JPS6222066A - Latex agglutination reaction measuring instrument - Google Patents
Latex agglutination reaction measuring instrumentInfo
- Publication number
- JPS6222066A JPS6222066A JP16246285A JP16246285A JPS6222066A JP S6222066 A JPS6222066 A JP S6222066A JP 16246285 A JP16246285 A JP 16246285A JP 16246285 A JP16246285 A JP 16246285A JP S6222066 A JPS6222066 A JP S6222066A
- Authority
- JP
- Japan
- Prior art keywords
- transmitted light
- amount
- sample
- initial stage
- time
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Links
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- Automatic Analysis And Handling Materials Therefor (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
Description
【発明の詳細な説明】
「産業上の利用分野」
この発明は、客観的測定による定量が可能で、測定効率
も良く、しかも操作性にも優れ、且つ安価に製造し得る
ラテックス凝集反応測定装置に関するものである。Detailed Description of the Invention "Industrial Application Field" The present invention provides a latex agglutination reaction measuring device that enables quantitative determination by objective measurement, has good measurement efficiency, has excellent operability, and can be manufactured at low cost. It is related to.
「従来技術及びその問題点」
免疫反応をラテックス凝集反応を用いて測定する方法ト
シテは、例えば、F[lP 、 CRP 、RA、 A
SLOなどの血中蛋白質の測定に、ガラス平板上の凝集
状態を目視で判定す°る方法が知られているが、この方
法は簡便である反°面、半定量であり、しかも稀釈操作
が繁雑であると共に判定に個人差が生ずる等の問題があ
った。"Prior art and its problems" A method for measuring an immune reaction using latex agglutination reaction includes, for example, F[lP, CRP, RA, A
A known method for measuring blood proteins such as SLO is to visually determine the state of aggregation on a glass plate, but while this method is simple, it is only semi-quantitative and requires dilution. There were problems such as being complicated and causing individual differences in judgment.
一方、光学的な吸光度の変化として凝集状態をとらえる
方法または装置も知られており、例えば特公昭5B−1
1575号公報、特開昭54−108883号公報、特
開昭54−108895号公報、°特開昭57−149
951号公報、特開昭57−183848号公報に記載
されているしかして上記方法は、客観的測定による定量
が回部である利点がある反面、単一の光源と検出器を用
いているため、マニュアル操作で測定の効率を1”fJ
″″′すると・検体試料の光学系〜の出し
。On the other hand, there are also known methods and devices that detect the state of aggregation as a change in optical absorbance; for example,
1575, JP 54-108883, JP 54-108895, JP 57-149
However, the above method described in Japanese Patent Application Laid-Open No. 57-183848 has the advantage that quantitative measurement is performed repeatedly by objective measurement, but on the other hand, it uses a single light source and a detector. , the measurement efficiency can be reduced to 1” fJ by manual operation.
″″Then, the optical system of the specimen is exposed.
.
入れを頻繁に行なわなければならないので、操作が煩雑
になる欠点があった。このような欠点を解消し、効率を
上げ操作性をよくするため、単一の光源と検出器を時分
割で使用する自動化された機械が市販されているが、こ
のものは非常に高価である難点があった。This has the disadvantage that the operation becomes complicated because it has to be inserted frequently. To overcome these shortcomings and improve efficiency and ease of operation, automated machines that use a single light source and detector in a time-sharing manner are commercially available, but they are very expensive. There was a problem.
この発明は、上記問題点を解消し、客観的な測定による
定量が可能で、測定の効率がよく、シかも操作性にも優
れ、且つ安価に製造し得るラテックス凝集反応測定装置
を提供することを目的とする。The present invention solves the above-mentioned problems, and provides a latex agglutination reaction measuring device that enables quantitative determination by objective measurement, has good measurement efficiency, has excellent operability, and can be manufactured at low cost. With the goal.
「発明の概要」
ラテックス凝集反応を透過光量の変化として、測定した
場合の反応タイムコースは、第3図のようになるが、複
数の試料を同時に別々の光学系で測定すると、感度の違
いがあるためI(t)の間の互換性は無い。"Summary of the Invention" The reaction time course when measuring the latex agglutination reaction as a change in the amount of transmitted light is as shown in Figure 3. However, when multiple samples are measured simultaneously using different optical systems, differences in sensitivity may occur. Therefore, there is no compatibility between I(t).
感度の違いを補正するため、例えば反応の初期段階の透
過光量IOに対するその後の透過光量r(t)の比率R
(t)= [I(t)/Iol X 100%を求める
と、その反応タイムコースは第4図のようになり、この
R(t)は複数の測定光学系の間で互換性のある量とな
る。In order to correct the difference in sensitivity, for example, the ratio R of the subsequent transmitted light amount r(t) to the transmitted light amount IO at the initial stage of the reaction.
(t) = [I(t)/Iol becomes.
+愈KJ卓竺J↓ r小プレ九ギl田1 愉島小廿籠の
透過光量の測定開始を独立して指示する例えばスイッチ
機構によって各試料の測定を開始し、スイッチと連動し
て各試料の反応時間をタイマで同時に並行してカウント
し、各試料の各々の時間でのR(t)を同時に求めてゆ
けば、複数試料の透過光量の時間変化を別々に測定でき
る非常に効率の良い操作性の優れた装置が構成できるこ
とを見出し、本発明に到達した。+Yu KJ Takuji J↓ r Small Pre-Kugilta 1 Independently instruct the start of measurement of the amount of transmitted light of the Yushima small cage.For example, start the measurement of each sample by a switch mechanism, and in conjunction with the switch, each If the reaction times of the samples are counted in parallel using a timer and the R(t) of each sample at each time is determined simultaneously, it is possible to measure the temporal change in the amount of transmitted light of multiple samples separately, which is very efficient. We have discovered that it is possible to construct a device with excellent operability, and have arrived at the present invention.
