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WO1991006369A2 - Temperature-equalization chamber for bringing the contents of a microtitration plate to a uniform temperature - Google Patents

Temperature-equalization chamber for bringing the contents of a microtitration plate to a uniform temperature Download PDF

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Publication number
WO1991006369A2
WO1991006369A2 PCT/AT1990/000107 AT9000107W WO9106369A2 WO 1991006369 A2 WO1991006369 A2 WO 1991006369A2 AT 9000107 W AT9000107 W AT 9000107W WO 9106369 A2 WO9106369 A2 WO 9106369A2
Authority
WO
WIPO (PCT)
Prior art keywords
temperature
heating
temperature control
plate
chamber according
Prior art date
Application number
PCT/AT1990/000107
Other languages
German (de)
French (fr)
Other versions
WO1991006369A3 (en
Inventor
Karl Puchegger
Josef Atzler
Original Assignee
Slt-Labinstruments Gesellschaft M.B.H.
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 Slt-Labinstruments Gesellschaft M.B.H. filed Critical Slt-Labinstruments Gesellschaft M.B.H.
Priority to FI913192A priority Critical patent/FI913192A7/en
Publication of WO1991006369A2 publication Critical patent/WO1991006369A2/en
Publication of WO1991006369A3 publication Critical patent/WO1991006369A3/en

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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
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates

Definitions

  • Temperature control chamber especially for temperature control of the contents of a microtitration plate
  • the invention relates to a temperature control chamber, in particular for temperature control of the content of a microtitration plate with a housing with a base plate designed as a temperature control plate, which has a controllable heat exchanger, which is preferably formed by an electrical, plate-shaped temperature control element and one Cover cap.
  • Such temperature chambers are used in particular in the photometric measurement of blood samples.
  • temperature devices are required which are suitable for microcuvettes and conventional microtitration plates in the existing measuring devices, e.g. Photometers can be used.
  • Temperature control chambers are known from the reading device, according to the more recent state of the art these are advantageously arranged directly next to or in the same, so that there is no change in temperature of the liquid contained in the microtitration plate when the latter is fed to the reading device.
  • the temperature control units require a quick warm-up and a corresponding temperature constancy (e.g. 37 degrees C. +/- 0.3 degrees C.).
  • a corresponding temperature constancy e.g. 37 degrees C. +/- 0.3 degrees C.
  • the object of the invention is to provide a temperature control device of the type mentioned at the outset which ensures better and more uniform heating or cooling of the contents of microtitration plates. It should also be possible to keep the temperature constant for as long as possible. This allows measurements to be carried out over a longer period of time, e.g. B. in the form of a series of measurements with several individual measurements at a distance of z. B. five minutes each.
  • An embodiment of the invention provides that the bottom plate has two heat exchangers, one heat exchanger surrounding the other and being assigned to the edge of the microtiter plate.
  • tempering means warming up because, for example, blood samples have to be warmed from room temperature (approx. 20 ° C.) or refrigerator temperature (approx. 4 ° C.) to body temperature (approx. 37 ° C.). In countries with high air temperature, however, the temperature control chamber can also be used for cooling.
  • the perforating chamber as a heating chamber, since this is the more frequently occurring case. It is advantageously provided that the heat exchangers are formed by heating circuits, for example by electrical resistance heating elements.
  • the construction according to the invention makes it possible, for example, to set the inner heating circuit to a higher temperature than the outer heating circuit during heating, so that a compensation is created for the cavities of the microtitration plate and all cavities are heated essentially the same regardless of their position become.
  • the outer heating circuit is set to a temperature which is increased with respect to the inner heating circuit.
  • a further exemplary embodiment of the invention provides that a heating circuit is assigned to the base plate and a heating circuit to the cover, the cover being designed like a flap and covering the microtitration plate like a bell.
  • the heat exchangers are formed by electrical temperature control elements which are embedded in foils or formed by heat-conducting plates.
  • a separation joint is provided in the film or plate between two heat exchangers.
  • the heat exchangers can be, for example, heating circuits of electrical resistance heaters.
  • the invention is not intended to be restricted to electrical temperature control elements, it could also be heated with pipes which carry a liquid, the construction with electrical temperature control elements nevertheless has constructive advantages, since such heaters are relatively are to be produced professionally.
  • the parting line between the foils results in better thermal delimitation of the heating and cooling circuits.
  • one or more temperature sensors are provided which are in contact with this when the microtiter plate is inserted; the starting temperature of the plate can be determined via these sensors or any temperature change during the reading process can be determined and via a corresponding one Control of the temperature control unit can be compensated.
  • the method for heating microtitration plates provides that the starting temperature and the target temperature of the contents of a microtitration plate are entered in a computer and, after taking the filling quantity into account, the amount of energy required to achieve the target temperature is calculated.
  • the method according to the invention makes it possible to significantly shorten the temperature setting, ensuring that the contents of the microtitration plate are not heated above the specified target temperature.
  • the heating-up time is calculated on the basis of the filling quantity.
  • the heating temperature can be chosen empirically.
  • FIG. 1 shows a diagram of a reading device for microtitration plates with a temperature chamber according to the invention
  • FIG. 2 shows a schematic top view of the device according to FIG. 1
  • FIG. 3 shows a longitudinal section through the temperature chamber
  • FIG. 4 shows a cross section through the temperature chamber
  • FIG. 5 shows the support of the outer edge of the cover in section
  • FIG. 6 shows a plan view of a temperature control element according to the invention, which FIG. 7 shows a temperature diagram and
  • FIG. 8 shows a circuit for performing the method according to the invention.
  • the actual reading device 1 and the temperature control chamber 2 are arranged directly next to one another and accommodated in a common housing 3.
  • the temperature control chamber 2, whose dimensions are adapted to a microtitration plate 4, is covered by a cover 5, which is designed as a flap-like cover.
  • the microtitration plate 4 rests on a slide 6 which is guided on rods 7 and moves back and forth between the temperature control chamber 2 and the reading device 1.
  • the microtitration plate 4 is therefore inserted into the temperature control chamber 2 and the cover 5 is closed.
  • the temperature chamber 2 is heated or cooled until the contents of the cavities in the microtitration plate 4 have reached the desired target temperature (generally 37 ° C.), whereupon the microtitration plate 4 is not exposed to room temperature, which in turn causes a change in temperature
  • the desired target temperature generally 37 ° C.
  • a temperature control film 8 is arranged on the bottom of the temperature chamber 2.
  • the tempering film 8 is usually not necessarily a heating film.
  • the tempering foil 8 is covered by an aluminum foil 9. Mainly, the microtitration plate 4 is heated from below by the temperature control film 8.
  • a temperature control film 10 is also provided on the underside of the cover 5, which in turn is covered with an aluminum film 9.
  • the tempering film 10 is assigned a separate heating or cooling circuit.
  • the lower temperature control film 8 is divided and has an inner heat exchanger 11 and an outer heat exchanger 12.
  • heating or cooling could also be installed in which a fluid is the heat transfer medium.
  • Ceramic or metallic plates with an applied semiconductor layer can also be used.
  • cooling devices can be used.
  • the heating chamber 2 is now provided with three heating circuits.
  • the heating circuits of the heat exchangers 11 and 12 are controlled in such a way that, during the heating phase, the heat exchanger 11 emits more heat than the heat exchanger 12. This ensures uniform heating of all cavities in the microtitration plate.
  • the heating circuit of the heat exchanger 12 After reaching the target temperature, the heating circuit of the heat exchanger 12 emits more heat than the heating circuit of the heat exchanger 11 over the duration of the stable phase, in which it is only important to keep the temperature constant, in order to compensate for the increased heat dissipation of the microtitration plate 4 at the edges .
  • sensors 13, 14 are also provided, which bear against the microtitration plate 4.
  • the temperatures which are measured by the sensors 13, 14 and passed on to the computer 18 correspond at least approximately to the temperature which really prevails in the interior of an adjacent cavity of the microtitration plate 4.
  • the cover 5 projects with an edge web 15 into a groove 16 in the side wall 17 of the heat chamber 2. This forms an obstacle that extends the path of the air flow.
  • the temperature values can be entered manually into the computer 16 or can also be detected by sensors and passed on directly.
  • the filling quantity of the liquid contained in the cavitates is entered into the computer 18, from which the computer calculates the amount of energy required for heating or cooling the contents of the microtitration plate 4 to the desired target temperature or the warming-up or cooling-down period.
  • the warm-up time is given on the abscissa in minutes, while the ordinate shows the temperature.
  • the curve FT shows the course of the temperature of the liquid contained in the cavities of the microtitration plate 4, the curve WT shows the course of the temperature of a heat exchanger 9, 11, 12.
  • Target temperature of z. B. 37 ° C can be reached quickly, without running the risk that the contents of the micro plate 4 ever, apart from a predetermined tolerance range, heats up above this value.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Clinical Laboratory Science (AREA)
  • Control Of Temperature (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Vaporization, Distillation, Condensation, Sublimation, And Cold Traps (AREA)

