JPS6332137B2 - - Google Patents

Info

Publication number
JPS6332137B2
JPS6332137B2 JP55150756A JP15075680A JPS6332137B2 JP S6332137 B2 JPS6332137 B2 JP S6332137B2 JP 55150756 A JP55150756 A JP 55150756A JP 15075680 A JP15075680 A JP 15075680A JP S6332137 B2 JPS6332137 B2 JP S6332137B2
Authority
JP
Japan
Prior art keywords
reaction
blood
current
buffer solution
sample blood
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
Application number
JP55150756A
Other languages
Japanese (ja)
Other versions
JPS5774654A (en
Inventor
Koichi Endo
Nobuhiko Tsuji
Keijiro Nakamura
Toshoshi Hamada
Keiichi Ishida
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.)
Fuji Electric Co Ltd
Original Assignee
Fuji Electric Co Ltd
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 Fuji Electric Co Ltd filed Critical Fuji Electric Co Ltd
Priority to JP55150756A priority Critical patent/JPS5774654A/en
Priority to US06/313,666 priority patent/US4407959A/en
Publication of JPS5774654A publication Critical patent/JPS5774654A/en
Publication of JPS6332137B2 publication Critical patent/JPS6332137B2/ja
Granted legal-status Critical Current

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N27/00Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
    • G01N27/26Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
    • G01N27/28Electrolytic cell components
    • G01N27/30Electrodes, e.g. test electrodes; Half-cells
    • G01N27/327Biochemical electrodes, e.g. electrical or mechanical details for in vitro measurements
    • G01N27/3271Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Electrochemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Description

【発明の詳細な説明】 この発明は、固定化グルコースオキシダーゼ膜
(以下、固定化酵素膜ともいう。)を用いた血糖値
分析方法に関する。
DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a blood sugar level analysis method using an immobilized glucose oxidase membrane (hereinafter also referred to as an immobilized enzyme membrane).

この種の分析装置は、酵素膜センサにブドウ糖
(グルコース)を含んだ検体を供給して反応させ
ると、グルコースに比例する値の反応電流が流れ
ることを利用して検体血液中に含まれる糖の量、
すなわち血糖量を測定するもので、反応電流(血
液中の血糖が固定化酵素により分解生成されて生
じる過酸化水素を還元する時に流れる還元電流を
測定する固定化酵素膜電極と、該固定化酵素膜電
極がセツトされるとゝもに検体血液または標準溶
液(以下、検体血液等という。)が注入される反
応セルと、固定化酵素を死活させないようにする
ための緩衝液を送つて反応セル内の洗浄を行なう
液体ポンプ等から構成されている。反応セルに検
体血液等を注入すると、固定化酵素との反応が始
まり、一定時間(数秒)後に反応が定常状態にな
り、血液中の血糖値に比例する分析値が得られ
る。定常状態になつた時点で反応終結と考えて、
次の検体または標準溶液を注入するために、緩衝
液を反応セル内部に送り、酵素膜を含めて反応セ
ル内部を洗浄する。
This type of analyzer utilizes the fact that when a sample containing glucose is supplied to an enzyme membrane sensor and reacted, a reaction current proportional to the glucose flows. amount,
In other words, it measures the amount of blood sugar, and includes an immobilized enzyme membrane electrode that measures the reaction current (reduction current that flows when reducing hydrogen peroxide produced when blood sugar in the blood is decomposed and produced by an immobilized enzyme), and the immobilized enzyme. When the membrane electrodes are set, there is a reaction cell into which sample blood or standard solution (hereinafter referred to as sample blood, etc.) is injected, and a buffer solution to keep the immobilized enzyme alive is sent to the reaction cell. It consists of a liquid pump that cleans the inside of the cell.When sample blood, etc. is injected into the reaction cell, a reaction with the immobilized enzyme begins, and after a certain period of time (several seconds), the reaction reaches a steady state, and the blood sugar level in the blood increases. An analysis value proportional to the value can be obtained.The reaction is considered to have ended when it reaches a steady state.
In order to inject the next specimen or standard solution, a buffer solution is sent into the reaction cell to wash the inside of the reaction cell including the enzyme membrane.

