EP0281958A2 - Device for controlling the temperature and mixing the contents of the vessels of a micro-titration plate - Google Patents

Device for controlling the temperature and mixing the contents of the vessels of a micro-titration plate Download PDF

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Publication number
EP0281958A2
EP0281958A2 EP88103357A EP88103357A EP0281958A2 EP 0281958 A2 EP0281958 A2 EP 0281958A2 EP 88103357 A EP88103357 A EP 88103357A EP 88103357 A EP88103357 A EP 88103357A EP 0281958 A2 EP0281958 A2 EP 0281958A2
Authority
EP
European Patent Office
Prior art keywords
vessels
mixing
contents
micro
vessel
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.)
Withdrawn
Application number
EP88103357A
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German (de)
French (fr)
Other versions
EP0281958A3 (en
Inventor
Jürgen Dr. Gross
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.)
Hoechst AG
Original Assignee
Hoechst AG
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 Hoechst AG filed Critical Hoechst AG
Publication of EP0281958A2 publication Critical patent/EP0281958A2/en
Publication of EP0281958A3 publication Critical patent/EP0281958A3/en
Withdrawn legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50851—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates specially adapted for heating or cooling samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/40—Mixers using gas or liquid agitation, e.g. with air supply tubes
    • B01F33/407—Mixers using gas or liquid agitation, e.g. with air supply tubes by blowing gas on the material from above
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids

Definitions

  • the invention relates to a device for thermostatting and mixing the contents of vessels of a microtitration plate for immunological tests.
  • antigens are surface-fixed on the vessel walls of a microtitration plate with which the antibodies (antigens) present in the sample bind during the first incubation period. After washing out unbound sample components, enzyme conjugate is dosed. After the second incubation has ended, excess conjugate is removed by washing and substrate is dosed. After the third incubation, the implementation is stopped. All steps are carried out at a certain temperature. The vessels must therefore be thermostatted. A disadvantage is not only the complex thermostatting of the microtitration plate, but also the relatively long incubation time. The invention seeks to remedy this.
  • a device which is characterized in that a hood corresponding to the surface of the microtitration plate is designed as a cavity which is closed on all sides, into which a gas line opens and whose boundary wall facing the microtitration plate is provided with gas outlet openings which are eccentric with respect to the Vessel axes are arranged and directed at an angle ⁇ to the surfaces of the liquids in the vessels.
  • the device offered the advantage that the liquid in the vessels was replaced by thermostated gas a circular movement is set, which not only improves the thermostatting of the liquid, but also the binding and reaction of the reagents with the samples in the wall area. This results in shorter incubation times and thus shorter test times.
  • the device consists essentially of a hood 1, the dimension of which corresponds to the area of the microtitration plate 2 with the vessels 7 and which is provided with a cavity 3 into which a gas line 4 for thermostatted gas, for. B. air from 30 ° to 50 ° C opens.
  • the boundary wall 5 for the cavity 3 of the hood 1 facing the microtitration plate 2 is provided with gas outlet openings 6.
  • the cavity 3 serves as a gas distributor for the gas outlet openings 6.
  • the gas outlet openings 6 can be designed as nozzles or cannulas. These are placed in the boundary wall 5 so that they are arranged eccentrically with respect to the vessel axes 8.
  • the air flow creates an indentation 11 on the radius R when it hits the liquid surface 10.
  • the nozzle axis is inclined by the angle ⁇ with respect to the surface 10.
  • the distance of the gas outlet opening from the vessel wall in the radial direction can be 0.2 to 0.5 vessel radii and the angle ⁇ at which the gas outlet opening is inclined toward the liquid surface can be 40 ° to 80 °.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Food-Manufacturing Devices (AREA)
  • Mixers With Rotating Receptacles And Mixers With Vibration Mechanisms (AREA)

Abstract

A hood (1) which corresponds to the area of the microtitration plate (2) is formed as a hollow space closed on all sides. A gas line (4) leads into the hollow space. Its boundary wall (5) facing the titration plate (2) is provided with gas outlet orifices (6) which are arranged eccentrically relative to the axes of the vessel and point under an angle to the surfaces of the liquids. <IMAGE>

Description

Gegenstand der Erfindung ist eine Vorrichtung zum Thermostatisieren und Mischen des Inhaltes von Gefäßen einer Mikrotitrationsplatte für immunologische Tests.The invention relates to a device for thermostatting and mixing the contents of vessels of a microtitration plate for immunological tests.

