WO2007031158A1 - Laboratory temperature control device with top face - Google Patents
Laboratory temperature control device with top face Download PDFInfo
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- WO2007031158A1 WO2007031158A1 PCT/EP2006/007814 EP2006007814W WO2007031158A1 WO 2007031158 A1 WO2007031158 A1 WO 2007031158A1 EP 2006007814 W EP2006007814 W EP 2006007814W WO 2007031158 A1 WO2007031158 A1 WO 2007031158A1
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- WO
- WIPO (PCT)
- Prior art keywords
- adapter
- vessels
- tempering device
- laboratory tempering
- crystallization
- 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.)
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions
-
- 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
- B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
-
- 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
- B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B29/00—Single crystals or homogeneous polycrystalline material with defined structure characterised by the material or by their shape
- C30B29/54—Organic compounds
- C30B29/58—Macromolecular compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/023—Adapting objects or devices to another adapted for different sizes of tubes, tips or container
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
- B01L2300/0829—Multi-well plates; Microtitration plates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/18—Means for temperature control
- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
- B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
-
- 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
- B01L3/06—Crystallising dishes
Definitions
- the invention relates to a laboratory tempering referred to in the preamble of claim 1 Art.
- Generic laboratory tempering devices are e.g. from US 5,525,300 A known. They are used to hold laboratory samples at certain temperatures. The laboratory samples are arranged in containers, which are arranged with parts of their outer surface in large-area thermal contact in the wells. It is also possible to arrange a plurality of vessels combined into a plate, so-called microtiter plates with their vessels projecting downwards from the plate into a plurality of wells of the laboratory tempering device, for which purpose the grid dimension of the wells must match the grid dimension of the vessels of the plate.
- DE 19646115 A1 also shows a generic construction which, in an embodiment variant, has recesses of different sizes closely nested in the upper side, so that two different vessel sizes and two different patterns can be used. However, other vessel sizes and rasters are not possible here either.
- the object of the present invention is to allow the use of different vessel sizes and plate grid in a generic Laborortemperier worn in a simple manner.
- the laboratory tempering is provided with an adapter which is adapted to its underside of the upper side of the laboratory tempering to flat heat contact and transports the heat to its top, which is adapted to other vessels to flat heat contact.
- an adapter which is adapted to its underside of the upper side of the laboratory tempering to flat heat contact and transports the heat to its top, which is adapted to other vessels to flat heat contact.
- vessels or plates of a second type can be recorded in surface heat contact
- the adapter is adapted on its underside of the top of the laboratory tempering, which in itself for completely different vessels or grid of a first type is formed.
- the adapter could be configured to contact the top over the recesses with a simple flat bottom.
- the features of claim 2 are provided.
- the contact of the upper side of the laboratory tempering devices takes place in their depressions, in which projections on the underside of the adapter engage in good heat-conducting, large-area contact.
- the heat transfer between the laboratory tempering device and the adapter takes place at the points of the recesses in which the set target temperatures are maintained particularly accurately.
- the laboratory tempering device generates a temperature gradient, advantageously according to claim 5, transversely to the lines.
- the rows are thus at different temperatures, which are transmitted separately upwards by the adapters arranged line by line.
- the vessels of the second type which contact the top of the adapters, are also brought line by line to different temperatures according to the set gradient.
- crystallization plates are increasingly being used, in whose vessels crystallization processes take place.
- crystallization plates are used for the determination of proteins by X-ray diffraction on a lattice produced by crystallization, eg in genetic research.
- suitable laboratory tempering devices for crystallization plates however, their exact temperature control has hitherto been very problematic.
- Crystallization plates are commercially available in a wide variety of forms, e.g. depending on the crystallization method, e.g. "Hanging Drop” or “Sitting Drop”.
- the crystallization vessels are easier with the "hanging drop” method and somewhat more complicated with the “sitting drop” method.
- crystallization plates with closely nested crystallization vessels and those with a common base plate down individually in the lateral distance hanging crystallization vessels.
- the features of claim 7 are advantageously provided, wherein the crystallization vessels are laterally encompassed by the wells of the adapter, so that temperature differences within the crystallization vessel, which could interfere with the Kritallisationslui be avoided.
- FIG. 1 shows a section through a laboratory tempering device in a first
- Fig. 5 is a plan view of the adapter in section along line 5 - 5 in
- Fig. 6 is a perspective view of an adapter in a third embodiment.
- the tempering elements 5 are, for example, Peltier elements which are supplied with electricity via lines which are not shown and which can heat or cool the block 3 as desired. If the plurality of tempering elements 5 arranged one behind the other in the longitudinal direction are operated at different temperatures, a temperature gradient can be set in the direction of the arrow 6, ie in the longitudinal direction of the upper side 2 in the direction of the arrow 6.
- Recesses 7 are formed in the upper side 2 of the laboratory tempering device 1 and are arranged, for example, in rows and columns, as is known from the documents cited at the beginning.
- they serve vessels of a first type, ie, for example, containing individual vessels containing reaction samples in a large area of good heat-conducting contact, or in the grid (eg 12 rows and 8 columns) suitable microtiter plates, in which an upper surface hanging vessels fit into the recesses 7.
- vessels of a different, second type namely vessels of a crystallization plate 8 are tempered with the laboratory tempering device 1, which is shown in section in FIG. 1 and in plan view in FIG. 3.
