JPH0365501B2 - - Google Patents
Info
- Publication number
- JPH0365501B2 JPH0365501B2 JP10342983A JP10342983A JPH0365501B2 JP H0365501 B2 JPH0365501 B2 JP H0365501B2 JP 10342983 A JP10342983 A JP 10342983A JP 10342983 A JP10342983 A JP 10342983A JP H0365501 B2 JPH0365501 B2 JP H0365501B2
- Authority
- JP
- Japan
- Prior art keywords
- measurement
- time
- detection circuit
- switch
- coagulation
- 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
Links
- 238000005259 measurement Methods 0.000 claims description 113
- 238000001514 detection method Methods 0.000 claims description 31
- 230000015271 coagulation Effects 0.000 claims description 19
- 238000005345 coagulation Methods 0.000 claims description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 230000023555 blood coagulation Effects 0.000 claims description 5
- 230000007274 generation of a signal involved in cell-cell signaling Effects 0.000 claims description 4
- 238000000034 method Methods 0.000 description 16
- 230000002159 abnormal effect Effects 0.000 description 8
- 206010053567 Coagulopathies Diseases 0.000 description 7
- 230000035602 clotting Effects 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 6
- 108010000499 Thromboplastin Proteins 0.000 description 4
- 102000002262 Thromboplastin Human genes 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- PGOHTUIFYSHAQG-LJSDBVFPSA-N (2S)-6-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylsulfanylbutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-oxopentanoyl]amino]-3-phenylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-oxopentanoyl]amino]hexanoic acid Chemical compound CSCC[C@H](N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(O)=O PGOHTUIFYSHAQG-LJSDBVFPSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 108010094028 Prothrombin Proteins 0.000 description 2
- 102100027378 Prothrombin Human genes 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 229940039716 prothrombin Drugs 0.000 description 2
- 238000007711 solidification Methods 0.000 description 2
- 230000008023 solidification Effects 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
Classifications
-
- 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
- G01N33/86—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood coagulating time or factors, or their receptors
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、血液の凝固時間を高精度で、かつ最
適の所要時間で測定することができる装置に関す
るものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a device that can measure blood coagulation time with high precision and in an optimal time.
従来、人または動物の血液の凝固時間を測定
し、疾病などの診断に寄与するための項目として
は、プロトロンビン時間（PT）、部分トロンボプ
ラスチン（PTT）、フイブリノーゲン量（Fbg）
あるいは欠乏因子定量、活性化部分トロンボプラ
スチン時間（APTT）、Ca再加時間などがある。
これらの項目は、加える試薬により血液中のどの
成分と反応させるかによつて定まる。たとえばプ
ロトロンビン時間（PT）の測定においては、遠
心分離後に血液成分中の血漿に、組織トロンボプ
ラスチンとカルシウムを十分に添加した場合に、
白色網状のフイブリン塊が生ずるまでの時間であ
り、別の例として、活性化部分トロンボプラスチ
ン時間（APTT）の測定においては、遠心分離
後に採取した血漿に、アクチンという試薬に加え
て、さらに塩化カルシウムを添加し、凝塊が生ず
るまでの時間を測定している。すなわち血液から
遠心分離した血漿を冷蔵庫内に保存しておき、こ
の血漿0.1mlを入れた試験管内に、37℃の水浴中
で１分間加温されたアクチン0.1mlを加え、37℃
で２分間加温し、ついで予め37℃の水浴中に置か
れていた0.02MのCaCl20.1mlを強く吹き込み、同
時にストツプウオツチを押す。ついで試験管を37
℃の水浴中に入れ、25秒間加温した後、試験管を
とり出して観察し、凝固の形成でストツプウオツ
チを停止させ、凝固時間を測定する。
Conventionally, the items used to measure the clotting time of human or animal blood and contribute to the diagnosis of diseases include prothrombin time (PT), partial thromboplastin (PTT), and fibrinogen content (Fbg).
Alternatively, there may be deficiency factor quantification, activated partial thromboplastin time (APTT), Ca replenishment time, etc.
These items are determined by which component in the blood is reacted with the reagent added. For example, when measuring prothrombin time (PT), if enough tissue thromboplastin and calcium are added to plasma in the blood components after centrifugation,
This is the time it takes for a white net-like fibrin mass to form. Another example is when measuring the activated partial thromboplastin time (APTT), in addition to a reagent called actin, calcium chloride is added to the plasma collected after centrifugation. The time required for coagulum to form is measured. In other words, plasma that has been centrifuged from blood is stored in a refrigerator, and 0.1 ml of actin that has been heated in a 37°C water bath for 1 minute is added to a test tube containing 0.1 ml of this plasma.