Bei immunologischen Tests, wie z. B. bei Enzyme-Linked-­Immuno-Sorbent-Assays (ELISA) sind auf den Gefäßwänden einer Mikrotitrationsplatte Antigene (Antikörper) oberflächenfixiert, mit denen sich während der ersten Inkubationszeit die in der Probe vorhandenen Antikörper (Antigene) binden. Nach Auswaschen nicht gebundener Probenbestandteile wird Enzym-Konjugat dosiert. Nach Ablauf der zweiten Inkubation wird überschüssiges Konjugat durch Waschen entfernt und Substrat dosiert. Nach Ablauf der dritten Inkubation wird die Umsetzung gestoppt. Alle Schritte werden bei einer bestimmten Temperatur durchgeführt. Die Gefäße müssen also thermostatisiert werden. Nachteilig ist nicht nur das aufwendige Thermostatisieren der Mikrotitrationsplatte, sondern auch die verhältnismäßig lange Inkubationszeit. Hier will die Erfindung Abhilfe schaffen.In immunological tests, such as. B. in enzyme-linked immunosorbent assays (ELISA), antigens (antibodies) are surface-fixed on the vessel walls of a microtitration plate with which the antibodies (antigens) present in the sample bind during the first incubation period. After washing out unbound sample components, enzyme conjugate is dosed. After the second incubation has ended, excess conjugate is removed by washing and substrate is dosed. After the third incubation, the implementation is stopped. All steps are carried out at a certain temperature. The vessels must therefore be thermostatted. A disadvantage is not only the complex thermostatting of the microtitration plate, but also the relatively long incubation time. The invention seeks to remedy this.

Die Aufgabe wird durch eine Vorrichtung gelöst, die dadurch gekennzeichnet ist, daß eine der Fläche der Mikrotitrationsplatte entsprechende Haube als allseits geschlossener Hohlraum ausgebildet ist, in den eine Gasleitung mündet und dessen der Mikrotitrationsplatte zugewandte Begrenzungswand mit Gasaustrittsöffnungen versehen ist, die exzentrisch in Bezug auf die Gefäßachsen angeordnet und unter einem Winkel α auf die Oberflächen der Flüssigkeiten in den Gefäßen gerichtet sind.The object is achieved by a device which is characterized in that a hood corresponding to the surface of the microtitration plate is designed as a cavity which is closed on all sides, into which a gas line opens and whose boundary wall facing the microtitration plate is provided with gas outlet openings which are eccentric with respect to the Vessel axes are arranged and directed at an angle α to the surfaces of the liquids in the vessels.

Die Vorrichtung bietete den Vorteil, daß die in den Gefäßen befindliche Flüssigkeit durch thermostatisiertes Gas in eine zirkulare Bewegung versetzt wird, wodurch nicht nur die Thermostatisierung der Flüssigkeit, sondern auch im Wandbereich die Bindung und Umsetzung der Reagenzien mit den Proben verbessert wird. Daraus resultieren kürzere Inkubationszeiten und damit kürzere Testzeiten.The device offered the advantage that the liquid in the vessels was replaced by thermostated gas a circular movement is set, which not only improves the thermostatting of the liquid, but also the binding and reaction of the reagents with the samples in the wall area. This results in shorter incubation times and thus shorter test times.

Im folgenden wird die Erfindung anhand von lediglich einen Ausführungsweg darstellenden Zeichnungen näher erläutert. Es zeigt:

  • Figur 1 die Vorrichtung zum Thermostatisieren und Mischen über einer Mikrotitrationsplatte angeordnet in perspektivischer Darstellung,
  • Figur 2 eine Gasaustrittsöffnung in ein einzelnes Gefäß geschnitten und
  • Figur 3 eine Gasaustrittsöffnung in ein einzelnes Gefäß in Draufsicht.
The invention is explained in more detail below with the aid of drawings which illustrate only one embodiment. It shows:
  • 1 shows the device for thermostatting and mixing arranged over a microtitration plate in a perspective view,
  • Figure 2 cut a gas outlet opening in a single vessel and
  • Figure 3 shows a gas outlet opening in a single vessel in plan view.