即ち本発明は、試料と試料中の抗原あるいは抗体と反応
して凝集反応を生起するラテックス試薬との混合物(被
検試料液)を収容する複数の試料キュベツトを保持する
手段と、該試料キュベツトに各々光線を照射し、各々の
透過光量を別々に検知する手段と、該各々の透過光量の
検知の感度差を補正する手段と、前記被検試料液の透過
光量の測定開始を指示する手段と、該被検試料液の透過
光量の測定開始時点からの経過時間を前記各々の試料キ
ュベツトについて別々に計時するタイマとを具備し、複
数試料の透過光量の時間変化を同時に並行して測定する
ことを特徴とする特要するに本発明は、従来が単一の光
源と検出器を使用することを考えているだけで、複数の
光学系での並列測定という点に考えが及んでいなかった
のに対し、異なる光学系間の感度補正をすることにより
、複数の光学系での並列測定を可能としたことを特徴と
する。That is, the present invention provides means for holding a plurality of sample cuvettes containing a mixture (test sample liquid) of a sample and a latex reagent that reacts with an antigen or antibody in the sample to cause an agglutination reaction, and means for irradiating each light beam and detecting the amount of transmitted light of each separately; means for correcting the difference in sensitivity in detecting the amount of transmitted light; and means for instructing the start of measurement of the amount of transmitted light of the test sample liquid. , and a timer that separately measures the elapsed time for each of the sample cuvettes from the start of measurement of the amount of transmitted light of the sample liquid to be tested, and simultaneously measures changes over time in the amount of transmitted light of a plurality of samples in parallel. Specifically, the present invention is characterized by the fact that conventional methods have only considered the use of a single light source and detector, but have not considered parallel measurement using multiple optical systems. On the other hand, it is characterized in that it enables parallel measurements with multiple optical systems by performing sensitivity correction between different optical systems.
即ち、第8図に示される本発明の原理的な構成ブロック
図において、試料キューベット1と、該試料キューベッ
トを照射する光源2と、試料キューベット1を通過した
透過光量を検知する手段3とからなる複数の光学系が、
光学系を保持する手段20に装備されている。そして、
光学系の感度差は、光学系の感度差を補正する手段21
により補正され、透過光量の測定開始は、透過光量の測
定開始を指示する手段4により開始され、被検試料液の
透過光量の測定開始時点からの経過時間は、タイマ22
により計時されるようになっている。That is, in the basic configuration block diagram of the present invention shown in FIG. 8, there are a sample cuvette 1, a light source 2 that irradiates the sample cuvette, and a means 3 for detecting the amount of transmitted light that has passed through the sample cuvette 1. Multiple optical systems consisting of
A means 20 for holding the optical system is provided. and,
The difference in sensitivity of the optical system is corrected by means 21 for correcting the difference in sensitivity of the optical system.
The measurement of the amount of transmitted light is started by the means 4 for instructing the start of measurement of the amount of transmitted light, and the elapsed time from the start of measurement of the amount of transmitted light of the test sample liquid is determined by the timer 22.
The time is measured by
「実施例」
次に本発明の望ましい実施例を図面を参照しながら説明
する。"Embodiments" Next, preferred embodiments of the present invention will be described with reference to the drawings.
第1図は本発明に係る測定装置のブロック図であり、試
料とラテックス試薬との混合物(被検試料液)を収容す
る複“数の試料キュベツト1と、複数の光源2から各々
対応する複数の試料キュベツト1に光線を照射し複数の
透過光量を別々に検知する光電検出器3と、光電検出器
3で検知された複数の透過光量I(t)を順次切替えて
次々に送信するマルチプレクサ5と、複数の検知の感度
差を補正する感度補正回路19と、この補正された結果
をデジタル値に変換するA/D変、換器7と、試料とラ
テックス試薬との混合に連動して各被検試料液の透過光
測定開始を指示するスイッチ機°構4と、とのスイッチ
機構の指示に連動して各被検試料液の透過光量の測定開
始時点からの経過時間を計時するタイマ10と、前記デ
ジタル化された透過光量の変化のデータ処理と装置全体
の動作を制御し、複数試料の透過光量の時間変化を同時
に測定処理す 【るコンピュータ8及びメモリ
11とから構成された例を示す、尚、キューベット1を
保持する手段は図では省略されている。FIG. 1 is a block diagram of a measuring device according to the present invention, which includes a plurality of sample cuvettes 1 containing a mixture of a sample and a latex reagent (test sample liquid), a plurality of light sources 2, and a corresponding plurality of a photoelectric detector 3 that irradiates a sample cuvette 1 with a light beam and separately detects a plurality of transmitted light quantities, and a multiplexer 5 that sequentially switches and transmits a plurality of transmitted light quantities I(t) detected by the photoelectric detector 3 one after another. , a sensitivity correction circuit 19 that corrects sensitivity differences between multiple detections, an A/D converter 7 that converts the corrected results into digital values, and a a switch mechanism 4 for instructing the start of measuring the amount of transmitted light of each sample liquid to be tested; and a timer 10 for measuring the elapsed time from the start of measurement of the amount of transmitted light for each sample liquid in conjunction with the instruction of the switch mechanism; and a computer 8 and a memory 11, which control the data processing of the digitalized changes in the transmitted light amount and the operation of the entire apparatus, and simultaneously measure and process the temporal changes in the transmitted light amount of multiple samples. Note that means for holding the cuvette 1 are omitted in the figure.
光源2としては、 LED 、タングステンランプ等の
発光素子を使用することができる。また光源2は、複数
段けなくとも、単一光源から光ファイバーで各試料キュ
ベツトに照射光を導いてもよい。As the light source 2, a light emitting element such as an LED or a tungsten lamp can be used. Furthermore, the light source 2 does not need to be arranged in multiple stages, and the irradiation light may be guided from a single light source to each sample cuvette using an optical fiber.