- the crystallization plate 8 is a crystallization plate with vessels designed for the "sitting drop” method.
- the crystallization plate 8 has for this purpose formed in a grid crystallization vessels 9, which are divided laterally by crossing continuous partitions 10, are open at the top and have a step 11, are placed on the drops with a protein solution to be crystallized, while in the lower Part of the vessel 9 solvent is arranged.
- all the crystallization vessels 9 are closed with a covering the entire crystallization plate 8 cover 12, as shown in Fig. 1.
- the closure can be done with an adhesive film.
- the crystallization plate 8 forms on its side facing the laboratory tempering 1 underside under the steps 11 in the direction perpendicular to the plane of the drawing of FIG. 1 extending, rectangular, downwardly open grooves 13.
- a precise temperature control of the crystallization vessels 9 of the crystallization plate 8 by placing it on the top side 2 of the laboratory tempering device 1 would be difficult because of insufficient contact surfaces.
- the bars 15 can thus be used with all-sided large-area and thus good heat-conducting surface contact in the grooves 13.
- the adapters 14 are provided with projections 16 projecting downwards, which, like FIG. 1, are adapted in their surface form exactly to the inner surface of the depressions 7 in the upper side 2 of the laboratory temperature control device 1.
- a plurality of elevations 16 are provided on an adapter 14, which are arranged linearly in a row which corresponds to the grid of depressions 7 in a row of the upper side 2 of the laboratory tempering device 1.
- Fig. 1 shows that the adapters 14 are inserted with their elevations 16 in the recesses 7 and are used with their beams 15 in the grooves 13 of the crystallization plate 8.
- the crystallization plate 8 is therefore heated over a large area and precisely via the adapters 14, which for this purpose are made of material which conducts heat well, e.g. Metal are formed, wherein it is particularly important to transport the heat in the direction perpendicular to the plane of the top 2 of the laboratory tempering 1.
- FIGS. 3a to 5c describe crystallization plates of another embodiment, which are essentially derived from the Crystallization plate 8 differ in that the crystallization vessels have no common partitions, but hang down freely in a lateral distance substantially downwards. Also, such a crystallization plate can be easily supplied with the present invention, as shown in FIGS. 4 and 5 show.
- FIG. 4 shows the same laboratory tempering device 1 with recesses 7 as in FIG. 1.
- Adapters 44 which largely correspond to the adapters 14, that is to say have elevations 46 which correspond to the depressions 7 in the grid and the shaping, are inserted into these are adapted.
- the adapters 44 are again designed as bars 45, which in the embodiment of FIGS. 4 and 5, however, have depressions 47 which are formed in a shape-matched manner to the outer surface of the crystallization vessels 49 of a crystallization plate 48.
- Fig. 6 shows in an embodiment variant of an adapter 64, which consists of individual adapters 44 of FIG. 5, which are placed side by side parallel to each other standing in the embodiment with a release layer 65 of thermally insulating material.
- the adapter 44 of FIG. 4 can be assembled to form a plate-shaped adapter 64, which can be handled as a whole. If the adapter 64 is used on a laboratory tempering device 1 according to FIG. 1, in which the gradient 6 is generated in the direction transverse to the longitudinal extension of the individual adapters 44, then the thermally insulating separating layer 65 ensures that the desired different temperatures in the individual adapters 44 can be adjusted trouble-free.
- the adapter 64 which is shown in Fig. 6, and the separating layer 65 can be omitted, so that the adapters is formed in its upper part as a continuous plate made of thermally conductive material. He would be in this form for Laboratory tempering suitable to generate over its top 2 across a uniform temperature. However, such an embodiment of an adapter would also be suitable when using a temperature gradient, which would then also be generated by appropriate heat flow in the adapter 64.
- a respective row of wells 7 serving adapter 14 (Fig. 1) or 44 (Fig. 4) is used, then connected to the top of the adapter vessels in their arrangement grid in the direction transverse to the extension of the adapter to the grid of the recesses 7 in the laboratory tempering 1 fit.
- the vessels adapted above may have a different grid than the depressions 7. This applies, for example, to the example shown in FIGS. 1 and 3, in which the grid of the crystallization vessels 9 in the direction of the arrow 6 must coincide with the grid of the recesses 7, may differ transversely thereto.
- an adapter used with a continuous plate which engages with elevations 46 in the recesses 7 of FIG. 1 may be arranged in any desired pattern on the upper side of the adapter , which completely deviates from the grid of the wells 7.
- the vessel shapes to be contacted above can be completely different from the vessel shape, which fits into the wells 7. So it can be e.g. to a laboratory tempering device with wells in 8x12 grid via a suitably designed adapter a microtiter plate are adapted with 16x24 grid.
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Abstract
Description
Labortemperiereinrichtung mit Oberseite Laboratory tempering device with top
Die Erfindung betrifft eine Labortemperiereinrichtung der im Oberbegriff des Anspruches 1 genannten Art.The invention relates to a laboratory tempering referred to in the preamble of claim 1 Art.
