EP0092140A1 - Microtitration plate - Google Patents

Microtitration plate Download PDF

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Publication number
EP0092140A1
EP0092140A1 EP83103517A EP83103517A EP0092140A1 EP 0092140 A1 EP0092140 A1 EP 0092140A1 EP 83103517 A EP83103517 A EP 83103517A EP 83103517 A EP83103517 A EP 83103517A EP 0092140 A1 EP0092140 A1 EP 0092140A1
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EP
European Patent Office
Prior art keywords
edge
plate
microtiter plate
vessels
webs
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.)
Granted
Application number
EP83103517A
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German (de)
French (fr)
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EP0092140B1 (en
Inventor
Hans-Detlef Dr. Dopatka
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Siemens Healthcare Diagnostics GmbH Germany
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Behringwerke AG
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Priority to AT83103517T priority Critical patent/ATE21048T1/en
Publication of EP0092140A1 publication Critical patent/EP0092140A1/en
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Publication of EP0092140B1 publication Critical patent/EP0092140B1/en
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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 microtiter 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 microtiter 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 done both by placing the plate on a heat-conducting base, for example the metal floor of an incubator, and by insulating the middle of the plate by the air cushion underneath. of 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 microtiter 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 placed on a base with a higher temperature is applied.
  • the object of the invention is that the shape of a conventional microtiter plate is changed so that the heatability of the edge depressions over the plate edge 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 breakthrough 4 reduces the heat transfer of the rapidly heating plate edge to the edge vessels.
  • the measures under a, b and c ensure that the air cushion underneath each plate is quickly removed even when the plates are stacked on top of one another (chute principle for the colder air). This allows the free-standing, large-area webs to heat up more quickly.
  • 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 plate edge.
  • the remaining influence of the plate edge is compensated for by the bevel of the web towards the plate edge.
  • microtiter plate according to the invention is torsionally stable, suitable for automatic machines, 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)
  • Electron Beam Exposure (AREA)
  • Paints Or Removers (AREA)
  • Manufacture Of Macromolecular Shaped Articles (AREA)
  • Laminated Bodies (AREA)
  • Micromachines (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Investigating Or Analysing Biological Materials (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 Mikrotiterplatte, 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 microtiter 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 Mikrotiterplatten 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 Mikrotiterplatten, obwohl von der Testanlage her ein nahezu gleicher Extinktionswert in allen Vertiefungen zu erwarten wäre.This frame effect is known as a source of error in the enzyme linked immunosorbent assay (ELISA) when it is carried out on microtiter 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 microtiter plates used, although an almost identical absorbance value could be expected in all depressions from the test system.

Diese typische Erhöhung der Farbintensität ist nicht mit den allgemein als "Ausreißer" bezeichneten Einzelabweichungen zu verwechseln, die zufallsverteilt über die Mikrotiterplatte 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, which are generally referred to as "outliers" and which appear to occur randomly across the microtiter plate. 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 Randvertiefungen und den übrigen Näpfchen der Mikrotiterplatte während der immunologischen Reaktionen und der Enzymreaktion des ELISA verursacht (Burt et al., J. Immunol. Meth. (1979) 31, 231).The frame effect, on the other hand, is caused by a temperature difference between the marginal depressions and the other wells of the microtiter 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 1,60C 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 1.60C 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 done both by placing the plate on a heat-conducting base, for example the metal floor of an incubator, and by insulating the middle of the plate by the air cushion underneath. of 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).

Die Erfindung hat sich die Aufgabe gestellt, eine Mikrotiterplatte, 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 microtiter 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 placed on a base with a higher temperature is applied.

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

Gegenstand der Erfindung ist, daß die Form einer herkömmlichen Mikrotiterplatte so verändert wird, daß die Erwärmbarkeit der Randvertiefungen über den Plattenrand stark reduziert und gleichzeitig die Erwärmbarkeit der übrigen Plattenvertiefungen erhöht wird. Beide Wärmetransporteffekte wirken in der Weise zusammen, daß der Rahmeneffekt eliminiert wird.The object of the invention is that the shape of a conventional microtiter plate is changed so that the heatability of the edge depressions over the plate edge 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 Mikrotiterplatte 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 Plattenrand (2) der Mikrotiterplatte wird bis auf wenige Verbindungspunkte (3), die von den gespitzten Enden von Stegen (5) gebildet werden, vom Plattenteil (1) getrennt, so daß ein umlaufender Durchbruch (4) entsteht;
    • b) gegebenenfalls sind diese senkrecht zur Plattenoberfläche stehenden Stege (5) so hoch wie möglich gehalten, ohne die Stapelfähigkeit der Mikrotiterplatte 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 Auflagekante des unteren Plattenrandes (7) 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 microtiter plate, which are described in more detail below or are similar, with the same effect
  • 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 plate edge (2) of the microtiter plate is separated from the plate part (1) except for a few connection points (3) which are formed by the pointed ends of webs (5), so that a circumferential opening (4) is formed;
    • b) if necessary, these webs (5) standing perpendicular to the plate surface are kept as high as possible without impairing the stackability of the microtiter 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 provided on the contact edge of the lower plate edge (7) 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 Plattenrandes auf die Randgefäße.The breakthrough 4 reduces the heat transfer of the rapidly heating plate edge to the edge vessels.