光電検出器3としては、透過光量に対応する電気信号が
発生するフォトダイオード、光電セル等の受光素子を使
用することができる。光電検出器も光源と同様に、単一
の光電検出器に光ファイバーで各試料キュベツトの透過
光を導いてもよい。As the photoelectric detector 3, a light receiving element such as a photodiode or a photocell that generates an electric signal corresponding to the amount of transmitted light can be used. Similar to the light source, the photodetector may also guide the transmitted light of each sample cuvette through an optical fiber to a single photodetector.
感度補正回路19は、上記実施例に於いては、比演算回
路6と1反応の初期段階のIoを設定するDIA変換器
或いは擬似被検試料の透過光量を設定する口/&変換器
8とから成る。感度補正回路19としては、被検試料液
の反応の初期段階の透過光量を記憶する手段と該初期段
階の透過光量に対するその後の透過光量の比を求める手
段、または↑疑似被検試料液の透過光量のブランク値と
被検試料液の透過光量との比あるいは該比率の対数を求
める手段であれば、他の手段であってもよい0例えば、
コンピュータ8とメモリ11によるプログラム動作で置
換えることもできる。In the above embodiment, the sensitivity correction circuit 19 includes a ratio calculation circuit 6, a DIA converter for setting Io at the initial stage of one reaction, or an input/& converter 8 for setting the amount of transmitted light of the pseudo test sample. Consists of. The sensitivity correction circuit 19 includes a means for storing the amount of transmitted light at the initial stage of the reaction of the test sample liquid, and a means for calculating the ratio of the amount of transmitted light thereafter to the amount of transmitted light at the initial stage, or Any other means may be used as long as it is a means for determining the ratio between the blank value of the light amount and the amount of transmitted light of the test sample liquid or the logarithm of the ratio. For example,
It can also be replaced by a program operation using the computer 8 and memory 11.
感度補正回路としては、被検試料液の反応の初期段階の
透過光量を記憶する手段と該初期段階の透過光量に対す
るその後の透過光量の比を求める手段とするのが、1つ
の被検試料液に対する透過光量の測定のみで検出感度の
補正ができ、非常に俺率が良く、また操作性にも優れて
いることから、好ましい。The sensitivity correction circuit has a means for storing the amount of transmitted light at the initial stage of the reaction of the test sample solution, and a means for calculating the ratio of the amount of transmitted light after that to the amount of transmitted light at the initial stage. This method is preferable because the detection sensitivity can be corrected only by measuring the amount of transmitted light relative to the object, the detection sensitivity is very good, and the operability is excellent.
感度補正回路として、擬似被検試料液の透過光量のブラ
ンク値と被検試料液の透過光量との比あるいは該比率の
対数を求める手段とする方法は、1つの被検試料液に対
する透過光量の測定の他、各検出光学系毎に擬似被検試
料(反応混合物の同一の系で抗原、抗体を含まないもの
)の測定が必要となり、操作がやや繁雑となる。As a sensitivity correction circuit, the method of calculating the ratio of the blank value of the amount of transmitted light of the pseudo test sample liquid to the amount of transmitted light of the test sample liquid, or the logarithm of the ratio, is based on the amount of transmitted light for one test sample liquid. In addition to measurement, it is necessary to measure a pseudo test sample (the same system of reaction mixture, but not containing antigen or antibody) for each detection optical system, which makes the operation somewhat complicated.
前記初期段階の透過光量は、初期段階一定時間内に於け
る、任意の特定の時点での透過光量であっても、最大値
であっても、最小値であっても或いは平均値であっても
よい。The amount of transmitted light in the initial stage may be the amount of transmitted light at any specific time within a certain period of time in the initial stage, the maximum value, the minimum value, or the average value. Good too.
最大値とする場合は、試薬と検体の混合時に気泡が混入
した場合が効果的であり、最小値とする場合は、試薬と
検体の混合液が均一となるのに時間がかかる場合が効果
的であり、また平均値とする場合は、細かな微粒子等に
より交流ノイズが信号に重畳する場合や比較的大きな粒
子の揺動による交流ノイズが生じる場合が効果的である
。また上記した試薬と検体の混合時に気泡が混入したり
、試薬と検体の乱合喬が均一となるのに時間がかかる場
合に、正しいlがとれる時間帯があらかじめ分っている
場合は、その特定時点での透過光量とするのがよい。When setting the maximum value, it is effective when air bubbles are mixed in when the reagent and sample are mixed; when setting the minimum value, it is effective when it takes time for the mixture of reagent and sample to become uniform. In addition, when using the average value, it is effective when AC noise is superimposed on the signal due to fine particles, etc., or when AC noise is generated due to the vibration of relatively large particles. In addition, if air bubbles are mixed in as described above when mixing the reagent and specimen, or if it takes time for the mixture of the reagent and specimen to become uniform, if the time period in which the correct l is obtained is known in advance, it is possible to It is preferable to use the amount of transmitted light at a specific point in time.
被検試料液の透過光量の測定開始を指示するスイッチ機
構4は、複数のキュベツトについて各々時間的あるいは
位置的に独立して指示する手段であっても、試料あるい
はラテックス試薬の分注器の分注動作と連動していても
よい、ここで1時間的に独立とは、2以上のキュベツト
について各々独立する任意のタイミングで測定開始でき
ることを意味し、例えば、1つのスイッチで操作者の手
順にあわせて適当に押すことで、複数キュベツトのlっ
ずつが測定開始されることを意味゛する。また、位置的
独立とは例えば、2以上のキュベツトに対応する2以上
の゛スイッチを設け、各々を独立して操作することで、
゛2以上のキュベツトについて各々独立して測定開始で
きることを意味する。The switch mechanism 4 for instructing the start of measurement of the amount of transmitted light of the test sample liquid is a means for instructing a plurality of cuvettes independently in terms of time or position. It may be linked to the measurement operation. Here, 1-hour independent means that measurement can be started at any independent timing for two or more cuvettes. For example, one switch can be used to adjust the operator's procedure By pressing the buttons appropriately at the same time, it means that measurement will be started for each of the multiple cuvettes. Also, positional independence means, for example, providing two or more switches corresponding to two or more cuvettes and operating each one independently.
