JPH06249855A - Blood coagulation time measurement and device therefor - Google Patents
Blood coagulation time measurement and device thereforInfo
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- JPH06249855A JPH06249855A JP6273793A JP6273793A JPH06249855A JP H06249855 A JPH06249855 A JP H06249855A JP 6273793 A JP6273793 A JP 6273793A JP 6273793 A JP6273793 A JP 6273793A JP H06249855 A JPH06249855 A JP H06249855A
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Abstract
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 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、従来次の〜に示す方法が提供されてい
る。 ．散乱光量をそのまま利用し、散乱光量の状態がある
一定量になる時点までの時間をもって凝固時間とする方
法。 ．散乱光量をそのまま利用し、散乱光量の最小値と最
大値の差の一定割合となる時点までの時間をもって凝固
時間とする方法（特公平3-34592 号）。 ．散乱光量の微分値を利用し、経時的に変化する散乱
光量の微分値がピークとなる時点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）で、且つ散乱光量
或いは前記微分値の二重積分値が一定のしきい値を越え
ることを条件としたもの。 ．微分値のピークを求め、その１／Ｎに相当する時点
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号）。 ．一定時間内の全変化量を測定し、全変化量の20〜50
％の範囲に達した時点の前後をデータ処理範囲として出
力を処理する方法（特開平4-318463号）。 そして上記〜の方法は、凝固時間そのものを求める
方法（、、、）と、付随するノイズを除去する
方法（、）の２つに分けることができる。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. The following methods (1) to (3) are conventionally provided in the broad classification of the light scattering method. ． A method in which the amount of scattered light is used as it is and the time until the state of the amount of scattered light reaches a certain amount is taken as the coagulation time. ． A method in which the amount of scattered light is used as it is and the coagulation time is defined as the time until a certain ratio of the difference between the minimum and maximum values of scattered light is reached (Japanese Patent Publication No. 3-34592). ． Using the differential value of the scattered light quantity, the method of setting the time until the differential value of the scattered light quantity that changes over time reaches the peak as the coagulation time (the maximum value method), and the scattered light quantity or the differential value The condition is that the double integral value exceeds a certain threshold value. ． 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).
No. 0777). ． 20 to 50 of the total change amount is measured by measuring the total change amount within a certain period of time.
A method of processing the output with the data processing range before and after reaching the range of% (Japanese Patent Laid-Open No. 318463/1992). The above methods (1) to (2) can be divided into two methods: a method for obtaining the coagulation time itself (,,,) and a method for removing accompanying noise (,).
【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。さらにの方法は既に凝固が完了してい
ても、一定時間までは必ず測定しないとデータ処理がで
きないため、測定に時間がかかり、多数の検体を次々と
迅速に処理して凝固時間を得るには問題があった。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. In addition, even if the coagulation is already completed, the data cannot be processed until the coagulation is completed for a certain period of time, so it takes time to measure a large number of specimens one after another to obtain the coagulation time. There was a problem.
【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、短時間で次々
と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 that does not become unmeasurable due to abnormal test samples such as low fibrinogen concentration test samples, and that the coagulation time can be stably and accurately measured one after another in a short time. An object of the present invention is to provide a method for measuring a coagulation time 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逐次散乱光量を測定し、リアル
タイムに得られるＡ／Ｄ変換データを平滑化及び原点調
整をして基準Ａ／Ｄ変換データとし、該基準Ａ／Ｄ変換
データから、更にこれを積分した基準積分データと、前
記基準Ａ／Ｄ変換データの各隣合う微小時間での積算値
の比である基準比データとを演算し、該基準比データが
予め定めた一定の基準比データ値になる時点のうち、前
記基準比データのピーク以降の時点で且つ前記基準積分
データが予め定めた一定のノイズ除去用しきい値以上と
なる時点における基準Ａ／Ｄ変換データ値を選出し、該
基準Ａ／Ｄ変換データ値の１／Ｎ（Ｎは１以上の一定整
数）の値が対応する時点までの混合時点からの時間をも
って凝固時間とすることを特徴としている。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リアルタイムでデジタル化する
Ａ／Ｄ変換手段と、該Ａ／Ｄ変換手段からのＡ／Ｄ変換
データを先ず微分演算すると共に平滑化処理して基準Ａ
／Ｄ変換データとして記憶し、次にこの基準Ａ／Ｄ変換
データから、更にこれを積分した基準積分データと、前
記基準Ａ／Ｄ変換データの各隣合う微小時間での積算値
の比である基準比データとをそれぞれ演算して記憶し、
次に前記基準比データが予め定めた一定の基準比データ
値になる時点を求めると共に該時点のうち、前記基準比
データのピーク以降の時点で且つ前記基準積分データが
予め定めた一定のノイズ除去用しきい値以上となる時点
を選出し、次にこの選出した時点における基準Ａ／Ｄ変
換データ値を選出し、次にこの基準Ａ／Ｄ変換データ値
の１／Ｎ（Ｎは１以上の一定整数）の値が対応する時点
までの混合時点からの時間を演算する機構を有するマイ
クロコンピュータと、該マイクロコンピュータの演算結
果を示す表示手段とを少なくとも有することを特徴とし
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 is successively measured from the time of mixing the reagents, the A / D conversion data obtained in real time is smoothed and the origin is adjusted to obtain reference A / D conversion data, and the reference A / D conversion data is further Is calculated, and the reference ratio data, which is the ratio of the integrated value of the reference A / D conversion data in each adjacent minute time, is calculated, and the reference ratio data is a predetermined constant ratio data. Selecting a reference A / D conversion data value at a time point after the peak of the reference ratio data and at a time point when the reference integration data is equal to or more than a predetermined constant noise removal threshold value, It is characterized in that the coagulation time is the time from the mixing time until the time corresponding to the value of 1 / N (N is a constant integer of 1 or more) of the reference A / D converted data value. 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 amplification means for amplifying the detection amount by the light amount detection means, an A / D conversion means for sampling the detection amount amplified by the amplification means at a constant minute time interval and digitizing it in real time, The A / D conversion data from the A / D conversion means is first differentiated and smoothed to obtain the reference A.