Then, 0.1 ml of 0.02 M CaCl 2 , which had been placed in a water bath at 37° C., was strongly blown into the tube, and the stopwatch was pressed at the same time. Then test tube 37
After being placed in a water bath at 0.degree. C. and warmed for 25 seconds, the test tube is removed and observed, stopping the stopwatch at the formation of a clot and measuring the clotting time.
上記の方法は人手によつて直接測定する方法で
あり、一般に用手法と称されている。この用手法
においては、検査員に相当の熟練を必要とし、誰
にでも容易に測定できるものではないという問題
点があつた。一方、この用手法に対し、近年、自
動分析装置の出現により、自動的に凝固時間の測
定が行なわれるようになつてきた。これは光学的
手段などにより、凝固塊を検出するものである
が、用手法に比べ局部的に凝固塊を検出するもの
であり、測定の条件によつては、バラツキが大き
く、再現性も悪いという欠点があつた。またさら
に、自動化された分析装置においては、その構成
上、いわゆる「凝固時間」をどう定義するかが問
題であり、一般には、光学的測定において所定の
光学レベルを設定し、そのレベルを横切つた時点
を凝固時間とする方法、あるいは変曲点（変化の
カーブを時間で微分しピークとなつた点）を凝固
時間とする方法などがある。 The above method is a method of direct measurement by hand, and is generally referred to as a manual method. This method requires considerable skill on the part of the inspector, and there is a problem in that it cannot be easily measured by anyone. On the other hand, in recent years, with the advent of automatic analyzers, the clotting time has come to be measured automatically. This method detects clots using optical means, but compared to manual methods, it detects clots locally, and depending on the measurement conditions, there are large variations and poor reproducibility. There was a drawback. Furthermore, due to the configuration of automated analyzers, it is a problem how to define the so-called "clotting time." Generally, a predetermined optical level is set in optical measurement, and that level is crossed. There are two methods: one method uses the point at which the change occurs as the coagulation time, and another method uses the inflection point (the point at which the curve of change is differentiated with respect to time and reaches a peak) as the coagulation time.
前者のレベル検知法においては、レベルの設定
如何によつては異常検体の場合、そのレベルに達
し得ないこともあり、通常は測定不能という形で
片づけられていた。すなわち第１図および第２図
において、レベルL3に設定した場合、異常検体
のカーブがレベルL3に達しないため、測定が
延々と続くことになる。一方、第３図および第４
図に示すように、後者の変曲点を求める方法にお
いても、異常検体においては第４図に示すよう
に、変曲点の検知が困難であり、少々の測定誤差
が生じても、それを誤つて変曲点として機械がと
らえてしまうというおそれがあつた。以上の測定
結果は、用手法で得られた測定結果とは必ずしも
一致するとは限らないので、診断に供するために
は、従来法との比較において測定値を補正する必
要があつた。 In the former level detection method, depending on how the level is set, in the case of an abnormal sample, it may not be possible to reach that level, and it is usually dismissed as unmeasurable. That is, in FIGS. 1 and 2, when the level is set to L3 , the measurement continues indefinitely because the curve of the abnormal sample does not reach level L3 . On the other hand, Figures 3 and 4
As shown in the figure, even with the latter method of determining the inflection point, it is difficult to detect the inflection point in abnormal samples, as shown in Figure 4, and even if a small measurement error occurs, it is difficult to detect the inflection point. There was a risk that the machine could mistakenly perceive it as an inflection point. The above measurement results do not necessarily agree with the measurement results obtained by manual methods, so in order to use it for diagnosis, it was necessary to correct the measurement values in comparison with the conventional method.
従来の凝固時間測定装置は、主として光学的手
段により凝固塊を検出し、その出力が所定の閾値
に達した点を凝固終了点とし、それまでの時間を
タイマーで測定し表示していた。しかるに、測定
に要する時間は、前記閾値に達した時点、あるい
は予め60秒といつた所定の時間に達するまでと一
義的に決めていた。また光学的手段の出力（たと
えば散乱光の変化）に対しては、単にアナログレ
コーダに記録するだけであり、凝固時間が異常に
長い異常検体に対しては、前記条件（時間あるい
は閾値の設定）をはずし、レコーダに記録される
出力波形を観察し、検査員が測定打ち切りなどの
判断を下していた。さらに検体によつては、予め
設定した所定の閾値に達し得ない検体もあり、こ
れらの異常検体によつて、検査測定の能率を著し
く阻害していた。
Conventional coagulation time measuring devices mainly detect a coagulated mass by optical means, define the point at which the output reaches a predetermined threshold as the coagulation end point, and measure and display the time up to that point using a timer. However, the time required for measurement has been uniquely determined to be the time when the threshold value is reached, or until a predetermined time such as 60 seconds is reached. In addition, the output of optical means (for example, changes in scattered light) is simply recorded on an analog recorder, and for abnormal samples with an abnormally long coagulation time, the conditions (time or threshold settings) The inspector would then remove the sensor, observe the output waveform recorded on the recorder, and make decisions such as discontinuing the measurement. Furthermore, some samples cannot reach a predetermined threshold value set in advance, and these abnormal samples significantly impede the efficiency of testing and measurement.