Die Vorrichtung besteht im wesentlichen aus einer Haube 1, deren Abmessung der Fläche der Mikrotitrationsplatte 2 mit den Gefäßen 7 entspricht und die mit einem Hohlraum 3 versehen ist, in den eine Gasleitung 4 für thermostatisiertes Gas, z. B. Luft von 30° bis 50°C mündet. Die der Mikrotitrationsplatte 2 zugewandte Begrenzungswand 5 für den Hohlraum 3 der Haube 1 ist mit Gasaustrittsöffnungen 6 versehen. Der Hohlraum 3 dient als Gasverteiler für die Gasaustrittsöffnungen 6. Die Gasaustrittsöffnungen 6 können als Düsen oder Kanülen ausgebildet sein. Diese sind in der Begrenzungswand 5 so plaziert, daß sie exzentrisch im Bezug auf die Gefäßachsen 8 angeordnet sind. Der Luftstrom erzeugt beim Auftreffen auf die Flüssigkeitsoberfläche 10 eine Einbuchtung 11 auf dem Radius R. Die Düsenachse ist im Bezug auf die Oberfläche 10 um den Winkel α geneigt. Dabei kann der Abstand der Gasaustrittsöffnung von der Gefäßwand in radialer Richtung 0,2 bis 0,5 Gefäßradien betragen und der Winkel α, unter dem die Gasaustrittsöffnung zur Flüssigkeitsoberfläche hin geneigt ist, 40° bis 80°.The device consists essentially of a hood 1, the dimension of which corresponds to the area of the microtitration plate 2 with the vessels 7 and which is provided with a cavity 3 into which a gas line 4 for thermostatted gas, for. B. air from 30 ° to 50 ° C opens. The boundary wall 5 for the cavity 3 of the hood 1 facing the microtitration plate 2 is provided with gas outlet openings 6. The cavity 3 serves as a gas distributor for the gas outlet openings 6. The gas outlet openings 6 can be designed as nozzles or cannulas. These are placed in the boundary wall 5 so that they are arranged eccentrically with respect to the vessel axes 8. The air flow creates an indentation 11 on the radius R when it hits the liquid surface 10. The nozzle axis is inclined by the angle α with respect to the surface 10. The distance of the gas outlet opening from the vessel wall in the radial direction can be 0.2 to 0.5 vessel radii and the angle α at which the gas outlet opening is inclined toward the liquid surface can be 40 ° to 80 °.

Durch Reibung der Luft mit der Flüssigkeitsoberfläche 10, vorrangig bei 11, entstehen zwei sich überlagernde Strömungen der Flüssigkeit, und zwar eine kreisförmige Strömung 12 um die Gefäßachse 8 und eine nach unten in die Flüssigkeit gerichtete bogenförmige Strömung 9. Durch diese sich überlagernden Strömungen 12 und 9 wird die Flüssigkeit intensiv an der Gefäßwand vorbeiführt. Damit kann die Inkubationszeit erheblich verkürzt werden, d. h. die chemische Reaktion zwischen den Molekülen der Flüssigkeit und der Wand beschleunigt werden. Die Inkubationszeit des ELISA-Tests geht zurück und der Probendurchsatz des ELISA-Testgerätesnimmt zu.By friction of the air with the liquid surface 10, primarily at 11, two overlapping flows of the liquid arise, namely a circular flow 12 around the vessel axis 8 and an arcuate flow 9 directed downwards into the liquid. Through these overlapping flows 12 and 9 the liquid is passed intensively past the vessel wall. This allows the incubation time to be shortened considerably. H. the chemical reaction between the molecules of the liquid and the wall are accelerated. The incubation time of the ELISA test is decreasing and the sample throughput of the ELISA test device is increasing.

Claims (1)

Vorrichtung zum Thermostatisieren und Mischen des Inhaltes von Gefäßen einer Mikrotitrationsplatte, dadurch gekennzeichnet, daß eine der Fläche der Mikrotitrationsplatte (2) entsprechende Haube (1) als allseits geschlossener Hohlraum (3) ausgebildet ist, in den eine Gasleitung (4) mündet und dessen der Titrationsplatte (2) zugewandte Begrenzungswand (5) mit Gasaustrittsöffnungen (6) versehen ist, die exzentrisch in Bezug auf die Gefäßachsen (8) angeordnet und unter einem Winkel α auf die Oberflächen (10) der Flüssigkeiten gerichtet sind.Device for thermostatting and mixing the contents of vessels of a microtitration plate, characterized in that a hood (1) corresponding to the surface of the microtitration plate (2) is designed as a cavity (3) which is closed on all sides and into which a gas line (4) opens and the latter The boundary wall (5) facing the titration plate (2) is provided with gas outlet openings (6) which are arranged eccentrically with respect to the vessel axes (8) and are directed at an angle α to the surfaces (10) of the liquids.
EP88103357A 1987-03-07 1988-03-04 Device for controlling the temperature and mixing the contents of the vessels of a micro-titration plate Withdrawn EP0281958A3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19873707368 DE3707368A1 (en) 1987-03-07 1987-03-07 DEVICE FOR THERMOSTATIZING AND MIXING THE CONTENT OF THE CONTAINERS OF A MICROTITRATION PLATE
DE3707368 1987-03-07