This is the ratio of the reference integration data stored as the A / D conversion data and then further integrating the reference A / D conversion data to the integrated value of the reference A / D conversion data in each adjacent minute time. Calculate and store the reference ratio data and
Next, a time point at which the reference ratio data reaches a predetermined constant reference ratio data value is determined, and at the time point after the peak of the reference ratio data and at a predetermined constant noise removal time of the reference integration data. A time point that is greater than or equal to the threshold for use, then selects the standard A / D conversion data value at the time of the selection, and then 1 / N (N is 1 or more) of this standard A / D conversion data value. At least a microcomputer having a mechanism for calculating a time from a mixing time until a time corresponding to a value of (a constant integer) and a display means for displaying a calculation result of the microcomputer are provided.
【０００６】[0006]
【作用】上記本発明方法の特徴によれば、試薬の混合時
点から逐次得られる散乱光量がリアルタイムでＡ／Ｄ変
換され、更にこのＡ／Ｄ変換データがリアルタイムで平
滑化及び原点調整されて基準Ａ／Ｄ変換データとなる。
そして前記基準Ａ／Ｄ変換データからは、更にこれを積
分した基準積分データと、前記基準Ａ／Ｄ変換データの
各隣合う微小時間での積算値の比である基準比データと
がリアルタイムで演算される。そして前記基準比データ
値が予め定めた一定の基準比データ値になる時点を選出
しながら、その時点が前記基準比データのピーク以降の
時点で且つ前記基準積分データのノイズ除去用しきい値
以上となる時点であるかの２つの条件が判定される。そ
の条件を満たせば、前記選出した時点での基準Ａ／Ｄ変
換データ値が選出され、この基準Ａ／Ｄ変換データ値の
１／Ｎが演算されて、その値に対応する時点までの混合
時点からの時間が演算される。得られた時間が凝固時間
となる。上記本発明方法の特徴によれば、散乱光量をそ
のままＡ／Ｄ変換した一次データではなく、該Ａ／Ｄ変
換データを平滑化及び原点調整をして基準Ａ／Ｄ変換デ
ータとして利用するので、前記一次データに生じる散乱
光量のバラツキや、検体の濁り等による一次データにお
ける基底レベルのバラツキが解消される。また、本発明
方法の特徴によれば、上記２つの条件を満たした一定の
基準比データ値が選出できると、その時点でただちに光
量測定動作を終了し、次の検体の測定動作に移ることが
できる。よって既に凝固が完了していても一定時間まで
は必ず測定しないとデータ処理ができないといった従来
の方法に比べて処理時間が短縮される。また、本発明方
法の特徴によれば、Ａ／Ｄ変換データの各隣合う微小時
間での積算値の比である基準比データを用い、該基準比
データが予め定めた一定の基準比データ値になる時点を
得ることで、最終的に凝固時間を演算する方法を採用し
ているので、本発明方法では、散乱光量の変化が生じれ
ば凝固時間の測定に十分で、その散乱光量の微分値にピ
ークが生じないような検体、即ち、散乱光量の変化（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、或いは低フィブリノゲン濃度の被検試料のよう
な光量変化量が小さく最大変化速度（微分値のピーク）
を的確にとらえられない検体に対しても確実に凝固時間
が得られる。また、本発明方法の特徴によれば、基準Ａ
／Ｄ変換データの各隣合う微小時間での積算値の比であ
る基準比データを用いているので、測定装置の個々の装
置に生じるゲインのバラツキの影響が少なくなるのは勿
論のこと、多チャンネル測定部を持つ測定装置の前記各
測定チャンネル毎のゲインのバラツキの影響も少なくな
り、信頼性の高い結果が得られる。また上記本発明装置
の特徴によれば、上記発明方法を現に行い、凝固時間を
得てこれを表示することができる。According to the features of the above-mentioned method of the present invention, the amount of scattered light sequentially obtained from the time of mixing the reagents is A / D converted in real time, and this A / D converted data is smoothed and adjusted in origin in real time for reference. It becomes A / D converted data.