本発明は上記の諸点に鑑みなされたもので、と
くに検体によつてバラツキの多い測定を、より高
精度で、かつ最適の所要時間で測定を行なうこと
ができる血液凝固時間測定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 in view of the above-mentioned points, and it is an object of the present invention to provide a blood coagulation time measuring device that can perform measurements that vary widely depending on the specimen with higher accuracy and in an optimal amount of time. The purpose is to
上記の目的を達成するために、本発明の血液凝
固時間測定装置は、第５図に示すように、血漿試
料を入れた試料容器２を収納する収納部３、この
収納部３を開閉する遮光用蓋４、試料容器２の側
部に隣接して設けられた光源５および受光素子
６、試料容器２内の試料を所定の温度に保つ温度
制御素子７を有する検出ブロツク１と、
予め所定の温度に保たれた試薬を試料容器２に
添加し添加時にスイツチが入り測定開始信号を発
するスイツチ付ピペツト８と、
検出ブロツク１からの信号を検出する検出回路
１０と、
測定項目の選択や種々の条件を入力させるため
のキーボードスイツチ１１と、
スイツチ付ピペツト８および検出回路１０に接
続されたスタート信号発生回路１２と、
キーボードスイツチ１１に接続された日付変更
手段１３および測定項目変更手段１４と、
日付変更手段１３および測定項目変更手段１４
に接続された日付・測定項目等記憶手段１５と、
検出回路１０に測定値書込手段１６、測定値記
憶手段１７を介して接続された計算手段１８と、
測定値記憶手段１７および日付・測定項目等記
憶手段１５に接続された表示手段および印字手段
とからなり、
測定項目変更手段１４と計算手段１８とが接続
され、測定項目変更手段１４と検出回路１０とが
接続されて、時間とともに測定時間間隔を広げ、
所定のインターバルでそれ以前に凝固が生じ完了
したか否かを判定し、未完の場合はさらに測定を
続けるようにしたことを特徴としている。
In order to achieve the above object, the blood coagulation time measuring device of the present invention, as shown in FIG. a detection block 1 having a lid 4, a light source 5 and a light receiving element 6 provided adjacent to the side of the sample container 2, a temperature control element 7 for keeping the sample in the sample container 2 at a predetermined temperature; A pipette with a switch 8 that adds a reagent maintained at a temperature to the sample container 2 and is turned on at the time of addition to issue a measurement start signal, a detection circuit 10 that detects the signal from the detection block 1, and a detection circuit 10 that selects measurement items and performs various operations. A keyboard switch 11 for inputting conditions; a start signal generation circuit 12 connected to the pipette with switch 8 and the detection circuit 10; a date change means 13 and a measurement item change means 14 connected to the keyboard switch 11; Changing means 13 and measurement item changing means 14
date/measurement item storage means 15 connected to the detection circuit 10 via the measurement value writing means 16 and measurement value storage means 17; the measurement value storage means 17 and the date/measurement It consists of display means and printing means connected to item storage means 15, measurement item change means 14 and calculation means 18 are connected, measurement item change means 14 and detection circuit 10 are connected, and measurements are made over time. Increase the time interval
It is characterized in that it is determined at a predetermined interval whether or not coagulation has occurred and has been completed before that time, and if it is not completed, the measurement is continued further.
