JPH0627115A - Method and apparatus for measuring blood coagulation time - Google Patents

Method and apparatus for measuring blood coagulation time

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Publication number
JPH0627115A
JPH0627115A JP20720692A JP20720692A JPH0627115A JP H0627115 A JPH0627115 A JP H0627115A JP 20720692 A JP20720692 A JP 20720692A JP 20720692 A JP20720692 A JP 20720692A JP H0627115 A JPH0627115 A JP H0627115A
Authority
JP
Japan
Prior art keywords
time
amount
scattered light
value
reagent
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.)
Granted
Application number
JP20720692A
Other languages
Japanese (ja)
Other versions
JP2934557B2 (en
Inventor
Hisahide Hiura
久英 日裏
Masahiro Okuda
昌宏 奥田
Katsumoto Matoba
功始 的場
Hiroshi Yagyu
宏 柳生
Michio Tsukahara
通男 塚原
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.)
Sysmex International Reagents Co Ltd
Original Assignee
International Reagents Corp
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 International Reagents Corp filed Critical International Reagents Corp
Priority to JP20720692A priority Critical patent/JP2934557B2/en
Publication of JPH0627115A publication Critical patent/JPH0627115A/en
Application granted granted Critical
Publication of JP2934557B2 publication Critical patent/JP2934557B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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  • Investigating Or Analysing Biological Materials (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

PURPOSE:To obtain a method and an apparatus for measuring blood coagulation time wherein measurement is not impossible even with an abnormal sample to be measured such as a sample having low fibrinogen concentration, and coagulation time can be measured stably and correctly in a short time without a fluctuation in coagulation time. CONSTITUTION:This is a method for measuring coagulation time T by detecting a scattered light amount while a certain light amount is applied to blood plasma to be measured with reagent mixed, wherein a scattered light amount Vf when predetermined certain regulated time Tf has elapsed from a time T0 when the reagent is mixed is measured, and difference between the scattered light amount Vf at the regulated time elapsed time Tf and a scattered light amount V0 at the reagent mixed time T0 is calculated. Time T from the reagent mixed time until when the scattered light amount has increased by an amount corresponding to 1/N (where N is a number of 1 or more which has been predetermined) of the difference is blood coagulation time.

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【産業上の利用分野】本発明は血液の凝固時間を測定す
る方法とその装置に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method and apparatus for measuring blood coagulation time.

【0002】[0002]

【従来の技術】血液の凝固時間を測定する方法として、
従来、血漿に試薬を混合し、これに側方から光を当てな
がらその散乱光量の状態変化を測定し、凝固時間を得る
方法、いわゆる光散乱方式の測定方法が提供されてい
る。そしてこの光散乱方式の測定方法という大きな分類
においては、次の、に示す散乱光量をそのまま利用
する方法の他、、に示す散乱光量の微分値を利用す
る方法が従来提供されている。 .散乱光量の状態がある一定量になる時刻までの時間
をもって凝固時間とする方法。 .散乱光量の最小値と最大値の差の一定割合となる時
刻までの時間をもって凝固時間とする方法(特公平3-34
592 )。 .経時的に変化する散乱光量の微分値がピークとなる
時刻までの時間をもって凝固時間とする方法(極大値法
とする)。 .微分値のピークを求め、その1/Nに相当する時刻
をまでの時間をもって凝固時間とする方法(特公昭61-1
0777)。
2. Description of the Related Art As a method for measuring the coagulation time of blood,
BACKGROUND ART Conventionally, there has been provided a method of obtaining a coagulation time by mixing a reagent with plasma and measuring the state change of the scattered light amount while irradiating light to the plasma from the side, that is, a so-called light scattering method. In addition, in the broad classification of the measurement method of the light scattering method, in addition to the following method of directly using the scattered light amount, the method of using the differential value of the scattered light amount is shown. . A method in which the time until the time when the amount of scattered light reaches a certain amount is the coagulation time. . A method of setting the coagulation time by the time until a certain ratio of the difference between the minimum and maximum values of scattered light is reached (Japanese Patent Publication No. 3-34).
592). . A method in which the coagulation time is defined as the time until the time when the differential value of the scattered light amount that changes with time reaches a peak (the maximum value method). . A method of obtaining the peak of the differential value and setting the time corresponding to 1 / N as the time until the coagulation time (Japanese Patent Publication No. 61-1).
0777).

【0003】[0003]

【発明が解決しようとする課題】ところが、上記の方
法では、被検試料(検体)によっては一定量に達しない
ものが生じたり、また基底レベル自体のバラツキを補正
できないといった問題があった。またの方法において
は、同様に試料によってはダラダラと光量が変化し、最
大値を検出するまで時間を要したり、また例えばフィブ
リノゲン濃度の低い被検試料等、明確な最大値を示さな
い検体に対しては測定できない問題があった。また、
の方法においては、光量の変化(微分値)が時間に対
して直線的(一次関数的)であるような検体については
微分値のピークを得ることが困難となる問題があった。
またこのような検体についてはピークが2以上生じたり
する問題があった。さらに低フィブリノゲン濃度の被検
試料のような異常検体では光量変化量が小さいため、最
大変化速度(微分値のピーク)を的確にとらえられない
問題があった。
However, in the above method, there are problems that some samples (specimens) do not reach a certain amount, and variations in the base level itself cannot be corrected. In the other method, similarly, the light intensity changes depending on the sample, and it takes time to detect the maximum value, or for a sample that does not show a clear maximum value, such as a test sample with low fibrinogen concentration. On the other hand, there was a problem that could not be measured. Also,
The method (1) has a problem that it is difficult to obtain the peak of the differential value for a sample in which the change in the light amount (differential value) is linear (linear function) with respect to time.
Further, such a sample has a problem that two or more peaks occur. Further, in an abnormal sample such as a test sample having a low fibrinogen concentration, since the amount of change in light amount is small, there is a problem that the maximum change rate (peak of differential value) cannot be accurately captured.

【0004】そこで本発明は上記従来の欠点を解消し、
低フィブリノゲン濃度の被検試料等の異常な被検試料に
よっても測定不能となったりすることなく、また凝固時
間をバラツキなく安定して、また正確に、短時間で測定
することができる血液凝固時間測定方法とその装置の提
供を目的とする。
Therefore, the present invention solves the above-mentioned conventional drawbacks,
Blood coagulation time that can be measured accurately and in a short time without the measurement being impossible due to abnormal test samples such as those with low fibrinogen concentration, and also with stable and stable coagulation time. The purpose is to provide a measuring method and its device.

