JP2934557B2 - Blood coagulation time measuring method and apparatus - Google Patents
Blood coagulation time measuring method and apparatusInfo
- Publication number
- JP2934557B2 JP2934557B2 JP20720692A JP20720692A JP2934557B2 JP 2934557 B2 JP2934557 B2 JP 2934557B2 JP 20720692 A JP20720692 A JP 20720692A JP 20720692 A JP20720692 A JP 20720692A JP 2934557 B2 JP2934557 B2 JP 2934557B2
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- Prior art keywords
- time
- amount
- scattered light
- reagent
- value
- Prior art date
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Description
【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 an apparatus for measuring the coagulation time of blood.
【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,
2. Description of the Related Art Conventionally, there has been provided a method of obtaining a coagulation time by mixing a reagent with plasma and measuring the change in the amount of scattered light while irradiating light from the side to obtain a coagulation time. In the broad category of the light scattering measurement method, a method using a differential value of the scattered light amount shown in the following has been conventionally provided in addition to a method using the scattered light amount shown in the following as it is. . A method in which the time until the time when the state of the amount of scattered light reaches a certain amount is defined as the coagulation time. . Coagulation time is defined as the time until the time when the difference between the minimum value and the maximum value of the amount of scattered light reaches a certain ratio (Tokuhei 3-34)
592). . A method in which the time until the differential value of the scattered light amount that changes with time reaches a peak is defined as the coagulation time (the maximum value method). . A method in which the peak of the differential value is obtained, and the time corresponding to 1 / N is defined as the coagulation time.
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, the above-mentioned method has a problem that some test samples (specimens) do not reach a certain amount, and variations in the base level itself cannot be corrected. In the other method, the amount of light changes in the same manner 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, for example, a test sample having a low fibrinogen concentration. There was a problem that could not be measured. Also,
In the method (1), there is a problem that it is difficult to obtain a peak of the differential value for a sample in which the change in the light amount (the differential value) is linear (linear function) with respect to time.
In addition, such a sample has a problem that two or more peaks occur. Further, in the case of an abnormal specimen such as a test sample having a low fibrinogen concentration, the amount of change in the amount of light is small, so that there is a problem that the maximum rate of change (peak of the differential value) cannot be accurately detected.
【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。Accordingly, the present invention solves the above-mentioned conventional disadvantages,
Blood coagulation time that can be measured accurately and in a short time without being unmeasurable even with abnormal test samples such as test samples with low fibrinogen concentration, and with stable and accurate coagulation time The purpose is to provide a measuring method and an apparatus therefor.
【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, a blood coagulation time measuring method according to the present invention is characterized in that a test plasma mixed with a reagent is irradiated with a certain amount of light while detecting the amount of scattered light. A method for measuring clotting time,
The amount of scattered light at the time when a predetermined fixed time has elapsed from the mixing of the reagents 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 mixing the reagent is calculated. The first feature is that the blood coagulation time is the time from the reagent mixing time up to the time when the amount of scattered light corresponding to 1 / N (N is a predetermined number or more) is increased. The blood coagulation time measuring device of the present invention,
A cell body into which the test plasma and the reagent are put; a light emitting unit for irradiating a constant amount of light from outside into the cell body; a light amount detecting unit for detecting a scattered light amount from the cell body; Amplifying means for amplifying, A / D converting means for sampling and digitizing the detection amount amplified by the amplifying means at a fixed minute time interval, and input values from the A / D converting means from the time of mixing the reagent. It is stored over time up to the elapse of a predetermined time, and the difference between the amount of scattered light at the time of the elapse of the specified time and the amount of scattered light at the time of mixing the reagent is obtained. A microcomputer for calculating the time from the time of mixing the reagent until the time when the amount of scattered light increases by one or more predetermined numbers), and a display means for displaying the calculation result.