Abstract

A temperature-equalization chamber for bringing the contents of a microtitration plate (4) to a uniform temperature has a base plate designed as a temperature-equalization plate, a cover (5) and at least two independently controllable heat-exchangers (9, 11, 12). The base plate advantageously has two heat-exchangers (11, 12), one of which (12) surrounds the other and is connected to the edge of the microtitration plate (4).

Description

Temperierkammer, insbesondere für die Temperierung des Inhalts einer Mikrotitrationsplatte Temperature control chamber, especially for temperature control of the contents of a microtitration plate

Die Erfindung bezieht sich auf eine Temperierkammer, insbe¬ sondere für die Temperierung des Inhalts einer Mikrotitra¬ tionsplatte mit einem Gehäuse mit einer als Temperierplatte ausgebildeten Bodenplatte, die einen steuerbaren Wärmetau¬ scher aufweist, der vorzugsweise von einem elektrischen, plattenförmigen Temperierelement gebildet wird und einer Ab¬ deckkappe.The invention relates to a temperature control chamber, in particular for temperature control of the content of a microtitration plate with a housing with a base plate designed as a temperature control plate, which has a controllable heat exchanger, which is preferably formed by an electrical, plate-shaped temperature control element and one Cover cap.

Derartige Temperierkammern kommen insbesondere bei der photo¬ metrischen Messung von Blutproben zur Anwendung.Such temperature chambers are used in particular in the photometric measurement of blood samples.

Mikrotitrationsplatten in Form der Anordnung von 8x12=96 Mi¬ krokuvetten, stellen seit wenigen Jahren einen quasi Standard für photometrische Tests in der Mikrobiologie und verwandten Fachgebieten dar.Microtitration plates in the form of the arrangement of 8x12 = 96 microcuvettes have been a quasi standard for photometric tests in microbiology and related fields for a few years.