This means that measurements can be started independently for two or more cuvettes.
上記構成を有する本発明の測定装置の機能を十分発揮せ
しめるため、上記実施例に於いては、データの数値表示
装置12(LED、CRTディスプレイ等)、データの
数値表示制御スイッチ13、データの印字プリンター1
4.外部コンビ・ユータとの通信装置15及び各試料キ
ュベツトの測定状態を表示する表示装置18を設けてい
る。In order to fully exhibit the functions of the measuring device of the present invention having the above configuration, in the above embodiment, a data numerical display device 12 (LED, CRT display, etc.), a data numerical display control switch 13, a data printing Printer 1
4. A communication device 15 for communicating with an external combination computer and a display device 18 for displaying the measurement status of each sample cuvette are provided.
第2図は、具体的に構成された本発明の測定装置の斜視
図を示すもので、12′は測定した試料のデータを表示
するスイッチ、13’は複数の表示データを切換えるス
イッチ、16は試料キュベツトを保持するホルダー、1
7はピペッタ−1!8は測定状態表示装置である。ここ
では1例としてte本の同時保持を行なう例を示した。FIG. 2 shows a perspective view of a specifically configured measuring device of the present invention, in which 12' is a switch for displaying data of the measured sample, 13' is a switch for switching between a plurality of display data, and 16 is a switch for displaying data of a measured sample. A holder for holding a sample cuvette, 1
7 is a pipettor 1! 8 is a measurement status display device. Here, as an example, an example is shown in which te books are held simultaneously.
ピペッタ−17は試料またはラテックス試薬を分注する
ものであるが、このピペッタ−17の動作がスイッチ4
と連動しており、ピペッタ−17の分注動作により試料
とラテックス試薬とを分注混合すると、測光動作が開始
し、タイマlOがスタートする。このタイマ10と連動
して、測定状態表示装置118が点燈し、どの試料キュ
ベツトが測定動作中であるかを報知する。The pipettor 17 is for dispensing the sample or latex reagent, and the operation of this pipetter 17 is controlled by the switch 4.
When the sample and latex reagent are dispensed and mixed by the dispensing operation of the pipetter 17, the photometry operation starts and the timer IO starts. In conjunction with this timer 10, the measurement status display device 118 lights up to notify which sample cuvette is undergoing measurement operation.
「作用」
次に、本発明の測定装置を使用し、ラテックス凝集反応
を測定した例を示す。"Effect" Next, an example in which latex agglutination reaction was measured using the measuring device of the present invention will be shown.
試験は、下記試薬及び試料を使用し、下記測定操作によ
り行った。The test was conducted using the following reagents and samples and by the following measurement operations.
試薬:平均粒径0.085 g mのポリスチレンラテ
ックスにFDPを感作させたラテックス試薬と抗体価5
0JLg Ag/mlの抗FDP溶液(ウサギ由来)試
料;内径6騰層の試験管キュベツトに適当な濃度に稀釈
した標準FDP試料50IL1をとり、これに抗FDP
溶液200pLlを加えて混合し、37℃で30分間加
温したものを試料とする。Reagent: A latex reagent made by sensitizing polystyrene latex with FDP with an average particle size of 0.085 g m and an antibody titer of 5.
0JLg Ag/ml anti-FDP solution (rabbit origin) sample: Take a standard FDP sample 50IL1 diluted to an appropriate concentration into a test tube cuvette with an inner diameter of 6 layers, and add anti-FDP to this.
Add 200 pL of the solution, mix, and heat at 37° C. for 30 minutes to use as a sample.
測定操作;上記250ILlの試料にラテックス試薬を
200plスイッチ付ピペッタ−で分注し、分注と同時
に測定をスタートする。 18箇所の同時測定が可能な
本発明の装置で次々に試料の透過光量を測定し、初期段
階の透過光量値Ioに対するその後の透過光量I(t)
の比率R(t)を、測定装置のコンピュータから得た。Measurement operation: Dispense the latex reagent into the 250 IL sample using a 200 pl pipettor with a switch, and start measurement at the same time as the dispensing. The amount of transmitted light of the sample is measured one after another using the device of the present invention that can perform simultaneous measurements at 18 locations, and the subsequent amount of transmitted light I(t) is calculated with respect to the initial transmitted light amount value Io.
The ratio R(t) was obtained from the computer of the measuring device.
但し、本試験でのR(t)は、次式によって計算した。However, R(t) in this test was calculated using the following formula.
R(t)= It/Io X255
t=2分とt−3分の場合について、標準FDP試料か
ら調製した数種濃度の試料について、各々8箇所の光学
系で同時に測定を行なった。結果は次の如くであった。R(t)=It/Io The results were as follows.