The feature is. 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 the test plasma mixed with the reagent with a certain amount of light, wherein the scattered light amount is measured with time. The third characteristic is that the blood coagulation time is defined as the time from the mixing of the reagent to the time when the differential value reaches a predetermined constant value. In addition, in addition to the third feature, the blood coagulation time measuring method of the present invention further comprises the step of determining that the peak of the differential curve including the specified value continuously maintains a differential value equal to or more than a certain value for a certain time or more. A fourth feature is that the time required to reach the specified value existing at the peak of the curve is defined as the blood coagulation time. Further, in addition to the third feature, the blood coagulation time measuring method according to the present invention further comprises the above-mentioned specified curve present on the peak of the differential curve provided that the peak of the differential curve including the specified value has a certain area or more. A fifth feature is that the blood clotting time is defined as the time required to reach the value. Further, the blood coagulation time measuring apparatus of the present invention comprises a cell body for containing a test plasma and a reagent, a light emitting means for irradiating a constant amount of light from outside into the cell body, and a light amount detection for detecting a scattered light amount from the cell body. Means, amplifying means for amplifying the amount detected by the light amount detecting means, A / D converting means for sampling and digitizing the detected amount amplified by the amplifying means at a fixed minute time interval, and A microcomputer for differentiating the input value from the conversion means and calculating a time from the time of mixing the reagent until the obtained differential value reaches a predetermined value stored in advance, and a display means for displaying the calculation result The sixth feature is to have at least the following.
【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 of mixing of the reagent to the time of the lapse of a predetermined predetermined time is stored with time, and the amount of scattered light at the time of the lapse of the predetermined time is stored. The difference from the amount of scattered light at the time of mixing the reagent is determined.
Then, the time from the reagent mixing time until the time when the light amount increases by 1 / N of the difference is calculated, and the obtained calculation result value is set as the coagulation time. According to the first feature, a test plasma having a fibrinogen concentration which takes a long time to detect a maximum value due to a scattered increase in the amount of scattered light, or a test plasma having a plurality of peaks of scattered light, etc. Even for a test plasma which is substantially difficult to measure by the method for measuring the clotting time using the maximum value of the scattered light amount, the scattered light amount at the time when a predetermined time elapses without using the maximum value of the scattered light amount By using the method, the coagulation time can be reliably obtained, and the comparison of each coagulation time can be made effective. According to the second feature of the present invention, the difference between the amount of scattered light at the time when a predetermined time has elapsed from the time of mixing the reagent and the amount of scattered light at the time of mixing the reagent is calculated, and the difference of 1 is calculated.
The blood coagulation time measurement method according to the first feature, wherein a time from the reagent mixing time up to a time point when the amount of scattered light corresponding to / N (N is a predetermined number or more) increases is defined as a blood coagulation time. Can be performed. Further, according to the third feature of the present invention, at the time of mixing the reagents, the scattered light amount does not change yet, so that the differential value is zero. When the coagulation reaction is started, the amount of scattered light increases, and the differential value also increases from zero. Then, 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 point at which the coagulation reaction is considered to be maximizing.
It is considered that the coagulation reaction was completed when the value finally became zero. Since the coagulation reaction proceeds relatively reliably from the beginning of the reaction for a while, the differential value also obtains an ascending gradient (increase) relatively reliably from zero to a short time after the start of the reaction. Therefore, the ascending slope (increase) of the differential value from the start of the reaction, which is likely to appear surely, is captured, and the time from the time when the reagent is mixed, from the rise of the differential value to the time when the predetermined value is reached, is determined. By setting the blood coagulation time, the blood coagulation time can be reliably obtained regardless of the type of the test plasma. In the case where the peak time of the differential value is captured and the time until the peak is taken as the blood clotting time, a plurality of peaks may occur, and the blood clotting time tends to vary depending on which peak is used. In the case of the third characteristic, since a reliable change in the initial stage of the reaction is observed, the measurement hardly varies. In addition, since the time from the time when the differential value rises from zero to a certain prescribed value may be measured, the measurement time can be reduced as compared with the case where the time until the peak of the differential value is required. According to the fourth feature, the third feature
In addition to the effects of the above characteristics, even if peaks of the pseudo-differential curve may be generated due to noise or the like at the time of measurement, the measurement is not performed unless the peak continues for a certain time or more for a certain time or more. Is not adopted, so that a measurement error due to a virtual pseudo curve can be eliminated. According to the fifth feature, in addition to the effect of the third feature, even if a peak of a pseudo differential curve may occur due to noise or the like at the time of measurement, the peak has a certain area or more. Unless otherwise, the measurement is not adopted, so that in this case also, a measurement error due to a virtual pseudo curve can be eliminated. According to the device of the present invention described in the sixth aspect,
The time from when the reagent is mixed to when the differential value reaches a predetermined constant value is defined as the third blood coagulation time.