Durch das Aufkommen von kinetischen Mikrotests werden Tempe¬ riergeräte benötigt, die für Mikrokuvetten sowie herkömmliche Mikrotitrationsplatten bei den vorhandenen Meßgeräten, wie z.B. Photometer verwendet werden können. Obwohl vom Lesegerät örtlich getrennte Temperierkammern bekannt sind, werden diese nach dem neueren Stand der Technik vorteilhaft unmittelbar neben oder in demselben angeordnet, sodaß es zu keiner Tempe¬ raturänderung der in der Mikrotitrationsplatte enthaltenen Flüssigkeit kommt, wenn letztere dem Lesegerät zugeführt wird.Due to the advent of kinetic microtests, temperature devices are required which are suitable for microcuvettes and conventional microtitration plates in the existing measuring devices, e.g. Photometers can be used. Although locally separate temperature control chambers are known from the reading device, according to the more recent state of the art these are advantageously arranged directly next to or in the same, so that there is no change in temperature of the liquid contained in the microtitration plate when the latter is fed to the reading device.

Von den Temperiergeräten werden eine schnelle Aufwärmcng und eine entsprechende Temperaturkonstanz (z. B. 37 Grad C. +/- 0,3 Grad C.) gefordert. Bisherige Temperiereinrichtungen er- füllen in keiner Weise diese Forderungen.The temperature control units require a quick warm-up and a corresponding temperature constancy (e.g. 37 degrees C. +/- 0.3 degrees C.). Existing temperature control devices in no way meet these requirements.

Schwierigkeiten treten bei herkömmlichen Geräten bei der Tem¬ perierung der Mikrotitrationsplatte und falls Messungen über eine längere Zeit durchgeführt werden sollen, bei der Kon- stanthaltung der Temperatur auf. Dazu ist zu berücksichtigen, daß während des Aufheizens bei herkömmlichen Geräten durch geometrisch bedingte Unterschiede in den thermischen Eigenschaften die Ränder und Ecken schnel- 1er erwärmt werden als der mittlere Bereich der Mikrotitra¬ tionsplatte. Dies steht im Gegensatz zu dem Bestreben, daß sämtliche Kavitäten der Mikrotitrationsplatte zumindestens während des Lesevorganges gleiche Temperatur aufweisen sol¬ len. Erschwerend kommt dazu, daß es innerhalb der Wärmekammer und der Lesekammer möglichst zu keiner Luftbewegung kommen soll, da letztere die Verdunstung fördert.Difficulties arise with conventional devices in the tempering of the microtitration plate and, if measurements are to be carried out over a longer period of time, in keeping the temperature constant. In addition, it must be taken into account that during heating in conventional devices, due to geometrically caused differences in the thermal properties, the edges and corners are heated faster than the central region of the microtitration plate. This is in contrast to the endeavor that all cavities of the microtitration plate should have the same temperature at least during the reading process. To make matters worse, there should be no air movement within the heating chamber and the reading chamber, since the latter promotes evaporation.

Aufgabe der Erfindung ist es, eine Temperiereinrichtung der eingangs erwähnten Art zu schaffen, die eine bessere und gleichmäßigere Erwärmung oder Kühlung des Inhalts von Mikro¬ titrationsplatten gewährleistet. Ebenso soll es möglich sein, die Temperatur über möglichst lange Zeit konstant zu halten. Damit können Messungen auch über längere Zeit durchgeführt werden, z. B. in Form einer Meßreihe mit mehreren Einzelmes- sungen im Abstand von z. B. je fünf Minuten.The object of the invention is to provide a temperature control device of the type mentioned at the outset which ensures better and more uniform heating or cooling of the contents of microtitration plates. It should also be possible to keep the temperature constant for as long as possible. This allows measurements to be carried out over a longer period of time, e.g. B. in the form of a series of measurements with several individual measurements at a distance of z. B. five minutes each.

Dies wird erfindungsgemäß dadurch gelöst, daß mindestens zwei unterschiedlich steuerbare Wärmetauscher vorgesehen sind.This is achieved according to the invention in that at least two differently controllable heat exchangers are provided.

Ein Ausführungsbeispiel der Erfindung sieht vor, daß die Bo¬ denplatte zwei Wärmetauscher aufweist, wobei ein Wärmetau¬ scher den anderen umgibt und dem Rand der Mikrotiterplatte zugeordnet ist.An embodiment of the invention provides that the bottom plate has two heat exchangers, one heat exchanger surrounding the other and being assigned to the edge of the microtiter plate.

Im allgemeinen bedeutet Temperierung Aufwärmung, weil bei¬ spielsweise Blutproben von Raumtemperatur (ca. 20° C) oder Kühlschranktemperatur (ca. 4° C) auf Körpertemperatur (ca. 37° C) erwärmt werden müssen. In Ländern mit hoher Lufttempe¬ ratur kann die Temperierkammer jedoch auch zur Abkühlung verwendet werden.In general, tempering means warming up because, for example, blood samples have to be warmed from room temperature (approx. 20 ° C.) or refrigerator temperature (approx. 4 ° C.) to body temperature (approx. 37 ° C.). In countries with high air temperature, however, the temperature control chamber can also be used for cooling.

Nachfolgend wird auf die Ausbildung der Te perierkammer als Wärmekammer bezug genommen, da dies der häufiger auftretende Fall ist. Vorteilhaft ist vorgesehen, daß die Wärmetauscher von Heiz¬ kreisen, beispielsweise von elektrischen Widerstandsheizele¬ menten gebildet werden.In the following, reference is made to the design of the perforating chamber as a heating chamber, since this is the more frequently occurring case. It is advantageously provided that the heat exchangers are formed by heating circuits, for example by electrical resistance heating elements.

Durch die erfindungsgemäße Konstruktion ist es möglich, bei¬ spielsweise während des Aufheizens den inneren Heizkreis auf eine höhere Temperatur einzustellen als den äußeren Heiz¬ kreis, sodaß für die Kavitaten der Mikrotitrationsplatte ein Ausgleich geschaffen wird und alle Kavitaten unabhängig von ihrer Position im wesentlichen gleich erwärmt werden.The construction according to the invention makes it possible, for example, to set the inner heating circuit to a higher temperature than the outer heating circuit during heating, so that a compensation is created for the cavities of the microtitration plate and all cavities are heated essentially the same regardless of their position become.