(1)補正による測定値の互換性
各測定光学系でのIoとI(t) (但し、t−2分或
いは3分)との差をΔlとして、R(t)との比較を行
表1:t=2分 表2:t=3分いずれの場合
も、各光学系の感度が異なっているためΔ■の互換性は
ないが、本発明によるR(t)の値は、光学系の感°度
差が補正されているので、異なる光学系の間で互゛換性
のある量となっている(2)検量関係
(1)で光学系間の互換性が認められたR(t)につい
て、FDP濃度との検量関係を測定した。結果を第5図
に示す。(1) Compatibility of measured values due to correction The difference between Io and I(t) (however, t-2 minutes or 3 minutes) in each measurement optical system is defined as Δl, and the comparison with R(t) is shown in the following table. 1: t = 2 minutes Table 2: t = 3 minutes In either case, since the sensitivity of each optical system is different, Δ■ is not compatible, but the value of R(t) according to the present invention is Since the difference in sensitivity has been corrected, it is a compatible amount between different optical systems. (2) R( t), the calibration relationship with FDP concentration was measured. The results are shown in Figure 5.
(3,)再現性
t=2分とt=3分の場合で、それぞれ2種の試料につ
き、各光学系で測定したR(t)を、第5図の検量線を
用いて濃度値に換算した。結果を次表3及び4に示す。(3,) Reproducibility R(t) measured with each optical system for two types of samples in the cases of t = 2 minutes and t = 3 minutes is converted into a concentration value using the calibration curve in Figure 5. Converted. The results are shown in Tables 3 and 4 below.
、ル/、千金≦)
′1代職
・・、r
表3 : t−2分
表4 : t=3分
t=2分の場合、上記(1)〜(3)で測定した48試
料につき、測定操作から結果が得られる迄の時間は僅か
!2分程度であり、本発明によれば多量の検体を簡便な
操作で迅速に測定することができる。, Ru/, Senkin ≦) '1 Daisoku..., r Table 3: t-2 minutes Table 4: When t = 3 minutes and t = 2 minutes, for the 48 samples measured in (1) to (3) above , it takes only a short time to get results from measurement operations! It takes about 2 minutes, and according to the present invention, a large amount of specimen can be measured quickly with a simple operation.
「発明の効果」
以上述べた如く、本発明によれば、任意のタイミングで
複数の試料を次々に測定開始することができ、測光ホル
ダーが試料キュベ−/ )で一杯になる頃には最初の試
料の測定が終了するので、それを再び使用することで、
空き時間なく、非常に効率よく多数の試料を迅速に測定
できる。"Effects of the Invention" As described above, according to the present invention, it is possible to start measuring multiple samples one after another at any timing, and by the time the photometry holder is full of sample cubes, the first Now that the sample measurement has been completed, by using it again,
A large number of samples can be measured quickly and efficiently without any idle time.
また、簡単な構成であるのでこのような多量検体処理装
置が安価に製造できると共に、各試料を任意のタイミン
グで独立して操作できるため、操作性にも優れている。Moreover, since it has a simple configuration, such a large-volume sample processing apparatus can be manufactured at low cost, and each sample can be operated independently at any timing, so it has excellent operability.
第1図は本発明の実施例を示すブロック図、第2図は本
発明の測定装置の斜視図、第3図はラテックス凝集反応
を透過光量の変化として測定した場合の反応タイムコー
スを示すグラフ、第4図は透過光l比と反応時間との関
係を示すグラフ、第5図は本発明の測定装置を使用しF
DP濃度との検量関係を測定したグ°ラフ、第6図は本
発明の原理的なブロック図である°。
図中。
l・・・試料キュベツト、2・・・光源、3・・・光電
検出器、4・・・透過光測定開始を指示するスイッチ機
構、5・・・マルチプレクサ、7・・・A/D変換器、
8・・・コンピュータ、lO・・・タイマ、11・・・
メモリ、16・・・ホルダー、17・・・ピペッタ−1
18・・・感1度補正回路特許出願人 和光純薬工業株
式会社
「
第2図
第3図
1(t)
した時間 (min、)
第4図
反に−Bu’i (mi n、 )
第5図
FDP濃度 (、ug/rr+z )
第6図
手続補正書
昭和61年 70月 7日
1、事件の表示
昭和60年 特許願第162462号
λ 発明の名称
ラテックス凝集反応測定装置
連絡先7):L03−270−85714、補正命令の
日付
自 発
5、補正の対象
明細書の発明の詳細な説明の欄。
6、補正の内容
(1)明細書3頁16行目に記載の「測定効率も良く」
を「測定効率が高く」と補正する。
(2)明細書4頁7行目から5頁2行目にかけて記載の
「一方、光学的な・・・・・・難点があっ゛た。、」を
削除し、代わシにその個所に以下の文章を挿入する。
「一方、光学的な吸光度の変化として凝集状態をとらえ
る方法又は装置も数、多く知られておシ、例え、ば■A
rch、 Biochem、 Biophys、、旦互
、338〜355(1955)、■Croatica
Chemiea Actj土2,457〜466(19
70)、■英国特許第989,617号明細書。
■特公昭58−11575号公報、■特開昭54−10
8693号公報、■特開昭54−108695号公報、
の特開昭57−149951号公報、■特開昭57−1
63848号公報等に記載されている。即ち、例えば■
時分 「昭58−11575号公報は分光光度計参
照側セルに抗体又は抗原を担持した不溶性担体粒子又は
これを含有する懸濁液と被検体の基礎媒体との混合物を