Then, from the reference A / D conversion data, reference integration data obtained by further integrating the reference A / D conversion data and reference ratio data which is a ratio of integrated values of the reference A / D conversion data at adjacent small times are calculated in real time. To be done. Then, while selecting a time point at which the reference ratio data value becomes a predetermined constant reference ratio data value, the time point is a time point after the peak of the reference ratio data and is equal to or more than a noise removal threshold value of the reference integration data. Two conditions are determined as to whether or not If the condition is satisfied, the standard A / D conversion data value at the time of the selection is selected, 1 / N of the standard A / D conversion data value is calculated, and the mixing time until the time corresponding to the value is calculated. The time from is calculated. The time obtained is the coagulation time. According to the features of the method of the present invention, not the primary data obtained by A / D converting the scattered light amount as it is, but the A / D converted data is used as the reference A / D converted data after smoothing and origin adjustment. Variations in the amount of scattered light that occur in the primary data and variations in the base level in the primary data due to turbidity of the sample are eliminated. Further, according to the feature of the method of the present invention, when a constant reference ratio data value satisfying the above two conditions can be selected, the light amount measurement operation is immediately terminated at that point, and the next sample measurement operation can be started. it can. Therefore, the processing time can be shortened as compared with the conventional method in which data processing cannot be performed unless measurement is performed for a certain time even if the coagulation is already completed. Further, according to the feature of the method of the present invention, the reference ratio data, which is a ratio of the integrated values of the A / D converted data at each adjacent minute time, is used, and the reference ratio data has a predetermined constant reference ratio data value. By adopting the method of finally calculating the coagulation time by obtaining the time point, the method of the present invention is sufficient for measuring the coagulation time if a change in the scattered light amount occurs, and the differential of the scattered light amount. A sample that does not have a peak in its value, that is, a sample whose change in the scattered light amount (differential value) is linear (linear function) with respect to time, or a light amount such as a test sample with a low fibrinogen concentration Small change amount and maximum change speed (peak of differential value)
The coagulation time can be reliably obtained even for a sample that cannot be accurately captured. According to the characteristic of the method of the present invention, the criterion A
Since the reference ratio data, which is the ratio of the integrated values of the A / D conversion data in each adjacent minute time, is used, the influence of the gain variation occurring in each of the measuring devices is of course reduced. The influence of gain variation among the respective measurement channels of the measuring apparatus having the channel measuring unit is reduced, and highly reliable results can be obtained. Further, according to the features of the device of the present invention, it is possible to actually perform the above-mentioned method of the present invention, obtain the coagulation time, and display it.
【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はマイクロコンピュータが有する凝固時間演算
機構のフローチャート、図３から図７は本発明の方法と
装置を説明する図で、図３は検出された散乱光量のオリ
ジナルのＡ／Ｄ変換データを時間を横軸にして表したオ
リジナルＡ／Ｄ変換データ曲線図、図４はオリジナルＡ
／Ｄ変換データを微分した微分データ曲線図、図５は微
分データを平滑化した平滑化データ曲線図、図６は平滑
化データを積分して得た基準Ａ／Ｄ変換データと該基準
Ａ／Ｄ変換データを積分した基準積分データとを時間を
横軸にして表した曲線図、図７は基準Ａ／Ｄ変換データ
の各隣合う微小時間での積算値の比データである基準比
データを、基準Ａ／Ｄ変換データと基準積分データと共
に時間を横軸にして表した曲線図、図８は選出した凝固
完了点から凝固時間を演算する方法を説明する図であ
る。また図９は本発明の基準比データを用いる方法と従
来の微分データを用いる方法との差を説明する図であ
る。DESCRIPTION OF THE PREFERRED EMBODIMENTS FIG. 1 is a schematic configuration diagram showing an embodiment of the device of the present invention, FIG. 2 is a flow chart of a coagulation time calculation mechanism of a microcomputer, and FIGS. 3 to 7 are views for explaining the method and device of the present invention. 3 is an original A / D conversion data curve diagram showing the original A / D conversion data of the detected scattered light amount with time as the horizontal axis, and FIG. 4 is the original A / D conversion data curve.
FIG. 5 is a differential data curve diagram obtained by differentiating the / D conversion data, FIG. 5 is a smoothed data curve diagram obtained by smoothing the differential data, and FIG. 6 is a reference A / D conversion data obtained by integrating the smoothed data and the reference A / D. FIG. 7 is a curve diagram showing the reference integration data obtained by integrating the D conversion data with time as the horizontal axis, and FIG. 7 shows the reference ratio data, which is the ratio data of the integrated values of the reference A / D conversion data at each adjacent minute time. FIG. 8 is a curve diagram in which the horizontal axis represents time together with the reference A / D conversion data and the reference integration data, and FIG. 8 is a diagram illustrating a method of calculating the coagulation time from the selected coagulation completion point. FIG. 9 is a diagram for explaining the difference between the method using the reference ratio data of the present invention and the conventional method using the differential data.