Wird die stabile Phase erreicht, d. h. die Temperatur der in den Kavitaten der Mikrotitrationsplatte enthaltene Flüssig¬ keit ist auf den gewünschten Wert (vorzugsweise 37° C) einge- schwungen, erfolgt eine Umschaltung. Da die Kavitaten durch die bereits erwähnten thermischen Eigenschaften an den Rän¬ dern und in Ecken der Mikrotitrationsplatte mehr Wärme abge¬ ben als die Kavitaten im Inneren der Mikrotitrationsplatte, wird der äußere Heizkreis auf eine in Bezug auf den inneren Heizkreis erhöhte Temperatur eingestellt.If the stable phase is reached, i.e. H. the temperature of the liquid contained in the cavities of the microtitration plate has risen to the desired value (preferably 37 ° C.), a switchover takes place. Since the cavities give off more heat at the edges and in the corners of the microtitration plate due to the thermal properties already mentioned than the cavitates inside the microtitration plate, the outer heating circuit is set to a temperature which is increased with respect to the inner heating circuit.

Ein weiteres Ausführungsbeispiel der Erfindung sieht vor, daß ein Heizkreis der Bodenplatte und ein Heizkreis der Abdeckung zugeordnet ist, wobei die Abdeckung klappenartig ausgeführt ist und die Mikrotitrationsplatte glockenartig überdeckt.A further exemplary embodiment of the invention provides that a heating circuit is assigned to the base plate and a heating circuit to the cover, the cover being designed like a flap and covering the microtitration plate like a bell.

Vorteilhaft ist vorgesehen, daß die Wärmetauscher von elek¬ trischen Temperierelementen gebildet werden, die in Folien eingebettet oder von wärmeleitenden Platten gebildet werden. Dabei ist zwischen zwei Wärmetauschern eine Trennfuge in der Folie oder Platte vorgesehen. Die Wärmetauscher können bei¬ spielsweise Heizkreise elektrischer Widerstandsheizungen sein.It is advantageously provided that the heat exchangers are formed by electrical temperature control elements which are embedded in foils or formed by heat-conducting plates. A separation joint is provided in the film or plate between two heat exchangers. The heat exchangers can be, for example, heating circuits of electrical resistance heaters.

Obwohl die Erfindung nicht auf elektrische Temperierelemente eingeschränkt sein soll, so könnte ebenfalls mit Rohren, die eine Flüssigkeit führen, erwärmt werden, so bringt die Kon¬ struktion mit elektrischen Temperierelementen doch konstruk¬ tive Vorteile mit sich, da derartige Heizungen relativ ein- fach herzustellen sind. Durch die Trennfuge zwischen den Fo¬ lien kommt es zu einer besseren thermischen Abgrenzung der Heiz- bzw. Kühlkreise.Although the invention is not intended to be restricted to electrical temperature control elements, it could also be heated with pipes which carry a liquid, the construction with electrical temperature control elements nevertheless has constructive advantages, since such heaters are relatively are to be produced professionally. The parting line between the foils results in better thermal delimitation of the heating and cooling circuits.

In einem weiteren Ausführungsbeispiel der Erfindung sind ein oder mehrere Temperatursensoren vorgesehen, die bei einge¬ setzter Mikrotiterplatte an dieser anliegen, über diese Sen¬ soren kann die Ausgangstemperatur der Platte ermittelt werden bzw. eine etwaige Temperaturänderung während des Lesevorgan- ges festgestellt und über eine entsprechende Steuerung der Temperiereinheit kompensiert werden.In a further exemplary embodiment of the invention, one or more temperature sensors are provided which are in contact with this when the microtiter plate is inserted; the starting temperature of the plate can be determined via these sensors or any temperature change during the reading process can be determined and via a corresponding one Control of the temperature control unit can be compensated.

Das Verfahren zur Erwärmung von Mikrotitrationsplatten sieht vor, daß in einem Rechner die Ausgangstemperatur und die Solltemperatur des Inhaltes einer Mikrotitrationsplatte ein¬ gegeben und nach Berücksichtigung der Füllmenge die zur Er¬ reichung der Solltemperatur benötigte Energiemenge errechnet wird.The method for heating microtitration plates provides that the starting temperature and the target temperature of the contents of a microtitration plate are entered in a computer and, after taking the filling quantity into account, the amount of energy required to achieve the target temperature is calculated.

Durch das erfindungsgemäße Verfahren ist es möglich, die Tem¬ perierzeit wesentlich zu verkürzen, wobei sichergestellt ist, daß der Inhalt der Mikrotitrationsplatte nicht über die ein¬ gegebene Solltemperatur erwärmt wird.The method according to the invention makes it possible to significantly shorten the temperature setting, ensuring that the contents of the microtitration plate are not heated above the specified target temperature.

Insbesondere ist vorgesehen, daß aufgrund der Füllmenge die Aufheizdauer errechnet wird. Die Aufheiztemperatur kann empi¬ risch gewählt werden.In particular, it is provided that the heating-up time is calculated on the basis of the filling quantity. The heating temperature can be chosen empirically.

Nachfolgend wird ein Ausführungsbeispiel der Erfindung anhand der Figuren der beiliegenden Zeichnungen beschrieben.An exemplary embodiment of the invention is described below with reference to the figures in the accompanying drawings.