【0005】[0005]

【課題を解決するための手段】上記目的を達成するた
め、本発明の血液凝固時間測定方法は、試薬を混合した
被検血漿に一定光量の光を照射しながらその散乱光量を
検出することにより凝固時間を測定する方法であって、
前記試薬の混合時点から予め定めた一定の規定時間の経
過時点における散乱光量を測定し、該規定時間経過時点
での散乱光量と試薬混合時点での散乱光量との差を演算
し、該差の1/N(Nは予め定めた1以上の数)に相当
する散乱光量だけ増加した時点までの前記試薬混合時点
からの時間をもって血液凝固時間とすることを第1の特
徴としている。また本発明の血液凝固時間測定装置は、
被検血漿と試薬を入れるセル体と、該セル体内へ外から
一定光量の光を照射する射光手段と、セル体内からの散
乱光量を検出する光量検出手段と、該光量検出手段によ
る検出量を増幅する増幅手段と、該増幅手段で増幅され
た検出量を一定の微小時間間隔でサンプリングしてデジ
タル化するA−D変換手段と、該A−D変換手段からの
入力値を試薬混合時点から予め定めた一定の規定時間の
経過時点まで経時的に記憶すると共に該規定時間経過時
点での散乱光量と前記試薬混合時点での散乱光量との差
を求めて該差の1/N(Nは予め定めた1以上の数)に
相当する散乱光量だけ増加した時点までの前記試薬混合
時点からの時間を演算するマイクロコンピュータと、演
算結果を示す表示手段とを少なくとも有することを第2
の特徴としている。また本発明の血液凝固時間測定方法
は、試薬を混合した被検血漿に一定光量の光を照射しな
がらその散乱光量を検出することにより凝固時間を測定
する方法であって、前記散乱光量を経時的に検出すると
共にその微分値を演算し、前記試薬の混合時点から微分
値が予め定めた一定の規定値に達するまでの時間をもっ
て血液凝固時間とすることを第3の特徴としている。ま
た本発明の血液凝固時間測定方法は、上記第3の特徴に
加えて、規定値を含む微分曲線の山が連続して一定以上
の微分値を一定時間以上持続することを条件として、該
微分曲線の山に存在する前記規定値に達するまでの時間
をもって血液凝固時間とすることを第4の特徴としてい
る。また本発明の血液凝固時間測定方法は、上記第3の
特徴に加えて、規定値を含む微分曲線の山が一定以上の
面積を有することを条件として、該微分曲線の山に存在
する前記規定値に達するまでの時間をもって血液凝固時
間とすることを第5の特徴としている。また本発明の血
液凝固時間測定装置は、被検血漿と試薬を入れるセル体
と、該セル体内へ外から一定光量の光を照射する射光手
段と、セル体内からの散乱光量を検出する光量検出手段
と、該光量検出手段による検出量を増幅する増幅手段
と、該増幅手段で増幅された検出量を一定の微小時間間
隔でサンプリングしてデジタル化するA−D変換手段
と、該A−D変換手段からの入力値を微分演算すると共
に得られた微分値が予め記憶させておいた一定の規定値
に達するまでの試薬混合時点からの時間を演算するマイ
クロコンピュータと、演算結果を示す表示手段とを少な
くとも有することを第6の特徴としている。
In order to achieve the above object, the method for measuring blood coagulation time of the present invention comprises detecting the amount of scattered light while irradiating a test plasma mixed with a reagent with a constant amount of light. A method of measuring coagulation time, comprising:
The amount of scattered light at the time when a predetermined fixed time has elapsed from the time of mixing the reagent is measured, and the difference between the amount of scattered light at the time when the specified time has elapsed and the amount of scattered light at the time of reagent mixing is calculated, and the difference The first feature is that the time from the reagent mixing time until the time when the scattered light amount corresponding to 1 / N (N is a predetermined number of 1 or more) is increased is the blood coagulation time. Further, the blood coagulation time measuring device of the present invention,
The cell body containing the test plasma and the reagent, the light emitting means for irradiating the cell body with a constant amount of light from the outside, the light amount detecting means for detecting the scattered light amount from the cell body, and the detection amount by the light amount detecting means Amplifying means for amplifying, A-D converting means for sampling and digitizing the detected amount amplified by the amplifying means at constant minute time intervals, and input values from the A-D converting means from the time of mixing the reagents. The difference between the amount of scattered light at the time when the specified time has elapsed and the amount of scattered light at the time of mixing the reagent is calculated by 1 / N (N is Secondly, at least a microcomputer for calculating the time from the reagent mixing time until the time when the amount of scattered light corresponding to a predetermined number 1 or more) is increased, and a display means for displaying the calculation result are provided.
It is a feature of. Further, the blood coagulation time measuring method of the present invention is a method of measuring the coagulation time by detecting the amount of scattered light while irradiating a test plasma mixed with a reagent with a constant amount of light, and the scattered light amount is measured with time. The third characteristic is that the blood coagulation time is defined as the time from the time when the reagents are mixed to the time when the differential value reaches a predetermined fixed value. In addition to the third feature, the method for measuring blood coagulation time according to the present invention is characterized in that, in addition to the third feature, the peak of the differential curve including the specified value continuously maintains a differential value of a certain value or more for a certain time or more. The fourth feature is that the time until the specified value existing in the peak of the curve is reached is the blood coagulation time. The blood coagulation time measuring method of the present invention is, in addition to the third feature described above, provided that the peak of the differential curve including the specified value has a certain area or more, and the peak existing in the peak of the differential curve is specified. The fifth characteristic is that the time until the value is reached is the blood coagulation time. Further, the blood coagulation time measuring device of the present invention comprises a cell body containing a test plasma and a reagent, a light emitting means for irradiating the cell body with a constant amount of light from the outside, and a light amount detection for detecting a scattered light amount from the cell body. Means, an amplifying means for amplifying the detected amount by the light amount detecting means, an A-D converting means for sampling and digitizing the detected amount amplified by the amplifying means at a constant minute time interval, and the A-D A microcomputer for performing a differential operation on the input value from the converting means and for calculating a time from the reagent mixing time until the obtained differential value reaches a predetermined memorized predetermined value, and a display means for showing the operation result. The sixth feature is that at least and are included.

【0006】[0006]