【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
セットされる。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、血液凝固時間測定が開始される。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リアルタイムで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
入時点情報と、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 is a transparent cell body for holding a mixture of test plasma and a reagent, and the cell body 1 containing the test plasma is set at a predetermined measurement position by the cell moving means 12. To be done. Reference numeral 11 denotes 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 time measurement. Reference numeral 3 denotes a light emitting means for irradiating a constant amount of light into the cell body 1 from outside, and the light emitting means 3 and the light amount detecting means 4 for detecting the scattered light amount 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. Reference numeral 6 denotes an A / D conversion means for sampling the amplified electric signal at a constant minute time interval and converting it into a digital signal in real time, 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 information on the point of time of mixing the reagent from the reagent dispensing pipette 11, the arithmetic expression called from the memory 8 and a predetermined and stored reference. Time and value and the A / D
The blood coagulation time T is calculated by the digital signal from the conversion means 6 and the like, and is output to the output device 9.
【０００９】図２〜図８も参照して、前記マイコン７に
よる血液凝固時間Ｔの演算機構を説明する。今、試薬分
注ピペット11によって試薬が投入されると、それと同時
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を経てリアルタイムで散乱光量のＡ／Ｄ変換デ
ータ、即ちオリジナルＡ／Ｄ変換データを入力し（図２
のＳ１）（図３）、このオリジナルＡ／Ｄ変換データを
リアルタイムで微分する（図２のＳ２）（図４）。この
微分は微小時間間隔におけるオリジナルＡ／Ｄ変換デー
タ値の差を演算することで得ることができる。そして更
に得られた微分データを、リアルタイム的に、例えばメ
ジアン法を用いて平滑化する（図２のＳ３）（図５）。
前記メジアン法は、あるサンプリングポイントの前後、
任意のｎ個のポイントの微分データのメジアンをそのポ
イントのデータとする方法である。従来の移動平行法で
は、突発的なノイズの除去は困難であるが、メジアン法
ではそれが除去できる。The mechanism of calculating the blood coagulation time T by the microcomputer 7 will be described with reference to FIGS. Now, when a reagent is introduced by the reagent dispensing pipette 11, at the same time, the microcomputer 7 goes through the light amount detecting means 4, the amplifying means 5 and the A / D converting means 6 in real time to obtain the A / D converted data of the scattered light amount, that is, the original. Input A / D conversion data (Fig. 2
S1) (FIG. 3), and the original A / D converted data is differentiated in real time (S2 in FIG. 2) (FIG. 4). This differentiation can be obtained by calculating the difference between the original A / D converted data values in a minute time interval. Further, the obtained differential data is smoothed in real time using, for example, the median method (S3 in FIG. 2) (FIG. 5).
The median method is before and after a certain sampling point,
In this method, the median of the differential data of arbitrary n points is used as the data of that point. It is difficult to remove sudden noise by the conventional moving parallel method, but it can be removed by the median method.
【００１０】次に前記平滑化されて得た微分データを再
びリアルタイムで積分し、そのデータを基準Ａ／Ｄ変換
データＸとして記憶する（Ｓ４）（図６）。前記Ｓ２の
微分操作とＳ３の平滑化操作を経た基準Ａ／Ｄ変換デー
タＸにおいては、オリジナルＡ／Ｄ変換データのノイズ
や原点変動（測定ベースラインの変動）が取り除かれ、
平滑で一定の原点（測定ベースライン）をもつデータと
なる。次に演算される前記基準Ａ／Ｄ変換データＸをリ
アルタイムで積分して、これを基準積分データＹとして
記憶する（図２のＳ５）（図６）。また前記基準Ａ／Ｄ
変換データＸの各サンプリングポイントの前後のｎ点の
積算値の比、即ち基準Ａ／Ｄ変換データＸの各隣合う微
小時間での積算値の比を演算し、これを基準比データＺ
として記憶する（図２のＳ５）（図７）。Next, the smoothed differential data is again integrated in real time, and the data is stored as reference A / D conversion data X (S4) (FIG. 6). In the reference A / D converted data X that has undergone the differential operation of S2 and the smoothing operation of S3, noise and origin fluctuation (variation of measurement baseline) of the original A / D converted data are removed,
The data is smooth and has a fixed origin (measurement baseline). Next, the reference A / D conversion data X calculated next is integrated in real time and stored as reference integration data Y (S5 in FIG. 2) (FIG. 6). Also, the standard A / D
The ratio of the integrated values of the n points before and after each sampling point of the converted data X, that is, the ratio of the integrated values of the reference A / D converted data X in each adjacent minute time is calculated, and this is calculated as the reference ratio data Z.
(S5 in FIG. 2) (FIG. 7).
【００１１】次に、マイコン７は、前記リアルタイム的
に演算される前記基準比データＺが、予め定めた一定の
基準比データ値Ｚs となるのを常時監視し（図２のＳ
６）（図７）、前記一定の基準比データ値Ｚs となる都
度、その時点（Ｔ1 、Ｔ2 ・・Ｔn ）が基準比データＺ
のピークＺp 以降の時点であるか（図２のＳ７）、その
時点（Ｔ1 、Ｔ2 ・・Ｔn ）における前記基準積分デー
タ値（Ｙ1 、Ｙ2 ・・Ｙn ）が予め定めた一定のノイズ
除去用しきい値Ｙs 以上であるか（図２のＳ８）、及び
前記基準Ａ／Ｄ変換データ値（Ｘ1 、Ｘ2 ・・Ｘn ）が
予め定めた一定のノイズ除去用しきい値Ｘs 以上である
か（図２のＳ９）の３つの条件を判定し、その３つの条
件を満足する時点（Ｔ2 ）が得られると、その時点（Ｔ
2 ）での基準Ａ／Ｄ変換データ値（Ｘ2 ）を選出し、仮
の凝固点（Ｘd ) とする（図２のＳ10）（図７、図
８）。Next, the microcomputer 7 constantly monitors that the reference ratio data Z calculated in real time has a predetermined constant reference ratio data value Z s (S in FIG. 2).