Gattungsgemäße Labortemperiereinrichtungen sind z.B. aus der US 5,525,300 A bekannt. Sie dienen dazu, Laborproben auf bestimmten Temperaturen zu halten. Die Laborproben sind dabei in Behältern angeordnet, welche mit Teilen Ihrer äußeren Oberfläche in großflächigem Wärmekontakt in den Vertiefungen angeordnet sind. Es können auch mehrere zu einer Platte zusammengefaßte Gefäße, sog. Mikrotiterplatten mit ihren von der Platte nach unten ragenden Gefäßen in mehreren Vertiefungen der Labortemperiereinrichtung angeordnet werden, wozu das Rastermaß der Vertiefungen zu dem Rastermaß der Gefäße der Platte passen muss.Generic laboratory tempering devices are e.g. from US 5,525,300 A known. They are used to hold laboratory samples at certain temperatures. The laboratory samples are arranged in containers, which are arranged with parts of their outer surface in large-area thermal contact in the wells. It is also possible to arrange a plurality of vessels combined into a plate, so-called microtiter plates with their vessels projecting downwards from the plate into a plurality of wells of the laboratory tempering device, for which purpose the grid dimension of the wells must match the grid dimension of the vessels of the plate.
Wie in der vorgenannten Schrift angegeben, können gattungsgemäße Labortemperiereinrichtungen sowohl dazu ausgebildet sein, auf der gesamten Oberseite, also in allen Vertiefungen, dieselben Temperaturen zu halten, als auch dazu, über die Ebene der Oberseite hinweg einen Temperaturgradienten auszubilden, so dass in unterschiedlichen Vertiefungen unterschiedliche Temperaturen eingestellt werden. Gattungsgemäße Labortemperiereinrichtungen werden insbesondere zur Durchführung der PCR (Polymerase Chain Reaction) verwendet, auch mit Gradientenausbildung zur Optimierung der PCR. Nachteilig bei den gattungsgemäßen bekannten Labortemperiereinrichtungen ist die Tatsache, dass die Gefäße hinsichtlich ihrer Formgebung zum Erreichen eines guten Wärmekontaktes exakt in die Vertiefungen passen müssen und bei Gefäßplatten das Raster übereinstimmen muss. Werden anderen Gefäßgrößen oder Platten mit anderen Rasternmaßen verwendet, so muss eine andere daran angepaßte Labortemperiereinrichtung verwendet werden, bzw. muss in bekannter Weise eine Labortemperiereinrichtung verwendet werden, bei der die Oberseite auswechselbar ist, was mit erheblichen Mühen und Kosten verbunden ist.As indicated in the aforementioned document, generic Labortemperiereinrichtungen can both be designed to hold on the entire top, so in all wells, the same temperatures, as well as over the level of the top of a temperature gradient form, so that in different wells different Temperatures are set. Generic laboratory tempering devices are used in particular for carrying out the PCR (polymerase chain reaction), even with gradient formation for optimizing the PCR. A disadvantage of the generic known Laborortemperiereinrichtungen is the fact that the vessels must fit exactly in the wells in terms of their shape to achieve a good thermal contact and must match the grid in vessel plates. If other vessel sizes or plates with different screen dimensions are used, then another adapted laboratory tempering device must be used, or in a known manner a laboratory tempering device must be used in which the top is replaceable, which is associated with considerable effort and expense.
Auch die DE 19646115 Al zeigt eine gattungsgemäße Konstruktion, die in einer Ausführungsvariente in der Oberseite eng geschachtelte Vertiefungen unterschiedlicher Größe aufweist, so dass zwei unterschiedliche Gefäßgrößen und zwei unterschiedliche Raster verwendbar sind. Weitere Gefäßgrößen und Raster sind jedoch auch hier nicht möglich.DE 19646115 A1 also shows a generic construction which, in an embodiment variant, has recesses of different sizes closely nested in the upper side, so that two different vessel sizes and two different patterns can be used. However, other vessel sizes and rasters are not possible here either.
Die Aufgabe der vorliegenden Erfindung besteht darin, bei einer gattungsgemäßen Labortemperiereinrichtung die Verwendung unterschiedlicher Gefäßgrößen und Plattenraster auf einfache Weise zu ermöglichen.The object of the present invention is to allow the use of different vessel sizes and plate grid in a generic Laborortemperiereinrichtung in a simple manner.
Diese Aufgabe wird mit dem Merkmal des Anspruches 1 gelöst.This object is achieved with the feature of claim 1.
Erfindungsgemäß ist die Labortemperiereinrichtung mit einem Adapter versehen, der an seiner Unterseite der Oberseite der Labortemperiereinrichtung zu flächigem Wärmekontakt angepaßt ist und die Wärme zu seiner Oberseite transportiert, die an andere Gefäße zu flächigem Wärmekontakt angepaßt ist. Auf der Oberseite des Adapters können also Gefäße oder Platten einer zweiten Art in flächigem Wärmekontakt aufgenommen werden, während der Adapter auf seiner Unterseite der Oberseite der Labortemperiereinrichtung angepaßt ist, die an sich für ganz andere Gefäße oder Raster einer ersten Art ausgebildet ist. Auf diese Weise ist es möglich, eine gattungsgemäße Labortemperiereinrichtung durch einfaches Aufsticken von Adaptern zum Temperieren anderer Gefäße oder von Platten mit anderem Raster umzurüsten.According to the invention the laboratory tempering is provided with an adapter which is adapted to its underside of the upper side of the laboratory tempering to flat heat contact and transports the heat to its top, which is adapted to other vessels to flat heat contact. On the top of the adapter so vessels or plates of a second type can be recorded in surface heat contact, while the adapter is adapted on its underside of the top of the laboratory tempering, which in itself for completely different vessels or grid of a first type is formed. In this way it is possible to retrofit a generic laboratory tempering by simply attaching adapters for tempering other vessels or plates with different raster.
