EP0163631A1 - Methode de determination des resultats de reactions d'agglutination - Google Patents

Methode de determination des resultats de reactions d'agglutination

Info

Publication number
EP0163631A1
EP0163631A1 EP19830903791 EP83903791A EP0163631A1 EP 0163631 A1 EP0163631 A1 EP 0163631A1 EP 19830903791 EP19830903791 EP 19830903791 EP 83903791 A EP83903791 A EP 83903791A EP 0163631 A1 EP0163631 A1 EP 0163631A1
Authority
EP
European Patent Office
Prior art keywords
agglutination
reaction
measurement
light
results
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
Application number
EP19830903791
Other languages
German (de)
English (en)
Inventor
Osmo Suovaniemi
Pertti Ekholm
Esko Kaukanen
Paul Partanen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Thermo Fisher Scientific Oy
Original Assignee
Labsystems Oy
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Labsystems Oy filed Critical Labsystems Oy
Publication of EP0163631A1 publication Critical patent/EP0163631A1/fr
Pending legal-status Critical Current

Links

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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor

Definitions

  • the present invention is concerned with a method for the measurement of the results of agglutination reactions in an analyzer of vertical measurement.
  • agglutination tests are used, e.g., for the establishment of bacteria, viruses, antigen components of fungi or of their antibodies as well as of abnormal proteins (e.g. tumour-specific proteins).
  • hemagglutination HA
  • HI hemagglutination inhibition
  • indirect hemagglutination as well as latex agglutination.
  • the said tests are used in serological diagnostics, serotyping, as well as in various establishments of antigens. For example, in epidemy studies as well as in the specific diagnostics of infection diseases, the said tests are highly usable.
  • a positive result of agglutination may mean either a positive result or a negative result.
  • Hemagglutination can be ascertained on the bottom of the reaction vessel as a diffuse covering. For example, in a HA-test, viruses and bacteria have an ability to agglutinate red blood cells under certain conditions on the bottom of the reaction vessel over a large area. If no hemagglutination takes place, the red blood cells are assembled in the reaction vessel usually as distinctly limited area, a so-called button.
  • agglutination tests have been read visually.
  • the criteria for the interpretation of the results vary.
  • the agglutination tests may also be connected with a colour indicator, whose visual interpretation, in a negative or positive test, is, however, laborious.
  • Tests of this type are used extensively in different determinations. What is also frequently concerned is tests carried out in massive numbers, such as syphilis and rheumatism tests, blood group determinations, and establishment of pregnancy. In such cases, the performance of the tests must be simple, automated, accurate, and reliably reproducible.
  • the agglutinated reaction mixture is shaken before measurement so strongly that the agglutination mix is dispensed in the reaction mixture (GB Pat. No. 1,229,971). 2.
  • the reaction mixture is measured by means of two separate beams of measurement (GB Pat. No. 1,229,971 and US Pat. No. 3,883,308), the values yielded by them being compared with two separate threshold values.
  • the method in accordance with the present invent ⁇ on and with the said earlier invention permits, e.g., the measurement of the results of agglutination reactions, among other things, in a spectrophotometer, adsorption photometer, fluorometer, and nefelometer.
  • the method in accordance with the present invention permits, e.g., the formation, measurement and production of the output of agglutination reactions reliably and rapidly either automatically or partly non-automatically.
  • agglutinations are promoted by appropriate centrifuging or shaking.
  • the reaction mixture is incubated.
  • the shaking of the reaction mixture is performed so that even a weak agglutination mix is not scattered in the reaction mixture but remains on the bottom of the reaction vessel, but, however, strongly enough so that the non-agglutinated part can be placed homogeneously in the reaction mixture.
  • the reaction mixture is measured.
  • the absorbance of the agglutination produced on the bottom of the cuvette of the reaction mixture is measured (preferably, e.g., by means of a vertical beam of measurement) so that the source of light or the reaction vessel is moved in the horizontal plane and, at the same time, the intensity of the light passing through is measured at several phases along the path of movement.
  • the absorbance values measured by means of one beam of measurement at several different points are analyzed and compared in accordance with a program. The production of the output takes place automatically.
  • Figure 1a shows an agglutination placed on the bottom of a cuvette for reaction mixture, the result being in this case positive,