Publications (2)

Publication Number Publication Date
EP0281958A2 true EP0281958A2 (en) 1988-09-14
EP0281958A3 EP0281958A3 (en) 1989-03-22

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP88103357A Withdrawn EP0281958A3 (en) 1987-03-07 1988-03-04 Device for controlling the temperature and mixing the contents of the vessels of a micro-titration plate

Country Status (7)

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EP (1) EP0281958A3 (en)
JP (1) JPS63242335A (en)
AU (1) AU1264588A (en)
DE (1) DE3707368A1 (en)
DK (1) DK119288A (en)
FI (1) FI880988A (en)
NO (1) NO880974L (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0589363A1 (en) * 1992-09-25 1994-03-30 Boehringer Mannheim Gmbh Method and device for automatic mixing without contact of a reaction mixture in a analysing device
WO1994019097A1 (en) * 1993-02-26 1994-09-01 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Process and device for mixing liquids in microtitration plates
WO1999017881A1 (en) * 1997-10-07 1999-04-15 The Perkin-Elmer Corporation Apparatus for a fluid impingement thermal cycler
EP1174703A2 (en) * 2000-07-18 2002-01-23 Volker Barkey Evaporator for samples
EP1362115A1 (en) * 2001-02-08 2003-11-19 Irm Llc Multi-sample fermentor and method of using same
WO2004008154A1 (en) * 2002-07-16 2004-01-22 H+P Labortechnik Ag Sample treatment station
WO2008000312A1 (en) * 2006-06-29 2008-01-03 Ika-Werke Gmbh & Co.Kg Microtiter plate with stirring elements
ITPD20080371A1 (en) * 2008-12-17 2010-06-18 Univ Padova MECHANICAL MIXING DEVICE FOR CULTIVATION PLATES
US9156012B2 (en) 2004-06-11 2015-10-13 Roche Diagnostics Operations, Inc. Method and device for mixing samples on a support
DE102019103029A1 (en) * 2019-02-07 2020-08-13 Thyssenkrupp Ag Procedure for handling melt samples in a steel mill laboratory and a steel mill laboratory

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Publication number Priority date Publication date Assignee Title
JPH0639266A (en) * 1992-07-04 1994-02-15 Kyowa Medex Co Ltd Method and device for agitating liquid
JP3567187B2 (en) * 1995-02-23 2004-09-22 アークレイ株式会社 Stirring device for sample liquid, etc.
DE19712575C2 (en) * 1997-03-26 2000-05-11 Desaga Gmbh C Incubation device
DE19815696C2 (en) * 1998-04-08 2000-06-29 Gsf Forschungszentrum Umwelt Temperature controlled overflow equipment for biological samples
DE10036159B4 (en) * 2000-07-25 2006-11-09 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Microtiter plates with fumigation
DE10144225C1 (en) * 2001-09-08 2003-02-06 Eppendorf Ag Process for drying filters in cavities of micro-titration plate involves using device with nozzles and unit for producing air stream through nozzles
DE10329983A1 (en) * 2003-06-27 2005-03-31 Siemens Ag Micro-reactor module allows multiple different reactions to be performed simultaneously and to be serviced by a standard automatic micro-titer head, is formed of a multiple recessed base plate which is sealed by a releasable cover plate
JP2006343245A (en) * 2005-06-09 2006-12-21 Olympus Corp Dispenser and analyzer
DE102005034175A1 (en) * 2005-07-21 2007-01-25 Roche Diagnostics Gmbh Method and device for generating a moist air flow with defined relative humidity
JP5217439B2 (en) * 2005-12-02 2013-06-19 和光純薬工業株式会社 Liquid stirring apparatus and method
JP2007318170A (en) * 2007-08-06 2007-12-06 Sanyo Electric Co Ltd Manufacture and manufacturing apparatus of solid-state electrolytic capacitor
JP5659698B2 (en) * 2010-10-29 2015-01-28 ソニー株式会社 Sample inflow device, sample inflow tip, and sample inflow method