Der Adapter könnte so ausgebildet sein, dass er mit einer einfachen flachen Unterseite die Oberseite über die Vertiefungen hinweg kontaktiert. Vorteilhaft sind jedoch die Merkmale des Anspruches 2 vorgesehen. Hierbei erfolgt die Kontak- tierung der Oberseite der Labortemperiereinrichtungen in deren Vertiefungen, in die Erhebungen an der Unterseite des Adapters in gut wärmeleitendem, grossflächigem Kontakt eingreifen. Dadurch erfolgt die Wärmeübertragung zwischen der Labortemperiereinrichtung und dem Adapter an den Stellen der Vertiefungen, an denen die eingestellten Soll-Temperaturen besonders genau eingehalten werden. Außerdem ergibt sich dadurch durch Formschlußeingriff der Erhebungen in den Vertiefungen ein fester Halt des Adapters.The adapter could be configured to contact the top over the recesses with a simple flat bottom. Advantageously, however, the features of claim 2 are provided. Here, the contact of the upper side of the laboratory tempering devices takes place in their depressions, in which projections on the underside of the adapter engage in good heat-conducting, large-area contact. As a result, the heat transfer between the laboratory tempering device and the adapter takes place at the points of the recesses in which the set target temperatures are maintained particularly accurately. In addition, this results from positive engagement of the elevations in the wells a firm grip of the adapter.
Dabei sind vorteilhaft die Merkmale des Anspruches 3 vorgesehen, wonach mehrere Erhebungen an der Unterseite des Adapters in eine Zeile von Vertiefungen der Labortemperiereinrichtungen passen. Zur vollflächigen Bestückung einer Labortemperiereinrichtung sind somit mehrere Adapter zeilenweise anzuordnen.In this case, the features of claim 3 are advantageously provided, after which a plurality of elevations on the underside of the adapter fit into a row of depressions of the laboratory tempering devices. For full-surface placement of a laboratory tempering device thus several adapters are to be arranged line by line.
Die Labortemperiereinrichtung erzeugt vorteilhaft gemäß Anspruch 4 einen Temperaturgradienten und zwar vorteilhaft gemäß Anspruch 5 quer zu den Zeilen. Die Zeilen liegen somit auf unterschiedlichen Temperaturen, die durch die zeilenweise angeordnete Adapter getrennt nach oben übertragen werden. Auf diese Weise werden die Gefäße der zweiten Art, die die Oberseite der Adapter kontaktieren, ebenfalls zeilenweise auf unterschiedliche Temperaturen entsprechend dem eingestellten Gradienten gebracht. In jüngerer Zeit finden zunehmend Kristallisationsplatten Verwendung, in deren Gefäßen Kristallisationsprozesse stattfinden. Insbesondere werden Kristallisationsplatten zur Bestimmung von Proteinen durch Röntgenbeugung an einem durch Kristallisation hergestellten Gitter verwendet, z.B. in der Genforschung. Mangels geeigneterer Labortemperiereinrichtungen für Kristallisationsplatten ist jedoch bisher deren exakte Temperierung sehr problematisch. Vorteilhaft sind daher die Merkmale des Anspruches 6 vorgesehen. Auf diese Weise können Kri- tallisationsplatten mit entsprechend ausgebildeten Adaptern auf herkömmlichen Labortemperiereinrichtungen wie sie im Labor verfügbar sind, sehr einfach und präzise temperiert werden. Es ist dabei auch möglich, unter Ausbildung eines Temperaturgradienten die Kristallisationstemperaturen zu optimieren, was bisher nicht möglich war.Advantageously, the laboratory tempering device generates a temperature gradient, advantageously according to claim 5, transversely to the lines. The rows are thus at different temperatures, which are transmitted separately upwards by the adapters arranged line by line. In this way, the vessels of the second type, which contact the top of the adapters, are also brought line by line to different temperatures according to the set gradient. More recently, crystallization plates are increasingly being used, in whose vessels crystallization processes take place. In particular, crystallization plates are used for the determination of proteins by X-ray diffraction on a lattice produced by crystallization, eg in genetic research. In the absence of suitable laboratory tempering devices for crystallization plates, however, their exact temperature control has hitherto been very problematic. Advantageously, therefore, the features of claim 6 are provided. In this way, crystallization plates with appropriately designed adapters on conventional laboratory tempering devices, such as are available in the laboratory, can be tempered very simply and precisely. It is also possible to optimize the formation of a temperature gradient, the crystallization temperatures, which was previously not possible.