6) (FIG. 7), each time the constant reference ratio data value Z s is reached, the time (T 1 , T 2 ... T n ) is changed to the reference ratio data Z.
Determined whether a time after the peak Z p (S7 in FIG. 2), the reference integrated data value at that time (T 1, T 2 ·· T n) (Y 1, Y 2 ·· Y n) in advance Is equal to or more than a constant noise removal threshold value Y s (S8 in FIG. 2), and the reference A / D conversion data value (X 1 , X 2 ... X n ) is predetermined noise removal. When three conditions (T 2 ) satisfying the three conditions are determined by determining three conditions that are equal to or more than the threshold value X s (S9 in FIG. 2), the time (T
Reference A / D conversion data values in 2) (X 2) elected, as the temporary freezing point (X d) (S10 in FIG. 2) (Fig. 7, Fig. 8).
【００１２】前記予め定めた一定の基準比データ値Ｚs
は、予め実験により適当な値を採用して、マイコンに記
憶させておく。同様に、基準積分データＹにおける一定
のノイズ除去用しきい値Ｙs も、予め実験によりノイズ
を除去するのに適当な値を採用してマイコンに記憶させ
ておく。このノイズ除去用しきい値Ｙs は被検試料（検
体）の凝固が現に進行しており、基準Ａ／Ｄ変換データ
値が増加状態にあることを確認するもので、基準Ａ／Ｄ
変換データＸに生じる高くて幅の狭いノイズ等を除去す
るのに有効である。又、前記基準Ａ／Ｄ変換データＸに
おける一定のノイズ除去用しきい値Ｘs についても、予
め実験によりノイズを除去するのに適当な値を採用して
マイコンに記憶させておく。このノイズ除去用しきい値
Ｘs は、基準Ａ／Ｄ変換データＸに生じる低くて幅のあ
るノイズ等を除去するのに有効である。尚、前記基準Ａ
／Ｄ変換データＸにおける一定のノイズ除去用しきい値
Ｘs についての条件（図２のＳ９）については、これを
省いてもよい。The predetermined constant reference ratio data value Z s
Is stored in the microcomputer by using an appropriate value in advance through experiments. Similarly, the constant noise removal threshold value Y s in the reference integrated data Y is also stored in the microcomputer in advance by adopting an appropriate value for removing noise by experiments. This noise removal threshold value Y s is used to confirm that coagulation of the test sample (specimen) is actually in progress and the reference A / D conversion data value is in an increasing state.
This is effective in removing high and narrow noises and the like generated in the converted data X. Moreover, also the reference A / D conversion data constant noise removal threshold value in X X s, advance and stored in the microcomputer employs a suitable value to remove noise by experiment. This noise removal threshold value X s is effective in removing low and wide noise generated in the reference A / D conversion data X. The above criteria A
This may be omitted for the condition (S9 in FIG. 2) regarding the constant noise removal threshold value X s in the / D conversion data X.
【００１３】上記のようにして仮の凝固点（Ｘd ) を選
出した後（図２のＳ10）、該仮の凝固点（Ｘd ) を用い
て、該Ｘd の１／Ｎ（Ｎは１以上の一定整数）の値Ｘc
を演算し、基準Ａ／Ｄ変換データ値がこの値Ｘc となる
時点Ｔc までの混合時点からの時間Ｈをもって凝固時間
とする（図２のＳ12）（図８）。得られた凝固時間Ｈを
出力装置９を介して表示し（図２のＳ13）、測定動作を
終了する（図２のＳ14）。[0013] After elected as the temporary freezing point (X d) (S10 in FIG. 2), with the freezing point of the temporary a (X d), 1 / N (N is 1 or more of the X d Value X c
Is calculated, and the time H from the mixing time until the time point T c when the reference A / D converted data value becomes this value X c is defined as the coagulation time (S12 in FIG. 2) (FIG. 8). The obtained coagulation time H is displayed via the output device 9 (S13 in FIG. 2), and the measurement operation is finished (S14 in FIG. 2).
【００１４】前記ステップＳ10で仮の凝固点（Ｘd ) が
選出された時点からステップＳ13で凝固時間Ｈが演算さ
れるまでは、瞬時的になされるので、測定に必要な時間
は、実質上、前記ステップＳ６〜Ｓ９の条件が満たされ
た前記仮の凝固点（Ｘd ) に対応する時点Ｔ2 までの時
間ですむ。そしてこの時点Ｔ2 で測定動作を終了し、次
の測定動作に移ることが可能となる。即ち、決められた
時間を必ず経なければ次の測定動作に移れないといった
従来の問題が解消され、全体として多数の検体の凝固時
間の測定を無駄な時間を少なくして、迅速に行うことが
できる。Since the tentative freezing point (X d ) is selected in step S10 until the freezing time H is calculated in step S13, the time required for measurement is substantially the same. The time up to time T 2 corresponding to the temporary freezing point (X d ) satisfying the conditions of steps S6 to S9 is sufficient. Then, at this time point T 2 , the measurement operation can be ended and the next measurement operation can be started. That is, the conventional problem that the next measurement operation cannot be started unless the predetermined time is definitely passed is solved, and it is possible to quickly measure the coagulation time of a large number of specimens by reducing unnecessary time. it can.
