JPS59105543A - Detector for antigen-antibody reaction - Google Patents
Detector for antigen-antibody reactionInfo
- Publication number
- JPS59105543A JPS59105543A JP21485482A JP21485482A JPS59105543A JP S59105543 A JPS59105543 A JP S59105543A JP 21485482 A JP21485482 A JP 21485482A JP 21485482 A JP21485482 A JP 21485482A JP S59105543 A JPS59105543 A JP S59105543A
- Authority
- JP
- Japan
- Prior art keywords
- antigen
- reaction
- antibody reaction
- antibody
- plate
- 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.)
- Pending
Links
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 50
- 238000001514 detection method Methods 0.000 claims abstract description 9
- 230000005540 biological transmission Effects 0.000 claims description 4
- 230000004520 agglutination Effects 0.000 abstract description 7
- 239000002245 particle Substances 0.000 abstract description 4
- 239000007788 liquid Substances 0.000 abstract 2
- 238000002835 absorbance Methods 0.000 description 8
- 238000010586 diagram Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 3
- 230000010355 oscillation Effects 0.000 description 3
- 238000004445 quantitative analysis Methods 0.000 description 3
- 230000003321 amplification Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/82—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a precipitate or turbidity
Landscapes
- Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plasma & Fusion (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (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
本発明は、抗原抗体反応を定量的た検出する装置に関す
るもので、臨床検査分野等に利用しようとするものであ
る。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a device for quantitatively detecting antigen-antibody reactions, and is intended to be used in the field of clinical testing and the like.
従来列の構成とその問題点
従来の抗原抗体反応検出装置は、第１図に示すように構
成されていた。近赤外線を発する光源１の出力光を・・
−フミラー２で分光し、補償用検出器３で、光源の変動
を電気信号に変換する。一方２ ベーご
ハーフミラ−２を透過した光を、抗体抗原反応混合物を
入れたセル４に照射し、その透過光の強度を試料用検出
器５によシミ気信号に変換する。このようにセル４で行
われた抗原抗体反応の一定時間内の吸光度、吸光率の変
化量を検出器６で電気信号に変換し、まだ光源１の光の
変動を検出器３で電気信号に変換したものと組合せて増
巾器６に入力する。増巾器６により吸光度、吸光率に比
例した出力電圧をマイクロコンビ＾−ターフ等の記録、
演算部にて各濃度における標準曲線と比較演算処理を行
い、プリンター８で抗原抗体反応の定量分析値を表示す
る。Conventional Array Configuration and Its Problems A conventional antigen-antibody reaction detection device was constructed as shown in FIG. The output light of light source 1 that emits near-infrared rays...
- The light beam is separated by the mirror 2, and the fluctuation of the light source is converted into an electrical signal by the compensation detector 3. On the other hand, the light transmitted through the half-mirror 2 is irradiated onto the cell 4 containing the antibody-antigen reaction mixture, and the intensity of the transmitted light is converted into a stain signal by the sample detector 5. In this way, the amount of change in absorbance and absorbance within a certain period of time of the antigen-antibody reaction performed in the cell 4 is converted into an electrical signal by the detector 6, and the fluctuation of light from the light source 1 is converted into an electrical signal by the detector 3. The converted signal is combined with the converted signal and input to the amplifier 6. The amplifier 6 records the absorbance and the output voltage proportional to the absorbance using a microcombi turf, etc.
The arithmetic unit performs calculation processing for comparison with the standard curve at each concentration, and the printer 8 displays the quantitative analysis value of the antigen-antibody reaction.
上述した通りこの装置では、抗原抗体反応の定量分析値
を求めるため、試料規定量を試験管等に採り、その検体
の反応中の近赤外線の一定時間での吸光度、吸光率変化
量を求め、標準となる抗原抗体反応曲線値と比較演算し
て求める方法をとっている。そのため抗原抗体反応に必
要な高価な試薬および血液より微量に採集される検体と
々る血清も５０ｎｆ／ｍｌ使用される。また健康体およ
び健３ ページ
庫体に近い人の抗原抗体反応でに１定量分析値（６ｎ
ｙ／ｍ ｌ以下）の再現性が困難となっている。さらに
現在、一般に普及している抗原抗体反応をガラス板上で
行い肉眼で視覚判定を行う方法と直接比較することも困
難であった。As mentioned above, in order to obtain a quantitative analysis value of an antigen-antibody reaction, this device takes a specified amount of a sample into a test tube, calculates the absorbance of the near-infrared rays over a certain period of time during the reaction of the sample, and calculates the change in absorbance. The method used is to calculate the value by comparing it with the standard antigen-antibody reaction curve value. Therefore, 50nf/ml of expensive reagents required for antigen-antibody reactions and serum, which is a very small amount of specimen collected from blood, are used. In addition, 1 quantitative analysis value (6n
y/ml or less) is difficult to reproduce. Furthermore, it has been difficult to directly compare this method with the currently widely used method of performing antigen-antibody reactions on a glass plate and making visual judgments with the naked eye.
