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EP0092140B1 - Microtitration plate - Google Patents

Microtitration plate Download PDF

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Publication number
EP0092140B1
EP0092140B1 EP83103517A EP83103517A EP0092140B1 EP 0092140 B1 EP0092140 B1 EP 0092140B1 EP 83103517 A EP83103517 A EP 83103517A EP 83103517 A EP83103517 A EP 83103517A EP 0092140 B1 EP0092140 B1 EP 0092140B1
Authority
EP
European Patent Office
Prior art keywords
plate
frame
vessels
microtitration plate
central part
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.)
Expired
Application number
EP83103517A
Other languages
German (de)
French (fr)
Other versions
EP0092140A1 (en
Inventor
Hans-Detlef Dr. Dopatka
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.)
Siemens Healthcare Diagnostics GmbH Germany
Original Assignee
Behringwerke 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 Behringwerke AG filed Critical Behringwerke AG
Priority to AT83103517T priority Critical patent/ATE21048T1/en
Publication of EP0092140A1 publication Critical patent/EP0092140A1/en
Application granted granted Critical
Publication of EP0092140B1 publication Critical patent/EP0092140B1/en
Expired legal-status Critical Current

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    • 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
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/807—Apparatus included in process claim, e.g. physical support structures
    • Y10S436/809—Multifield plates or multicontainer arrays

Definitions

  • the invention relates to a microtest plate in which the peripheral areas and the central part heat up evenly when placed on a base with a higher temperature, so that there is no temperature gradient between reaction solutions in vessels at the edge and those in the central part.
  • This plate therefore has properties that avoid the so-called edge effect of conventional plates.
  • the frame effect is caused by a temperature difference between the marginal depressions and the other wells of the microtest plate during the immunological reactions and the enzyme reaction of the ELISA (Burt et al., J. Immunol. Meth. (1979) 31, 231).
  • temperature-dependent reactions such as antigen-antibody binding or an enzyme reaction proceed faster than in the rest of the plate. This manifests itself in an increased color intensity of the affected cells in the ELISA.
  • the temperature gradient between the edge depressions and the center of the plate results from the faster heating of the plate edge. This can be explained both by the support of the plate on a heat-conducting base, for example the metal floor of an incubator, and by the thermal insulation of the center of the plate by the air cushion under the plate. The higher the incubation temperatures and the shorter the incubation times, the stronger the frame effect is normally.
  • the frame effect can be reduced by stacking the plates on one another and eliminated by floating the microtiter plate without bubbles in a warm water bath or using suitable heating fans.
  • the invention has for its object to provide a micro test plate, that is, a device which consists essentially of a plate-shaped carrier with several vessels, which ensures a uniform temperature change in the content of all vessels when the device is on a base with a higher Temperature is applied.
  • the shape of a conventional microtest plate is changed according to the invention so that the heatability of the edge depressions over the plate edge (frame) is greatly reduced and at the same time the heatability of the other plate depressions is increased. Both heat transport effects work together in such a way that the frame effect is eliminated.
  • the opening 4 reduces the heat transfer of the rapidly warming frame to the peripheral vessels.
  • the heated webs emit the heat evenly to the respectively adjacent vessels, the heating by the web itself taking place faster than via the connection points with the frame.
  • the remaining influence of the frame is compensated for by the bevel of the web towards the frame.
  • micro test plate according to the invention is torsionally stable, machine-compatible, stackable and can be labeled.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Polishing Bodies And Polishing Tools (AREA)
  • Paints Or Removers (AREA)
  • Manufacture Of Macromolecular Shaped Articles (AREA)
  • Laminated Bodies (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Micromachines (AREA)
  • Electron Beam Exposure (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

A microtitration plate wherein a frame and a central part are separated from one another via a continuous break and ridges are arranged at the lower face of the plate so that differences in temperature on heating between edge vessels and vessels in the central part are avoided, said differences in temperature causing the well-known "edge-effect".

Description

Die Erfindung betrifft eine Mikrotestplatte, bei der sich Randbezirke und Mittelteil gleichmäßig erwärmen, wenn sie auf eine Unterlage mit höherer Temperatur aufgelegt wird, so daß kein Temperaturgradient zwischen Reaktionslösungen in Gefäßen am Rand und solchen im Mittelteil entsteht. Diese Platte hat demnach Eigenschaften, die den sogenannten Rahmeneffekt (edge effect) herkömmlicher Platten vermeiden.The invention relates to a microtest plate in which the peripheral areas and the central part heat up evenly when placed on a base with a higher temperature, so that there is no temperature gradient between reaction solutions in vessels at the edge and those in the central part. This plate therefore has properties that avoid the so-called edge effect of conventional plates.