この緩衝液による反応セルの洗浄は、従来は、
緩衝液の量を一定として一定の洗浄時間で行なう
のが普通であるが、この方法には次のような欠点
がある。すなわち、高濃度の検体血液等が反応セ
ルに注入されると、場合によつては完全に洗浄さ
れないことがあり、次の検体の測定時に未洗浄分
の血糖値が加算されることになつて、測定精度が
低下する。このために、例えば再度洗浄を行なう
等の対策が必要にある。一方、検体血液等が低濃
度の場合には、洗浄に要する緩衝液は少量で済む
から一定量、一定時間の洗浄を行なうと緩衝液が
無駄に消費されることになる。
Conventionally, washing the reaction cell with this buffer solution was
It is common practice to use a constant amount of buffer solution and a constant washing time, but this method has the following drawbacks. In other words, if a highly concentrated sample, such as blood, is injected into the reaction cell, it may not be completely washed in some cases, and the unwashed blood glucose level will be added when the next sample is measured. , measurement accuracy decreases. For this reason, it is necessary to take measures such as cleaning again. On the other hand, if the sample blood or the like has a low concentration, only a small amount of buffer is required for washing, so if washing is performed in a fixed amount and for a fixed period of time, the buffer will be wasted.

したがつて、この発明は、検体血液等の濃度に
応じた適量の緩衝液で反応セル内の洗浄を行なう
ようにして、上記のような欠点を除去することを
目的とする。
Therefore, it is an object of the present invention to eliminate the above-mentioned drawbacks by washing the inside of a reaction cell with an appropriate amount of buffer solution depending on the concentration of sample blood, etc.

上記の目的は、この発明によれば、検体血液等
の注入によつて固定化酵素膜電極に発生する反応
電流(血液中の血糖が固定化酵素により分解生成
されて生じる過酸化水素を還元する時に流れる還
元電流)の立上り点を検出する毎にその時点の電
流レベルを記憶するとゝもに、反応終結後に緩衝
液の供給を開始し、該緩衝液の供給によつて前記
反応電流レベルが前記立上り点における電流レベ
ルまで低下したときまたは反応電流の変化が零と
なつたときに緩衝液の供給を停止することにより
達成される。
According to the present invention, the above purpose is to reduce the reaction current generated in the immobilized enzyme membrane electrode by the injection of sample blood, etc. Each time the rising point of the reduction current (current flowing at the same time) is detected, the current level at that time is memorized, and after the reaction is completed, supply of buffer is started, and by supplying the buffer, the reaction current level increases to the level above. This is achieved by stopping the supply of buffer when the current level at the rise point is reduced or when the change in reaction current becomes zero.

以下、この発明が実施される血糖値分析装置を
図面を参照して説明する。
DESCRIPTION OF THE PREFERRED EMBODIMENTS A blood glucose level analyzer embodying the present invention will be described below with reference to the drawings.

第1図は、この発明の実施例を示す概略構成図
である。
FIG. 1 is a schematic diagram showing an embodiment of the present invention.

同図において、血糖値に比例する反応電流を測
定するグルコース測定電極1は、白金および銀電
極表面にグルコースオキシダーゼ膜を密着させて
構成され、温度電極2とゝもにセルCEにセツト
されている。緩衝液4は液体ポンプ3により吸引
され、セルCEに送り込まれてセルCE内の洗浄を
行ない、反応後は廃液5として廃棄される。エア
ポンプ6は、反応セルCE内へ注入口OPより注入
される検体血液等をシリコンダイヤフラムSDを
振動させることによつて撹拌し、セルCE内の濃
度を均一にする。マイクロコンピユータからなる
制御装置CCは、ラインL1〜L6によつて血糖値分
析装置GUと接続されており、ラインL1を介して
測定電極1からの反応電流を読取り、ラインL2
L4を介してセルCEおよび測定部アルミブロツク
の温度の測定または制御を行ない、また、ライン
L3およびL6を介して液体ポンプ3およびエアポ
ンプ6の動作を制御するとゝもに、ラインL7
L11によつて各種スイツチMO1〜MO4、DS1
DS2、表示装置DIおよびプリンタPと接続され
て、これらの入出力制御等の装置全体の制御を行
なう。
In the figure, the glucose measuring electrode 1, which measures a reaction current proportional to the blood sugar level, is composed of a glucose oxidase membrane in close contact with the surface of a platinum and silver electrode, and the temperature electrode 2 is also set in the cell CE. . The buffer solution 4 is sucked by the liquid pump 3 and sent into the cell CE to clean the inside of the cell CE, and after the reaction is discarded as a waste solution 5. The air pump 6 stirs the sample blood, etc. injected into the reaction cell CE from the injection port OP by vibrating the silicon diaphragm SD, thereby making the concentration in the cell CE uniform. The control device CC consisting of a microcomputer is connected to the blood glucose level analyzer GU through lines L1 to L6 , reads the reaction current from the measuring electrode 1 through the line L1 , and reads the reaction current from the measuring electrode 1 through the lines L2 ,
The temperature of the cell CE and the measuring aluminum block is measured or controlled via L4 .
The operation of the liquid pump 3 and air pump 6 is controlled via L 3 and L 6, and the lines L 7 to
Various switches MO 1 to MO 4 , DS 1 , depending on L 11
It is connected to DS 2 , display device DI, and printer P, and controls the entire device such as input/output control of these devices.