発明の目的
本発明は−に記欠点を除去するため、抗原抗体反応で生
ずる抗原抗体の凝集度合（凝集塊の量）を、ラインセン
サーカメラにて、粒子を検出し、不透過部分（凝集塊）
の画素数を積算し、定量的に判定することを目的とする
ものである。Purpose of the Invention In order to eliminate the drawbacks described in -, the present invention detects particles using a line sensor camera to measure the degree of agglutination (amount of aggregates) of antigen-antibodies generated in antigen-antibody reactions, and )
The purpose of this is to integrate the number of pixels and make a quantitative determination.
発明の構成
本発明は、上記の目的を達成するために、抗原抗体反応
により生ずる凝集塊を、下記から均一な近赤外光を出す
光源で照射し、その上に近赤外光を通す板−Ｆで、抗原
抗体反応を生じさせ、またその板上部に配置したライン
センサーカメラで、上記反応面を走査して、粒子を検出
し、カメラ出力を赤外光透過、不透過による２値化電気
信号に変換し、不透過部分のビットを積算し、その演算
値で抗原抗体反応による、凝集度合を表示しようとする
ものである。Structure of the Invention In order to achieve the above object, the present invention irradiates aggregates generated by antigen-antibody reactions with a light source that emits uniform near-infrared light from the following, and provides a plate on which near-infrared light passes. -F causes an antigen-antibody reaction, and a line sensor camera placed on the top of the plate scans the reaction surface to detect particles, and the camera output is binarized by infrared light transmission and non-transmission. It converts it into an electrical signal, integrates the bits in the opaque part, and uses the calculated value to display the degree of agglutination caused by the antigen-antibody reaction.
実施例の説明
以下本発明の一実施例について第２図に基すいて説明す
る。同図において１１は近赤外光を発光する光源、１２
は光源１１を均一な赤外光とするための平行光用レンズ
である（下記板上での抗原抗体反応によって生ずる凝集
塊を、より明瞭にさせる）。１３は近赤外光を通す板で
、この板上で抗原抗体反応を生じさせる。１４は、上記
板」二の抗原抗体で生ずる凝集度合をライセンザーに透
過光、不透過光を拡大してより明瞭にさせる拡大用レン
ズ、１６はラインセンサーであり、上記板１３上で抗原
抗体反応によって生ずる凝集度合をこのラインセンサー
の各画素ごとに近赤外透過光を出力レベル大の電気信号
に、凝集塊によって生ずる近赤外不透過光を出力レベル
小の電気信号に変換するものである。１６はラインセン
サー出力を増巾する信号増巾回路、１７は信号増巾回路
１６からの信号を基準電圧源の出力コンパレートする二
５ ページ
値化回路であり、例えば上記近赤外透過光を明レベル（
５ｖ）に、不透過光を暗レベル（ＯＶ）の出力電圧に２
値化している。１８は発振回路で、ラインセンサ−１６
の１画素ごとの読み出し同期用クロック信号および二値
化回路１７で２値化された信号のカウント用クロック信
号を発生する。DESCRIPTION OF THE EMBODIMENTS An embodiment of the present invention will be described below with reference to FIG. In the same figure, 11 is a light source that emits near-infrared light;
is a lens for parallel light to make the light source 11 a uniform infrared light (to make the aggregate formed by the antigen-antibody reaction on the plate described below more clear). Reference numeral 13 denotes a plate that transmits near-infrared light, and an antigen-antibody reaction occurs on this plate. 14 is a magnifying lens that magnifies the transmitted light and non-transmitted light to the licenser to make the degree of agglutination caused by the antigen-antibody on the plate 2 more clear; 16 is a line sensor that detects the antigen-antibody reaction on the plate 13; For each pixel of this line sensor, near-infrared transmitted light is converted into an electrical signal with a high output level, and near-infrared opaque light produced by the aggregates is converted into an electrical signal with a low output level. . 16 is a signal amplification circuit for amplifying the line sensor output, and 17 is a page value conversion circuit for comparing the signal from the signal amplification circuit 16 with the output of the reference voltage source. Bright level (
5v), and the opaque light to the dark level (OV) output voltage 2
It is valued. 18 is an oscillation circuit, and line sensor 16
A clock signal for readout synchronization for each pixel and a clock signal for counting the signal binarized by the binarization circuit 17 are generated.
