whole blood samples and serum samples were prepared from the same blood, and the correlation between urea nitrogen concentrations in whole blood and serum was examined.

測定結果は４５試料に対して、回帰直線Ｙ　”＝　０．
７９ｘ＋０．９（ｙ　：全血値、ｘ：血清値）相関係数
γ−０９８が得られ、全血値と血清値の相関は良好であ
ることがわかった。更に、血清にヘモグロビンを添加し
、ヘモグロビンの尿素窒素測定に対する影響を検討した
が、ヘモグロビン２００　ｍ　ｇ　／　ｄ　Ｌまで影響
されないことが明らかとなった。The measurement results are for 45 samples, and the regression line Y''=0.
A correlation coefficient γ-098 of 79x+0.9 (y: whole blood value, x: serum value) was obtained, indicating that the correlation between whole blood values and serum values was good. Furthermore, hemoglobin was added to serum to examine the effect of hemoglobin on urea nitrogen measurements, and it was found that there was no effect up to hemoglobin of 200 mg/dL.

全血試料を１０００回連続測定し、電導度測定電極１の
全血による汚染を検討したが、１ｏｏｏ回では汚染によ
る劣化は認められなかったことから、多孔性膜１０の有
効性が裏づけられた。なお、この実施例で用いた多孔性
膜１０は孔径０．０３μの孔が多数おいている厚さ７μ
のポリカーボネート膜であるが、セルロースアセテート
膜、ポリビニルクロライド膜がどこの分野で周知のいか
なる膜を用いてもよいことは明らかである。孔径は０．
００１〜１μ、膜厚は０．５〜１００μの範囲の多孔性
膜が使用できるが、好ましくは孔径０．０１５〜０．１
μ、厚さ２〜１０μである。Whole blood samples were continuously measured 1000 times to examine contamination of the conductivity measurement electrode 1 by whole blood, and no deterioration due to contamination was observed in 100 times, supporting the effectiveness of the porous membrane 10. . The porous membrane 10 used in this example has a thickness of 7 μm and has many pores with a pore diameter of 0.03 μm.
However, it is clear that any cellulose acetate membrane or polyvinyl chloride membrane known in any field may be used. The pore diameter is 0.
Porous membranes with a pore diameter of 0.001 to 1μ and a membrane thickness of 0.5 to 100μ can be used, but preferably a pore size of 0.015 to 0.1μ.
μ, thickness 2 to 10 μ.

第５図に、本発明の一具体例である尿素窒素分析装置の
系統図を示す。ここで１４は第１図に示した尿素窒素検
出部、１５は尿素窒素検出部１４に緩衝溶液を供給する
ための緩衝溶液供給部、１６は緩衝溶液を測定セル室４
へ導入、排出するためのへリスタボンブ、１７は排液用
溶器である。１８は電導度測定電極間に得られるコンダ
クタンス葡測定するための電導度迎」定装置で、公知の
コールラウシュブリッジなどが用いられる。１９は表示
部である。FIG. 5 shows a system diagram of a urea nitrogen analyzer that is a specific example of the present invention. Here, 14 is the urea nitrogen detection section shown in FIG. 1, 15 is a buffer solution supply section for supplying a buffer solution to the urea nitrogen detection section 14, and 16 is a buffer solution supply section for supplying the buffer solution to the measurement cell chamber 4.
A helister bomb is used for introducing and discharging liquid into the liquid, and 17 is a draining vessel. Reference numeral 18 denotes a conductance measurement device for measuring the conductance obtained between the conductivity measurement electrodes, and a known Kohlrausch bridge or the like is used. 19 is a display section.