Die Fig. 1 zeigt schaubildlich ein Lesegerät für Mikrotitra¬ tionsplatten mit einer erfindungsgemäßen Temperierkammer; die Fig. 2 zeigt eine schematische Draufsicht auf das Gerät gemäß Fig. 1, die Fig. 3 zeigt einen Längsschnitt durch die Tempe¬ rierkammer, die Fig. 4 zeigt einen Querschnitt durch die Tem¬ perierkammer, die Fig. 5 zeigt die Auflage des äußeren Randes der Abdeckung im Schnitt, die Fig. 6 zeigt eine Draufsicht auf ein erfindungsgemäßes Temperierelement, die Fig. 7 zeigt ein Temperaturdiagramm und die Fig. 8 zeigt einen Schaltkreis zur Durchführung des erfindungsgemäßen Verfahrens.1 shows a diagram of a reading device for microtitration plates with a temperature chamber according to the invention; FIG. 2 shows a schematic top view of the device according to FIG. 1, FIG. 3 shows a longitudinal section through the temperature chamber, FIG. 4 shows a cross section through the temperature chamber, FIG. 5 shows the support of the outer edge of the cover in section, FIG. 6 shows a plan view of a temperature control element according to the invention, which FIG. 7 shows a temperature diagram and FIG. 8 shows a circuit for performing the method according to the invention.

Wie aus den Fig. 1 und 2 ersichtlich, sind das eigentliche Lesegerät 1 und die Temperierkammer 2 unmittelbar nebeneinan¬ der angeordnet und in einem gemeinsamen Gehäuse 3 unterge¬ bracht. Die Temperierkammer 2, die in ihren Abmessungen einer Mikrotitrationsplatte 4 angepaßt ist, wird von einer Abdek- kung 5, die als klappenartiger Deckel ausgebildet ist, abge- deckt.As can be seen from FIGS. 1 and 2, the actual reading device 1 and the temperature control chamber 2 are arranged directly next to one another and accommodated in a common housing 3. The temperature control chamber 2, whose dimensions are adapted to a microtitration plate 4, is covered by a cover 5, which is designed as a flap-like cover.

In der Temperierkammer 2 rastet die Mikrotitrationsplatte 4 auf einem Schlitten 6, der auf Stangen 7 geführt ist und zwi¬ schen der Temperierkammer 2 und dem Lesegerät 1 hin- und her- fährt.In the temperature control chamber 2, the microtitration plate 4 rests on a slide 6 which is guided on rods 7 and moves back and forth between the temperature control chamber 2 and the reading device 1.

Die Mikrotitrationsplatte 4 wird also in die Temperierkammer 2 eingelegt und die Abdeckung 5 wird geschlossen. Die Tempe¬ rierkammer 2 wird solange aufgeheizt oder gekühlt, bis der Inhalt der Kavitaten der Mikrotitrationsplatte 4 die ge¬ wünschte Solltemperatur erreicht hat (im allgemeinen 37° C) , worauf die Mikrotitrationsplatte 4 ohne der Raumtemperatur ausgesetzt zu werden, was wiederum eine Temperaturänderung zur Folge hätte, mit dem Schlitten 6 unmittelbar des Lesege- rät 1 zugeführt wird.The microtitration plate 4 is therefore inserted into the temperature control chamber 2 and the cover 5 is closed. The temperature chamber 2 is heated or cooled until the contents of the cavities in the microtitration plate 4 have reached the desired target temperature (generally 37 ° C.), whereupon the microtitration plate 4 is not exposed to room temperature, which in turn causes a change in temperature The consequence would be that the carriage 6 is fed directly to the reading device 1.

Wie aus den Fig. 3 und 4 ersichtlich, ist am Boden der Tempe¬ rierkammer 2 eine Temperierfolie 8 angeordnet. Die Temperier¬ folie 8 ist meistens aber nicht unbedingt eine Heizfolie. Die Temperierfolie 8 wird von einer Aluminiumfolie 9 abgedeckt. Hauptsächlich wird die Mikrotitrationsplatte 4 von unten durch die Temperierfolie 8 erwärmt.As can be seen from FIGS. 3 and 4, a temperature control film 8 is arranged on the bottom of the temperature chamber 2. The tempering film 8 is usually not necessarily a heating film. The tempering foil 8 is covered by an aluminum foil 9. Mainly, the microtitration plate 4 is heated from below by the temperature control film 8.

Damit es zu keiner Verdunstung kommt und zu einer gleichmäßi- gen Temperierung, ist an der Unterseite der Abdeckung 5 ebenso eine Temperierfolie 10 vorgesehen, die wiederum mit einer Aluminiumfolie 9 abgedeckt ist. Im Ausführungsbeispiel ist der Temperierfolie 10 ein separater Heiz- oder Kühlkreis zugeordnet. Die untere Temperierfolie 8 ist, wie aus der Fig. 6 ersicht¬ lich, geteilt und weist einen inneren Wärmetauscher 11 und einen äußeren Wärmetauscher 12 auf.So that there is no evaporation and a uniform temperature control, a temperature control film 10 is also provided on the underside of the cover 5, which in turn is covered with an aluminum film 9. In the exemplary embodiment, the tempering film 10 is assigned a separate heating or cooling circuit. As can be seen from FIG. 6, the lower temperature control film 8 is divided and has an inner heat exchanger 11 and an outer heat exchanger 12.

Wie eingangs bereits erwähnt, könnte anstatt der elektrischen Widerstandsheizung auch eine Heizung oder Kühlung eingebaut werden, bei der ein Fluid das Wärmeträgermedium ist. Weiters können auch keramische oder metallische Platten mit aufge- brachter Halbleiterschichte zum Einsatz kommen. Analog dazu sind die verschiedensten Kühlvorrichtungen einsetzbar.As already mentioned at the beginning, instead of electrical resistance heating, heating or cooling could also be installed in which a fluid is the heat transfer medium. Ceramic or metallic plates with an applied semiconductor layer can also be used. Similarly, a wide variety of cooling devices can be used.