Kristallisationsplatten sind in einer großen Formenvielfalt handelsüblich, z.B. je nach Kristallisationsmethode, also z.B. "Hanging Drop" oder "Sitting Drop". Dabei sind die Kristallisationsgefäße bei der "Hanging Drop" Methode einfacher und bei der "Sitting Drop" Methode etwas komplizierter geformt. Es sind Kristallisationsplatten mit eng aneinander geschachtelten Kristallisationsgefäßen bekannt und solche mit von einer gemeinsamen Grundplatte nach unten einzeln im seitlichen Abstand hängenden Kristallisationsgefäßen. Bei letzterer Ausbildung sind vorteilhaft die Merkmale des Anspruches 7 vorgesehen, wobei die Kristallisationsgefäße von den Vertiefungen des Adapters seitlich umfaßt werden, so dass Temperaturunterschiede innerhalb des Kristallisationsgefäßes, die sich störend auf den Kritallisationsprozess auswirken könnten, vermieden werden.Crystallization plates are commercially available in a wide variety of forms, e.g. depending on the crystallization method, e.g. "Hanging Drop" or "Sitting Drop". The crystallization vessels are easier with the "hanging drop" method and somewhat more complicated with the "sitting drop" method. There are known crystallization plates with closely nested crystallization vessels and those with a common base plate down individually in the lateral distance hanging crystallization vessels. In the latter embodiment, the features of claim 7 are advantageously provided, wherein the crystallization vessels are laterally encompassed by the wells of the adapter, so that temperature differences within the crystallization vessel, which could interfere with the Kritallisationsprozess be avoided.
Bei einer Kritallisationsplatte mit eng aneinander gesetzten Kristallisationsgefäßen für die "Sitting Drop" Methode, bei denen zwischen Gefäßzeilen glatt durchlaufende Nuten existieren, die zur Unterseite offen sind, sind vorteilhaft die Merkmale des Anspruches 8 vorgesehen. In den Zeichnungen ist die Erfindung beispielsweise und schematisch dargestellt. Es zeigen:In a Kritallisationsplatte with closely juxtaposed crystallization vessels for the "sitting drop" method in which there are smoothly running grooves between vascular lines, which are open to the bottom, the features of claim 8 are advantageously provided. In the drawings, the invention is shown for example and schematically. Show it:
Fig. 1 einen Schnitt durch eine Labortemperiereinrichtung in einer ersten1 shows a section through a laboratory tempering device in a first
Ausführungsform,embodiment,
Fig. 2 einen Schnitt nach Linie 2 - 2 in Figur 1,2 shows a section along line 2 - 2 in Figure 1,
Fig. 3 einen Schnitt nach Linie 3 - 3 in Figur 1,3 shows a section along line 3 - 3 in Figure 1,
Fig. 4 einen Schnitt durch einen Adapter einer zweiten Ausführungsform,4 shows a section through an adapter of a second embodiment,
Fig. 5 eine Draufsicht auf den Adapter im Schnitt gemäß Linie 5 - 5 inFig. 5 is a plan view of the adapter in section along line 5 - 5 in
Fig. 4 und4 and
Fig. 6 eine perspektivische Ansicht eines Adapters in einer dritten Ausführungsform.Fig. 6 is a perspective view of an adapter in a third embodiment.
Fig. 1 zeigt im Längsschnitt eine Labortemperierenrichtung 1, deren ebene Oberseite 2 von einem thermisch gut leitfähigen Block 3 ausgebildet wird, der auf seiner Unterseite 4 mit mehreren Temperierelementen 5 flächig belegt ist. Bei den Temperierelementen 5 handelt es sich z.B. um über nicht dargestellten Leitungen elektrisch versorgte Peltier-Elemente, die den Block 3 je nach Wunsch heizen oder kühlen können. Werden die mehreren in Längsrichtung hintereinander angeordneten Temperierelemente 5 mit unterschiedlichen Temperaturen betrieben, so läßt sich in Richtung des Pfeiles 6, also in Längsrichtung der Oberseite 2 auf dieser in Richtung des Pfeiles 6 ein Temperaturgradient einstellen. In der Oberseite 2 der Labortemperiereinrichtung 1 sind Vertiefungen 7 ausgebildet, die z.B., wie aus den eingangs zitierten Schriften bekannt, in Reihen und Spalten angeordnet sind. Sie dienen bei einer herkömmlichen Labortemperiereinrichtung 1 dazu, Gefäße einer ersten Art, also z.B. einzelne Gefäße, die Reaktionsproben enthalten, in großflächigem gut wärmeleitendem Kontak aufzunehmen, oder auch im Raster (z.B. 12 Reihen und 8 Spalten) passende Mikrotiter- platten, bei denen von einer oberen Fläche hängend ausgebildete Gefäße in die Vertiefungen 7 passen. In dem in Fig. 1 dargestelltem Ausführungsbeispiel sollen mit der Labortemperiereinrichtung 1 jedoch Gefäße einer anderen zweiten Art, nämlich Gefäße einer Kristallisationsplatte 8 temperiert werde, die in Fig. 1 im Schnitt und in Fig. 3 in Draufsicht dargestellt ist.1 shows a longitudinal section of a laboratory tempering direction 1, the planar upper side 2 of which is formed by a thermally highly conductive block 3, which is covered on its underside 4 with a plurality of tempering elements 5 in a planar manner. The tempering elements 5 are, for example, Peltier elements which are supplied with electricity via lines which are not shown and which can heat or cool the block 3 as desired. If the plurality of tempering elements 5 arranged one behind the other in the longitudinal direction are operated at different temperatures, a temperature gradient can be set in the direction of the arrow 6, ie in the longitudinal direction of the upper side 2 in the direction of the arrow 6. Recesses 7 are formed in the upper side 2 of the laboratory tempering device 1 and are arranged, for example, in rows and columns, as is known from the documents cited at the beginning. In a conventional laboratory tempering device 1, they serve vessels of a first type, ie, for example, containing individual vessels containing reaction samples in a large area of good heat-conducting contact, or in the grid (eg 12 rows and 8 columns) suitable microtiter plates, in which an upper surface hanging vessels fit into the recesses 7. In the embodiment shown in FIG. 1, however, vessels of a different, second type, namely vessels of a crystallization plate 8, are tempered with the laboratory tempering device 1, which is shown in section in FIG. 1 and in plan view in FIG. 3.