【作用】上記本発明の第1の特徴によれば、試薬の混合
時点から予め定めた一定の規定時間経過時点までの散乱
光量が経時的に記憶され、該規定時間経過時点での散乱
光量と試薬混合時点での散乱光量との差が求められる。
そしてその差の1/Nに相当する光量だけ増加した時点
までの試薬混合時点からの時間が演算され、得られる演
算結果値が凝固時間とされる。この第1の特徴において
は、散乱光量の増加がダラダラと生じて最大値を検出す
るまでに長時間を要するフィブリノゲン濃度の被検血漿
等や或いはまた散乱光量のピークが複数回生じる被検血
漿等、散乱光量の最大値を利用する凝固時間の測定方法
では測定が実質上困難な被検血漿に対しても、散乱光量
の最大値を用いることなく、予め定めた規定時間経過時
点での散乱光量を用いることで、確実に凝固時間を得る
ことができ、また各凝固時間の比較も有効にすることが
できる。また本発明の第2の特徴によれば、試薬の混合
時点から予め定めた規定時間経過時点での散乱光量と前
記試薬混合時点での散乱光量との差を演算し、該差の1
/N(Nは予め定めた1以上の数)に相当する散乱光量
だけ増加した時点までの前記試薬混合時点からの時間を
もって血液凝固時間とする上記第1の特徴に示す血液凝
固時間測定方法を実行することができる。また上記本発
明の第3の特徴によれば、試薬の混合時点では、未だ散
乱光量は変化しないので、微分値はゼロである。そして
凝固反応が開始されると散乱光量が増加してゆき、微分
値もまたゼロから増加してゆく。そして凝固反応の進行
とに共に微分値が次第に増加し、通常はやがてピークを
迎え、その後減少して再びゼロになる。前記ピークは凝
固反応が最大に行われていると考えられる時点である。
また最終的にゼロになることで凝固反応が終了したと考
えられる。前記凝固反応は、反応初期から暫くの間は比
較的確実に進行するので、微分値もまた反応開始のゼロ
から暫くの期間は比較的確実に上り勾配(増加)を得る
こととなる。したがって、そのような確実に現れやすい
反応開始からの微分値の上り勾配(増加)をとらえ、微
分値の立ち上がりから予め定めた一定の規定値に達した
時刻までの、試薬混合時点からの時間をもって血液凝固
時間とすることで、被検血漿の種類によらず確実に血液
凝固時間を得ることができる。また微分値のピークをと
らえてピークまでの時間を血液凝固時間とするもので
は、ピークが複数生じる場合があって、いずれのピーク
を採用するかで血液凝固時間がバラツキやすいのに比
べ、この第3の特徴による場合は、反応初期における確
実な変化を観測しているため、測定にバラツキが生じに
くい。また、微分値がゼロから一定の規定値にまで立ち
上がった時刻までの時間を測定すればよいので、微分値
のピークまでの時間を必要とするもの等に対して、測定
時間が短縮できる。また上記第4の特徴によれば、第3
の特徴による作用に加えて、測定時のノイズその他によ
って、疑似の微分曲線の山が生じることがあっても、そ
の山が連続して一定以上の微分値を一定時間以上持続し
ない限り、測定には採用されないので、事実上の疑似曲
線による測定ミスを排除することができる。また上記第
5の特徴によれば、第3の特徴による作用に加えて、測
定時のノイズその他によって、疑似の微分曲線の山が生
じることがあっても、その山が一定以上の面積を有しな
い限り、測定には採用されないので、この場合にも、事
実上の疑似曲線による測定ミスを排除することができ
る。また上記第6の特徴に示す本発明の装置によれば、
試薬の混合時点から微分値が予め定めた一定の規定値に
達するまでの時間をもって血液凝固時間とする前記第3
の特徴に示す血液凝固時間測定方法を実行することがで
きる。
According to the first feature of the present invention, the amount of scattered light from the time when the reagents are mixed to the time when a predetermined fixed time elapses is stored over time, and the amount of scattered light at the time when the specified time elapses is stored. The difference from the amount of scattered light at the time of mixing the reagents is obtained.
Then, the time from the reagent mixing time until the time when the light amount corresponding to 1 / N of the difference is increased is calculated, and the obtained calculation result value is set as the coagulation time. In the first feature, a test plasma having a fibrinogen concentration, which takes a long time to detect the maximum value due to an increase in scattered light amount, or a test plasma having a plurality of scattered light amount peaks, etc. The amount of scattered light at the time when a predetermined specified time elapses without using the maximum value of scattered light, even for test plasma that is practically difficult to measure with the method of measuring the coagulation time using the maximum value of scattered light By using, it is possible to reliably obtain the coagulation time, and it is possible to effectively compare the respective coagulation times. Further, according to the second feature of the present invention, the difference between the scattered light amount at the time when a predetermined prescribed time has elapsed from the time of mixing the reagent and the scattered light amount at the time of mixing the reagent is calculated, and the difference of 1 is calculated.
/ N (N is a predetermined number equal to or greater than 1), the blood coagulation time is measured by the time from the reagent mixing time until the time when the amount of scattered light is increased. Can be executed. In addition, according to the third feature of the present invention, since the amount of scattered light does not change yet at the time of mixing the reagents, the differential value is zero. When the coagulation reaction starts, the amount of scattered light increases, and the differential value also increases from zero. The differential value gradually increases with the progress of the coagulation reaction, usually reaches a peak, and then decreases and becomes zero again. The peak is the time when the coagulation reaction is considered to be maximal.
It is also considered that the coagulation reaction has ended when it finally reaches zero. Since the coagulation reaction relatively reliably proceeds from the initial stage of the reaction for a while, the differential value also relatively reliably obtains an upslope (increase) during a period from zero at the start of the reaction. Therefore, by grasping the upward gradient (increase) of the differential value from the start of the reaction that is likely to occur reliably, the time from the reagent mixing time from the rise of the differential value to the time when it reaches a predetermined fixed value is set. By setting the blood coagulation time, it is possible to reliably obtain the blood coagulation time regardless of the type of plasma to be tested. Also, in the case where the peak of the differential value is captured and the time to the peak is used as the blood coagulation time, multiple peaks may occur, and the blood coagulation time tends to vary depending on which peak is used. In the case of the characteristic of No. 3, since a reliable change is observed in the early stage of the reaction, the measurement is less likely to vary. Further, since it is sufficient to measure the time from the time when the differential value rises from zero to a certain specified value, the measurement time can be shortened for those that require the time to the peak of the differential value. According to the above-mentioned fourth characteristic, the third
In addition to the function of the above, even if a peak of the pseudo differential curve is generated due to noise or the like at the time of measurement, as long as the peak does not continuously maintain a differential value of a certain value or more for a certain time or more, Is not adopted, it is possible to eliminate measurement errors due to the virtual curve. Further, according to the fifth feature, in addition to the action of the third feature, even if a peak of the pseudo differential curve is generated due to noise or the like at the time of measurement, the peak has a certain area or more. Unless it is not used for the measurement, the measurement error due to the virtual curve can be eliminated in this case as well. Further, according to the device of the present invention shown in the sixth feature,
The third aspect in which the blood coagulation time is defined as the time from when the reagents are mixed to when the differential value reaches a predetermined constant value.
It is possible to execute the blood coagulation time measuring method shown in the characteristics of.

【0007】[0007]

【実施例】図1は本発明装置の実施例を示す概略構成
図、図2は本発明の方法を説明する散乱光量変化曲線
図、図3は本発明の方法を異常検体の血液凝固時間の測
定に適応する場合を説明する今一つの散乱光量変化曲線
図である。
FIG. 1 is a schematic configuration diagram showing an embodiment of the device of the present invention, FIG. 2 is a scattered light amount change curve diagram for explaining the method of the present invention, and FIG. 3 is a diagram of the blood coagulation time of an abnormal sample according to the method of the present invention. It is another scattered light quantity change curve figure explaining the case where it adapts to measurement.