Durch die Maßnahmen unter a, b und c wird auch bei übereinandergestapelten Platten ein schneller Abbau des Luftpolsters unterhalb jeder Platte erzielt(Fallschachtprin- zip für die kältere Luft). Hierdurch können sich die freistehenden und großflächigen Stege schneller erwärmen.The measures under a, b and c ensure that the air cushion underneath each plate is quickly removed even when the plates are stacked on top of one another (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 Plattenrand erfolgt. Der Resteinfluß des Plattenrandes wird durch die Abschrägung des Steges zum Plattenrand 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 plate edge. The remaining influence of the plate edge is compensated for by the bevel of the web towards the plate edge.

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

Die erfindungsgemäße Mikrotiterplatte ist verwindungsstabil, automatengerecht, stapelbar und beschriftbar.The microtiter plate according to the invention is torsionally stable, suitable for automatic machines, stackable and can be labeled.

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

Claims (9)

1. Mikrotiterplatte mit einem aufliegenden Rand und einem mit Gefäßen versehenen Mittelteil, dadurch gekennzeichnet, daß sie eine gleichmäßige Temperaturveränderung des Inhalts aller Gefäße gewährleistet, wenn sie auf eine Unterlage mit höherer als der Temperatur der Platte aufgelegt wird.1. A microtiter plate with an overlying edge and a central part provided with vessels, characterized in that it ensures a uniform temperature change in the contents of all vessels when it is placed on a support with a higher temperature than the plate. 2. Mikrotiterplatte, insbesondere nach Anspruch 1, dadurch gekennzeichnet, daß Rand und Mittelteil durch einen Durchbruch weitgehend voneinander getrennt und nur an einigen Stellen miteinander verbunden sind.2. Microtiter plate, in particular according to claim 1, characterized in that the edge and middle part are largely separated from one another by an opening and are connected to one another only at some points. 3. Mikrotiterplatte, insbesondere nach Anspruch 1, dadurch gekennzeichnet, daß an der Plattenunterseite in einer Richtung verlaufende Stege angeordnet sind.3. Microtiter plate, in particular according to claim 1, characterized in that webs extending in one direction are arranged on the underside of the plate. 4. Mikrotiterplatte, insbesondere nach Anspruch 1, dadurch gekennzeichnet, daß am aufliegenden Plattenrand Aussparungen vorhanden sind.4. A microtiter plate, in particular according to claim 1, characterized in that there are recesses on the plate edge resting thereon. 5. Mikrotiterplatte nach Anspruch 2, dadurch gekennzeichnet, daß der Durchbruch zwischen Rand und Mittelteil so nahe wie möglich an den Gefäßen am Rand angeordnet ist.5. Microtiter plate according to claim 2, characterized in that the opening between the edge and the middle part is arranged as close as possible to the vessels on the edge. 6. Mikrotiterplatte nach Anspruch 2 und/oder 5, dadurch gekennzeichnet, daß der Durchbruch zwischen Rand und Mittelteil zu Aussparungen erweitert ist.6. Microtiter plate according to claim 2 and / or 5, characterized in that the opening between the edge and the central part is expanded to form recesses. 7. Mikrotiterplatte nach Anspruch 2, dadurch gekennzeichnet, daß die Gefäße in Reihen angeordnet sind und zwischen jeweils zwei Reihen ein senkrechter Steg angebracht ist.7. Microtiter plate according to claim 2, characterized in that the vessels are arranged in rows and a vertical web is attached between two rows. 8. Mikrotiterplatte nach Anspruch 2 und/oder 3,dadurch gekennzeichnet, daß die Enden der Stege gespitzt sind und Rand und Mittelteil verbinden.8. A microtiter plate according to claim 2 and / or 3, characterized in that the ends of the webs are pointed and connect the edge and middle part. 9. Mikrotiterplatte nach Anspruch 2 und/oder 4, dadurch gekennzeichnet, daß die Aussparungen am Plattenrand sich zwischen den Stegen gegenüberliegen und kerbförmig ausgebildet sind.9. A microtiter plate according to claim 2 and / or 4, characterized in that the recesses on the plate edge lie opposite one another between the webs and are notch-shaped.
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
DE19823214317 DE3214317A1 (en) 1982-04-19 1982-04-19 MICROTITER PLATE
DE3214317 1982-04-19

Publications (2)

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

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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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Also Published As

Publication number Publication date
DK169883A (en) 1983-10-20
DE3214317A1 (en) 1983-12-15
ES271504Y (en) 1984-04-01
DK169883D0 (en) 1983-04-18
EP0092140B1 (en) 1986-07-30
ATE21048T1 (en) 1986-08-15
CA1216735A (en) 1987-01-20
US4545958A (en) 1985-10-08
DE3364865D1 (en) 1986-09-04
ES271504U (en) 1983-10-01
JPS58190763A (en) 1983-11-07

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