Bei der Kristallisationsplatte 8 handelt es sich um eine Kristallisationsplatte mit Gefäßen, die für die "Sitting Drop" Methode ausgebildet sind. Die Kristallisationsplatte 8 weist dazu in einem Raster ausgebildete Kristallisationsgefäße 9 auf, die seitlich durch gekreuzt durchlaufende Trennwände 10 abgeteilt sind, nach oben offen sind und eine Stufe 11 aufweisen, auf die Tropfen mit einer zu kristallisierenden Protein-Lösung gesetzt werden, während im tiefer liegenden Teil des Gefäßes 9 Lösungsmittel angeordnet wird. Zur Durchführung des Kristallisationsprozesses, der längere Zeit in Anspruch nimmt, werden alle Kristallisationsgefäße 9 mit einem die gesamte Kristallisationsplatte 8 abdeckenden Deckel 12 verschlossen, wie dies in Fig. 1 dargestellt ist. Alternativ kann der Verschluß mit einer Klebefolie erfolgen.The crystallization plate 8 is a crystallization plate with vessels designed for the "sitting drop" method. The crystallization plate 8 has for this purpose formed in a grid crystallization vessels 9, which are divided laterally by crossing continuous partitions 10, are open at the top and have a step 11, are placed on the drops with a protein solution to be crystallized, while in the lower Part of the vessel 9 solvent is arranged. To carry out the crystallization process, which takes a long time, all the crystallization vessels 9 are closed with a covering the entire crystallization plate 8 cover 12, as shown in Fig. 1. Alternatively, the closure can be done with an adhesive film.
Die Kristallisationsplatte 8 bildet auf ihrer der Labortemperiereinrichtung 1 zugewandten Unterseite unter den Stufen 11 in Richtung senkrecht zur Zeichnungsebene gemäß Fig. 1 verlaufende, rechteckige, nach unten offene Nuten 13 aus. Eine präzise Temperierung der Kristallisationsgefäße 9 der Kristallisationsplatte 8 durch Aufsetzen auf die Oberseite 2 der Labortemperiereinrichtung 1 wäre mangels ausreichender Kontaktflächen schwierig. Es sind daher mehrere in Fig. 1 und 2 dargestellte Adapter 14 vorgesehen, die an ihrer Oberseite als rechteckig geformter Balken 15 ausgebildet sind, der in seinem Querschnitt, wie die Fig. 1 zeigt, genau an die Querschnittsform der Nut 13 angepaßt ist. Die Balken 15 lassen sich also mit allseitiger großflächiger und somit gut wärmeleitender Flächen- kontaktierung in die Nuten 13 einsetzen.The crystallization plate 8 forms on its side facing the laboratory tempering 1 underside under the steps 11 in the direction perpendicular to the plane of the drawing of FIG. 1 extending, rectangular, downwardly open grooves 13. A precise temperature control of the crystallization vessels 9 of the crystallization plate 8 by placing it on the top side 2 of the laboratory tempering device 1 would be difficult because of insufficient contact surfaces. There are therefore provided a plurality of adapters 14 shown in FIGS. 1 and 2, which are formed on their upper side as a rectangular shaped beam 15, which in its cross section, as shown in FIG. 1, is adapted exactly to the cross-sectional shape of the groove 13. The bars 15 can thus be used with all-sided large-area and thus good heat-conducting surface contact in the grooves 13.
An ihrer Unterseite sind die Adapter 14 mit nach unten ragenden Erhebungen 16 versehen, die wie Fig. 1 zeigt, in ihrer Oberflächenform exakt der Innenfläche der Vertiefungen 7 in der Oberseite 2 der Labortemperiereinrichtung 1 angepaßt sind.On its underside, the adapters 14 are provided with projections 16 projecting downwards, which, like FIG. 1, are adapted in their surface form exactly to the inner surface of the depressions 7 in the upper side 2 of the laboratory temperature control device 1.
Wie Fig. 2 zeigt, sind mehrere Erhebungen 16 an einem Adapter 14 vorgesehen, die linear in einer Zeile angeordnet sind, die dem Raster von Vertiefungen 7 in einer Zeile der Oberseite 2 der Labortemperiereinrichtung 1 entspricht.As shown in FIG. 2, a plurality of elevations 16 are provided on an adapter 14, which are arranged linearly in a row which corresponds to the grid of depressions 7 in a row of the upper side 2 of the laboratory tempering device 1.