【0008】図1において、1は被検血漿と試薬との混
合体を保持する透明のセル体で、セル移動手段12によっ
て、被検血漿が入れられたセル体1が所定の測定位置に
せっとされる。11は試薬分注ピペットで、該試薬分注ピ
ペット11によって試薬がセル体1内の被検血漿に混入さ
れることで、血液凝固試験が開始される。3はセル体1
内へ外から一定光量の光を照射する射光手段で、該射光
手段3とセル体1内からの散乱光量を検出する光量検出
手段4とで対をなす。該光量検出手段4は、前記セル体
1内の混合液からの散乱光量を検知して電気信号に変換
して出力する。5は前記電気信号の増幅手段である。6
は前記増幅された電気信号を一定の微小時間間隔でサン
プリングしてデジタル信号化するA−D変換手段で、前
記散乱光量をデジタル信号としてマイクロコンピュータ
(以下マイコンとする)7に入力する。マイコン7は射
光手段3の点灯回路10、セル移動手段12を制御し、また
試薬分注ピペット11からの試薬混入時刻情報と、メモリ
8から呼び出した演算式及び予め決められ記憶された基
準となる時間や値と、前記A−D変換手段6からのデジ
タル信号等により、血液凝固時間Tを演算して出力装置
9に出力する。
In FIG. 1, reference numeral 1 denotes a transparent cell body for holding a mixture of test plasma and a reagent, and the cell moving means 12 holds the cell body 1 containing the test plasma at a predetermined measurement position. It is said that Reference numeral 11 is a reagent dispensing pipette, and the reagent dispensing pipette 11 mixes the reagent with the test plasma in the cell body 1 to start the blood coagulation test. 3 is a cell body 1
The light emitting means 3 irradiates a constant amount of light from the inside to the outside, and the light emitting means 3 and the light amount detecting means 4 for detecting the amount of scattered light from the inside of the cell body 1 make a pair. The light amount detecting means 4 detects the amount of scattered light from the mixed liquid in the cell body 1, converts it into an electric signal, and outputs it. Reference numeral 5 is a means for amplifying the electric signal. 6
Is an AD converting means for sampling the amplified electric signal at a constant minute time interval and converting it into a digital signal, and inputs the scattered light amount as a digital signal to a microcomputer (hereinafter referred to as a microcomputer) 7. The microcomputer 7 controls the lighting circuit 10 of the light emitting means 3 and the cell moving means 12, and also serves as the reagent mixing time information from the reagent dispensing pipette 11, an arithmetic expression called from the memory 8 and a predetermined and stored reference. The blood coagulation time T is calculated based on the time and value, the digital signal from the A / D conversion means 6 and the like, and is output to the output device 9.

【0009】図2も参照して、前記マイコン7による血
液凝固時間Tの演算は、次のようにして行う。先ず試薬
分注ピペット11によって試薬が投入されると同時にマイ
コン7は光量検出手段4、増幅手段5、A−D変換手段
6を経て入力される散乱光量の経時的記憶を開始する。
そしてメモリ8に予め記憶させておいた一定の規定時間
f が経過する時点での散乱光量をとらえ、この規定時
間Tf 経過時点での散乱光量Vf から前記試薬混合時点
0 での散乱光量V0 を引き算し、更に得られた差の1
/Nを演算する。ここでNは1以上の一定値として予め
定めておく。そして得られた1/Nの値に相当する光量
だけ増加した時点までの試薬混合時点T0 からの時間T
が演算され、得られる演算結果値が凝固時間Tとされ
る。この凝固時間Tは出力装置9を介して表示される。
Referring also to FIG. 2, the blood coagulation time T is calculated by the microcomputer 7 as follows. First, at the same time when the reagent is put in by the reagent dispensing pipette 11, the microcomputer 7 starts the temporal storage of the scattered light amount inputted through the light amount detecting means 4, the amplifying means 5, and the AD converting means 6.
Then, the amount of scattered light stored in advance in the memory 8 at a time when a certain specified time T f has elapsed is captured, and the scattered light amount V f at the time when the specified time T f has elapsed is scattered at the reagent mixing time T 0. Subtracting the light quantity V 0 , and further obtaining the difference of 1
Calculate / N. Here, N is set in advance as a constant value of 1 or more. The time T from the reagent mixing time T 0 until the time when the light amount corresponding to the obtained value of 1 / N is increased
Is calculated, and the obtained calculation result value is set as the coagulation time T. This coagulation time T is displayed via the output device 9.

【0010】前記規定時間Tf は予め得た実験データに
基づいて、適当な時間が予め定められる。具体的には数
十秒から数百秒程度の間の値となる。また前記1/Nの
Nについても、予め得た実験データに基づいて、適当な
時間を予め定めておく。具体的には1.5 〜5程度の間の
値となる。
The specified time T f is set in advance based on experimental data obtained in advance. Specifically, the value is between several tens of seconds and several hundreds of seconds. Also, for N of 1 / N, an appropriate time is set in advance based on experimental data obtained in advance. Specifically, it is a value between about 1.5 and 5.

【0011】図3に示すような異常検体の場合には、散
乱光量がダラダラと長時間にわたって徐々に増大して行
き、飽和値になかなか達しないので、飽和値を測定して
凝固時間を得るという測定方法では、事実上において凝
固時間を求めることができないか、或いは長時間を要す
る。しかし、上記した本発明の方法、及び装置では規定
時間Tf を用いることで、このような異常検体に対する
凝固時間を数値として得ることができ、他の検体との比
較も可能となる。特にフィブリノゲン濃度の低い検体に
対する凝固時間の測定に対しては、散乱光量がダラダラ
と長時間にわたって徐々に増大して行くので、従来の散
乱光量の最大値を必要とする測定方法や散乱光量の微分
値のピークを必要とする測定方法においては、測定不能
という結果になる場合が多くあったが、本発明の方法で
は凝固時間の測定ができ、それら相互の比較も可能とな
った。
In the case of an abnormal sample as shown in FIG. 3, the amount of scattered light gradually increases over a long period of time and does not reach the saturation value at all, so the saturation value is measured to obtain the coagulation time. In the measurement method, the coagulation time cannot be practically obtained or it takes a long time. However, by using the specified time T f in the above-described method and apparatus of the present invention, the coagulation time for such an abnormal sample can be obtained as a numerical value, and comparison with other samples is possible. Especially for the measurement of coagulation time for samples with low fibrinogen concentration, the scattered light amount gradually increases over a long period of time, so the conventional measurement method that requires the maximum value of the scattered light amount or the derivative of the scattered light amount. In many cases, the measurement method that requires the peak of the value resulted in the inability to be measured, but the method of the present invention allowed the measurement of the coagulation time and the comparison between them.

【0012】また本発明の方法では、図7に示すような
散乱光量にプレピークを示すような場合であっても、そ
のピークに惑わされることなく、凝固時間を得ることが
できる。
Further, according to the method of the present invention, even when the amount of scattered light shows a pre-peak as shown in FIG. 7, the coagulation time can be obtained without being confused by the peak.