第５図において、１は検出ブロツクで、この検
出ブロツクは血漿試料を入れた試料容器２を収納
する収納部３、この収納部３を開閉する遮光用蓋
４、試料容器２の側部に隣接して設けられた光源
５および受光素子６、試料容器２内の試料を所定
の温度に保つ温度制御素子７を有している。８は
スイツチ付ピペツトで、予め所定の温度に保たれ
た試薬を試料容器２に添加し、添加時にスイツチ
が入り測定開始信号を発するようになつている。
受光素子６には、検出ブロツク１からの信号を検
出する検出回路１０が接続されている。１１は測
定項目の選択や種々の条件を入力させるためのキ
ーボードスイツチである。スイツチ付ピペツト８
および検出回路１０にはスタート信号発生回路１
２が接続され、キーボードスイツチ１１には日付
変更手段１３および測定項目変更手段１４が接続
され、日付変更手段１３および測定項目変更手段
１４には日付・測定項目等記憶手段１５が接続さ
れている。さらに前記検出回路１０には測定値書
込手段１６、測定値記憶手段１７を介して計算手
段１８が接続され、測定値記憶手段１７および日
付・測定項目等記憶手段１５に、表示手段および
印字手段が接続されている。この表示手段は表示
制御手段２０と表示器２１とからなり、印字手段
は印字制御手段２２とプリンタ２３とからなつて
いる。また測定項目変更手段１４と計算手段１８
とが接続され、測定項目変更手段１４と検出回路
１０とが接続されて、時間とともに測定時間間隔
を広げ所定のインターバルでそれ以前に凝固が生
じ完了したか否かを判定し、未完の場合はさらに
測定を続けるように構成されている。２４は温度
制御回路、２５は試薬容器、２６は電源回路であ
る。 In FIG. 5, 1 is a detection block, which includes a storage section 3 that stores a sample container 2 containing a plasma sample, a light-shielding lid 4 that opens and closes this storage section 3, and a side adjacent to the sample container 2. The sample container 2 has a light source 5 and a light receiving element 6, and a temperature control element 7 that maintains the sample in the sample container 2 at a predetermined temperature. Reference numeral 8 denotes a pipette with a switch, which adds a reagent maintained at a predetermined temperature to the sample container 2, and is turned on at the time of addition to issue a measurement start signal.
A detection circuit 10 for detecting a signal from the detection block 1 is connected to the light receiving element 6 . 11 is a keyboard switch for selecting measurement items and inputting various conditions. Pipette with switch 8
and the detection circuit 10 has a start signal generation circuit 1.
2 is connected to the keyboard switch 11, a date changing means 13 and a measurement item changing means 14 are connected, and a date/measurement item storage means 15 is connected to the date changing means 13 and the measurement item changing means 14. Further, a calculation means 18 is connected to the detection circuit 10 via a measurement value writing means 16 and a measurement value storage means 17, and a display means and a printing means are connected to the measurement value storage means 17 and the date/measurement item storage means 15. is connected. The display means consists of a display control means 20 and a display 21, and the printing means consists of a print control means 22 and a printer 23. Also, the measurement item changing means 14 and the calculation means 18
are connected, and the measurement item changing means 14 and the detection circuit 10 are connected, and the measurement time interval is increased over time, and it is determined at a predetermined interval whether or not coagulation has occurred and completed before that time, and if it is not completed, It is configured to continue making further measurements. 24 is a temperature control circuit, 25 is a reagent container, and 26 is a power supply circuit.
上記のように構成された装置において、予め所
定の温度に保たれた血漿試料に、同様に温度をコ
ントロールされた試薬が、スイツチ付ピペツト８
により添加されると、測定開始時間が設定され、
遮光用蓋４を閉じると測定が開始され、測定値は
検出回路１０から計算手段１８に送られ刻々と記
憶される。なお、遮光用蓋４が開いているときに
は、外光の影響を受けるため、測定が不能である
が、遮光用蓋４を閉じた時点から、光学的測定が
可能となる。これらの測定値は、表示手段を通し
てモニタすることも可能である。曲線が変化して
一定の値をとるようになり飽和状態に達すると、
検出回路１０に指令を出して測定を終了させると
同時に、表示器１２に測定が終了したことを表示
する。以上の最終測定値（飽和値）を100％とし
演算が行なわれ、記憶手段の残りのスペースに演
算結果が再記憶される。予めキーボードスイツチ
１１により、20％、50％、80％などの値を持つと
きの時間を、結果として印字や表示するように設
定しておけば、それぞれの値が算定される。たと
えば第６図に示すような正常な検体、あるいは第
７図に示すような異常な検体においても、20％、
50％、80％などの算定は容易であり、このうち80
％近辺にセツトしたときの値は、従来の用手法に
よつて測定したときの凝固時間と良く一致する。
In the apparatus configured as described above, a reagent whose temperature is also controlled is added to a plasma sample that has been kept at a predetermined temperature in advance through a pipette with a switch 8.
When added, the measurement start time is set,
When the light-shielding lid 4 is closed, measurement is started, and the measured values are sent from the detection circuit 10 to the calculation means 18 and stored every moment. Note that when the light-shielding lid 4 is open, measurement is impossible due to the influence of external light, but optical measurement becomes possible from the time the light-shielding lid 4 is closed. These measurements can also be monitored through display means. When the curve changes and takes a constant value and reaches saturation,
At the same time as issuing a command to the detection circuit 10 to end the measurement, the display 12 indicates that the measurement has ended. Calculation is performed with the final measured value (saturation value) as 100%, and the calculation result is stored again in the remaining space of the storage means. If the keyboard switch 11 is set in advance to print or display the time when the value is 20%, 50%, 80%, etc. as a result, each value can be calculated. For example, in normal specimens as shown in Figure 6 or abnormal specimens as shown in Figure 7, 20%
It is easy to calculate 50%, 80%, etc., of which 80%
%, the values are in good agreement with the clotting times measured by conventional techniques.