入れた時の近赤外領域の光線の透過光の強さを工。とじ
、試料側吸光セルに抗体又は抗原を担持した不溶性担体
粒子を含有する懸濁液と、抗原及び/又は抗体を含有す
る被検体との反応混合物を入れた時の近赤外領域の光線
の透過光の強さをIとして、式A = log IO/
rから吸光度Aを求め濁度の測定をしている。この様
に凝集状態を吸光度の変化としてとらえる方法は、従来
から、光源や検出器の不安定さをカバーするため上記例
の如く参照例及び試料側吸光セルの一対を用いて行なわ
れてきた。しかして上記の方法は、客観的測定による高
精度の定量が可能という利点がある反面、−検体毎の測
定装置であるのでマニュアル操作で複数個の試料の吸光
度の変化を測定するためには、反応時間を厳密に管理し
ながら繰シ返し試料セルを光学系へ出し入れしなければ
ならない。しかしながら、これは非常に煩雑で極めて困
難を伴うものである。特に反応途上の2以上の時点で吸
光度を測定する動的測定では、多数の試料を出し入れし
て並行測定することは実際上不可能である。通常は一つ
の試料が測定終了迄光学系を専有する方法がとられるた
め、測定の効率は極めて低くなる。
繰り返し試料セルを光学系へ出し入れする煩わしさを解
消するため、上記の吸光度測定システムを複数個内蔵さ
せることも考えられるが、参照側も同時に内蔵させなけ
ればならず、構造が複雑になり、製作可能としても高価
になり、また、内蔵させる吸光度測定システムの個数も
自ずから限られてくる。
一方、単一の光源と検出器を備え、自動的に複数個の試
料セルを入れ替える機械が市販されているが、これは非
常に高価という難点があった。
また、いずれの方法にしても、被検体の基礎媒体を用い
た試料の吸光度をブランクとすることは、実際の被検体
に着色、濁シがある場合、正しいブランク吸光度の測定
を保証するものではなかった」(3)明細書5頁3行目
に記載の「この発明は、」を「本発明は、」と補正する
。
(4)明細書5頁4行目に記載の「効率がよく、」を「
効率が高く、」と補正する。
(5)明細書5頁14行目に記載の「感度の違いを」を
「しかしながら、感度及び検体ブランクの違いを」と補
正する。
(6)明細書5頁14行目に記載の「例えば」を削除す
る。
(7)明細書5頁17行目から同頁18行目にかけて記
載の「このR(t)は」を「生化学反応系に於てとのR
(t)は」と補正する。
(8)明細書5頁19行目に記載の「なる。」を「なる
ことがわかった。」と補正する。
(9)明細書5頁20行目に記載の「本発明者等は、」
を「さらに、本発明者等は、」と補正する。
αQ明明細書7捲4
載の「異なる光学系間の感度補正をすることによシ、」
を「異なる光学系間の該感度補正法を考案、実施するこ
とにより、」と補正する。
αめ明細書7頁6行目に記載の「特徴とする。」の次に
改行して「さらにこの方法は検体ブランクの補正も可能
にしている。」を挿入する。
(6)明細書7頁12行目に記載の「光学系の」を「光
学系間の」と補正する。
(ハ)明細書8頁8行目に記載の「複数の検知の」を「
複数の光学系間の検知の」と補正する。
θ峰明細書10頁1゛行目に記載の「こともできる。」
の次に「また、タイマー10も1つの基本タイマーとコ
ンピューター8とメモリ11によるプログラム動作で置
換えることができる。」を挿入する。
(ト)明細書10頁5行目に記載の「1つの」を「1つ
の」と補正する。
αe明明細書1貞
「1つの」と補正する。
cLつ明細書10頁13行目に記載ア「(反応混合物」
を「(例えば反応混合物」と補正する。
Qll明細1ニ1
「1つの」と補正する。
α呻明細書12頁1行目に記載の「1つずつ」を「1つ
ずつ」と補正する。 「翰
明細書12頁15行目に記載の「スイッチ」を「数置表
示装置」と補正する。
以上
手続補正書
昭和61年10月20日Fig. 1 is a block diagram showing an embodiment of the present invention, Fig. 2 is a perspective view of the measuring device of the present invention, and Fig. 3 is a graph showing the reaction time course when the latex agglutination reaction is measured as a change in the amount of transmitted light. , Fig. 4 is a graph showing the relationship between transmitted light l ratio and reaction time, and Fig. 5 is a graph showing the relationship between transmitted light l ratio and reaction time.
FIG. 6 is a graph showing the measurement of the calibration relationship with the DP concentration, and is a basic block diagram of the present invention. In the figure. 1...Sample cuvette, 2...Light source, 3...Photoelectric detector, 4...Switch mechanism for instructing the start of transmitted light measurement, 5...Multiplexer, 7...A/D converter ,
8... Computer, lO... Timer, 11...
Memory, 16...Holder, 17...Pipetter-1
18... Sensitivity 1 degree correction circuit Patent applicant Wako Pure Chemical Industries, Ltd. "Figure 2 Figure 3 Figure 1 (t) Time (min,) Figure 4 -Bu'i (min,) Figure 5 FDP concentration (, ug/rr+z) Figure 6 Procedural amendment July 7, 1985 1, Indication of the incident 1985 Patent application No. 162462 λ Name of the invention Latex agglutination reaction measuring device Contact information 7): L03-270-85714, Date of amendment order. 5. Detailed description of the invention in the specification subject to amendment. 6. Contents of amendment (1) "Measurement efficiency is also well"
is corrected as ``high measurement efficiency.'' (2) The statement "On the other hand, there was an optical problem..." from line 7 on page 4 to line 2 on page 5 of the specification has been deleted, and the following is replaced in its place: Insert the text. ``On the other hand, there are many known methods and devices that detect the state of aggregation as a change in optical absorbance.