こゝで、動作について説明する。 Here, the operation will be explained.

第2図は、第1図に示される装置の動作を説明
するためのフローチヤートである。
FIG. 2 is a flowchart for explaining the operation of the apparatus shown in FIG.

同図において、電源が投入されて測定が開始(イ)
されると、タイマ時間等の初期設定(ロ)がなされ、
分析装置GUの暖器運転(ハ)が行われる。暖器に要
する所定時間が経過して電極の温度(ニ)が測定可能
な温度になると、制御装置CCは電極出力の監視
(ホ)を始め、電極出力が安定した時点で準備完了(ヘ)
ということになる。電極の温度が測定可能な温度
にならなかつたり、電極出力が安定しない場合
は、暖器運転を続ける。こゝで、操作モード選択
スイツチMO1〜MO4のうちのRUNスイツチMO4
が押されている(ト)ならば、まずセルCE内の洗浄
(ル)が行なわれ、これが終了(オ)すると、検体血
液等の注入(ワ)が行われる。なお、検体血液の
測定の前には必ず較正(キヤリブレーシヨン)を
行なうことになつているから、この場合も標準溶
液が注入されることになる。したがつて、標準溶
液による反応が開始されるので、制御装置CCは
反応電流の読み込みを開始する。そして、まず測
定電極上に発生する反応電流の立上り点〓を検出
し、この点を基準点としてその時点における電流
値を記憶する。この立上り点が検出されると、反
応セルCE内では反応(タ)が進行し、立上り時
点から所定の時間、例えば20秒が経過すると、一
応反応が終結(レ)したものとして、次の測定を
行なうべく緩衝液を供給してセルCE内の洗浄を
行なう。この反応終結に伴なう緩衝液の供給によ
つて反応電流レベルは順次低下するが、この電流
レベルが先に記憶された立上り点の電流レベルと
一致するか、または電流レベルが低下する変化の
度合(反応電流変化分/時間=taoθ)が零にな
つた時点を検出すると、制御装置CCは緩衝液の
供給を停止し、洗浄を完了する。以下、標準溶液
を用いて複数回の測定を行なうことにより分析装
置の較正を行ない、較正後に検体血液の測定を上
記と同様にして行なう。もちろん、この場合の測
定は1回だけであるが、その測定結果は上記の較
正データによつて自動的に較正され、表示装置
DIによつて表示される。
In the figure, the power is turned on and measurement begins (A).
Then, the initial settings (b) of timer time etc. are made.
The analyzer GU is warmed up (c). When the predetermined time required for warming up has passed and the electrode temperature (d) reaches a measurable temperature, the control device CC starts monitoring the electrode output.
Starting from (E), preparation is complete when the electrode output becomes stable (F)
It turns out that. If the electrode temperature does not reach a measurable temperature or the electrode output is unstable, continue warm-up operation. Here, select the RUN switch MO 4 of the operation mode selection switches MO 1 to MO 4.
If is pressed (G), the inside of the cell CE is first cleaned (R), and when this is completed (O), sample blood, etc. is injected (W). Note that since calibration is always performed before measuring the sample blood, the standard solution will be injected in this case as well. Therefore, since the reaction with the standard solution is started, the controller CC starts reading the reaction current. First, the rising point of the reaction current generated on the measuring electrode is detected, and the current value at that point is stored using this point as a reference point. When this rising point is detected, the reaction (Ta) progresses in the reaction cell CE, and when a predetermined period of time, for example 20 seconds, has passed from the rising point, the reaction is assumed to have ended (R) and the next measurement is started. In order to do this, a buffer solution is supplied to wash the inside of the cell CE. The reaction current level sequentially decreases as the buffer solution is supplied as the reaction ends, but if this current level matches the previously memorized current level at the rising point, or if the change in current level decreases. When detecting the point in time when the degree (change in reaction current/time = t ao θ) becomes zero, the controller CC stops supplying the buffer solution and completes the washing. Thereafter, the analyzer is calibrated by performing multiple measurements using the standard solution, and after the calibration, the sample blood is measured in the same manner as above. Of course, in this case the measurement is only made once, but the measurement result is automatically calibrated using the above calibration data and displayed on the display.
Displayed by DI.