Im Ausführungsbeispiel ist die Wärmekammer 2 nun mit drei Heizkreisen versehen. Die Heizkreise der Wärmetauscher 11 und 12 sind dabei derart gesteuert, daß während der Aufheizphase der Wärmetauscher 11 mehr Wärme abgibt als der Wärmetauscher 12. Dadurch wird eine gleichmäßige Erwärmung sämtlicher Kavi¬ taten der Mikrotitrationsplatte erreicht.In the exemplary embodiment, the heating chamber 2 is now provided with three heating circuits. The heating circuits of the heat exchangers 11 and 12 are controlled in such a way that, during the heating phase, the heat exchanger 11 emits more heat than the heat exchanger 12. This ensures uniform heating of all cavities in the microtitration plate.

Nach Erreichung der Solltemperatur wird über die Dauer der stabilen Phase, in der es nur darauf ankommt, die Temperatur gleichbleibend zu halten, der Heizkreis des Wärmetauschers 12 mehr Wärme abgeben als der Heizkreis des Wärmetauschers 11 um die verstärkte Wärmeabgabe der Mikrotitrationsplatte 4 an den Rändern auszugleichen.After reaching the target temperature, the heating circuit of the heat exchanger 12 emits more heat than the heating circuit of the heat exchanger 11 over the duration of the stable phase, in which it is only important to keep the temperature constant, in order to compensate for the increased heat dissipation of the microtitration plate 4 at the edges .

Im Ausführungsbeispiel sind weiters Sensoren 13, 14 vorgese¬ hen, die an der Mikrotitrationsplatte 4 anliegen. Die Tempe¬ raturen, die von den Sensoren 13, 14 gemessen und an den Rechner 18 weitergegeben werden, entsprechen zumindestens in etwa der Temperatur, die im Inneren einer benachbarten Kavi- tät der Mikrotitrationsplatte 4 wirklich herrscht.In the exemplary embodiment, sensors 13, 14 are also provided, which bear against the microtitration plate 4. The temperatures which are measured by the sensors 13, 14 and passed on to the computer 18 correspond at least approximately to the temperature which really prevails in the interior of an adjacent cavity of the microtitration plate 4.

Um die Beeinflussung der Temperatur in der Temperierkammer durch die Umgebungsluft zu verringern, ragt die Abdeckung 5 mit einem Randsteg 15 in eine Nut 16 in der Seitenwand 17 der Wärmekammer 2. Dadurch wird ein Hindernis gebildet, das den Weg des Luftstromes verlängert. Um beispielsweise das Aufheizen zu beschleunigen, ist es er¬ findungsgemäß vorgesehen, in den Rechner 18 die zu erzielende Solltemperatur der Flüssigkeit, die sich in den Kavitaten der Mikrotitrationsplatte 4 befindet und die Ausgangstemperatur (Raumtemperatur oder Kuhlschranktemperautr) einzugeben. Die Temperaturwerte können in den Rechner 16 manuell eingegeben werden oder auch von Sensoren erfaßt und unmittelbar weiter¬ geleitet werden.In order to reduce the influence of the ambient air on the temperature in the temperature control chamber, the cover 5 projects with an edge web 15 into a groove 16 in the side wall 17 of the heat chamber 2. This forms an obstacle that extends the path of the air flow. In order to accelerate the heating, for example, it is provided according to the invention to enter into the computer 18 the desired temperature of the liquid to be achieved, which is in the cavities of the microtitration plate 4, and the starting temperature (room temperature or refrigerator temperature). The temperature values can be entered manually into the computer 16 or can also be detected by sensors and passed on directly.

Als dritter Parameter wird in den Rechner 18 die Füllmenge der in den Kavitaten enthaltenen Flüssigkeit eingegeben, wo¬ raus der Rechner die zur Erwärmung oder Kühlung des Inhaltes der Mikrotitrationsplatte 4 zur gewünschten Solltemperatur benötigte Energiemenge bzw. die Aufwärm- oder Abkühldauer er- rechnet.As a third parameter, the filling quantity of the liquid contained in the cavitates is entered into the computer 18, from which the computer calculates the amount of energy required for heating or cooling the contents of the microtitration plate 4 to the desired target temperature or the warming-up or cooling-down period.

In diesem Zusammenhang wird auf das Diagramm der Fig. 7 ver¬ wiesen. Auf der Abszisse ist die Aufwärmzeit in Minuten ange¬ geben, während die Ordinate die Temperatur anzeigt. Die Kurve FT zeigt den Verlauf der Temperatur, der in den Kavitaten der Mikrotitrationsplatte 4 enthaltenen Flüssigkeit, die Kurve WT zeigt den Verlauf der Temperatur eines Wärmetauscher 9, 11, 12.In this connection, reference is made to the diagram in FIG. 7. The warm-up time is given on the abscissa in minutes, while the ordinate shows the temperature. The curve FT shows the course of the temperature of the liquid contained in the cavities of the microtitration plate 4, the curve WT shows the course of the temperature of a heat exchanger 9, 11, 12.

Durch das erfindungsgemäße Verfahren kann die angestrebteThe process according to the invention can achieve the desired

Solltemperatur von z. B. 37° C schnell erreicht werden, ohne daß die Gefahr gelaufen wird, daß sich der Inhalt der Mikro- ti irationsplatte 4 jemals, abgesehen von einem vorgegebenen Toleranzbereich, über diesen Wert erwärmt. Target temperature of z. B. 37 ° C can be reached quickly, without running the risk that the contents of the micro plate 4 ever, apart from a predetermined tolerance range, heats up above this value.