以上の％値による測定結果の算定は、装置自体
の誤差、たとえばランプの劣化、受光部の変質、
調整の不備などによらず、常に一定の値を結果と
して出力するので、非常に有効である。 Calculation of measurement results using the above percentage values is due to errors in the device itself, such as deterioration of the lamp, deterioration of the light receiving part, etc.
It is extremely effective because it always outputs a constant value as a result, regardless of any imperfections in adjustment.
本発明は上記のように構成されているので、従
来の凝固時間の終了点（エンドポイント）がレベ
ルや変曲点の検知であつたものを、％表示にする
ことにより、従来法との相関は勿論、測定上の再
現性が飛躍的に向上する。また装置のドリフトな
どによる誤差が軽減されるとともに、異常検体の
測定が容易であるなどの効果がある。 Since the present invention is configured as described above, the end point of the clotting time in the conventional method was the detection of the level or inflection point, but by expressing it in percentage, the correlation with the conventional method can be improved. Of course, the reproducibility of measurements is dramatically improved. Furthermore, errors due to device drift are reduced, and abnormal samples can be easily measured.
前述のように従来の装置においては、主として
検出回路の出力をレコーダに記録するとともに、
所定の閾値を越える点を凝固点として判定してい
たのに対し、本発明の装置においては、それぞれ
の時間における検出回路１０の出力がメモリーに
記憶される。 As mentioned above, in conventional devices, the output of the detection circuit is mainly recorded on the recorder, and
Whereas a point exceeding a predetermined threshold value was determined as a freezing point, in the apparatus of the present invention, the output of the detection circuit 10 at each time is stored in a memory.
本発明の実施例として、第８図に示すように、
０〜60秒までは0.1秒間隔で測定値がメモリーに
送られ記憶される。60秒の時点で、第１回目の判
定、すなわち検出回路１０の出力が零の平坦な状
態から変化が生じ、再び所定の出力値で再び平坦
な状態に収斂しているかどうかの判定が行なわれ
る。もしも未完の場合においては、続いて同様の
測定が行なわれるが、測定間隔は0.2秒に切り換
えられる。これを120秒まで続け、もし凝固が完
了していない場合には、以下、
120〜240秒：0.5秒間隔
240〜600秒：１秒間隔
600〜1440秒：２秒間隔
1440〜3600秒：５秒間隔
とし、3600秒、すなわち60分までは測定が実施で
きるようにする。
As an embodiment of the present invention, as shown in FIG.
From 0 to 60 seconds, measured values are sent to memory and stored at 0.1 second intervals. At the time of 60 seconds, the first determination is made, that is, whether the output of the detection circuit 10 has changed from a flat state of zero and has converged to a flat state again at a predetermined output value. . If it is not completed, the same measurement is performed subsequently, but the measurement interval is switched to 0.2 seconds. Continue this until 120 seconds, and if coagulation is not completed, do the following: 120 to 240 seconds: 0.5 second intervals 240 to 600 seconds: 1 second intervals 600 to 1440 seconds: 2 second intervals 1440 to 3600 seconds: 5 Measurements can be taken at intervals of seconds, up to 3600 seconds, or 60 minutes.
また測定間隔の別の実施例として、第９図に示
すように、60秒までは0.1秒間隔とし、それ以降
を曲線的に測定間隔を変える方法がある。この方
法は１つ目の実施例（第８図）に比べ、測定を終
了するか否かを判断する点近傍における測定結果
の数値（時間）自体の増加がより自然であり、好
ましい実施例である。 As another example of the measurement interval, as shown in FIG. 9, there is a method in which the measurement interval is set at 0.1 second intervals up to 60 seconds, and thereafter the measurement interval is changed in a curved manner. In this method, compared to the first embodiment (Fig. 8), the numerical value (time) of the measurement result itself increases more naturally near the point at which it is judged whether or not to end the measurement, and is a preferred embodiment. be.
第８図のように測定間隔を階段状に広げて行つ
た場合には、ある時点を境にして、それまで例え
ば、１秒間隔で測定していたものが急に２秒間隔
で測定することになり、測定結果として得られる
曲線に不連続点が生ずる可能性がある。もちろん
これは、測定結果を微視的に観察した場合の話で
あつて、測定結果の曲線全体を眺めた場合には、
顕著な不連続点が認められるわけではなく、実用
上は全く問題ない。 When the measurement interval is expanded stepwise as shown in Figure 8, at a certain point, for example, what was previously being measured at 1-second intervals may suddenly be measured at 2-second intervals. , and there is a possibility that discontinuities may occur in the curve obtained as a measurement result. Of course, this is only when observing the measurement results microscopically, and when looking at the entire curve of the measurement results,
There are no noticeable discontinuities, and there is no problem in practice.