こゝで、測定サイクルと分析値との関係がこの
発明によつてどのように改良されたかについて、
従来例と比較して説明する。
Here, we will explain how the relationship between measurement cycles and analysis values has been improved by this invention.
This will be explained in comparison with a conventional example.

第3図aおよびbは、横軸を測定サイクル、縦
軸を分析値で表わしたグラフであつて、前者は従
来の分析装置による測定結果を、また後者はこの
発明による測定結果をそれぞれ示すものである。
Figures 3a and 3b are graphs in which the horizontal axis represents measurement cycles and the vertical axis represents analytical values, with the former showing the measurement results by a conventional analyzer and the latter showing the measurement results by the present invention. It is.

こゝに、Aは検体血液等の注入時点、Bは反応
の定常時点または反応終結時点、Cは洗浄開始時
点、Dは洗浄の終了時点をそれぞれ示し、また、
B1,B2は分析値の基準線を示す。これらの図を
対比すれば明らかなように、従来のものが未洗浄
の血糖による増加分が積算されるために分析値の
基準線B1が測定サイクル毎に次第に増加してい
るのに対し、この発明によるものでは、基準線
B2の上昇がないため次の検体血液等の測定時に
は影響を与えず、したがつて測定精度を良好に保
ち得ることがわかる。
Here, A indicates the time of injection of sample blood, etc., B indicates the steady state of the reaction or the end of the reaction, C indicates the start of washing, and D indicates the end of washing, and
B 1 and B 2 indicate the reference line of the analytical values. As is clear from comparing these figures, in contrast to the conventional method, the reference line B1 of the analysis value gradually increases with each measurement cycle because the increase due to unwashed blood sugar is integrated. According to this invention, the reference line
It can be seen that since there is no increase in B2 , there is no effect on the measurement of the next sample blood, etc., and therefore the measurement accuracy can be maintained at a good level.

なお、この発明のようにすると、洗浄後の電流
値の変化が定常状態にならなかつたり、立上り点
のレベルと同一のレベルにならなかつたりして連
続的に洗浄を行なうおそれがあるので、洗浄を開
始してから一定時限、例えば30秒後には洗浄を停
止する機能を付加することゝし、その判断および
制御は制御装置CCで行なうようにする。
However, if the present invention is used, there is a risk that the change in the current value after cleaning will not reach a steady state or will not reach the same level as the rise point, resulting in continuous cleaning. A function is added to stop the cleaning after a certain period of time, for example, 30 seconds after it starts, and the judgment and control thereof will be performed by the control device CC.

以上のように、この発明によれば、検体血液等
の濃度に応じてセルの洗浄を行なうようにしたか
ら、未洗浄の血糖が蓄積されることがなく、した
がつて測定誤差が少なく、測定精度の高い血糖値
分析装置を提供することができる。また、低濃度
の検体血液等の測定時には、洗浄が早く完了する
から、緩衝液の消費量を従来のものに比し低減さ
せることができるものである。
As described above, according to the present invention, since the cell is cleaned according to the concentration of sample blood, etc., unwashed blood sugar does not accumulate, and therefore measurement errors are small and measurement A highly accurate blood sugar level analyzer can be provided. Furthermore, when measuring low-concentration blood samples, etc., cleaning is completed quickly, so the amount of buffer solution consumed can be reduced compared to conventional methods.