１９はカウンター回路で、二値化された暗レベル中の画
素に対応したクロック数をカウントし、これにより凝集
塊の大きさを計測する。２ｏは演算回路であり、カウン
タ回路９によるカウント数をｎ乗し、その和を演算し、
抗原抗体反応による凝集度合を演算するものである。２
１はプリンター回路であり、抗原抗体反応度合を記録用
にプリントする。２２は微動載物台であり、これに固定
された板１３上の抗原抗体反応の位置を少しづつ移動さ
せて、ラインセンサー１５での計測を面で行うようにす
る。A counter circuit 19 counts the number of clocks corresponding to pixels in the binarized dark level, thereby measuring the size of the aggregate. 2o is an arithmetic circuit which raises the number counted by the counter circuit 9 to the nth power and calculates the sum thereof;
This is to calculate the degree of agglutination due to antigen-antibody reaction. 2
1 is a printer circuit that prints the degree of antigen-antibody reaction for recording purposes. Reference numeral 22 denotes a micro-movement stage, and the position of the antigen-antibody reaction on the plate 13 fixed to this stage is moved little by little so that the measurement by the line sensor 15 is performed on a surface.
次に上記実施例の動作について要部を拡大した第３図と
共に説明する、光源１２により発光された近赤外光（波
長ｓｏｏｎｍ〜９６０ ｎｕの発光６ペーミ゛
素子）は、レンズ１２によシ均一な平行光源となり、抗
原抗体反応を行う板３の下部よシ照射させる。板１３上
では各５ｎｆ／ｍｌｌの抗原抗体液を２１程度の面積に
拡散させて積極的に混合し、反応を生じさせると、３０
秒〜１分で、抗原抗体反応に比例した凝集塊が、第４図
、第６図のように、板１３上に安定した状態で現われる
。（第４図は、大きな凝集塊の場合、第５図は、細かな
凝集塊の場合を示す）、第１０図のように、凝集塊部で
は、近外光はさえぎられ、凝集塊以外の部分では、近赤
外光は直進する、直進した近赤外光は、レンズ１４で８
〜１０倍に拡大され、ラインセンサー１６で受光され、
受光した光の量に比例した電圧が、ラインセンサーの各
受光素子に１個目から順々にクロックパルス（１μｓｅ
ｃ ）で走査きれながら、他端の最終Ｎ個目迄順々に出
力される（個々の受光素子を画素と表現し、受光素子の
出力電圧を画素出力電圧という）。このようにして出力
された電圧は、第２図の増巾回路１６で、第７図第９図
のように増巾されビデオ信号波形となる。このビ７ ペ
ージ
デオ信号波形を第２図の２値化回路１７で、基準電圧２
３でコンパレートすると、第７図の波形は第１１図人、
第９図の波形は第２図人のように整形された波形となる
。これと第２図の発振回路１８のクロックパルス（第１
１図Ｂ、第１２図Ｂはクロックパルス波形）を組合せる
ことにより、第１１図、第１２図Ｃのクロックパルス波
形が得られる、この第１１図、第１２図Ｃの１．２．３
・・・・・・了と各部分ごとにクロックパルスをカウン
タ回路１９でカウントし、演算回路２０で個々のカウン
ト数をｎ乗し、その和の演算を行々う。次に抗原抗体反
応を生じさせている板３を微動載物台２２により、少し
移動させ、抗原抗体反応している場所を第４図、第６図
のように１−＋２−３−４と変化させて同様に計測を行
なう。このように一定面積上の凝集度合を粒子網側し、
その和をプリンター回路２１にて表示し抗原抗体反応を
検出する。又、ラインセンサー１６の個所にエリアセン
サーを使用しても同様の検出はできる。Next, the operation of the above embodiment will be explained with reference to FIG. It becomes a uniform parallel light source and irradiates the lower part of the plate 3 where the antigen-antibody reaction occurs. On the plate 13, each 5nf/ml antigen-antibody solution is diffused over an area of about 21 cm and actively mixed to cause a reaction.