Dieser Rahmeneffekt ist als Fehlerquelle im Enzyme Linked Immuno Sorbent Assay (ELISA) bekannt, wenn dieser auf Mikrotestplatten ausgeführt wird (Denmark und Chessum, Med. Lab. Sci. (1978) 35, 227). Die Verfälschung des Testergebnisses besteht in einer Erhöhung der Farbintensität in den Randvertiefungen der verwendeten Mikrotestplatten, obwohl von der Testanlage her ein nahezu gleicher Extinktionswert in allen Vertiefungen zu erwarten wäre.This frame effect is known to be a source of error in the enzyme linked immunosorbent assay (ELISA) when it is carried out on microtest plates (Denmark and Chessum, Med. Lab. Sci. (1978) 35, 227). The falsification of the test result consists in an increase in the color intensity in the marginal depressions of the microtest plates used, although an almost identical absorbance value could be expected in all wells from the test system.

Diese typische Erhöhung der Farbintensität ist nicht mit den allgemein als « Ausreißer bezeichneten Einzelabweichungen zu verwechseln, die zufallsverteilt über die Mikrotestplatte aufzutreten scheinen. Hier sind Fehler bei der Testdurchführung, der Plattenbeschichtung oder der Materialqualität der Platte die Ursachen.This typical increase in color intensity should not be confused with the individual deviations, commonly referred to as "outliers", which appear to occur randomly across the microplate. The causes of errors in test execution, plate coating or the material quality of the plate are the cause.

Der Rahmeneffekt dagegen wird durch ein Temperaturgefälle zwischen den Randvertiefüngen und den übrigen Näpfchen der Mikrotestplatte während der immunologischen Reaktionen und der Enzymreaktion des ELISA verursacht (Burt et al., J. Immunol. Meth. (1979) 31, 231).The frame effect, however, is caused by a temperature difference between the marginal depressions and the other wells of the microtest plate during the immunological reactions and the enzyme reaction of the ELISA (Burt et al., J. Immunol. Meth. (1979) 31, 231).

Bei einer in den Randvertiefungen bis zu 1,6 °C höheren Temperatur verlaufen dort temperaturabhängige Reaktionen wie die Antigen-Antikörper-Bindung oder eine Enzymreaktion schneller als in der übrigen Platte. Dies manifestiert sich in einer erhöhten Farbintensität der betroffenen Näpfchen im ELISA.At a temperature up to 1.6 ° C higher in the marginal depressions, temperature-dependent reactions such as antigen-antibody binding or an enzyme reaction proceed faster than in the rest of the plate. This manifests itself in an increased color intensity of the affected cells in the ELISA.

Der Temperaturgradient zwischen Randvertiefungen und Plattenmitte entsteht durch die schnellere Erwärmung des Plattenrandes. Dies kann sowohl mit der Auflage der Platte auf eine gut wärmeleitende Unterlage, beispielsweise dem Metallboden eines Brutschrankes, als auch mit der Wärmeisolierung der Plattenmitte durch das Luftpolster unter der Platte erklärt werden. Je höher die Inkubationstemperaturen und je kürzer die Inkubationszeiten, desto stärker ist normalerweise der Rahmeneffekt ausgeprägt. Durch Aufeinanderstapeln der Platten läßt sich der Rahmeneffekt mindern und durch blasenfreies Aufschwimmen der Mikrotiterplatte in einem Warmwasserbad oder Verwendung geeigneter Heizgebläse eliminieren.The temperature gradient between the edge depressions and the center of the plate results from the faster heating of the plate edge. This can be explained both by the support of the plate on a heat-conducting base, for example the metal floor of an incubator, and by the thermal insulation of the center of the plate by the air cushion under the plate. The higher the incubation temperatures and the shorter the incubation times, the stronger the frame effect is normally. The frame effect can be reduced by stacking the plates on one another and eliminated by floating the microtiter plate without bubbles in a warm water bath or using suitable heating fans.

Die beiden letztgenannten Möglichkeiten sind jedoch entweder schwierig durchzuführen oder technisch aufwendig (Oliver et al., J. Immunol. Meth. (1981) 42, 195).However, the latter two options are either difficult to implement or technically complex (Oliver et al., J. Immunol. Meth. (1981) 42, 195).