The method for measuring blood clotting time described in the above item can be executed.
【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 structural view showing an embodiment of the apparatus of the present invention, FIG. 2 is a diagram showing a change in the amount of scattered light explaining the method of the present invention, and FIG. FIG. 10 is another scattered light amount change curve diagram for explaining a case where measurement is applied.
【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 a test plasma and a reagent. The cell body 1 containing the test plasma is moved to a predetermined measurement position by a cell moving means 12. It is said. Reference numeral 11 denotes a reagent dispensing pipette. When a reagent is mixed into the test plasma in the cell body 1 by the reagent dispensing pipette 11, a blood coagulation test is started. 3 is a cell 1
Light emitting means for irradiating a certain amount of light from inside to outside, and the light emitting means 3 and light amount detecting means 4 for detecting the amount of scattered light from inside 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 the scattered light amount into an electric signal, and outputs the electric signal. Reference numeral 5 denotes a means for amplifying the electric signal. 6
Is an analog-to-digital (A / D) conversion means for sampling the amplified electric signal at a predetermined minute time interval and converting it into a digital signal, and inputs the scattered light amount to a microcomputer 7 as a digital signal. The microcomputer 7 controls the lighting circuit 10 and the cell moving means 12 of the light emitting means 3, and serves as a reagent mixing time information from the reagent dispensing pipette 11, an arithmetic expression called from the memory 8, and a predetermined stored reference. The blood coagulation time T is calculated based on the time and value and the digital signal from the A / D conversion means 6 and 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
Ｔf 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
BR>Ｔ0 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 to FIG. 2, the calculation of the blood coagulation time T by the microcomputer 7 is performed as follows. First, at the same time as the reagent is dispensed by the reagent dispensing pipette 11, the microcomputer 7 starts the temporal storage of the scattered light amount input through the light amount detection means 4, the amplification means 5, and the A / D conversion means 6.
And capture the scattered light at the time a certain specified time T f which had been previously stored in the memory 8 has passed, the reagent mixing time from the scattered light intensity V f at the time the specified time T f elapses
Subtracting the scattered light intensity V 0 which in BR> T 0, calculates the 1 / N of the further resulting difference. Here, N is predetermined as a constant value of 1 or more. Then, the time T from the reagent mixing time T 0 up to the time when the amount of light 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. The 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 Tf is determined in advance based on experimental data obtained in advance. Specifically, the value is between several tens of seconds and several hundreds of seconds. For N of 1 / N, an appropriate time is determined in advance based on experimental data obtained in advance. Specifically, the value is 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 specimen as shown in FIG. 3, the amount of scattered light gradually increases over a long period of time and does not easily reach a saturation value, so that the saturation value is measured to obtain the coagulation time. In the measurement method, the coagulation time cannot be determined practically or a long time is required. However, by using the specified time Tf in the method and apparatus of the present invention described above, the coagulation time for such an abnormal sample can be obtained as a numerical value, and comparison with other samples is also possible. In particular, when measuring the coagulation time for a sample with a low fibrinogen concentration, the scattered light gradually increases over a long period of time, so conventional measurement methods that require the maximum value of the scattered light and differentiation of the scattered light In many cases, a measurement method requiring a peak value resulted in measurement failure, but the method of the present invention enabled measurement of the coagulation time and 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 scattered light quantity shows a pre-peak as shown in FIG. 7, the coagulation time can be obtained without being disturbed 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 embodiment data will be described. 240mg / dl
Of fibrinogen is diluted with Oren-Veronal buffer (pH 7.2), and then 3 times, 5 times, 10 times, 20 times, 30 times
A 1:40, 1:50 diluted sample was prepared. The diluted sample 10
50 μl of thrombin reagent (containing 100 units / ml thrombin) was added to 0 μl, and the clotting time was measured. FIG. 4 shows the results. The log of the coagulation time obtained at that time (LOG
(mg / dl)) is the logarithm of the fibrinogen concentration in the sample (LOG
Second). FIG. 5 shows the results. In the method of the present invention, the clotting time is calculated as 100 times as the specified time Tf.