Claims

P a t e n t a n s p r ü c h e : Patent claims: 1. Temperierkammer, insbesondere für die Temperierung des Inhaltes einer Mikrotitrationsplatte mit einem Gehäuse mit einer als Temperierplatte ausgebildeten Bodenplatte, die einen steuerbaren Wärmetauscher aufweist, der vorzugsweise von einem elektrischen, plattenförmigen Temperierelement gebildet wird und einer Abdeckkappe, dadurch gekennzeichnet, daß min- destens zwei unterschiedlich steuerbare Wärmetau¬ scher (9,11,12) vorgesehen sind.1. temperature control chamber, in particular for temperature control of the contents of a microtitration plate with a housing with a base plate designed as a temperature control plate, which has a controllable heat exchanger, which is preferably formed by an electrical, plate-shaped temperature control element and a cover cap, characterized in that at least two differently controllable heat exchangers (9, 11, 12) are provided. 2. Temperierkammer nach Anspruch 1, dadurch gekenn¬ zeichnet, daß die Bodenplatte zwei Wärmetauscher (11,12) aufweist, wobei ein Wärmetauscher (12) den anderen umgibt und dem Rand der Mikrotitrations¬ platte (4) zugeordnet ist.2. temperature chamber according to claim 1, characterized gekenn¬ characterized in that the base plate has two heat exchangers (11, 12), one heat exchanger (12) surrounding the other and the edge of the Mikrotitrations¬ plate (4) is assigned. 3. Temperierkammer nach Anspruch 1, dadurch gekenn- zeichnet, daß ein Wärmetauscher der Bodenplatte und ein Wärmetauscher (9) der Abdeckung (5) zugeordnet ist.3. Temperature chamber according to claim 1, characterized in that a heat exchanger is assigned to the base plate and a heat exchanger (9) to the cover (5). 4. Temperierkammer nach Anspruch 1, dadurch gekenn- zeichnet, daß die Temperierelemente der Wärmetau¬ scher (9,11,12) in Folien eingebettet sind und daß zwischen den Wärmetauschern (11,12) eine Trennfuge in den Folien vorgesehen ist.4. Temperature control chamber according to claim 1, characterized in that the temperature control elements of the heat exchangers (9, 11, 12) are embedded in foils and that a separating joint is provided in the foils between the heat exchangers (11, 12). 5. Temperierkammer nach Anspruch 1, dadurch gekenn¬ zeichnet, daß die Temperierelemente der Wärmetau¬ scher (9,11,12) von keramischen oder metallischen Platten mit aufgebrachter Halbleiterschichte gebil¬ det werden.5. tempering chamber according to claim 1, characterized gekenn¬ characterized in that the tempering elements of the Wärmetau¬ shear (9,11,12) of ceramic or metallic plates with an applied semiconductor layer are formed. 6. Temperierkammer nach mindestens einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, daß die Wärmetau- scher (9,11,12) von Heizkreisen, beispielsweise von elektrischen Widerstandsheizelementen gebildet wer¬ den.6. temperature chamber according to at least one of claims 1 to 5, characterized in that the heat exchanger shear (9, 11, 12) are formed by heating circuits, for example by electrical resistance heating elements. 7. Temperierkammer nach Anspruch 2 und/oder 6, gekenn¬ zeichnet durch eine automatische Steuerung, mittels der beide Heizkreise (11,12) auf unterschiedlicher Temperatur gehalten werden und die, wenn mindestens einer der Temperatursensoren (13,14) einen vorgege- benen Sollwert anzeigt, die Temperaturen beider Heizkreise (11,12) absenkt und umschaltet, sodaß der Heizkreis (11) , der vorher höhere Temperatur abgegeben hat, die niedrigere Temperatur abgibt.7. temperature control chamber according to claim 2 and / or 6, marked by an automatic control, by means of which the two heating circuits (11, 12) are kept at different temperatures and which, if at least one of the temperature sensors (13, 14) is a predetermined one Indicates setpoint, lowers the temperatures of both heating circuits (11, 12) and switches over, so that the heating circuit (11), which has previously given off higher temperature, gives off the lower temperature. 8. Temperierkammer nach einem der Ansprüche 1 bis 8, gekennzeichnet durch einen Schlitten zur Aufnahme der Mikrotitrationsplatte oder dergleichen, der zwischen (6) der Wärmekammer (2) und einer benach¬ barten Lesestation (1) hin und her fährt.8. temperature control chamber according to one of claims 1 to 8, characterized by a carriage for receiving the microtitration plate or the like, which moves back and forth between (6) the heating chamber (2) and a neighboring reading station (1). 9. Temperierkammer nach Anspruch 1 und/oder 3, dadurch gekennzeichnet, daß an mindestens einer Seite der Abdeckung (5) im Bereich zwischen der Abdeckung (5) und dem Rand (17) der Wärmekammer (2) Barrieren vorgesehen sind, die den Weg der ausströmenden Warmluft verlängern.9. temperature control chamber according to claim 1 and / or 3, characterized in that on at least one side of the cover (5) in the region between the cover (5) and the edge (17) of the heat chamber (2) barriers are provided which the way extend the outflowing warm air. 10.Verfahren zur Steuerung mindestens eines Heizkreises in einer Wärmekammer zur Erwärmung von Mikrotitra- tionsplatten, dadurch gekennzeichnet, daß in einem Rechner die Ausgangstemperatur und die Solltempera¬ tur des Inhaltes einer Mikrotitrationsplatte (4) eingegeben und nach Ermittlung der Füllmenge die zur Erreichung der Solltemperatur benötigte Ener- giemenge errechnet wird. 10.Procedure for controlling at least one heating circuit in a heating chamber for heating microtitration plates, characterized in that the starting temperature and the target temperature of the contents of a microtitration plate (4) are entered in a computer and, after determining the filling quantity, that required to achieve the target temperature required amount of energy is calculated. 11.Verfahren nach Anspruch 10, dadurch gekennzeichnet, daß aufgrund der Füllmenge die Aufheizdauer errech¬ net wird. 11. The method according to claim 10, characterized in that the heating-up time is calculated on the basis of the filling quantity.
PCT/AT1990/000107 1989-11-02 1990-11-02 Temperature-equalization chamber for bringing the contents of a microtitration plate to a uniform temperature WO1991006369A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
FI913192A FI913192A7 (en) 1989-11-02 1990-11-02 Temperature equalization chamber, especially for temperature equalization of the contents of a microtiter plate