rch, Biochem, Biophys, Dango, 338-355 (1955), ■Croatica
Chemiea Actj Sat 2, 457-466 (19
70), ■Specification of British Patent No. 989,617. ■Special Publication No. 58-11575, ■Japanese Patent Publication No. 54-10
Publication No. 8693, ■Japanese Unexamined Patent Publication No. 54-108695,
JP 57-149951, ■ JP 57-1
It is described in Publication No. 63848 and the like. That is, for example, ■
Hours and Minutes "Publication No. 11575/1983 describes the near-infrared rays when a mixture of insoluble carrier particles carrying antibodies or antigens or a suspension containing them and the basic medium of the subject is placed in the reference side cell of a spectrophotometer. By controlling the intensity of the transmitted light in the outer region, a reaction between a suspension containing insoluble carrier particles carrying antibodies or antigens in the sample-side absorption cell and an analyte containing the antigen and/or antibody is generated. When the mixture is added, the intensity of transmitted light in the near-infrared region is I, and the formula A = log IO/
The absorbance A is determined from r and the turbidity is measured. Conventionally, this method of determining the state of aggregation as a change in absorbance has been carried out using a reference example and a pair of sample-side absorption cells, as in the above example, in order to cover for the instability of the light source and detector. However, although the above method has the advantage of allowing highly accurate quantification through objective measurement, it requires manual operation to measure changes in the absorbance of multiple samples because it is a measuring device for each sample. The sample cell must be repeatedly moved in and out of the optical system while strictly controlling the reaction time. However, this is very complicated and extremely difficult. Particularly in dynamic measurements in which absorbance is measured at two or more points in the course of a reaction, it is practically impossible to take in and take out a large number of samples and perform parallel measurements. Usually, a method is adopted in which one sample monopolizes the optical system until the end of the measurement, which results in extremely low measurement efficiency. In order to eliminate the trouble of repeatedly putting the sample cell in and out of the optical system, it is possible to incorporate multiple absorbance measurement systems as described above, but the reference side must also be built in at the same time, which would complicate the structure and increase manufacturing costs. Even if it were possible, it would be expensive, and the number of built-in absorbance measurement systems would also be limited. On the other hand, there are commercially available machines that are equipped with a single light source and detector and can automatically exchange multiple sample cells, but these have the drawback of being very expensive. In addition, regardless of the method, blanking the absorbance of the sample using the basic medium of the specimen does not guarantee correct blank absorbance measurement if the actual specimen has coloration or turbidity. (3) "This invention" written on page 5, line 3 of the specification is amended to read "this invention is". (4) “Efficiency” stated on page 5, line 4 of the specification is replaced with “
"It's highly efficient," he corrected. (5) "Difference in sensitivity" stated on page 5, line 14 of the specification is corrected to "However, difference in sensitivity and sample blank." (6) "For example" written on page 5, line 14 of the specification is deleted. (7) “This R(t)” written from line 17 to line 18 on page 5 of the specification is changed to “R(t) in a biochemical reaction system.”
(t) is”. (8) "Naru." written on page 5, line 19 of the specification is amended to "It turns out to be naru." (9) “The inventors are” stated on page 5, line 20 of the specification.
be amended to read, "Furthermore, the inventors of the present invention, etc.""By correcting sensitivity between different optical systems," stated in αQ Mei Specification, Volume 7, Volume 4.
is corrected as "by devising and implementing a method for correcting the sensitivity between different optical systems." Next to "Characteristics" written on page 7, line 6 of the alpha specification, insert a new line and insert "Furthermore, this method also makes it possible to correct sample blanks." (6) "Of the optical system" stated on page 7, line 12 of the specification is corrected to "between the optical systems." (c) "Multiple detections" stated on page 8, line 8 of the specification is replaced with "
Detection between multiple optical systems is corrected. "It is also possible" written on page 10, line 1 of the θmine specification.
Next, insert "Also, the timer 10 can be replaced by one basic timer and a program operation using the computer 8 and memory 11." (g) "One" written on page 10, line 5 of the specification is amended to "one". αe Akira Specification 1 is amended to read "one". cL Description on page 10, line 13 of the specification A “(reaction mixture)”
amend it to "(for example, a reaction mixture"). Qll Specification 1 Ni 1 Amend it to "one". Amend "one by one" written on page 12, line 1 of the alpha specification to "one by one". ``The ``switch'' described on page 12, line 15 of the Kan specification is amended to read ``numeric display device.'' The above procedural amendment dated October 20, 1986
Claims (9)
て凝集反応を生起するラテックス試薬との混合物(被検
試料液)を収容する複数の試料キュベットを保持する手
段と、 [2]該試料キュベットに各々光線を照射し、各々の透
過光量を別々に検知する手段と、 [3]該各々の透過光量の検知の感度差を補正する手段
と、 [4]前記被検試料液の透過光量の測定開始を指示する
手段と、 [5]該被検試料液の透過光量の測定開始時点からの経
過時間を前記各々の試料キュベットについて別々に計時
するタイマと、 を具備し、複数試料の透過光量の時間変化を測定するこ
とを特徴とするラテックス凝集反応測定装置。(1) [1] A means for holding a plurality of sample cuvettes containing a mixture (test sample liquid) of the sample and a latex reagent that reacts with the antigen or antibody in the sample to cause an agglutination reaction; [2] means for irradiating each of the sample cuvettes with a light beam and separately detecting the amount of transmitted light for each; [3] means for correcting the difference in sensitivity in detecting the amount of transmitted light for each; a means for instructing the start of measurement of the amount of transmitted light; and [5] a timer for separately measuring the elapsed time from the start of measurement of the amount of transmitted light of the test sample liquid for each of the sample cuvettes; A latex agglutination reaction measuring device characterized by measuring changes over time in the amount of transmitted light.
試料液の反応の初期段階の透過光量を記憶する手段と、
該初期段階の透過光量に対するその後の透過光量の比を
求める手段とを含む特許請求の範囲第1項記載の測定装
置。(2) the means for correcting the sensitivity difference in detecting the amount of transmitted light is a means for storing the amount of transmitted light at an initial stage of reaction of the test sample liquid;
2. The measuring device according to claim 1, further comprising means for determining a ratio of a subsequent amount of transmitted light to the amount of transmitted light at the initial stage.