Second, 2 was used as N of 1 / N. In the conventional method (indicated by V max ) shown in comparison, the maximum change rate, that is, the time showing 2/3 of the peak of the differential value, was taken 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 samples having a 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 amount change curve diagram for explaining another method of the present invention, and FIG. 7 is another scattered light amount for explaining another method of the present invention applied to measurement of blood coagulation time of an abnormal sample. It is a change curve figure. As an apparatus for performing another method of the present invention, an apparatus similar to the above-described apparatus 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 microcomputer 7 by another method and the blood coagulation time T by another device of the present invention that executes the method is performed as follows with reference to FIGS.
First, at the same time as the reagent is dispensed by the reagent dispensing pipette 11, the microcomputer 7 sets the light amount detecting means 4, the amplifying means 5, AD
The differential operation of the input value input via the conversion means 6 is started. And comparing the predetermined specified value D f that has been stored in advance in the over time differential value memory 8 to be obtained, the time T from the reagent mixing time T 0 at the time when the differential value has reached a predetermined value D f Is calculated, and the obtained calculation result value is set as the coagulation time T. The 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。The prescribed value Df is set to an appropriate value based on experimental data in advance. This method uses the method of slope detection (change rate, differential value) that has been applied to the peak detection of chromatograms in gas chromatography and liquid chromatography and the calculation of peak areas. The change speed (differential value) of the amount of scattered light is not theoretically zero before the start of the process, and the change speed starts to increase when the coagulation is started. And although eventually will have a maximum value (peak), the maximum value instead of calculating the, captures the time when only the change speed is increased by a certain prescribed value D f from the speed change begins to occur, until said time point The time T from the reagent mixing time T 0 is the coagulation time. Since an increase in the degree of speed change from the speed change begins to occur (an increase in the differential value) is certainly caused, that you set the value of increase (increase in the differential value) of the degree of speed variation as a predefined value D f Thus, the coagulation time can be reliably measured for various samples. In the case of capturing the peak of the differential value and setting the time to the peak as the blood coagulation time, there may be a plurality of peaks,
The blood coagulation time tends to vary depending on which peak is adopted, but in this method, since a reliable change in the initial stage of the reaction is observed, the measurement hardly varies. Also, for it is only necessary to measure the time T until the time differential value rises from zero to a constant predetermined value D f, as need time to peak of the differential value, etc.,
Measurement time can be reduced.
【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 以
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. However, if these peaks exceed the specified value D f (N 2 ), it is true. A time that is not the clotting time of the slag may be taken as the clotting time. As a method to solve such inconvenience,
In the present invention, it can last more specified value D (Mountain N 2 and S corresponds to FIG. 7) mountain differential curve including f is continuously a differential value of a predetermined value or more D S fixed time T S or more the condition, with a time to reach the specified value D f that is present in the pile of a differentiated curve to the condition (the only S) can be made to the blood coagulation time T. By doing so, even if a peak of a pseudo differential curve may occur due to noise at the time of measurement or for other reasons, such a pseudo peak is not adopted, so that a measurement error due to a virtual pseudo curve is effectively eliminated. 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。[0017] In addition to eliminating the mountain of pseudo-differential curve from the measurement in the above, a certain period of time in more than a certain value D S T S
Although the condition of the above, instead, on condition that the peak of the derivative curve having an area more than a certain including prescribed value D f,
The specified value D f existing at the peak of the differential curve meeting the condition
The blood coagulation time may be the time T required to reach the blood coagulation time.