In seconds to 1 minute, aggregates proportional to the antigen-antibody reaction appear in a stable state on the plate 13, as shown in FIGS. 4 and 6. (Figure 4 shows the case of large aggregates, and Figure 5 shows the case of fine aggregates.) As shown in Figure 10, near and external light is blocked in the aggregate area, In the section, the near-infrared light travels straight, and the near-infrared light that travels straight is
~10 times magnified and received by the line sensor 16,
A voltage proportional to the amount of light received is applied to each light-receiving element of the line sensor in turn by clock pulses (1 μse
c), while the final Nth light receiving element at the other end is output in sequence (each light receiving element is expressed as a pixel, and the output voltage of the light receiving element is called a pixel output voltage). The thus output voltage is amplified by the amplifying circuit 16 of FIG. 2, as shown in FIGS. 7 and 9, and becomes a video signal waveform. This bi7 page deo signal waveform is converted to a reference voltage of 2 by the binarization circuit 17 shown in FIG.
When compared with 3, the waveform in Figure 7 is the same as in Figure 11.
The waveform in FIG. 9 is shaped like the waveform in FIG. 2. This and the clock pulse (first pulse) of the oscillation circuit 18 in FIG.
By combining the clock pulse waveforms shown in Figures 1B and 12C, the clock pulse waveforms shown in Figures 11 and 12C are obtained. 1.2.3 of Figures 11 and 12C
. . . At the end, the counter circuit 19 counts clock pulses for each part, and the arithmetic circuit 20 raises each count to the nth power, and calculates the sum thereof. Next, the plate 3 on which the antigen-antibody reaction is occurring is moved slightly using the fine movement stage 22, and the location where the antigen-antibody reaction is occurring is 1-+2-3-4 as shown in FIGS. 4 and 6. Measure in the same way with different values. In this way, the degree of aggregation over a certain area is determined by the particle network,
The sum is displayed on the printer circuit 21 to detect the antigen-antibody reaction. Further, similar detection can be performed even if an area sensor is used in place of the line sensor 16.
又、結果の判定は、より有意差を明瞭にする為計測され
た、各凝集塊の大きさく画素数）を２乗し、その総和を
とることにより、面積として評価、３乗の総和をとれば
体積での評価になるので、より有意差が拡がる。In addition, in order to clarify the significant difference, the results can be evaluated by squaring the size and number of pixels of each aggregate measured and taking the sum, and then calculating the sum of the cubes. Since the evaluation is based on volume, the significant difference becomes wider.
なお上記実施例では光源１１として近赤外光を発するも
のを用いているが、普通光を発するものでもよい。In the above embodiment, a light source 11 that emits near-infrared light is used, but a light source that emits normal light may also be used.
発明の効果
以上のように本発明によれば、抗原抗体の各媒体液を従
来より微批で、抗原抗体反応構出が出来、しかも抗原抗
体反応検出結果と検出に使用した板上の抗原抗体反応を
肉眼で比較することができるという効果を有するもので
ある。Effects of the Invention As described above, according to the present invention, an antigen-antibody reaction can be formed with a finer adjustment of each antigen-antibody medium solution than in the past, and the antigen-antibody reaction detection result and the antigen-antibody reaction on the plate used for detection can be easily detected. This has the effect of allowing reactions to be compared with the naked eye.