この発明の思想は、いままで説明した尿素窒素の定量の
ほかに、 Ａ−−−→Ｂ＋尿素 のように尿素を生成する物質Ａの定量用として応用でき
る。かかる例としては、物質Ａとしてアルミニンがあり
、これは酵素としてアルミナーゼを用いたとき、物質Ｂ
としてのオルニチンと尿素を生じる。他の例では、Ａと
してのクレアチンは酵素クレアチナーゼによりＢとして
のザルコシンと尿素とに分解する。更には、臨床検査分
野のみならず、多孔性膜を用いているため汚水、土壌な
どを対象とした環境針側、プロセス計測の分野にも適用
できる。The idea of this invention can be applied not only to the determination of urea nitrogen as described above, but also to the determination of substance A that produces urea, such as A---→B+urea. As an example of this, there is aluminine as substance A, which becomes substance B when aluminase is used as the enzyme.
It produces ornithine and urea. In another example, creatine as A is degraded to sarcosine and urea as B by the enzyme creatinase. Furthermore, since it uses a porous membrane, it can be applied not only to the field of clinical testing, but also to the field of environmental needles and process measurement for wastewater, soil, etc.

〔発明の効果〕〔Effect of the invention〕

この発明によれば、尿素を特異的に加水分解する酵素ウ
レアーゼを用いたため、妨害物質の影参を受けずに尿素
窒素を定量できる。更に、多孔性膜を電導度測定電極の
先端に装着した電極を用いての電導度法を採用したため
、長期間にゎたり全血を簡便かつ迅速に測定できる。ｌ
だ、有害、悪臭な試薬は必要とせず試料を注入するだけ
で定量が行なえる。According to this invention, since the enzyme urease that specifically hydrolyzes urea is used, urea nitrogen can be quantified without being influenced by interfering substances. Furthermore, since we adopted a conductivity method using a porous membrane attached to the tip of the conductivity measurement electrode, whole blood can be measured simply and quickly over a long period of time. l
However, there is no need for harmful or foul-smelling reagents, and quantification can be performed simply by injecting the sample.

【図面の簡単な説明】[Brief explanation of drawings]

第１図はこの発明による装置の尿素窒素検出部の一部断
面とした概略構成図、第２図はこの発明による電導度測
定電極の断面図、第３図はこの発明による装ｆαの測定
中の溶液の電導率の変化を示す線図、第４図は被検液を
含む溶液の導電率変化量と尿素窒素濃度の関係を示す線
図、第５図はこの発明による尿素窒素分析装置の系統図
である。 １・・・電導度測定成極、＆・・・測定セル、４・・・
測定セル室、１０・・・多孔性膜、１１・・・白金極、
１４・・・尿素窒素検出部、１８・・・電導度揃定装置
。 寸１　閃 ｆ７２　　印 Ｂ寺内：　ｆ”ｚ− 屈季窒引落Ｎ翰個）FIG. 1 is a partial cross-sectional schematic diagram of the urea nitrogen detection section of the device according to the present invention, FIG. 2 is a cross-sectional view of the conductivity measuring electrode according to the present invention, and FIG. 3 is a partial cross-sectional view of the conductivity measuring electrode according to the present invention. FIG. 4 is a diagram showing the relationship between the amount of change in conductivity of a solution containing the test solution and the urea nitrogen concentration. FIG. It is a system diagram. 1... conductivity measurement polarization, &... measurement cell, 4...
Measurement cell chamber, 10... Porous membrane, 11... Platinum electrode,
14... Urea nitrogen detection unit, 18... Electrical conductivity leveling device. Dimension 1 Flash f72 Seal B Terauchi: f”z- Kuji Nitori N pcs)

Claims (1)

【特許請求の範囲】[Claims] 工）尿素をアンモニアと二酸化炭素に加水分解する液体
酵素ウレアーゼ、緩衝溶液及び被検液力・らなる混合液
を収容する測定セル室と、該測定セル室に設けられた多
孔性膜を装着した電導度測定電極と、前記混合液の導電
率の変化量もしくは変化率を電導度法に基づいて測定す
る手段とを備えたことを特徴とする尿素窒素分析装置。Engineering) A measurement cell chamber containing a mixture of urease, a liquid enzyme that hydrolyzes urea into ammonia and carbon dioxide, a buffer solution, and a test liquid, and a porous membrane installed in the measurement cell chamber. A urea nitrogen analyzer comprising: a conductivity measuring electrode; and means for measuring the amount or rate of change in the conductivity of the liquid mixture based on a conductivity method.