【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 practical data will be described. A plasma sample (50 μl) was placed in a transparent plastic cell (inner diameter 5 × 5 × height 20 mm), and 100 μl of a Ca 2+ -containing tissue thromboplastin reagent was added by a pipettor, and at the same time, the measurement of coagulation time was started. The determination of coagulation was made 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. The time required for obtaining the coagulation time T (measurement time) was obtained in seconds and used as data. In the conventional method shown in comparison, the time from the mixing time T 0 up to the maximum change rate, that is, the time when the peak of the differential value reaches 1/3, is defined as the coagulation time T. The time required for obtaining the coagulation time T (measurement time) was obtained in seconds and used as data. FIG. 8 shows the results. As is clear from FIG. 8, in the method of the present invention, the time (second) required for measurement is shorter than the measurement time (second) by the conventional method. That is, there is an advantage that the measurement time is shorter than the conventional method in which the peak of the differential value, which is the maximum change rate, is essential for the measurement of 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, there is provided the above construction.
According to the blood coagulation time measuring method described in the above, the amount of scattered light at the time when a predetermined time has elapsed since the mixing of the reagent is measured, and the amount of scattered light at the time when the specified time has elapsed and the scattered light at the time of mixing the reagent are measured. Calculate the difference with the light quantity and calculate 1 / N of the difference
(N is a predetermined number or more) The blood coagulation time is defined as the time from the mixing time of the reagent until the time when the amount of scattered light is increased by the amount corresponding to the scattered light. For example, a test plasma that requires a long time to detect the value or a test plasma in which the peak of the amount of scattered light occurs multiple times, such as a test plasma that is substantially difficult to measure by a method for measuring the coagulation time using the maximum value of the amount of scattered light However, it is possible to reliably obtain an effective coagulation time that can be compared with each other without using the maximum value of the amount of scattered light. According to the blood coagulation time measuring device according to claim 2, the difference between the amount of scattered light at the time when a predetermined time has elapsed from the time of mixing the reagent and the amount of scattered light at the time of mixing the reagent is calculated. Of 1
2. The blood coagulation time measuring method according to claim 1, wherein a time from said reagent mixing time up to a time point when the amount of scattered light corresponding to / N (N is a predetermined number or more) increases is defined as a blood coagulation time. can do. According to the blood coagulation time measuring method of the third aspect, the amount of scattered light is detected over time, and its differential value is calculated, and the differential value reaches a predetermined constant value from the mixing time of the reagent. The blood clotting time is defined as the time from the time of reagent mixing, so it takes a long time before the peak of the test plasma or the peak whose differential value is not clear appears. Even with the test plasma, the blood coagulation time can be reliably obtained regardless of the type of the test plasma. In the case of capturing the peak of the differential value and setting the time up to the peak as the blood clotting time, there may be a plurality of peaks, and the blood clotting time tends to vary depending on which peak is adopted. Since a reliable change is observed in the early stage of the reaction, there is an advantage that the measurement hardly varies. Also, in this method, the time until the differential value rises from zero to a certain specified value can be measured, so the measurement time is reduced compared to the case where the time until the peak of the differential value is required. There are advantages that can be done. According to the blood coagulation time measuring method of the fourth aspect, in addition to the above-mentioned effect of the blood coagulation time measuring method of the third aspect, the peak of the differential curve including the specified value is continuously higher than a certain value. Since the blood coagulation time is defined as the time required to reach the specified value existing at the peak of the differential curve under the condition that the value is maintained for a certain time or longer, noise during measurement and other causes may cause a pseudo differential curve. Even if peaks occur, they are not adopted for measurement unless the peaks continuously maintain a differential value equal to or more than a certain value for a certain time or more, so that a measurement error due to a peak of a pseudo differential curve can be eliminated. There are advantages. According to the blood clotting time measuring method of the fifth aspect, in addition to the effect of the blood clotting time measuring method of the third aspect, the peak of the differential curve including the specified value has a certain area or more. Since the blood coagulation time is defined as the time required to reach the specified value existing at the peak of the differential curve, even if a pseudo peak of the differential curve may occur due to noise during measurement, Is not adopted in the measurement unless it has a certain area or more. Therefore, also in this case, there is an advantage that a measurement error due to a peak of the pseudo curve can be eliminated. According to the blood coagulation time measuring device of the present invention, the time from when the reagent is mixed to when the differential value reaches a predetermined constant value is defined as the blood coagulation time. A time measurement method can be performed.