【００１５】本発明の測定方法では基準比データＺを利
用しているが、これによって、個々の装置間でのゲイン
のバラツキによる悪影響が少なくなるのは勿論のこと、
多チャンネル測定部を持つ測定装置の前記各測定チャン
ネル毎のゲインのバラツキによる悪影響も少なくなり、
信頼性の高い結果が得られる。この理由を図９に沿って
説明する。今、同一検体を２つの測定機によって、測定
した場合、測定機のゲインの差により、図９のイ、ロの
散乱光量−時間曲線が得られたとする。この場合、例え
ば図のｔ1 、ｔ2 の隣合う時点をとらえて説明すると、
本発明の方法では、Ａ／Ｄ変換データの各微小時間毎に
おける積算値の比を採用しているので、積算値（面積）
の比は、イの曲線では25／10（時間幅が僅かであるので
高さの比とし表される）となり、またロの曲線では50／
20となる。即ち、いずれの曲線においても比は2.5 とな
り、測定機によるゲインの差の影響は問題としなくな
り、凝固時間差が生じ難くなる。これに対して、従来法
の１つである微分法を採用した場合には、ｔ1 −ｔ2 ＝
１として計算すると、イの曲線では、（25−10）／１＝
15 となり、ロの曲線では、（50−20）／１＝30とな
り、微分値は両者で異なる。即ち、凝固時間差が出るこ
とになる。In the measuring method of the present invention, the reference ratio data Z is used. However, of course, the adverse effect due to the variation in the gain among the individual devices is reduced,
The adverse effect due to the variation in the gain of each of the measurement channels of the measurement device having the multi-channel measurement unit is reduced,
Reliable results are obtained. The reason for this will be described with reference to FIG. Now, when the same sample is measured by two measuring instruments, it is assumed that the scattered light amount-time curves of a and b of FIG. 9 are obtained due to the difference in gain of the measuring instruments. In this case, for example, when the time points adjacent to t 1 and t 2 in the figure are considered and described,
In the method of the present invention, since the ratio of the integrated value of A / D converted data at each minute time is adopted, the integrated value (area)
The ratio of is 25/10 in the curve of a (expressed as the ratio of height because the time width is small) and 50 / in the curve of b.
20. That is, the ratio is 2.5 in any curve, the influence of the difference in gain due to the measuring machine does not matter, and the difference in coagulation time hardly occurs. On the other hand, when the differential method, which is one of the conventional methods, is adopted, t 1 −t 2 =
When calculated as 1, the curve of (i) is (25-10) / 1 =
It becomes 15, and in the curve of B, it becomes (50-20) / 1 = 30, and the differential value is different for both. That is, there is a difference in coagulation time.
【００１６】本発明の方法、装置により、実際に検体凝
固時間を測定した実施例を示す。正常域の管理血漿を生
理食塩水で、1/2 、1/4 、1/8 、1/16と順次希釈した検
体を試料として、プロトロンビン時間を測定した。試料
中のフィブリノゲン濃度及び凝固因子濃度は希釈と共に
1/2 、1/4 、1/8 、1/16と減少する。このようにして異
常検体を人工的に調整して、本発明による凝固時間の測
定を行った。また比較例として、散乱光量の最大変化速
度、即ち微分値の最大値を基準とする方法（Ｖmax ）に
よる凝固時間の測定を行った。結果を表１に示す。各試
料を５回ずつ測定したところ、Ｖmax 法では、1/16の検
体は検出不能だったにもかかわらず、本発明による場合
には1/16の検体も検出できることが判った。即ち、本発
明では安定した凝固時間データを幅広い検出範囲で得ら
れることが判った。An example in which the coagulation time of a sample is actually measured by the method and apparatus of the present invention will be shown. The prothrombin time was measured using a sample obtained by serially diluting control plasma in the normal range with physiological saline to 1/2, 1/4, 1/8, 1/16. The concentration of fibrinogen and coagulation factor in the sample, along with dilution
Reduced to 1/2, 1/4, 1/8, 1/16. In this way, the abnormal sample was artificially adjusted and the coagulation time according to the present invention was measured. As a comparative example, the maximum change speed of the scattered light amount, that is, the coagulation time was measured by a method (V max ) using the maximum value of the differential value as a reference. The results are shown in Table 1. When each sample was measured 5 times, it was found that 1/16 sample could be detected by the V max method although 1/16 sample could not be detected by the V max method. That is, it was found that the present invention can obtain stable coagulation time data in a wide detection range.