【0013】次に実施データを説明する。240mg /dl
のフィブリノゲンを含む血漿をオーレン・ベロナール緩
衝液(pH7.2 )で希釈し、3倍、5倍、10倍、20倍、30
倍、40倍、50倍の希釈試料を調整した。その希釈試料10
0 μl にトロンビン試薬(100 単位/mlのトロンビンを
含む)50μl を添加し、凝固時間を測定した。結果を図
4に示す。またそのとき得られる凝固時間の対数(LOG
(mg/dl))を試料中のフィブリノゲン濃度の対数(LOG
秒)に対してプロットした。結果を図5に示す。凝固時
間の算出は本発明方法では、規定時間Tf として100
秒、1/NのNとして2を用いた。また比較して示す従
来の方法(Vmax で示す)では、最大変化速度、即ち微
分値のピークの2/3を示す時間を凝固時間とした。図
4、図5から明らかなように、従来の方法(Vmax )で
は20倍希釈を越える低フィブリノゲン濃度の検体では測
定不能であるのに対し、本発明の方法では凝固時間の測
定が十分可能であり、また低フィブリノゲン濃度の検体
での測定値同士の比較もできた。
Next, the implementation data will be described. 240mg / dl
The fibrinogen-containing plasma is diluted with Oren-Bernard buffer (pH 7.2), and diluted with 3 times, 5 times, 10 times, 20 times, 30 times.
Diluted samples of fold, 40 fold, and 50 fold were prepared. The diluted sample 10
50 μl of thrombin reagent (containing 100 units / ml thrombin) was added to 0 μl, and coagulation time was measured. The results are shown in Fig. 4. Also, the logarithm of the coagulation time obtained at that time (LOG
(mg / dl) is the logarithm of the fibrinogen concentration in the sample (LOG
Seconds). Results are shown in FIG. In the method of the present invention, the coagulation time is calculated as 100 times as the specified time T f.
Second, 2 was used as N of 1 / N. Further, in the conventional method shown by comparison (shown by V max ), the maximum change rate, that is, the time at which the peak of the differential value is ⅔ is set as the coagulation time. As is clear from FIGS. 4 and 5, the conventional method (V max ) cannot measure a sample having a low fibrinogen concentration exceeding 20-fold dilution, whereas the method of the present invention can sufficiently measure the coagulation time. It was also possible to compare the measured values of the samples with low fibrinogen concentration.

【0014】図6は本発明の今一つの方法を説明する散
乱光量変化曲線図、図7は本発明の今一つの方法を異常
検体の血液凝固時間の測定に適応する場合を説明する今
一つの散乱光量変化曲線図である。またこの本発明の今
一つの方法を行う装置としては図1に示す既述の装置と
同様の装置を用いるが、マイコン7における処理手段が
異なる。マイコン7による今一つの方法、及びそれを実
行する本発明の今1つの装置による血液凝固時間Tの演
算は、図1及び図6を参照して、次のようにして行う。
先ず試薬分注ピペット11によって試薬が投入されると同
時にマイコン7は光量検出手段4、増幅手段5、A−D
変換手段6を経て入力される入力値の微分演算を開始す
る。そして経時的に得られる微分値とメモリ8に予め記
憶させておいた一定の規定値Df とを比較し、微分値が
規定値Df に達した時点における試薬混合時点T0 から
の時間Tを求め、求められた演算結果値を凝固時間Tと
する。この凝固時間Tは出力装置9を介して表示する。
FIG. 6 is a scattered light quantity change curve diagram for explaining another method of the present invention, and FIG. 7 is another scattered light quantity for explaining the case of applying the other method of the present invention to the measurement of blood coagulation time of an abnormal sample. It is a change curve figure. Further, as the device for carrying out this another method of the present invention, the same device as the above-mentioned device shown in FIG. 1 is used, but the processing means in the microcomputer 7 is different. The calculation of the blood coagulation time T by the second method by the microcomputer 7 and the second apparatus of the present invention that executes the method is performed as follows with reference to FIGS. 1 and 6.
First, the reagent is introduced by the reagent pipetting pipette 11, and at the same time, the microcomputer 7 controls the light amount detecting means 4, the amplifying means 5, and AD.
The differential operation of the input value input via the conversion means 6 is started. Then, the differential value obtained with time is compared with a constant specified value D f stored in advance in the memory 8, and the time T from the reagent mixing time T 0 when the differential value reaches the specified value D f Is obtained, and the obtained calculation result value is set as the coagulation time T. This coagulation time T is displayed via the output device 9.

【0015】前記規定値Df は予めの実験データに基づ
いて、適当な値を予め定めておく。この方法は、従来か
らガスクロマトグラフィーや液体クロマトグラフィーの
クロマトグラムのピーク検出や、ピーク面積の算出に応
用されているスロープ検出(変化速度、微分値)の方法
を利用したもので、検体が凝固を開始しない間の散乱光
量の変化速度(微分値)は理論的にゼロであり、凝固が
開始されると変化速度が増加し始める。そしてやがて極
大値(ピーク)を持つようになるが、その極大値を算出
するのではなく、速度変化が起こり始めてから一定の規
定値Df だけ変化速度が増加した時点をとらえて、該時
点までの試薬混合時点T0 からの時間Tを凝固時間とす
るのである。速度変化が起こり始めてからある程度の速
度変化の増加(微分値の増加)は確実に生じるので、そ
のある程度の速度変化の増加(微分値の増加)の値を予
め規定値Df として定めておくことで、種々の検体に対
しても確実に凝固時間を測定することができる。また微
分値のピークをとらえてピークまでの時間を血液凝固時
間とするものでは、ピークが複数生じる場合があって、
いずれのピークを採用するかで血液凝固時間がバラツキ
やすいのに比べ、この方法では、反応初期における確実
な変化を観測しているため、測定にバラツキが生じにく
い。また、微分値がゼロから一定の規定値Df にまで立
ち上がった時刻までの時間Tを測定すればよいので、微
分値のピークまでの時間を必要とするもの等に対して、
測定時間が短縮できる。
As the prescribed value D f , an appropriate value is set in advance on the basis of experimental data in advance. This method uses peak detection in chromatograms of gas chromatography and liquid chromatography, and slope detection (rate of change, differential value) that has been applied to calculate peak areas. The change rate (differential value) of the scattered light amount before the start is theoretically zero, and the change rate starts to increase when coagulation starts. Then, eventually, the maximum value (peak) is reached, but the maximum value is not calculated, but the point at which the speed of change increases by a constant specified value D f after the speed change begins to occur is captured until that time. The time T from the time point T 0 of mixing the reagents is set as the coagulation time. Since some increase in speed change (increase in differential value) will surely occur after the speed change begins to occur, the value of the increase in speed change (increase in differential value) to some extent should be set in advance as the prescribed value D f. Thus, the coagulation time can be reliably measured for various samples. In the case of catching the peak of the differential value and setting the time to the peak as the blood coagulation time, multiple peaks may occur,
The blood coagulation time tends to vary depending on which peak is adopted, but in this method, since a reliable change is observed in the initial stage of the reaction, the measurement is less likely to vary. Further, since it is sufficient to measure the time T from the time when the differential value rises from zero to the fixed specified value D f , it is necessary to measure the time T until the peak of the differential value,
Measurement time can be shortened.