【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 the 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 amount curve diagram illustrating 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 the 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 graph showing data of the coagulation time obtained by the method of the present invention in logarithm.
【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 amount curve diagram illustrating 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 is a diagram showing data of coagulation time obtained by another method of the present invention.
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Reference Signs List 1 cell body 3 light emitting means 4 light quantity 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 elapsed time Amount of scattered light V 0 Amount of scattered light at time T 0 of mixing of reagents D f Specified value
───────────────────────────────────────────────────── フロントページの続き (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 302−403 (56)参考文献 特開 昭54−69497（ＪＰ，Ａ) 特開 昭63−305255（ＪＰ，Ａ) 特開 平４−318863（ＪＰ，Ａ) 特開 昭54−51893（ＪＰ，Ａ) 特公 昭61−10777（ＪＰ，Ｂ２) 特公 平３−34592（ＪＰ，Ｂ２) (58)調査した分野(Int.Cl.6，ＤＢ名) G01N 33/48 - 33/52 G01N 33/58 - 33/98 ──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Michio Tsukahara 2-19-2 Higashiochiai, Suma-ku, Kobe-shi, Hyogo 302-403 (56) References JP-A-54-69497 (JP, A) JP-A-63 JP-A-4-318863 (JP, A) JP-A-54-51893 (JP, A) JP-B-61-10777 (JP, B2) JP-B-3-34592 (JP, B2) (58) Fields surveyed (Int.Cl. 6 , DB name) G01N 33/48-33/52 G01N 33/58-33/98
Claims (6)
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 detecting the amount of scattered light while irradiating a test plasma mixed with a reagent with a certain amount of light, the method comprising the steps of: The amount of scattered light at the time when the specified time has elapsed 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 mixing the reagent is calculated, and 1 / N of the difference (where N is one or more predetermined values) A time from the mixing of the reagents up to the point of time when the amount of scattered light corresponding to the number of times increases) is defined as the blood clotting time.
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 for containing a test plasma and a reagent, a light emitting means for irradiating a predetermined amount of light from outside to 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 amount detected by the means, A / D conversion means for sampling and digitizing the detected amount amplified by the amplifying means at a fixed minute time interval, and
The input value from the conversion means is stored over time from the time of mixing the reagent to the time of a predetermined time, and the difference between the amount of scattered light at the time of the specified time and the amount of scattered light at the time of mixing the reagent is determined. A microcomputer for calculating the time from the reagent mixing time until the time when the difference is increased by 1 / N (N is a predetermined number or more) of the difference, and display means for displaying the calculation result A blood coagulation time measuring device comprising at least:
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 a scattered light amount while irradiating a test plasma mixed with a reagent with a constant light amount, wherein the scattered light amount is detected over time and A blood coagulation time measuring method, wherein a differential value is calculated, and a time from when the reagent is mixed to when the differential value reaches a predetermined constant value is defined as a blood coagulation time.
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. On the condition that the peak of the differential curve including the specified value continues for a predetermined value or more for a predetermined time or more, the time until the specified value existing on the peak of the differential curve is reached. The blood coagulation time measuring method according to claim 3, wherein the blood coagulation time is used.
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. A blood coagulation time is defined as a time required for the peak of the differential curve including the specified value to reach the specified value existing on the peak of the differential curve, provided that the peak has a certain area or more. The method for measuring blood coagulation time according to 1.