これに対し、第９図のように測定間隔を曲線的
に広げて行つた場合には、測定間隔は連続的に変
化するので、測定結果に不連続点が生ずる可能性
が全く無く、より自然な測定曲線が得られる。 On the other hand, when the measurement interval is expanded in a curved manner as shown in Figure 9, the measurement interval changes continuously, so there is no possibility of discontinuities occurring in the measurement results, making it more natural. A measurement curve can be obtained.
また、本来、測定結果（凝固終了時間）が増加
するにつれて測定誤差も大きくなりやすいが、た
とえば測定結果が10秒の場合、0.5秒の測定誤差
は相対的に大きいものと評価されるが、測定結果
が１分の場合、0.5秒の測定誤差は相対的に小さ
い（影響が少ない）ものと評価される。したがつ
て測定時間が長くなつた場合に、測定間隔を広げ
て測定精度を落としたとしても、測定結果に与え
る影響の程度は小さい。ゆえに、第８図または第
９図に示すいずれの方法を用いても、測定間隔を
広げることに対し何ら不都合は生じない。以上の
測定間隔ごとの吸光度あるいは散乱光の読みは、
それぞれの測定時間に対応するメモリーに書き込
まれる。測定時間が延びた場合には、測定時間間
隔が広がるようになつているので、不要な測定値
を記憶させることがなく、メモリー容量を膨大化
させずにすむ。 In addition, measurement errors tend to increase as the measurement result (coagulation completion time) increases, but for example, if the measurement result is 10 seconds, a measurement error of 0.5 seconds is evaluated to be relatively large; If the result is 1 minute, a measurement error of 0.5 seconds is considered relatively small (has little effect). Therefore, when the measurement time becomes longer, even if the measurement accuracy is lowered by increasing the measurement interval, the degree of influence on the measurement results is small. Therefore, using either method shown in FIG. 8 or FIG. 9, there is no problem in increasing the measurement interval. The absorbance or scattered light reading for each measurement interval above is as follows:
It is written to the memory corresponding to each measurement time. When the measurement time is extended, the measurement time interval is expanded, so unnecessary measurement values are not stored and the memory capacity does not need to be increased.
第１０図は本発明の装置全体の動作を示すフロ
ーチヤート、第１１図は本発明の装置における測
定時の動作を示すフローチヤートである。それぞ
れの判定を行なう点で、もしそれ以前に凝固が完
了していることが判定されると、その時点で測定
は中止される。すなわち、その判定点以前におい
て、検出出力が変化し再度所定の値に収束してい
ることであり、時間に対する微分した値が零から
変化し、ピークを通り再び零になつていることで
ある。続いて、その時点までのメモリー内に書き
込まれた検出出力の値のうち、初期の値を０％、
収束した最終の値を100％とし、それぞれの測定
時間におけるパーセンテージが表示あるいは印字
され、同時に凝固時間（凝固終了時間）として設
定されたパーセント値（たとえば80％値）を取る
測定時間が、凝固終了時間または凝固時間として
表示、印字される。 FIG. 10 is a flow chart showing the operation of the entire apparatus of the present invention, and FIG. 11 is a flow chart showing the operation of the apparatus of the present invention during measurement. If it is determined that coagulation is complete before each determination is made, the measurement is stopped at that point. That is, before that decision point, the detection output changes and converges to a predetermined value again, and the value differentiated with respect to time changes from zero, passes through a peak, and becomes zero again. Next, among the detection output values written in the memory up to that point, the initial value is set to 0%,
The final converged value is taken as 100%, and the percentage at each measurement time is displayed or printed.At the same time, the measurement time that takes the percentage value (e.g. 80% value) set as the coagulation time (coagulation end time) is the end of coagulation. Displayed and printed as time or clotting time.