【0016】図7に示すように散乱光量には、何らかの
理由によりプレピーク(山)や疑似のピーク(山)が生
じる場合がある。この場合にはその微分曲線にも疑似の
山N1 、N2 、N3 、N4 が生じるが、これらの山が前
記規定値Df を越えるようなことがあれば(N2 )、本
当の凝固時間ではない時間を凝固時間とすることが生じ
得る。このような不都合を解消するための方法として、
本発明では、さらに規定値Df を含む微分曲線の山(図
7でN2 とSの山が相当する)が連続して一定値DS
上の微分値を一定時間TS 以上持続することを条件とし
て、その条件にあった微分曲線の山(Sだけとなる)に
存在する前記規定値Df に達するまでの時間をもって血
液凝固時間Tとするようにすることができる。このよう
にすることで、測定時のノイズやその他の理由で疑似の
微分曲線の山が生じることがあっても、その様な疑似の
山は採用されないので、事実上の疑似曲線による測定ミ
スを排除することができる。
As shown in FIG. 7, the scattered light amount may have a pre-peak (peak) or a pseudo peak (peak) for some reason. In this case, pseudo peaks N 1 , N 2 , N 3 and N 4 are also generated in the differential curve, but if these peaks exceed the specified value D f (N 2 ), it is true. It may occur that the coagulation time is a time other than the coagulation time. As a method to eliminate such inconvenience,
In the present invention, the peaks of the differential curve including the specified value D f (corresponding to the peaks of N 2 and S in FIG. 7) are continuously maintained and the differential value of the constant value D S or more is maintained for the constant time T S or more. As a condition, the blood coagulation time T can be defined as the time until the specified value D f existing in the peak (only S) of the differential curve that meets the condition is reached. By doing so, even if a peak of the pseudo differential curve may occur due to noise at the time of measurement or other reasons, such a pseudo peak is not adopted. Can be eliminated.

【0017】また上記においては疑似の微分曲線の山を
測定から排除するのに、一定値DS以上で一定時間TS
以上を条件としたが、代わりに、規定値Df を含む微分
曲線の山が一定以上の面積を有することを条件として、
該条件にあった微分曲線の山に存在する前記規定値Df
に達するまでの時間Tをもって血液凝固時間としても良
い。
Further, in the above, in order to eliminate the peak of the pseudo differential curve from the measurement, a constant time T S or more for a constant value D S or more.
Although the above is the condition, instead, on the condition that the peak of the differential curve including the specified value D f has an area of a certain value or more,
The specified value D f existing in the peak of the differential curve that meets the condition
The blood coagulation time may be set to the time T until the time reaches.

【0018】次に実施データについてを説明する。血漿
検体50μl を透明プラスチックセル体(内径5×5×高
さ20mm)に入れ、Ca2+ 含有組織トロンボプラスチン試
薬100 μl を分注器で添加すると同時に凝固時間の測定
を開始した。凝固の判定は90度前方散乱光の光量変化を
モニターすることにより行った。凝固時間の算出は本発
明方法では、規定値Df として一秒間の変化量が50カウ
ントを採用し、試薬混合時点T0 から規定値Df を検出
するまでの時間をもって凝固時間Tとした。そしてその
凝固時間Tを得るまでにかかる時間(測定時間)を秒数
で求めてデータとした。また比較して示す従来方法で
は、最大変化速度、即ち微分値のピークの1/3を示す
時刻までの混合時点T0 からの時間を凝固時間Tとし
た。そしてその凝固時間Tを得るまでにかかる時間(測
定時間)を秒数で求めてデータとした。結果を図8に示
す。図8から明らかなように、本発明の方法において
は、測定に要する時間(秒)が従来の方法による測定時
間(秒)に比べて、短時間ですむ。すなわち、最大変化
速度である微分値のピークを凝固時間Tの測定に必須と
する従来の方法よりも測定時間が短くですむ利点があ
る。
Next, the implementation data will be described. 50 μl of the plasma sample was placed in a transparent plastic cell body (internal diameter 5 × 5 × height 20 mm), and 100 μl of Ca 2+ -containing tissue thromboplastin reagent was added by a dispenser, and measurement of coagulation time was started at the same time. The coagulation was determined by monitoring the change in the amount of 90 ° forward scattered light. In the present invention a method of calculating the coagulation time, the amount of change per second as defaults D f is adopted 50 counts, was time with a clotting time T to the detection of the specified value D f from reagent mixing time T 0. Then, the time (measurement time) required to obtain the coagulation time T was obtained in seconds and used as data. Further, in the conventional method shown by comparison, the coagulation time T is defined as the time from the mixing time T 0 until the maximum change speed, that is, the time at which 1/3 of the peak of the differential value is shown. Then, the time (measurement time) required to obtain the coagulation time T was obtained in seconds and used as data. The results are shown in Fig. 8. As is clear from FIG. 8, in the method of the present invention, the time required for measurement (seconds) is shorter than the measurement time (seconds) obtained by the conventional method. That is, there is an advantage that the measurement time can be shortened as compared with the conventional method in which the peak of the differential value which is the maximum change rate is indispensable for measuring the coagulation time T.

【0019】[0019]