  • Figure 1b shows an agglutination placed on the bottom of a cuvette for reaction mixture, the result being in this case negative
  • Figure 2 schematically illustrates the measurement of a block of cuvettes for reaction mixture
  • Figure 3 is an exemplifying embodiment of a system for the determination of blood groups
  • Figure 4a illustrates the measurement of the bottom of a cuvette at several different points
  • Figure 4b shows the corresponding measurement reaults.
  • the red blood cells are examined by means of an agglutination test as follows: 1) A cell suspension of about 2.5 % is made of the red blood cells to be examined, in physiological salt solution.
  • a cell suspension of about 2.5 % is made of A- and B-test cells in physiological salt solution.
  • the apparatus is reset to zero, e.g., by means of 100 ⁇ l of BSA-solution.
  • a suspension of about 2.5 % is made of the red blood cells to be examined, in physiological salt solution.
  • 50 ⁇ l of the suspension prepared under 1) as well as 50 ⁇ l of a - D - serum are pipetted into the FP-blood-group cuvettes.
  • a cell suspension of 2 .5 % or 5 % is made of washed cells .
  • 100 ⁇ l of a - D - serum and 100 ⁇ l of 2.5-% or 5-% cell suspension are pipetted into FP-bloodgroup cuvettes.
  • the apparatus is reset to zero, e.g., by means of 100 ⁇ l of a - human - serum.
  • Figure 1a shows an agglutination 2 on the bottom of the reaction-mixture cuvette 1 , the result being in this case positive.
  • Figure 1b shows a negative result, in respect of agglutination, in cuvette 3, wherein the red blood cells are evenly dispensed in the reaction mixture 4.
  • Figure 2 schematically shows how the block 5 of reaction-mixture cuvettes moves through the measurement beam 6 so that each reaction-mixture cuvette 7 in the cuvette block 5 is read by means of the vertical measurement beam 6 at different points.
  • the vertical measurement beam 6 starts from an opening 8 of appropriate size facing each reaction-mixture cuvette 7 and passes in the direction of the longitudinal axis of the reaction-mixture cuvette 7 to the corresponding detector 9.
  • the agglutination 10 on the bottom of each reaction-mixture cuvette 7 can be measured at several points by appropriately displacing the cuvette block 5 in the direction of the x-axis and/or, if required, also in the direction of the y-axis.
  • the measurement beam 6 may also pass in the opposite direction, from the top downwards to a detector placed underneath the reaction-mixture cuvette 7 , or the cuvette may also be stationary and the beam of light be displaced across the cuvette bottom.
  • the beam of light may also move across the cuvette bottom at several points.
  • Fig. 4a Reference numerals 11, 12 and 13 denote different paths of movement.
  • Figure 4b illustrates the corresponding measurement results.
  • the curve 15 corresponds, e.g., to the measurement of point 12 as measured photometrically.
  • the equipment can be constructed so that the agitator is placed in connection with the photometric measurement head.
  • outputs in accordance with the above can be produced, e.g., as a function of shaking intensities, thereby finding out differences between the intensities of different agglutinations.
  • the equipment is provided with appropriate computer equipment (Fig. 3 p) .
  • Figure 3 illustrates a system as an exemplifying embodiment of the method invention for the determination of blood groups : a. Whole-blood sample b. The blood-sample is centrifuged c. Plasma or serum and red blood cells separated in the tube d. The tube is placed in its position, indicated by the arrow e. 25 ⁇ l of red blood cells are taken out of the tube into a dosage-diluter (1) f. The dosage-diluter is emptied into an empty tube g. By means of a dosage-diluter, 1000 ⁇ l of reagent is added h. 50 ⁇ l of cell suspension is dosed by means of a dosage-diluter into four reaction-mixture cuvettes i.
  • 200 ⁇ l of plasma are taken into a second dosage-diluter (2) j.
  • 50 ⁇ l of plasma are dosed into each of the following four reaction-mixture cuvettes k.
  • 50 ⁇ l of reagent are added into the reaction- mixture cuvettes l.
  • the reaction-mixture cuvettes are incubated m. Centrifuging or shaking if required n. Shaking so that agglutinated mix is not dispensed in the reaction mixture.
  • non-agglutinated red blood cells are dispensed in the reaction mixture o.
  • the shaking is followed by automatic measurement by means of a vertical measurement beam at 5 to 10 different points through the bottom of each reaction-mixture cuvette p. Storage, calculation, analysis, and output of the measurement result.
  • systems can be constructed, e.g., with different degrees of automation or with different mechanical embodiments.
  • Such systems may comprise one apparatus or several separate apparatuses.
  • the measurement results may be compared, e.g., with standard values, with each other, and/or with positive or negative results, or with both.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • General Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Plasma & Fusion (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