Fig. 1 zeigt, dass die Adapter 14 mit ihren Erhebungen 16 in die Vertiefungen 7 eingesetzt sind und mit ihren Balken 15 in die Nuten 13 der Kristallisationsplatte 8 eingesetzt sind. Die Kristallisationsplatte 8 wird daher großflächig und präzise über die Adapter 14 beheizt, die zu diesem Zweck aus gut wärmeleitfähigem Material, z.B. Metall ausgebildet sind, wobei es insbesondere darauf ankommt, die Wärme in Richtung lotrecht zur Ebene der Oberseite 2 der Labortemperiereinrichtung 1 zu transportieren.Fig. 1 shows that the adapters 14 are inserted with their elevations 16 in the recesses 7 and are used with their beams 15 in the grooves 13 of the crystallization plate 8. The crystallization plate 8 is therefore heated over a large area and precisely via the adapters 14, which for this purpose are made of material which conducts heat well, e.g. Metal are formed, wherein it is particularly important to transport the heat in the direction perpendicular to the plane of the top 2 of the laboratory tempering 1.
Die US 2002/0141905 Al beschreibt unterschiedliche Kristallisationsplatten, wobei die in Fig. 2a dargestellte Konstruktion im Wesentlichen der Kristallisationsplatte 8 gemäß Fig. 1 entspricht. Die Figuren 3a bis 5c beschreiben Kristallisationsplatten einer anderen Ausführungsform, die sich im Wesentlichen von der Kristallisationsplatte 8 dadurch unterscheiden, dass die Kristallisationsgefäße keine gemeinsamen Trennwände aufweisen, sondern im Wesentlichen nach unten frei in seitlichem Abstand hängen. Auch eine solche Kristallisationsplatte kann mit der vorliegenden Erfindung sehr einfach versorgt werden, wie dies die Fig. 4 und 5 zeigen.US 2002/0141905 A1 describes different crystallization plates, the construction shown in FIG. 2 a substantially corresponding to the crystallization plate 8 according to FIG. 1. FIGS. 3a to 5c describe crystallization plates of another embodiment, which are essentially derived from the Crystallization plate 8 differ in that the crystallization vessels have no common partitions, but hang down freely in a lateral distance substantially downwards. Also, such a crystallization plate can be easily supplied with the present invention, as shown in FIGS. 4 and 5 show.
Fig. 4 zeigt dieselbe Labortemperiereinrichtung 1 mit Vertiefungen 7 wie in Fig. 1. In diese sind genauso wie gemäß Fig. 1 Adapter 44 eingesetzt, die weitgehend den Adaptern 14 entsprechen, also Erhebungen 46 aufweisen, die im Raster und der Formgebung den Vertiefungen 7 angepaßt sind. Auf ihrer Oberseite sind die Adaptern 44 wiederum als Balken 45 ausgebildet, die bei der Ausführungsform der Fig. 4 und 5 jedoch Vertiefungen 47 aufweisen, die flächig formangepaßt zu der Außenfläche der Kristallisationsgefäße 49 einer Kristallisationsplatte 48 ausgebildet sind.FIG. 4 shows the same laboratory tempering device 1 with recesses 7 as in FIG. 1. Adapters 44, which largely correspond to the adapters 14, that is to say have elevations 46 which correspond to the depressions 7 in the grid and the shaping, are inserted into these are adapted. On their upper side, the adapters 44 are again designed as bars 45, which in the embodiment of FIGS. 4 and 5, however, have depressions 47 which are formed in a shape-matched manner to the outer surface of the crystallization vessels 49 of a crystallization plate 48.
Fig. 6 zeigt in einer Ausführungsvariante einen Adapter 64, der aus einzelnen Adaptern 44 gemäß Fig. 5 besteht, die parallel zu einander stehend seitlich aneinander gesetzt sind und zwar im Ausführungsbeispiel mit einer Trennschicht 65 aus thermisch isolierendem Material. Auf diese Weise können die Adapter 44 der Fig. 4 zu einem plattenförmigen Adapter 64 zusammengefügt werden, der im Ganzen handhabbar ist. Wird der Adapter 64 auf einer Labortemperiereinrichtung 1 gemäß Fig. 1 eingesetzt, bei der der Gradient 6 in Richtung quer zur Längserstreckung der einzelnen Adapter 44 erzeugt wird, dann sorgt die thermisch isolierende Trennschicht 65 dafür, dass in den einzelnen Adaptern 44 die gewollten unterschiedlichen Temperaturen störungsfrei eingestellt werden können.Fig. 6 shows in an embodiment variant of an adapter 64, which consists of individual adapters 44 of FIG. 5, which are placed side by side parallel to each other standing in the embodiment with a release layer 65 of thermally insulating material. In this way, the adapter 44 of FIG. 4 can be assembled to form a plate-shaped adapter 64, which can be handled as a whole. If the adapter 64 is used on a laboratory tempering device 1 according to FIG. 1, in which the gradient 6 is generated in the direction transverse to the longitudinal extension of the individual adapters 44, then the thermally insulating separating layer 65 ensures that the desired different temperatures in the individual adapters 44 can be adjusted trouble-free.