【００１７】[0017]
【表１】 [Table 1]
【００１８】[0018]
【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、散乱光量をそ
のままＡ／Ｄ変換した一次データではなく、該Ａ／Ｄ変
換データを平滑化及び原点調整をして基準Ａ／Ｄ変換デ
ータとして利用するので、前記一次データに生じる散乱
光量のバラツキや、検体の濁り等による一次データにお
ける基底レベルのバラツキを解消することができる。ま
た、本発明方法によれば、２つの条件を満たした一定の
基準比データ値が選出できると、その時点でただちに光
量測定動作を終了し、次の検体の測定動作に移ることが
できる。よって既に凝固が完了していても一定時間まで
は必ず測定しないとデータ処理ができないといった従来
の方法に比べて処理時間を短縮することができる。ま
た、本発明方法によれば、Ａ／Ｄ変換データの各隣合う
微小時間での積算値の比である基準比データを用い、該
基準比データが予め定めた一定の基準比データ値になる
時点を得ることで、最終的に凝固時間を演算する方法を
採用しているので、よって本発明方法では、散乱光量の
変化が生じれば凝固時間の測定に十分で、その散乱光量
の微分値にピークが生じないような検体、即ち、散乱光
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、或いは低フィブリノゲン濃度の
被検試料のような光量変化量が小さく最大変化速度（微
分値のピーク）を的確にとらえられない検体、に対して
も確実に凝固時間を得ることができる。また、本発明方
法によれば、基準Ａ／Ｄ変換データの各隣合う微小時間
での積算値の比である基準比データを用いているので、
測定装置の個々の装置に生じるゲインのバラツキの影響
を少なくすることができるのは勿論のこと、多チャンネ
ル測定部を持つ測定装置の前記各測定チャンネル毎のゲ
インのバラツキの影響も少なくすることができ、信頼性
の高い結果を得ることができる。また上記本発明装置の
特徴によれば、上記発明方法を現に行い、凝固時間を得
てこれを表示することができる。According to the present invention, which has the above-described structure,
According to the blood coagulation time measuring method described in (1), not the primary data obtained by A / D converting the scattered light amount as it is, but the A / D converted data is used as reference A / D converted data after smoothing and origin adjustment. Therefore, it is possible to eliminate the variation in the amount of scattered light that occurs in the primary data and the variation in the base level in the primary data due to turbidity of the sample. Further, according to the method of the present invention, when a constant reference ratio data value satisfying the two conditions can be selected, the light amount measurement operation can be immediately terminated at that point, and the measurement operation of the next sample can be started. Therefore, the processing time can be shortened as compared with the conventional method in which data processing cannot be performed unless measurement is performed for a certain time even if the coagulation is already completed. Further, according to the method of the present invention, the reference ratio data, which is the ratio of the integrated value of the A / D conversion data at each adjacent minute time, is used, and the reference ratio data becomes a predetermined constant reference ratio data value. Since the method of finally calculating the coagulation time by obtaining the time point is adopted, the method of the present invention is therefore sufficient for measuring the coagulation time if a change in the scattered light amount occurs, and the differential value of the scattered light amount. That does not have a peak in the sample, that is, the change in the scattered light amount (differential value) is linear (linear function) with time, or the change in the light amount such as the test sample with low fibrinogen concentration The coagulation time can be reliably obtained even for a sample whose amount is small and the maximum rate of change (peak of differential value) cannot be accurately captured. Further, according to the method of the present invention, since the reference ratio data, which is the ratio of the integrated values of the reference A / D conversion data in adjacent small times, is used,
It is of course possible to reduce the influence of the gain variation occurring in each device of the measuring device, and also to reduce the influence of the gain variation of each of the measurement channels of the measuring device having the multi-channel measuring section. It is possible to obtain a reliable result. Further, according to the features of the device of the present invention, it is possible to actually perform the above-mentioned method of the present invention, obtain the coagulation time, and display it.
【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】マイクロコンピュータが有する凝固時間演算機
構のフローチャートである。FIG. 2 is a flowchart of a coagulation time calculation mechanism included in a microcomputer.
【図３】検出された散乱光量のオリジナルのＡ／Ｄ変換
データを時間を横軸にして表したオリジナルＡ／Ｄ変換
データ曲線図である。FIG. 3 is an original A / D conversion data curve diagram in which the original A / D conversion data of the detected scattered light amount is represented with time as the horizontal axis.
【図４】オリジナルＡ／Ｄ変換データを微分した微分デ
ータ曲線図である。FIG. 4 is a differential data curve diagram obtained by differentiating the original A / D converted data.
【図５】微分データを平滑化した平滑化データ曲線図で
ある。FIG. 5 is a smoothed data curve diagram obtained by smoothing differential data.
【図６】平滑化データを積分して得た基準Ａ／Ｄ変換デ
ータと該基準Ａ／Ｄ変換データを積分した基準積分デー
タとを時間を横軸にして表した曲線図である。FIG. 6 is a curve diagram showing the reference A / D conversion data obtained by integrating the smoothed data and the reference integration data obtained by integrating the reference A / D conversion data with time as the horizontal axis.
【図７】基準Ａ／Ｄ変換データの各隣合う微小時間での
積算値の比データである基準比データを、基準Ａ／Ｄ変
換データと基準積分データと共に時間を横軸にして表し
た曲線図である。FIG. 7 is a curve showing the reference ratio data, which is the ratio data of the integrated values of the reference A / D conversion data at adjacent small times, along with the reference A / D conversion data and the reference integration data, with the horizontal axis representing time. It is a figure.