【発明の効果】本発明は以上の構成よりなり、請求項1
に記載の血液凝固時間測定方法によれば、試薬の混合時
点から予め定めた一定の規定時間の経過時点における散
乱光量を測定し、該規定時間経過時点での散乱光量と試
薬混合時点での散乱光量との差を演算し、該差の1/N
(Nは予め定めた1以上の数)に相当する散乱光量だけ
増加した時点までの前記試薬混合時点からの時間をもっ
て血液凝固時間とするようにしたので、散乱光量の増加
がダラダラと生じて最大値を検出するまでに長時間を要
する被検血漿や散乱光量のピークが複数回生じる被検血
漿等、散乱光量の最大値を利用する凝固時間の測定方法
では測定が実質上困難な被検血漿に対しても、散乱光量
の最大値を用いることなく、相互に比較ができる有効な
凝固時間を確実に得ることが可能となった。また請求項
2に記載の血液凝固時間測定装置によれば、試薬の混合
時点から予め定めた規定時間経過時点での散乱光量と前
記試薬混合時点での散乱光量との差を演算し、該差の1
/N(Nは予め定めた1以上の数)に相当する散乱光量
だけ増加した時点までの前記試薬混合時点からの時間を
もって血液凝固時間とする請求項1に記載の血液凝固時
間測定方法を実行することができる。また請求項3に記
載の血液凝固時間測定方法によれば、散乱光量を経時的
に検出すると共にその微分値を演算し、前記試薬の混合
時点から微分値が予め定めた一定の規定値に達するまで
の時間をもって血液凝固時間とするようにしたので、試
薬混合時点からの時間をもって血液凝固時間とすること
で、微分値のピークが明確にでない被検血漿やピークが
出るまでに長時間を要する被検血漿であっても、被検血
漿の種類によらず確実に血液凝固時間を得ることができ
る。また微分値のピークをとらえてピークまでの時間を
血液凝固時間とするものでは、ピークが複数生じる場合
があって、いずれのピークを採用するかで血液凝固時間
がバラツキやすいのに比べ、この方法では反応初期にお
ける確実な変化を観測しているため、測定にバラツキが
生じにくい利点がある。また、この方法では微分値がゼ
ロから一定の規定値にまで立ち上がった時刻までの時間
を測定すればよいので、微分値のピークまでの時間を必
要とするもの等に対して、測定時間が短縮できる利点が
ある。また請求項4に記載の血液凝固時間測定方法によ
れば、請求項3に記載の血液凝固時間測定方法による上
記効果に加えて、規定値を含む微分曲線の山が連続して
一定以上の微分値を一定時間以上持続することを条件と
して、該微分曲線の山に存在する前記規定値に達するま
での時間をもって血液凝固時間としているので、測定時
のノイズ、その他の原因によって、疑似の微分曲線の山
が生じることがあっても、その山が連続して一定以上の
微分値を一定時間以上持続しない限り、測定には採用さ
れないので、疑似微分曲線の山による測定ミスを排除す
ることができる利点がある。また請求項5に記載の血液
凝固時間測定方法によれば、請求項3に記載の血液凝固
時間測定方法による上記効果に加えて、規定値を含む微
分曲線の山が一定以上の面積を有することを条件とし
て、該微分曲線の山に存在する前記規定値に達するまで
の時間をもって血液凝固時間としているので、測定時の
ノイズによって、疑似の微分曲線の山が生じることがあ
っても、その山が一定以上の面積を有しない限り、測定
には採用されないので、この場合にも、疑似曲線の山に
よる測定ミスを排除することができる利点がある。また
請求項6に記載の血液凝固時間測定装置によれば、試薬
の混合時点から微分値が予め定めた一定の規定値に達す
るまでの時間をもって血液凝固時間とする請求項3に記
載の血液凝固時間測定方法を実行することができる。
According to the present invention, which has the above-described structure,
According to the blood coagulation time measuring method described in, the amount of scattered light at the time point when a certain predetermined time has elapsed from the time of mixing the reagent is measured, and the amount of scattered light at the time point when the specified time passes and the scattering at the time of mixing the reagent. Calculate the difference from the light quantity and calculate 1 / N of the difference
(N is a predetermined number of 1 or more) Since the blood coagulation time is set to the time from the reagent mixing time until the time when the scattered light amount corresponding to (N is a predetermined number or more) is increased, the increase in the scattered light amount is erratic and the maximum. Test plasma that takes a long time to detect a value or test plasma in which peaks of scattered light amount occur multiple times, etc. Even with respect to the above, it became possible to reliably obtain an effective coagulation time that can be compared with each other without using the maximum value of the scattered light amount. Further, according to the blood coagulation time measuring device of claim 2, the difference between the scattered light amount at the time when a predetermined time has elapsed from the time of mixing the reagent and the scattered light amount at the time of mixing the reagent is calculated, and the difference is calculated. Of 1
The blood coagulation time measuring method according to claim 1, wherein the blood coagulation time is defined as the time from the reagent mixing time until the time when the amount of scattered light corresponding to / N (N is a predetermined number of 1 or more) is increased. can do. Further, according to the blood coagulation time measuring method of claim 3, the scattered light amount is detected over time, the differential value thereof is calculated, and the differential value reaches a predetermined constant value from the time of mixing the reagents. Since the blood coagulation time is defined as the time up to, the time from the reagent mixing time is defined as the blood coagulation time, so it takes a long time for the test plasma or peak where the differential value peak is not clear to appear. Even with the test plasma, the blood coagulation time can be reliably obtained regardless of the type of the test plasma. Also, in the case of catching the peak of the differential value and using the time to the peak as the blood coagulation time, there may be multiple peaks, and the blood coagulation time tends to vary depending on which peak is adopted. Since there is a reliable change observed in the initial stage of the reaction, there is an advantage that the measurement does not fluctuate. Also, with this method, it is sufficient to measure the time from the time when the differential value rises from zero to a certain specified value, so the measurement time can be shortened for those that require the time to the peak of the differential value. There are advantages. According to the blood coagulation time measuring method of claim 4, in addition to the effect of the blood coagulation time measuring method of claim 3, the peaks of the differential curve including the specified value are continuously differentiated by a certain value or more. As long as the value is maintained for a certain period of time or more, the blood coagulation time is defined as the time required to reach the specified value existing in the peak of the differential curve. Even if a peak occurs, it will not be used for measurement unless the peak continuously maintains a differential value above a certain level for a certain period of time, so it is possible to eliminate measurement errors due to the peak of the pseudo differential curve. There are advantages. According to the blood coagulation time measuring method of claim 5, in addition to the effect of the blood coagulation time measuring method of claim 3, the peak of the differential curve including the specified value has an area of a certain value or more. As a condition, the blood coagulation time is defined as the time required to reach the specified value existing in the peak of the differential curve. Is not used for measurement unless it has a certain area or more, there is an advantage in this case as well that it is possible to eliminate a measurement error due to the peak of the pseudo curve. According to the blood coagulation time measuring device of claim 6, the blood coagulation time is defined as the time from the time of mixing the reagents to the time when the differential value reaches a predetermined fixed value. A time measurement method can be implemented.

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

【図1】本発明装置の実施例を示す概略構成図である。FIG. 1 is a schematic configuration diagram showing an embodiment of a device of the present invention.

【図2】本発明の方法を説明する散乱光量変化曲線図で
ある。
FIG. 2 is a scattered light amount change curve diagram for explaining the method of the present invention.

【図3】本発明の方法を異常検体の血液凝固時間の測定
に適応する場合を説明する今一つの散乱光量変化曲線図
である。
FIG. 3 is another scattered light quantity change curve diagram for explaining a case where the method of the present invention is applied to measurement of blood coagulation time of an abnormal sample.

【図4】本発明の方法によって得た凝固時間のデータを
示す図である。
FIG. 4 is a diagram showing data of coagulation time obtained by the method of the present invention.

【図5】本発明の方法によって得た凝固時間のデータを
対数で示した図である。
FIG. 5 is a diagram showing logarithmic data of coagulation time obtained by the method of the present invention.

【図6】本発明の今一つの方法を説明する散乱光量変化
曲線図である。
FIG. 6 is a scattered light amount change curve diagram for explaining another method of the present invention.

【図7】本発明の今一つの方法を異常検体の血液凝固時
間の測定に適応する場合を説明する今一つの散乱光量変
化曲線図である。
FIG. 7 is another scattered light quantity change curve diagram for explaining a case where another method of the present invention is applied to measurement of blood coagulation time of an abnormal sample.

【図8】本発明の今一つの方法によって得た凝固時間の
データを示す図である。
FIG. 8 shows data of coagulation time obtained by another method of the present invention.