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

第1図は、この発明が実施される血糖値分析装
置を示す概略構成図、第2図は、第1図の動作を
説明するためのフローチヤート、第3図aは、従
来の分析装置における測定サイクルと分析値との
関係を示すグラフ、第3図bは、この発明による
分析装置を用いた場合の測定サイクルと分析値と
の関係を示すグラフである。 符号説明、1…測定電極、2…温度電極、3…
液体ポンプ、4…緩衝液、5…廃液、6…エアポ
ンプ、OP…注入口、CE…反応セル、SD…シリ
コンダイアフラム、CC…制御装置、MO1〜MO2
…操作モード選択スイツチ、DS1…検体番号設定
デイジタルスイツチ、SD2…標準溶液濃度設定デ
イジタルスイツチ、CAL…較正時に点灯するラ
ンプ、RUN…運転時に点灯するランプ、DI…表
示装置、P…プリンタ。
FIG. 1 is a schematic configuration diagram showing a blood glucose level analyzer in which the present invention is implemented, FIG. 2 is a flowchart for explaining the operation of FIG. 1, and FIG. 3a is a diagram showing a conventional analyzer. FIG. 3b is a graph showing the relationship between the measurement cycle and the analysis value when the analyzer according to the present invention is used. Explanation of symbols, 1...Measuring electrode, 2...Temperature electrode, 3...
Liquid pump, 4...Buffer solution, 5...Waste liquid, 6...Air pump, OP...Inlet, CE...Reaction cell, SD...Silicon diaphragm, CC...Control device, MO 1 to MO 2
...Operation mode selection switch, DS 1 ...Sample number setting digital switch, SD 2 ...Standard solution concentration setting digital switch, CAL...Lamp that lights up during calibration, RUN...Lamp that lights up during operation, DI...Display device, P...Printer.

Claims (1)

【特許請求の範囲】[Claims] 1 固定化酵素膜および測定電極を備えてなる反
応セルに検体血液または標準溶液(以下、検体血
液等という。)を注入し、該検体血液等と前記固
定化酵素膜との間で化学反応を生じさせ、該化学
反応にもとづいて前記測定電極に発生する反応電
流から検体血液等の血糖値を測定するとゝもに、
前記化学反応が終結する1サイクル毎に緩衝液を
供給して前記反応セル内の洗浄を行なうべく、前
記反応セル内に検体血液等を注入する毎に生じる
前記反応電流の立上り点をその都度検出して対応
する時点の電流レベルを1サイクル毎に記憶し、
反応終結後に前記緩衝液の供給を開始し、該緩衝
液の供給によつて前記反応電流レベルが前記立上
り点における電流レベルまで低下したときまたは
反応電流の変化がほぼ零となつたときに緩衝液の
供給を停止することを特徴とする血糖値分析方
法。
1. Sample blood or a standard solution (hereinafter referred to as sample blood, etc.) is injected into a reaction cell equipped with an immobilized enzyme membrane and a measurement electrode, and a chemical reaction is caused between the sample blood, etc. and the immobilized enzyme membrane. and measuring the blood glucose level of the sample blood etc. from the reaction current generated in the measurement electrode based on the chemical reaction,
In order to wash the inside of the reaction cell by supplying a buffer solution every cycle when the chemical reaction ends, the rising point of the reaction current that occurs each time a sample blood or the like is injected into the reaction cell is detected each time. and stores the current level at the corresponding time every cycle,
The supply of the buffer solution is started after the completion of the reaction, and when the reaction current level decreases to the current level at the rise point due to the supply of the buffer solution, or when the change in the reaction current becomes almost zero, the buffer solution is A blood sugar level analysis method characterized by stopping the supply of.
JP55150756A 1980-10-29 1980-10-29 Blood sugar value analyzer Granted JPS5774654A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP55150756A JPS5774654A (en) 1980-10-29 1980-10-29 Blood sugar value analyzer
US06/313,666 US4407959A (en) 1980-10-29 1981-10-21 Blood sugar analyzing apparatus

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP55150756A JPS5774654A (en) 1980-10-29 1980-10-29 Blood sugar value analyzer

Publications (2)

Publication Number Publication Date
JPS5774654A JPS5774654A (en) 1982-05-10
JPS6332137B2 true JPS6332137B2 (en) 1988-06-28

Family

ID=15503720

Family Applications (1)

Application Number Title Priority Date Filing Date
JP55150756A Granted JPS5774654A (en) 1980-10-29 1980-10-29 Blood sugar value analyzer

Country Status (1)

Country Link
JP (1) JPS5774654A (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6085359A (en) * 1983-10-14 1985-05-14 Matsushita Electric Works Ltd Substance quantification
JP6055847B2 (en) * 2013-01-23 2016-12-27 株式会社日立ハイテクノロジーズ Electrochemical measuring device

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5912601Y2 (en) * 1978-03-31 1984-04-16 株式会社日立製作所 liquid analyzer

Also Published As

Publication number Publication date
JPS5774654A (en) 1982-05-10

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