以上のように本発明の装置によれば、従来の血
液凝固測定装置が、予め設定された閾値を越えた
ときに測定を終了させるのに対し、60秒、120秒、
240秒…という具合に所定の時間インターバルを
取つて、その時点以前に凝固が完了しているか否
かを判定し、なおかつ、従来の凝固測定装置が所
定の閾値を取つたときまでの時間を、凝固時間と
しているのに対し、最終の値を100％、初期を０
％とし、所定のパーセント値（たとえば80％値）
を取つたときの時間を、凝固時間としている点が
大きく異なる。したがつて、凝固時間の決定はリ
アルタイムではなく、後の演算で得られるが、そ
の反面、精度は非常に高く、かつ従来の用手法と
の相関も非常に高い。さらに本実施例において
は、最大60分までの自動的な測定時間の延長が行
なえるが、これは人手によらず装置が自動的に行
なうものであり、かつ時間の経過につれて測定精
度が低下するが、それに伴い測定時間間隔も広が
り、不要な測定値の記憶の膨大化を防止してい
る。とくに曲線的に測定時間間隔を広げて行く方
法に対しては、測定時間間隔を無視し、等間隔目
盛上にそれぞれ％値を表示すると、その変化の具
合が０〜60秒と同様に明確に現われる。したがつ
て、印字、表示の結果がとても見易いという利点
が生ずる。 As described above, according to the device of the present invention, whereas conventional blood coagulation measuring devices terminate measurement when a preset threshold is exceeded,
A predetermined time interval such as 240 seconds is taken, and it is determined whether coagulation has been completed before that time, and the time until the conventional coagulation measuring device reaches a predetermined threshold value is calculated. The final value is 100% and the initial value is 0.
% and a given percentage value (e.g. 80% value)
The major difference is that the solidification time is defined as the time it takes to remove the liquid. Therefore, the determination of the coagulation time is not performed in real time but is obtained by subsequent calculations, but on the other hand, the accuracy is very high and the correlation with conventional methods is also very high. Furthermore, in this embodiment, the measurement time can be automatically extended to a maximum of 60 minutes, but this is done automatically by the device without manual intervention, and the measurement accuracy decreases as time passes. However, along with this, the measurement time interval also widens, which prevents the storage of unnecessary measurement values from becoming too large. In particular, for the method of increasing the measurement time interval in a curved manner, if you ignore the measurement time interval and display the percentage value for each on an equally spaced scale, the degree of change can be clearly seen as in 0 to 60 seconds. appear. Therefore, there is an advantage that the results of printing and display are very easy to see.
本発明は上記のように構成されているので、従
来の測定装置において凝固が生じ難い異常検体に
対しては、測定不能とかオーバーの表示のみで再
現の良い測定ができなかつたが、％値による凝固
完了点の設定、および測定間隔の自動変更と判定
時点での延長か終了かの判定などの採用により、
高精度でより効果的な測定が行なえるようにな
り、また測定値をグラフ化した場合、曲線的に測
定間隔を変更して行く方法を採用した場合、〔実
施例〕の項で説明したように、凝固の生ずる変化
の状態がより明確に観察できるという効果を有し
ている。
Since the present invention is configured as described above, conventional measuring devices can only display "unmeasurable" or "over" and cannot perform measurements with good reproducibility for abnormal samples that are difficult to coagulate. By setting the solidification completion point, automatically changing the measurement interval, and determining whether to extend or end at the judgment point,
It is possible to perform more accurate and more effective measurements, and when the measured values are graphed, the method of changing the measurement interval in a curved manner can be used as explained in the [Example] section. Another advantage is that the state of change that causes coagulation can be observed more clearly.
第１図および第２図は従来のレベル検知法の一
例を示すグラフ、第３図および第４図は従来の変
曲点を求める方法の一例を示すグラフ、第５図は
本発明の血液凝固時間測定装置の構成の一例を示
す説明図、第６図および第７図は測定原理を示す
グラフ、第８図および第９図は本発明の装置を用
いて測定した例を示すグラフ、第１０図は本発明
の装置全体の動作を示すフローチヤート、第１１
図は本発明の装置における測定時の動作を示すフ
ローチヤートである。
１……検出ブロツク、２……試料容器、３……
収納部、４……遮光用蓋、５……光源、６……受
光素子、７……温度制御素子、８……スイツチ付
ピペツト、１０……検出回路、１１……キーボー
ドスイツチ、１２……スタート信号発生回路、１
３……日付変更手段、１４……測定項目変更手
段、１５……日付・測定項目等記憶手段、１６…
…測定値書込手段、１７……測定値記憶手段、１
８……計算手段、２０……表示制御手段、２１…
…表示器、２２……印字制御手段、２３……プリ
ンタ、２４……温度制御回路、２５……試薬容
器、２６……電源回路。
Figures 1 and 2 are graphs showing an example of a conventional level detection method, Figures 3 and 4 are graphs showing an example of a conventional method for determining an inflection point, and Figure 5 is a graph showing an example of a conventional method for determining an inflection point. An explanatory diagram showing an example of the configuration of a time measuring device, FIGS. 6 and 7 are graphs showing the measurement principle, FIGS. 8 and 9 are graphs showing an example of measurement using the device of the present invention, and FIG. The figure is a flowchart showing the operation of the entire apparatus of the present invention, No. 11.
The figure is a flowchart showing the operation of the apparatus of the present invention during measurement. 1...Detection block, 2...Sample container, 3...