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AT252489A AT394323B (en) 1989-11-02 1989-11-02 TEMPERATURE CHAMBER, ESPECIALLY FOR TEMPERING THE CONTENT OF A MICROTITRATION PLATE, AND METHOD FOR CONTROLLING A HEATING CIRCUIT
ATA2524/89 1989-11-02

Publications (2)

Publication Number Publication Date
WO1991006369A2 true WO1991006369A2 (en) 1991-05-16
WO1991006369A3 WO1991006369A3 (en) 1991-08-08

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Country Link
EP (1) EP0451242A1 (en)
JP (1) JPH04502580A (en)
AT (1) AT394323B (en)
WO (1) WO1991006369A2 (en)

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EP0488769A3 (en) * 1990-11-29 1993-05-26 Perkin-Elmer Cetus Instruments Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control
DE4217868A1 (en) * 1992-05-29 1993-12-02 Univ Schiller Jena Temp.-controlled multiple test tube for optical study of liquids - has upper and lower aluminium plates having openings into which test tubes are placed at least one plate has surface foil heating element
DE19646115A1 (en) * 1996-11-08 1998-05-14 Eppendorf Geraetebau Netheler Temperature control block with temperature control devices
US6372486B1 (en) 1998-11-30 2002-04-16 Hybaid Limited Thermo cycler
US6767512B1 (en) 1996-11-08 2004-07-27 Eppendorf Ag Temperature-regulating block with temperature-regulating devices
DE19655141B4 (en) * 1996-11-08 2005-04-07 Eppendorf Ag Heating block for laboratory thermostats - has different heating fields for rapid setting of required temperature profile
DE19655282B4 (en) * 1996-11-08 2005-04-07 Eppendorf Ag Heating block for laboratory thermostats - has different heating fields for rapid setting of required temperature profile
DE102009015869A1 (en) 2009-04-01 2010-10-21 Schneckenburger, Herbert, Prof. Dr. Tempering device for tempering two-dimensionally arranged proteins in micro titer plate, has resistor elements attached at adapted admixture in regions, where measurements of sample parameters are accomplished during adjustment of sensor

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US6015534A (en) * 1990-11-29 2000-01-18 The Perkin-Elmer Corporation PCR sample tube
US5475610A (en) * 1990-11-29 1995-12-12 The Perkin-Elmer Corporation Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control
US5602756A (en) * 1990-11-29 1997-02-11 The Perkin-Elmer Corporation Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control
EP0812621A1 (en) * 1990-11-29 1997-12-17 The Perkin-Elmer Corporation Automated performance of the polymerase chain reaction
US5710381A (en) * 1990-11-29 1998-01-20 The Perkin-Elmer Corporation Two piece holder for PCR sample tubes
EP0488769A3 (en) * 1990-11-29 1993-05-26 Perkin-Elmer Cetus Instruments Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control
DE4217868A1 (en) * 1992-05-29 1993-12-02 Univ Schiller Jena Temp.-controlled multiple test tube for optical study of liquids - has upper and lower aluminium plates having openings into which test tubes are placed at least one plate has surface foil heating element
DE19646115A1 (en) * 1996-11-08 1998-05-14 Eppendorf Geraetebau Netheler Temperature control block with temperature control devices
DE19646115C2 (en) * 1996-11-08 2000-05-25 Eppendorf Geraetebau Netheler Use of temperature control devices for temperature control of a temperature control block
US6767512B1 (en) 1996-11-08 2004-07-27 Eppendorf Ag Temperature-regulating block with temperature-regulating devices
DE19655141B4 (en) * 1996-11-08 2005-04-07 Eppendorf Ag Heating block for laboratory thermostats - has different heating fields for rapid setting of required temperature profile
DE19655282B4 (en) * 1996-11-08 2005-04-07 Eppendorf Ag Heating block for laboratory thermostats - has different heating fields for rapid setting of required temperature profile
DE19655141C5 (en) * 1996-11-08 2013-12-05 Eppendorf Ag Gradient tempering block for laboratory thermostats
US6372486B1 (en) 1998-11-30 2002-04-16 Hybaid Limited Thermo cycler
DE102009015869A1 (en) 2009-04-01 2010-10-21 Schneckenburger, Herbert, Prof. Dr. Tempering device for tempering two-dimensionally arranged proteins in micro titer plate, has resistor elements attached at adapted admixture in regions, where measurements of sample parameters are accomplished during adjustment of sensor

Also Published As

Publication number Publication date
ATA252489A (en) 1991-09-15
AT394323B (en) 1992-03-10
WO1991006369A3 (en) 1991-08-08
EP0451242A1 (en) 1991-10-16
JPH04502580A (en) 1992-05-14

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