Der Erfindung liegt die Aufgabe zugrunde, eine Mikrotestplatte, das heißt eine Vorrichtung, die im wesentlichen aus einem plattenförmigen Träger mit mehreren Gefäßen besteht, zu schaffen, die eine zeitlich gleichförmige Temperaturveränderung des Inhalts aller Gefäße gewährleistet, wenn die Vorrichtung auf eine Unterlage mit einer höheren Temperatur aufgebracht wird.The invention has for its object to provide a micro test plate, that is, a device which consists essentially of a plate-shaped carrier with several vessels, which ensures a uniform temperature change in the content of all vessels when the device is on a base with a higher Temperature is applied.

Diese Aufgabe wird bei einer Mikrotestplatte mit einem Rahmen und einem mit Gefäßen versehenen Mittelteil: gemäß dem Kennzeichen des Anspruchs 1 gelöst.This object is achieved in the case of a microtest plate with a frame and a central part provided with vessels: according to the characterizing part of claim 1.

Es wurde überraschenderweise gefunden, daß die Entstehung eines Temperaturgradienten zwischen den Randbezirken und dem Inneren einer Mikrotestplatte beim Erwärmen durch eine geeignete Formgebung des Plattenmaterials vermieden werden kann.It has surprisingly been found that the formation of a temperature gradient between the peripheral regions and the inside of a micro test plate during heating can be avoided by suitable shaping of the plate material.

Die Form einer herkömmlichen Mikrotestplatte wird gemäß der Erfindung so verändert, daß die Erwärmbarkeit der Randvertiefungen über den Plattenrand (Rahmen) stark reduziert und gleichzeitig die Erwärmbarkeit der übrigen Plattenvertiefungen erhöht wird. Beide Wärmetransporteffekte wirken in der Weise zusammen, daß der Rahmeneffekt eliminiert wird.The shape of a conventional microtest plate is changed according to the invention so that the heatability of the edge depressions over the plate edge (frame) is greatly reduced and at the same time the heatability of the other plate depressions is increased. Both heat transport effects work together in such a way that the frame effect is eliminated.

Dies wird erfindungsgemäß durch die im folgenden näher beschriebenen oder ähnliche, wirkungsgleiche Formveränderungen einer herkömmlichen Mikrotestplatte erreicht, wobei

  • Figur 1 eine Aufsicht auf eine erfindungsgemäße Platte,
  • Figur 2 die Ansicht von unten dieser Platte,
  • Figur 3 eine Seitenansicht dieser Platte und
  • Figur 4 - den Schnitt IV-IV in der Figur 1 zeigt :
    • a) Der obere Rand (2) des Rahmens der Mikrotestplatte wird bis auf wenige Verbindungspunkte (3), die von den gespitzten Enden von Stegen (5) gebildet werden, vom Mittelteil (1) getrennt, so daß ein umlaufender Durchbruch (4) entsteht, der zu Aussparungen erweitert sein kann ;
    • b) gegebenenfalls sind diese senkrecht zur Plattenoberfläche stehenden Stege (5) so hoch wie möglich gehalten, ohne die Stapelfähigkeit der Mikrotestplatte zu beeinträchtigen. Die Stege können zwischen der ersten und zweiten, dritten und vierten, fünften und sechsten, siebten und achten, neunten und zehnten sowie elften und zwölften Reihe der Gefäße (8) angelegt sein, wie in den Figuren 1 und 2 dargestellt. Die Stege (5) können aber auch senkrecht zu den Gefäßreihen zwischen den Gefäßzeilen A bis H angeordnet sein ;
    • c) gegebenenfalls werden Aussparungen (6), vorzugsweise kleine Kerben, an der unteren Auflagekante (7) des Rahmens so angebracht, daß sie sich zwischen den Stegen (5) gegenüberliegen.
This is achieved according to the invention by means of the shape changes of a conventional microtest plate which have the same effect or are described in more detail below, wherein
  • FIG. 1 shows a top view of a plate according to the invention,
  • FIG. 2 shows the bottom view of this plate,
  • Figure 3 is a side view of this plate and
  • Figure 4 - shows the section IV-IV in Figure 1:
    • a) The upper edge (2) of the frame of the microplate is apart from a few connection points (3), which are formed by the pointed ends of webs (5), separated from the central part (1), so that a circumferential opening (4) is formed that can be expanded to recesses;
    • b) if necessary, these webs (5), which are perpendicular to the plate surface, are kept as high as possible without impairing the stackability of the microtest plate. The webs can be arranged between the first and second, third and fourth, fifth and sixth, seventh and eighth, ninth and tenth as well as eleventh and twelfth row of the vessels (8), as shown in FIGS. 1 and 2. The webs (5) can also be arranged perpendicular to the rows of vessels between the rows of vessels A to H;
    • c) if necessary, recesses (6), preferably small notches, are attached to the lower contact edge (7) of the frame in such a way that they lie opposite one another between the webs (5).