【符号の説明】[Explanation of symbols]

1 セル体 3 射光手段 4 光量検出手段 5 増幅手段 6 A−D変換手段 7 マイコン 8 メモリ 9 出力装置 T 凝固時間 T0 試薬混合時点 Tf 規定時間 TS 一定時間 Vf 規定時間Tf 経過時点での散乱光量 V0 試薬混合時点T0 での散乱光量 Df 規定値DESCRIPTION OF SYMBOLS 1 Cell body 3 Light emitting means 4 Light intensity detecting means 5 Amplifying means 6 A-D converting means 7 Microcomputer 8 Memory 9 Output device T Coagulation time T 0 Reagent mixing time T f Specified time T S constant time V f Specified time T f lapsed time Scattered light quantity at V 0 Scattered light quantity at time T 0 of reagent mixing D f Specified value

フロントページの続き (72)発明者 柳生 宏 兵庫県芦屋市精道町1−17 芦南マンショ ン103 (72)発明者 塚原 通男 兵庫県神戸市須磨区東落合2丁目19番302 −403Front Page Continuation (72) Inventor Hiroshi Yagyu 1-17 Sekido-cho, Ashiya-shi, Hyogo 103 Ashin Mansion 103 (72) Inventor Michio Tsukahara 2-chome, Higashiochiai, Suma-ku, Kobe, Hyogo 302-403

Claims (6)

【特許請求の範囲】[Claims] 【請求項1】 試薬を混合した被検血漿に一定光量の光
を照射しながらその散乱光量を検出することにより凝固
時間を測定する方法であって、前記試薬の混合時点から
予め定めた一定の規定時間の経過時点における散乱光量
を測定し、該規定時間経過時点での散乱光量と試薬混合
時点での散乱光量との差を演算し、該差の1/N(Nは
予め定めた1以上の数)に相当する散乱光量だけ増加し
た時点までの前記試薬混合時点からの時間をもって血液
凝固時間とすることを特徴とする血液凝固時間測定方
法。
1. A method for measuring coagulation time by irradiating a test plasma mixed with a reagent with a constant light amount of light and detecting the amount of scattered light thereof, which is a predetermined constant from the time of mixing the reagent. The amount of scattered light at the elapse of a specified time is measured, and the difference between the amount of scattered light at the elapse of the specified time and the amount of scattered light at the time of mixing the reagent is calculated, and 1 / N of the difference (N is a predetermined value of 1 or more). The method for measuring blood coagulation time is characterized in that the blood coagulation time is defined as the time from the time of mixing the reagents until the time when the amount of scattered light corresponding to (1) is increased.
【請求項2】 被検血漿と試薬を入れるセル体と、該セ
ル体内へ外から一定光量の光を照射する射光手段と、セ
ル体内からの散乱光量を検出する光量検出手段と、該光
量検出手段による検出量を増幅する増幅手段と、該増幅
手段で増幅された検出量を一定の微小時間間隔でサンプ
リングしてデジタル化するA−D変換手段と、該A−D
変換手段からの入力値を試薬混合時点から予め定めた一
定の規定時間の経過時点まで経時的に記憶すると共に該
規定時間経過時点での散乱光量と前記試薬混合時点での
散乱光量との差を求めて該差の1/N(Nは予め定めた
1以上の数)に相当する散乱光量だけ増加した時点まで
の前記試薬混合時点からの時間を演算するマイクロコン
ピュータと、演算結果を示す表示手段とを少なくとも有
する血液凝固時間測定装置。
2. A cell body containing a test plasma and a reagent, a light emitting means for irradiating a constant light amount of light into the cell body, a light amount detecting means for detecting a scattered light amount from the cell body, and the light amount detection. Amplifying means for amplifying the detected amount by the means, A-D converting means for sampling and digitizing the detected amount amplified by the amplifying means at a constant minute time interval, and the A-D
The input value from the converting means is stored with time from the time of mixing the reagent to the time of elapse of a predetermined fixed time, and the difference between the amount of scattered light at the time of elapse of the specified time and the amount of scattered light at the time of mixing the reagent is stored. A microcomputer for calculating and calculating the time from the reagent mixing time until the time when the amount of scattered light corresponding to 1 / N (N is a predetermined number of 1 or more) of the difference is increased, and display means for displaying the calculation result. A blood coagulation time measuring device including at least.
【請求項3】 試薬を混合した被検血漿に一定光量の光
を照射しながらその散乱光量を検出することにより凝固
時間を測定する方法であって、前記散乱光量を経時的に
検出すると共にその微分値を演算し、前記試薬の混合時
点から微分値が予め定めた一定の規定値に達するまでの
時間をもって血液凝固時間とすることを特徴とする血液
凝固時間測定方法。
3. A method for measuring coagulation time by detecting the amount of scattered light while irradiating a test plasma mixed with a reagent with a constant amount of light, which comprises detecting the scattered light amount over time and A method for measuring blood coagulation time, wherein a blood coagulation time is calculated by calculating a differential value and setting a time from the time of mixing the reagents until the differential value reaches a predetermined constant value set in advance.
【請求項4】 規定値を含む微分曲線の山が連続して一
定以上の微分値を一定時間以上持続することを条件とし
て、該微分曲線の山に存在する前記規定値に達するまで
の時間をもって血液凝固時間とする請求項3に記載の血
液凝固時間測定方法。
4. The time until reaching the specified value existing in the peak of the differential curve is provided on the condition that the peak of the differential curve including the specified value continuously maintains a differential value of a certain value or more for a certain time or more. The blood coagulation time measuring method according to claim 3, wherein the blood coagulation time is used.
【請求項5】 規定値を含む微分曲線の山が一定以上の
面積を有することを条件として、該微分曲線の山に存在
する前記規定値に達するまでの時間をもって血液凝固時
間とする請求項3に記載の血液凝固時間測定方法。
5. The blood coagulation time is defined as the time until the specified value existing in the peak of the differential curve is reached, provided that the peak of the differential curve including the specified value has a certain area or more. The method for measuring blood coagulation time according to.
【請求項6】 被検血漿と試薬を入れるセル体と、該セ
ル体内へ外から一定光量の光を照射する射光手段と、セ
ル体内からの散乱光量を検出する光量検出手段と、該光
量検出手段による検出量を増幅する増幅手段と、該増幅
手段で増幅された検出量を一定の微小時間間隔でサンプ
リングしてデジタル化するA−D変換手段と、該A−D
変換手段からの入力値を微分演算すると共に得られた微
分値が予め記憶させておいた一定の規定値に達するまで
の試薬混合時点からの時間を演算するマイクロコンピュ
ータと、演算結果を示す表示手段とを少なくとも有する
血液凝固時間測定装置。
6. A cell body containing a test plasma and a reagent, a light emitting means for irradiating a constant light amount of light into the cell body, a light amount detecting means for detecting a scattered light amount from the cell body, and the light amount detection. Amplifying means for amplifying the detected amount by the means, A-D converting means for sampling and digitizing the detected amount amplified by the amplifying means at a constant minute time interval, and the A-D
A microcomputer for performing a differential operation on the input value from the converting means and for calculating a time from the reagent mixing time until the obtained differential value reaches a predetermined memorized predetermined value, and a display means for showing the operation result. A blood coagulation time measuring device including at least.
JP20720692A 1992-07-10 1992-07-10 Blood coagulation time measuring method and apparatus Expired - Lifetime JP2934557B2 (en)

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