Méthode permettant de mesurer le résultat d'une réaction d'agglutination et selon laquelle le mélange de réaction est secoué après incubation, de sorte que la partie non agglutinée est répartie de manière homogène dans le mélange de réaction. Ensuite le pouvoir d'absorption de l'agglutination restant sur le fond du récipient de réaction est mesuré dans un analyseur qui mesure verticalement de sorte que le faisceau lumineux ou le récipient de réaction est déplacé dans le plan horizontal et le pouvoir absorbant est mesuré en plusieurs points différents. Le résultat de la réaction d'agglutination est obtenu par comparaison des valeurs de pouvoir d'absorption.
EP19830903791 1983-11-21 1983-11-21 Methode de determination des resultats de reactions d'agglutination Pending EP0163631A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/FI1983/000073 WO1985002259A1 (fr) 1983-11-21 1983-11-21 Methode de determination des resultats de reactions d'agglutination

Publications (1)

Publication Number Publication Date
EP0163631A1 true EP0163631A1 (fr) 1985-12-11

Family

ID=8556340

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19830903791 Pending EP0163631A1 (fr) 1983-11-21 1983-11-21 Methode de determination des resultats de reactions d'agglutination

Country Status (3)

Country Link
EP (1) EP0163631A1 (fr)
JP (1) JPS61501162A (fr)
WO (1) WO1985002259A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3422616A1 (de) * 1984-06-19 1985-12-19 Behringwerke Ag, 3550 Marburg Verfahren zur bestimmung eines partners einer reaktion und vorrichtung dazu
US4730921A (en) * 1985-10-31 1988-03-15 Genetic Systems, Inc. Photodensitometer for minimizing the refractive effects of a fluid sample
EP0229355A3 (fr) * 1986-01-06 1988-01-07 Orion Corporation Ltd Appareil et procédé pour la mise en oeuvre des essais photométriques
DE3919260A1 (de) * 1989-06-13 1990-12-20 Hoechst Ag Verfahren zum quantitativen auswerten von agglutinationsreaktionen
TW351766B (en) * 1993-05-17 1999-02-01 Fujirebio Kk Method and apparatus for indirect agglutination immunoassay

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1598944A1 (de) * 1966-07-21 1971-06-24 Pfizer & Co C Verfahren und Vorrichtung zum selbsttaetigen Nachweisen von Agglutinationen in einer Reaktionszonc
FR95147E (fr) * 1967-05-12 1970-07-24 Centre Nat Rech Scient Appareillage destiné plus particulierement a la détermination automatique des groupes sanguins.
FI56905C (fi) * 1978-02-28 1980-04-10 Osmo A Suovaniemi Foerfarande och anordning foer automatisk maetning av agglutinationsprov t ex i spektrofotometer adsoptionsfotometer fluorometer eller nefelometer
JPS6145479Y2 (fr) * 1979-09-10 1986-12-20
WO1982000360A1 (fr) * 1980-07-24 1982-02-04 Oy Labsystems Procede et equipement de mesure des proprietes d'un liquide
EP0056413A1 (fr) * 1980-07-24 1982-07-28 Labsystems Oy Procede et appareil de mesure des proprietes d'un agglomerat
WO1982000357A1 (fr) * 1980-07-24 1982-02-04 Oy Labsystems Procede et appareil de mesure des proprietes d'un agglomerat
EP0056414A1 (fr) * 1980-07-24 1982-07-28 Labsystems Oy Procede et appareil de mesure des proprietes d'un agglomerat
FR2488691A1 (fr) * 1980-08-14 1982-02-19 Commissariat Energie Atomique Procede et dispositif pour la detection et la quantification d'agglutinats en temps reel
FR2509860A1 (fr) * 1981-07-17 1983-01-21 Louis Serge Procede et appareil pour l'execution des reactions d'immuno-agglutination du sang

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8502259A1 *

Also Published As

Publication number Publication date
WO1985002259A1 (fr) 1985-05-23
JPS61501162A (ja) 1986-06-12

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Inventor name: SUOVANIEMI, OSMO

Inventor name: EKHOLM, PERTTI

Inventor name: PARTANEN, PAUL

Inventor name: KAUKANEN, ESKO