Storage section, 4...Light shielding lid, 5...Light source, 6...Light receiving element, 7...Temperature control element, 8...Pipette with switch, 10...Detection circuit, 11...Keyboard switch, 12... Start signal generation circuit, 1
3...Date changing means, 14...Measurement item changing means, 15...Date/measurement item etc. storage means, 16...
...Measurement value writing means, 17...Measurement value storage means, 1
8... Calculation means, 20... Display control means, 21...
... Display device, 22 ... Print control means, 23 ... Printer, 24 ... Temperature control circuit, 25 ... Reagent container, 26 ... Power supply circuit.
Claims (1)
部３、この収納部３を開閉する遮光用蓋４、試料
容器２の側部に隣接して設けられた光源５および
受光素子６、試料容器２内の試料を所定の温度に
保つ温度制御素子７を有する検出ブロツク１と、 予め所定の温度に保たれた試薬を試料容器２に
添加し添加時にスイツチが入り測定開始信号を発
するスイツチ付ピペツト８と、 検出ブロツク１からの信号を検出する検出回路
１０と、 測定項目の選択や種々の条件を入力させるため
のキーボードスイツチ１１と、 スイツチ付ピペツト８および検出回路１０に接
続されたスタート信号発生回路１２と、 キーボードスイツチ１１に接続された日付変更
手段１３および測定項目変更手段１４と、 日付変更手段１３および測定項目変更手段１４
に接続された日付・測定項目等記憶手段１５と、 検出回路１０に測定値書込手段１６、測定値記
憶手段１７を介して接続された計算手段１８と、 測定値記憶手段１７および日付・測定項目等記
憶手段１５に接続された表示手段および印字手段
とからなり、 測定項目変更手段１４と計算手段１８とが接続
され、測定項目変更手段１４と検出回路１０とが
接続されて、時間とともに測定時間間隔を広げ、
所定のインターバルでそれ以前に凝固が生じ完了
したか否かを判定し、未完の場合はさらに測定を
続けるようにしたことを特徴とする血液凝固時間
測定装置。[Claims] 1. A storage section 3 that stores a sample container 2 containing a plasma sample, a light-shielding lid 4 that opens and closes this storage section 3, a light source 5 provided adjacent to the side of the sample container 2, and A detection block 1 includes a light receiving element 6, a temperature control element 7 that keeps the sample in the sample container 2 at a predetermined temperature, and a reagent kept at a predetermined temperature in advance is added to the sample container 2, and a switch is turned on at the time of addition to start measurement. A pipette with a switch 8 that emits a signal, a detection circuit 10 that detects the signal from the detection block 1, a keyboard switch 11 that allows selection of measurement items and input of various conditions, and a pipette with a switch 8 and the detection circuit 10. The connected start signal generation circuit 12; the date change means 13 and the measurement item change means 14 connected to the keyboard switch 11; the date change means 13 and the measurement item change means 14.
date/measurement item storage means 15 connected to the detection circuit 10 via the measurement value writing means 16 and measurement value storage means 17; the measurement value storage means 17 and the date/measurement It consists of display means and printing means connected to item storage means 15, measurement item change means 14 and calculation means 18 are connected, measurement item change means 14 and detection circuit 10 are connected, and measurements are made over time. Increase the time interval
A blood coagulation time measuring device characterized in that it is determined at a predetermined interval whether or not coagulation has occurred and completed before that time, and if the coagulation is not completed, the measurement is continued further.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10342983A JPS59228167A (en) | 1983-06-09 | 1983-06-09 | Time measuring apparatus of blood coagulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10342983A JPS59228167A (en) | 1983-06-09 | 1983-06-09 | Time measuring apparatus of blood coagulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS59228167A JPS59228167A (en) | 1984-12-21 |
| JPH0365501B2 true JPH0365501B2 (en) | 1991-10-14 |
Family
ID=14353790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10342983A Granted JPS59228167A (en) | 1983-06-09 | 1983-06-09 | Time measuring apparatus of blood coagulation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59228167A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015098473A1 (en) * | 2013-12-25 | 2015-07-02 | 株式会社日立ハイテクノロジーズ | Automatic analysis device and analysis method |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102640004B (en) * | 2009-12-04 | 2015-04-15 | 株式会社日立高新技术 | Blood coagulation analyzer |
| US20210382080A1 (en) * | 2018-10-10 | 2021-12-09 | Lsi Medience Corporation | Analyzer |
-
1983
- 1983-06-09 JP JP10342983A patent/JPS59228167A/en active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015098473A1 (en) * | 2013-12-25 | 2015-07-02 | 株式会社日立ハイテクノロジーズ | Automatic analysis device and analysis method |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS59228167A (en) | 1984-12-21 |
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