第１図は従来の吸光度・吸光率にて抗原抗体反応検出器
の基本構造を示す系統図、第２図は、本発明の一実施例
における抗原抗体反応検出器の基本構成を示す系統図、
第３図はその光学系のブロック図、第４図および第５図
は板上の抗原抗体反応による凝集塊とラインセンサーで
の検出位置を９ ページ
示す図、第６図および第８図はラインセンサーの受光素
子面から見た、抗原抗体反応における凝集塊を示す図、
第７図および第９図はそれぞれ第６図および第８図にお
けるラインセンサーの赤外光の強さに比例した電気信号
を増巾した信号の波形図、第１０図は板上における抗原
抗体反応により近赤外光が透過光と不透過光になってい
る部分を示す図、第１１図および第１２図は２値化状態
を示す波形図である。
１１・・・・・・光源、１３・・・・・・板、１６・・
・・・・ラインセンサー、１７・・・・・・二値化回路
、１８・・・・・・発振回路、１９・・・・・・カウン
タ回路、２ｏ・・・・演算回路、２１・・・・・・プリ
ンタ回路。
代理人の氏名 弁理士 中 尾 敏 男 ほか１名２２
１
特開昭５９−１０５５４３ （４）
第４図
１早乏で５ミ〒く７１面ン］扉クビ玉４ミ１５第６図
第１１図 群
１１２図FIG. 1 is a system diagram showing the basic structure of an antigen-antibody reaction detector using conventional absorbance and absorbance; FIG. 2 is a system diagram showing the basic structure of an antigen-antibody reaction detector according to an embodiment of the present invention;
Figure 3 is a block diagram of the optical system, Figures 4 and 5 are 9 pages showing the aggregates caused by the antigen-antibody reaction on the plate and the detection positions by the line sensor, and Figures 6 and 8 are the line A diagram showing aggregates in an antigen-antibody reaction, seen from the light-receiving element surface of the sensor.
Figures 7 and 9 are waveform diagrams of signals obtained by amplifying the electrical signals proportional to the infrared light intensity of the line sensor in Figures 6 and 8, respectively, and Figure 10 is the antigen-antibody reaction on the plate. 11 and 12 are waveform diagrams showing the binarized state. 11... Light source, 13... Board, 16...
... Line sensor, 17 ... Binarization circuit, 18 ... Oscillation circuit, 19 ... Counter circuit, 2o ... Arithmetic circuit, 21 ... ...Printer circuit. Name of agent: Patent attorney Toshio Nakao and 1 other person22
1 Unexamined Japanese Patent Publication No. 59-105543 (4) Fig. 4 1 Early poverty 5 mm x 71 pages] Door cracker 4 mm 15 Fig. 6 Fig. 11 Group 112 Fig.
Claims (1)
て生じた凝集塊による前記光の透過、不透過を検出する
光電検出カメラ、およびその検出結果によシ前記凝集塊
の大きさをカウント演算する手段とを設けたことを特徴
とする抗原抗体反応検出器。A transparent plate for photo-reacting the antigen-antibody solution, a photoelectric detection camera for detecting the transmission or non-transmission of the light by the aggregates generated by the reaction, and a counting operation for calculating the size of the aggregates based on the detection results. 1. An antigen-antibody reaction detector comprising: means for detecting a reaction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21485482A JPS59105543A (en) | 1982-12-08 | 1982-12-08 | Detector for antigen-antibody reaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21485482A JPS59105543A (en) | 1982-12-08 | 1982-12-08 | Detector for antigen-antibody reaction |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS59105543A true JPS59105543A (en) | 1984-06-18 |
Family
ID=16662643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21485482A Pending JPS59105543A (en) | 1982-12-08 | 1982-12-08 | Detector for antigen-antibody reaction |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS59105543A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61215948A (en) * | 1985-03-22 | 1986-09-25 | Fujirebio Inc | Particle flocculation discriminating device |
| EP0198327A2 (en) * | 1985-04-03 | 1986-10-22 | The Green Cross Corporation | Method of automatically detecting agglutination reaction and apparatus therefor |
| JPH05256764A (en) * | 1992-12-21 | 1993-10-05 | Fujirebio Inc | Particle aggregation judging method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5334595A (en) * | 1976-09-10 | 1978-03-31 | Michio Kudou | Detecting method of coagulation state in blood and the like |
-
1982
- 1982-12-08 JP JP21485482A patent/JPS59105543A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5334595A (en) * | 1976-09-10 | 1978-03-31 | Michio Kudou | Detecting method of coagulation state in blood and the like |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61215948A (en) * | 1985-03-22 | 1986-09-25 | Fujirebio Inc | Particle flocculation discriminating device |
| EP0198327A2 (en) * | 1985-04-03 | 1986-10-22 | The Green Cross Corporation | Method of automatically detecting agglutination reaction and apparatus therefor |
| JPH05256764A (en) * | 1992-12-21 | 1993-10-05 | Fujirebio Inc | Particle aggregation judging method |
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