Wirkungsweise und VerbesserungenEffectiveness and improvements

Der Durchbruch 4 reduziert die Wärmeübertragung des sich schnell erwärmenden Rahmens auf die Randgefäße.The opening 4 reduces the heat transfer of the rapidly warming frame to the peripheral vessels.

Durch die Maßnahmen unter a, b und c wird auch bei übereinandergestapelten Platten ein schneller Abbau des Luftpolsters unterhalb jederThanks to the measures under a, b and c, even with stacked panels, the air cushion underneath each is broken down quickly

Platte erzielt (Fallschachtprinzip für die kältere Luft). Hierdurch können sich die freistehenden und großflächigen Stege schneller erwärmen.Plate achieved (chute principle for the colder air). This allows the free-standing, large-area webs to heat up more quickly.

Durch die Maßnahme unter b) geben die erwärmten Stege die Wärme gleichmäßig an die jeweils benachbarten Gefäße ab, wobei die Erwärmung durch den Steg selbst schneller als über die Verbindungspunkte mit dem Rahmen erfolgt. Der Resteinfluß des Rahmens wird durch die Abschrägung des Steges zum Rahmen hin ausgeglichen.As a result of the measure under b), the heated webs emit the heat evenly to the respectively adjacent vessels, the heating by the web itself taking place faster than via the connection points with the frame. The remaining influence of the frame is compensated for by the bevel of the web towards the frame.

Die Summe dieser Maßnahmen eliminiert den Rahmeneffekt.The sum of these measures eliminates the frame effect.

Die erfindungsgemäße Mikrotestplatte ist verwindungsstabil, automatengerecht, stapelbar und beschriftbar.The micro test plate according to the invention is torsionally stable, machine-compatible, stackable and can be labeled.

Sie ist besonders für den Gebrauch in Wärmeschränken geeignet.It is particularly suitable for use in hot cupboards.

Claims (5)

1. Microtitration plate having a frame and a central part (1) provided with vessels (8), characterized in that the upper edge (2) of the frame of the microtitration plate is separated from the central part (1) except for connections at a few sites (3) such that a circular gap (4) is formed, and that there are ridges (5) vertical to the surface of the plate and that there are recesses (6), preferably small indentations at the lower edge of the frame (7), which recesses are located between the ridges (5) and face one another.
2. The microtitration plate of claim 1, wherein the gap (4) is placed as closely as possible to the vessels (8) at the edges of the central part (1).
3. The microtitration plate of claim 1, wherein the gap (4) is widened to form recesses.
4. The microtitration plate of claim 1, wherein the vessels (8) are arranged in rows and wherein between two rows each there is a vertical ridge (5).
5. The microtitration plate of claim 1, wherein the ends of the ridges (5) are tapered and connect the upper edge (2) of the frame and the central part (1).
EP83103517A 1982-04-19 1983-04-12 Microtitration plate Expired EP0092140B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT83103517T ATE21048T1 (en) 1982-04-19 1983-04-12 MICROTEST PLATE.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3214317 1982-04-19
DE19823214317 DE3214317A1 (en) 1982-04-19 1982-04-19 MICROTITER PLATE

Publications (2)

Publication Number Publication Date
EP0092140A1 EP0092140A1 (en) 1983-10-26
EP0092140B1 true EP0092140B1 (en) 1986-07-30

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EP83103517A Expired EP0092140B1 (en) 1982-04-19 1983-04-12 Microtitration plate

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US (1) US4545958A (en)
EP (1) EP0092140B1 (en)
JP (1) JPS58190763A (en)
AT (1) ATE21048T1 (en)
CA (1) CA1216735A (en)
DE (2) DE3214317A1 (en)
DK (1) DK169883A (en)
ES (1) ES271504Y (en)

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DE3266735D1 (en) * 1981-02-18 1985-11-14 Eisai Co Ltd An enzyme immuno-assay for simultaneously measuring a plurality of samples and test vessel for carrying out this method

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Publication number Publication date
ES271504Y (en) 1984-04-01
US4545958A (en) 1985-10-08
JPS58190763A (en) 1983-11-07
DK169883A (en) 1983-10-20
CA1216735A (en) 1987-01-20
EP0092140A1 (en) 1983-10-26
ES271504U (en) 1983-10-01
DK169883D0 (en) 1983-04-18
ATE21048T1 (en) 1986-08-15
DE3214317A1 (en) 1983-12-15
DE3364865D1 (en) 1986-09-04

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