【図８】選出した凝固完了点から凝固時間を演算する方
法を説明する図である。FIG. 8 is a diagram illustrating a method of calculating a coagulation time from a selected coagulation completion point.
【図９】本発明の基準比データを用いる方法と従来の微
分データを用いる方法との差を説明する図である。FIG. 9 is a diagram for explaining the difference between the method using the reference ratio data of the present invention and the conventional method using differential data.
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 Ｘ 基準Ａ／Ｄ変換データ Ｙ 基準積分データ Ｚ 基準比データ 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 X reference A / D conversion data Y reference integration data Z reference ratio data
Claims (2)
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
逐次散乱光量を測定し、リアルタイムに得られるＡ／Ｄ
変換データを平滑化及び原点調整をして基準Ａ／Ｄ変換
データとし、該基準Ａ／Ｄ変換データから、更にこれを
積分した基準積分データと、前記基準Ａ／Ｄ変換データ
の各隣合う微小時間での積算値の比である基準比データ
とを演算し、該基準比データが予め定めた一定の基準比
データ値になる時点のうち、前記基準比データのピーク
以降の時点で且つ前記基準積分データが予め定めた一定
のノイズ除去用しきい値以上となる時点における基準Ａ
／Ｄ変換データ値を選出し、該基準Ａ／Ｄ変換データ値
の１／Ｎ（Ｎは１以上の一定整数）の値が対応する時点
までの混合時点からの時間をもって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 of 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, and measuring the amount of scattered light sequentially from the time of mixing the reagents. And A / D obtained in real time
The converted data is smoothed and the origin is adjusted to form reference A / D converted data, and the reference integrated data obtained by further integrating the reference A / D converted data and the reference A / D converted data are adjacent to each other. The reference ratio data, which is the ratio of the integrated value over time, is calculated, and at a time point after the peak of the reference ratio data and at the time when the reference ratio data becomes a predetermined constant reference ratio data value. Reference A at the time when the integrated data becomes equal to or higher than a predetermined constant noise removal threshold value
A / D conversion data value is selected, and the time from the mixing time until the time corresponding to the value of 1 / N (N is a constant integer of 1 or more) of the reference A / D conversion data value is taken as the coagulation time. A characteristic method for measuring blood coagulation 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
リングしてリアルタイムでデジタル化するＡ／Ｄ変換手
段と、該Ａ／Ｄ変換手段からのＡ／Ｄ変換データを先ず
微分演算すると共に平滑化処理して基準Ａ／Ｄ変換デー
タとして記憶し、次にこの基準Ａ／Ｄ変換データから、
更にこれを積分した基準積分データと、前記基準Ａ／Ｄ
変換データの各隣合う微小時間での積算値の比である基
準比データとをそれぞれ演算して記憶し、次に前記基準
比データが予め定めた一定の基準比データ値になる時点
を求めると共に該時点のうち、前記基準比データのピー
ク以降の時点で且つ前記基準積分データが予め定めた一
定のノイズ除去用しきい値以上となる時点を選出し、次
にこの選出した時点における基準Ａ／Ｄ変換データ値を
選出し、次にこの基準Ａ／Ｄ変換データ値の１／Ｎ（Ｎ
は１以上の一定整数）の値が対応する時点までの混合時
点からの時間を演算する機構を有するマイクロコンピュ
ータと、該マイクロコンピュータの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. An amplifying means for amplifying the detected amount by the means, an A / D converting means for sampling the detected amount amplified by the amplifying means at a constant minute time interval and digitizing it in real time; The A / D converted data is first subjected to a differential operation and smoothed to be stored as reference A / D converted data. Next, from this reference A / D converted data,
Further, the reference integration data obtained by integrating this and the reference A / D
The reference ratio data, which is the ratio of the integrated value of each adjacent minute time of the converted data, is calculated and stored, and the time when the reference ratio data becomes a predetermined constant reference ratio data value is obtained. Of the time points, a time point after the peak of the reference ratio data and a time point at which the reference integration data becomes equal to or higher than a predetermined constant noise removal threshold value is selected, and the reference A / at the time point is selected. Select the D-converted data value, and then select 1 / N (N
Is a constant integer of 1 or more), a blood coagulation time measuring device including at least a microcomputer having a mechanism for calculating a time from a mixing time until a time corresponding to the value, and a display means for displaying a calculation result of the microcomputer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6273793A JP2938302B2 (en) | 1993-02-25 | 1993-02-25 | Blood coagulation time measuring method and apparatus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6273793A JP2938302B2 (en) | 1993-02-25 | 1993-02-25 | Blood coagulation time measuring method and apparatus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06249855A true JPH06249855A (en) | 1994-09-09 |
| JP2938302B2 JP2938302B2 (en) | 1999-08-23 |
Family
ID=13209002
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6273793A Expired - Fee Related JP2938302B2 (en) | 1993-02-25 | 1993-02-25 | Blood coagulation time measuring method and apparatus |
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| Country | Link |
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| JP (1) | JP2938302B2 (en) |
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