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 for containing a test plasma and a reagent, a light emitting means for irradiating a constant amount of light from outside to 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 amount detected by the means, A / D conversion means for sampling and digitizing the detected amount amplified by the amplifying means at a fixed minute time interval, and
A microcomputer for differentiating the input value from the conversion means and calculating a time from the time of mixing the reagent until the obtained differential value reaches a predetermined value stored in advance, and a display means for displaying the calculation result A blood coagulation time measuring device comprising at least:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20720692A JP2934557B2 (en) | 1992-07-10 | 1992-07-10 | Blood coagulation time measuring method and apparatus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20720692A JP2934557B2 (en) | 1992-07-10 | 1992-07-10 | Blood coagulation time measuring method and apparatus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0627115A JPH0627115A (en) | 1994-02-04 |
| JP2934557B2 true JP2934557B2 (en) | 1999-08-16 |
Family
ID=16535995
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP20720692A Expired - Lifetime JP2934557B2 (en) | 1992-07-10 | 1992-07-10 | Blood coagulation time measuring method and apparatus |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2934557B2 (en) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5708591A (en) * | 1995-02-14 | 1998-01-13 | Akzo Nobel N.V. | Method and apparatus for predicting the presence of congenital and acquired imbalances and therapeutic conditions |
| US6898532B1 (en) | 1995-06-07 | 2005-05-24 | Biomerieux, Inc. | Method and apparatus for predicting the presence of haemostatic dysfunction in a patient sample |
| US6321164B1 (en) | 1995-06-07 | 2001-11-20 | Akzo Nobel N.V. | Method and apparatus for predicting the presence of an abnormal level of one or more proteins in the clotting cascade |
| US6429017B1 (en) | 1999-02-04 | 2002-08-06 | Biomerieux | Method for predicting the presence of haemostatic dysfunction in a patient sample |
| US6502040B2 (en) | 1997-12-31 | 2002-12-31 | Biomerieux, Inc. | Method for presenting thrombosis and hemostasis assay data |
| ES2231167T3 (en) | 1999-02-04 | 2005-05-16 | Biomerieux, Inc. | PROCEDURE AND APPARATUS TO PREACH HEMOSTATIC DYSFUNCTION IN A PATIENT SAMPLE. |
| US7179612B2 (en) | 2000-06-09 | 2007-02-20 | Biomerieux, Inc. | Method for detecting a lipoprotein-acute phase protein complex and predicting an increased risk of system failure or mortality |
| JP4799116B2 (en) * | 2005-10-11 | 2011-10-26 | シスメックス株式会社 | Sample analyzer, sample analysis method, and computer program |
| JP5164388B2 (en) * | 2007-01-31 | 2013-03-21 | シスメックス株式会社 | Sample measuring device |
| JP4505045B2 (en) * | 2008-06-18 | 2010-07-14 | 積水メディカル株式会社 | How to determine the cause of prolonged blood clotting time |
| CN101949841A (en) * | 2010-09-27 | 2011-01-19 | 西南大学 | Blood coagulation index detecting system based on LabVIEW platform |
| WO2014189067A1 (en) | 2013-05-23 | 2014-11-27 | 日本電信電話株式会社 | Blood coagulation detection method |
| JP6871673B2 (en) * | 2015-03-31 | 2021-05-12 | 学校法人東日本学園 | Methods, devices and computer programs for determining blood samples, and blood sample analyzers |
| JP6952668B2 (en) | 2018-09-28 | 2021-10-20 | シスメックス株式会社 | Blood coagulation analysis method, blood coagulation analyzer, program |
| EP4134675A4 (en) * | 2020-04-07 | 2024-01-17 | Sekisui Medical Co Ltd | Method for measuring blood coagulation time |
| CN112161955A (en) * | 2020-07-22 | 2021-01-01 | 三诺生物传感股份有限公司 | Testing method for four blood coagulation items |
| CN116472354A (en) * | 2020-10-29 | 2023-07-21 | 积水医疗株式会社 | Method for detecting coagulation reaction |
| CN114636828B (en) * | 2022-05-07 | 2022-10-25 | 深圳市帝迈生物技术有限公司 | Sample real-time detection method and device, sample analyzer and storage medium |
-
1992
- 1992-07-10 JP JP20720692A patent/JP2934557B2/en not_active Expired - Lifetime
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| Publication number | Publication date |
|---|---|
| JPH0627115A (en) | 1994-02-04 |
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