被検試料液の透過光量のブランク値と被検試料液の透過
光量との比あるいは該比率の対数を求める手段を含むこ
とを特徴とする特許請求の範囲第1項記載の測定装置。(3) The means for correcting the sensitivity difference in detecting the amount of transmitted light includes means for calculating the ratio of the blank value of the amount of transmitted light of the pseudo test sample liquid and the amount of transmitted light of the test sample liquid, or the logarithm of the ratio. A measuring device according to claim 1, characterized in that:
手段が、前記複数のキュベットについて各々時間的ある
いは位置的に独立して指示する手段である特許請求の範
囲第1項ないし第3項のいずれか1項に記載の測定装置
。(4) Claims 1 to 3, wherein the means for instructing the start of measuring the amount of transmitted light of the test sample liquid is a means for instructing each of the plurality of cuvettes independently in time or position. The measuring device according to any one of Items.
手段が、試料あるいはラテックス試薬の分注器の分注動
作と連動している特許請求の範囲第1項ないし第3項の
いずれか1項に記載の測定装置。(5) Any one of claims 1 to 3, wherein the means for instructing the start of measuring the amount of transmitted light of the test sample liquid is linked to the dispensing operation of a sample or latex reagent dispenser. The measuring device according to item 1.
に於ける任意の特定の時点での透過光量である特許請求
の範囲第2項記載の測定装置。(6) The measuring device according to claim 2, wherein the amount of transmitted light in the initial stage is the amount of transmitted light at any specific time within a certain period of time in the initial stage.
に於ける透過光量の最大値である特許請求の範囲第2項
記載の測定装置。(7) The measuring device according to claim 2, wherein the amount of transmitted light in the initial stage is the maximum value of the amount of transmitted light within a certain period of time in the initial stage.
に於ける透過光量の平均値である特許請求の範囲第2項
記載の測定装置。(8) The measuring device according to claim 2, wherein the amount of transmitted light in the initial stage is an average value of the amount of transmitted light within a certain period of time in the initial stage.
に於ける透過光量の最小値である特許請求の範囲第2項
記載の測定装置。(9) The measuring device according to claim 2, wherein the amount of transmitted light in the initial stage is the minimum value of the amount of transmitted light within a certain period of time in the initial stage.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60162462A JPH0619351B2 (en) | 1985-07-23 | 1985-07-23 | Latex agglutination reaction measuring device |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60162462A JPH0619351B2 (en) | 1985-07-23 | 1985-07-23 | Latex agglutination reaction measuring device |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS6222066A true JPS6222066A (en) | 1987-01-30 |
JPH0619351B2 JPH0619351B2 (en) | 1994-03-16 |
Family
ID=15755075
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP60162462A Expired - Lifetime JPH0619351B2 (en) | 1985-07-23 | 1985-07-23 | Latex agglutination reaction measuring device |
Country Status (1)
Country | Link |
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JP (1) | JPH0619351B2 (en) |
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WO2020080262A1 (en) | 2018-10-15 | 2020-04-23 | 富士フイルム株式会社 | Electrode composition, electrode sheet for all-solid-state secondary battery, and all-solid-state secondary battery, as well as methods for manufacturing electrode composition, electrode sheet for all-solid-state secondary battery, and all-solid-state secondary battery |
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WO2021039468A1 (en) | 2019-08-30 | 2021-03-04 | 富士フイルム株式会社 | Composition containing inorganic solid electrolyte, sheet for all-solid secondary batteries, all-solid secondary battery, method for manufacturing sheet for all-solid secondary batteries, and method for manufacturing all-solid secondary battery |
WO2021039950A1 (en) | 2019-08-30 | 2021-03-04 | 富士フイルム株式会社 | Inorganic solid electrolyte-containing composition, sheet for solid-state secondary batteries, solid-state secondary battery, and methods for producing solid-state secondary battery and sheet for solid-state secondary batteries |
JP2021522483A (en) * | 2018-04-23 | 2021-08-30 | メオン・メディカル・ソリューションズ・ゲー・エム・ベー・ハー・ウント・コー・カー・ゲーMeon Medical Solutions Gmbh & Co Kg | Optical measurement method for obtaining measurement signals from automatic analyzers and liquid media |
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JP6660669B2 (en) * | 2015-03-06 | 2020-03-11 | 三菱重工業株式会社 | Solution Absorption Analyzer and Solution Component Analyzer |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57132038A (en) * | 1981-02-10 | 1982-08-16 | Olympus Optical Co Ltd | Photometric device |
JPS57163848A (en) * | 1982-03-02 | 1982-10-08 | Teikoku Hormone Mfg Co Ltd | Reaction recorder |
-
1985
- 1985-07-23 JP JP60162462A patent/JPH0619351B2/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57132038A (en) * | 1981-02-10 | 1982-08-16 | Olympus Optical Co Ltd | Photometric device |
JPS57163848A (en) * | 1982-03-02 | 1982-10-08 | Teikoku Hormone Mfg Co Ltd | Reaction recorder |
Cited By (30)
Publication number | Priority date | Publication date | Assignee | Title |
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US6489133B2 (en) | 1986-08-13 | 2002-12-03 | Lifescan, Inc. | Apparatus for determinating the concentration of glucose in whole blood |
JPH02245662A (en) * | 1989-03-18 | 1990-10-01 | Jeol Ltd | Automatic immnoassay apparatus |
JP2003294628A (en) * | 2002-03-29 | 2003-10-15 | Fuji Photo Film Co Ltd | Method for making biochemical analysis data and scanning device used therefor |
JP2005233938A (en) * | 2004-01-23 | 2005-09-02 | Sysmex Corp | Nucleic acid detector |
JP2006329920A (en) * | 2005-05-30 | 2006-12-07 | Hitachi High-Technologies Corp | Sample analysis apparatus |
JP4616079B2 (en) * | 2005-05-30 | 2011-01-19 | 株式会社日立ハイテクノロジーズ | Sample analyzer |
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