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WO1985003571A1 (en) * 1984-02-01 1985-08-15 Hulette William C Clinical analysis systems and methods
EP0176014A2 (en) * 1984-09-22 1986-04-02 Eppendorf-Netheler-Hinz Gmbh Method and device for mixing a liquid sample to be analysed
DE3441179A1 (en) * 1984-11-10 1986-05-22 Dynatech Deutschland GmbH, 7306 Denkendorf Temperature-control device for microcell arrangements, in particular microtitration plates
WO1987000281A1 (en) * 1985-07-10 1987-01-15 Labsystems Oy A thermostated cuvette set

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* Cited by examiner, † Cited by third party
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US3398935A (en) * 1964-03-25 1968-08-27 Bausch & Lomb Mixing means
WO1985003571A1 (en) * 1984-02-01 1985-08-15 Hulette William C Clinical analysis systems and methods
EP0176014A2 (en) * 1984-09-22 1986-04-02 Eppendorf-Netheler-Hinz Gmbh Method and device for mixing a liquid sample to be analysed
DE3441179A1 (en) * 1984-11-10 1986-05-22 Dynatech Deutschland GmbH, 7306 Denkendorf Temperature-control device for microcell arrangements, in particular microtitration plates
WO1987000281A1 (en) * 1985-07-10 1987-01-15 Labsystems Oy A thermostated cuvette set

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Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0589363A1 (en) * 1992-09-25 1994-03-30 Boehringer Mannheim Gmbh Method and device for automatic mixing without contact of a reaction mixture in a analysing device
US5362147A (en) * 1992-09-25 1994-11-08 Boehringer Mannheim Gmbh Method and apparatus for the contactless automatic mixing of a reaction mixture in an analysis unit
WO1994019097A1 (en) * 1993-02-26 1994-09-01 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Process and device for mixing liquids in microtitration plates
WO1999017881A1 (en) * 1997-10-07 1999-04-15 The Perkin-Elmer Corporation Apparatus for a fluid impingement thermal cycler
EP1174703A2 (en) * 2000-07-18 2002-01-23 Volker Barkey Evaporator for samples
EP1174703A3 (en) * 2000-07-18 2003-04-16 Volker Barkey Evaporator for samples
EP1362115A1 (en) * 2001-02-08 2003-11-19 Irm Llc Multi-sample fermentor and method of using same
EP1362115A4 (en) * 2001-02-08 2004-06-23 Irm Llc Multi-sample fermentor and method of using same
DE10232202A1 (en) * 2002-07-16 2004-02-05 Herz, Helmut, Dr.-Ing. Sample treatment station
WO2004008154A1 (en) * 2002-07-16 2004-01-22 H+P Labortechnik Ag Sample treatment station
DE10232202B4 (en) * 2002-07-16 2005-08-25 H+P Labortechnik Ag Sample treatment station
US9156012B2 (en) 2004-06-11 2015-10-13 Roche Diagnostics Operations, Inc. Method and device for mixing samples on a support
WO2008000312A1 (en) * 2006-06-29 2008-01-03 Ika-Werke Gmbh & Co.Kg Microtiter plate with stirring elements
US20100034048A1 (en) * 2006-06-29 2010-02-11 Ika-Werke Gmbh & Co. Kg Microtiter Plate with Stirring Elements
CN101484238B (en) * 2006-06-29 2012-02-01 艾卡工厂有限及两合公司 Microtiter plate with stirring elements
US8317389B2 (en) 2006-06-29 2012-11-27 Ika-Werke Gmbh & Co. Kg Microtiter plate with stirring elements
TWI380852B (en) * 2006-06-29 2013-01-01 Ika Werke Gmbh & Co Kg Microtiter plate with stirring element
ITPD20080371A1 (en) * 2008-12-17 2010-06-18 Univ Padova MECHANICAL MIXING DEVICE FOR CULTIVATION PLATES
DE102019103029A1 (en) * 2019-02-07 2020-08-13 Thyssenkrupp Ag Procedure for handling melt samples in a steel mill laboratory and a steel mill laboratory

Also Published As

Publication number Publication date
FI880988A (en) 1988-09-08
DE3707368A1 (en) 1988-09-15
JPS63242335A (en) 1988-10-07
DK119288A (en) 1988-09-08
FI880988A0 (en) 1988-03-03
EP0281958A3 (en) 1989-03-22
AU1264588A (en) 1988-09-08
NO880974L (en) 1988-09-08
NO880974D0 (en) 1988-03-04
DK119288D0 (en) 1988-03-04

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