Bei dem Adapter 64, der in Fig. 6 dargestellt ist, kann auch die Trennschicht 65 entfallen, so dass der Adaptern in seinem Oberteil als durchgehende Platte aus thermisch leitfähigem Material ausgebildet ist. Er wäre in dieser Form für Labortemperiereinrichtungen geeignet, die über ihre Oberseite 2 hinweg eine gleichmäßige Temperatur erzeugen sollen. Eine solche Ausführungsform eines Adapters wäre allerdings auch bei Verwendung eines Temperaturgradienten geeignet, der dann auch durch entsprechenden Wärmefluß im Adapter 64 erzeugt würde.In the adapter 64, which is shown in Fig. 6, and the separating layer 65 can be omitted, so that the adapters is formed in its upper part as a continuous plate made of thermally conductive material. He would be in this form for Laboratory tempering suitable to generate over its top 2 across a uniform temperature. However, such an embodiment of an adapter would also be suitable when using a temperature gradient, which would then also be generated by appropriate heat flow in the adapter 64.
Werden jeweils eine Zeile von Vertiefungen 7 versorgende Adapter 14 (Fig. 1) oder 44 (Fig. 4) verwendet, dann müssen die auf der Oberseite der Adapter angeschlossenen Gefäße in ihrem Anordnungsraster in Richtung quer zur Erstreckung der Adapter zum Raster der Vertiefungen 7 in der Labortemperiereinrichtung 1 passen. In der anderen Richtung, nämlich in Längsrichtung der Adapter 14 bzw. 44 können allerdings die oben angepaßten Gefäße ein anderes Raster aufweisen, als die Vertiefungen 7. Dies gilt beispielsweise für das in den Figuren 1 und 3 dargestellte Beispiel, bei dem das Raster der Kristallisationsgefäße 9 in Richtung des Pfeiles 6 mit dem Raster der Vertiefungen 7 übereinstimmen muss, in Richtung quer dazu abweichen kann.If a respective row of wells 7 serving adapter 14 (Fig. 1) or 44 (Fig. 4) is used, then connected to the top of the adapter vessels in their arrangement grid in the direction transverse to the extension of the adapter to the grid of the recesses 7 in the laboratory tempering 1 fit. In the other direction, namely in the longitudinal direction of the adapters 14 and 44, however, the vessels adapted above may have a different grid than the depressions 7. This applies, for example, to the example shown in FIGS. 1 and 3, in which the grid of the crystallization vessels 9 in the direction of the arrow 6 must coincide with the grid of the recesses 7, may differ transversely thereto.
Wird, wie zur Fig. 6 als alternative Ausführung beschrieben, eine Adapter mit einer durchgehenden Platte verwendet, die mit Erhebungen 46 in die Vertiefungen 7 der 1 greift, so können auf der Oberseite des Adapters Vertiefungen, wie die Vertiefungen 47 in beliebigem Raster angeordnet sein, das völlig abweicht vom Raster der Vertiefungen 7. Auch die oben zu kontaktierenden Gefäßformen können völlig abweichen von der Gefäßform, die in die Vertiefungen 7 paßt. Es kann also z.B. an eine Labortemperiereinrichtung mit Vertiefungen im 8x12 Raster über einen geeignet ausgebildeten Adapter eine Mikrotiterplatte mit 16x24 Raster angepaßt werden. If, as described for Fig. 6 as an alternative embodiment, an adapter used with a continuous plate which engages with elevations 46 in the recesses 7 of FIG. 1, depressions, such as depressions 47, may be arranged in any desired pattern on the upper side of the adapter , which completely deviates from the grid of the wells 7. Also, the vessel shapes to be contacted above can be completely different from the vessel shape, which fits into the wells 7. So it can be e.g. to a laboratory tempering device with wells in 8x12 grid via a suitably designed adapter a microtiter plate are adapted with 16x24 grid.
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06763011A EP1924361A1 (en) | 2005-09-14 | 2006-08-08 | Laboratory temperature control device with top face |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102005044021.5 | 2005-09-14 | ||
| DE200510044021 DE102005044021A1 (en) | 2005-09-14 | 2005-09-14 | Laboratory tempering device with top |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2007031158A1 true WO2007031158A1 (en) | 2007-03-22 |
Family
ID=37000122
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2006/007814 Ceased WO2007031158A1 (en) | 2005-09-14 | 2006-08-08 | Laboratory temperature control device with top face |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1924361A1 (en) |
| DE (1) | DE102005044021A1 (en) |
| WO (1) | WO2007031158A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104114282B (en) * | 2011-09-30 | 2017-07-04 | 生命技术公司 | Systems and methods for biological analysis |
| SG11201805240PA (en) | 2015-12-22 | 2018-07-30 | Life Technologies Corp | Thermal cycler systems and adaptor |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5061630A (en) * | 1988-05-13 | 1991-10-29 | Agrogen Foundation, Seyffer & Co. & Ulrich C. Knopf | Laboratory apparatus for optional temperature-controlled heating and cooling |
| EP0611598A2 (en) * | 1993-02-16 | 1994-08-24 | The Perkin-Elmer Corporation | In situ PCR amplification system |
| US5459300A (en) * | 1993-03-03 | 1995-10-17 | Kasman; David H. | Microplate heater for providing uniform heating regardless of the geometry of the microplates |
| DE19646115A1 (en) * | 1996-11-08 | 1998-05-14 | Eppendorf Geraetebau Netheler | Temperature control block with temperature control devices |
| US20020114734A1 (en) * | 1996-05-09 | 2002-08-22 | Pantoliano Michael W. | Microplate thermal shift assay apparatus for ligand development and multi-variable protein chemistry optimization |
| US20020141905A1 (en) * | 2001-03-19 | 2002-10-03 | Corning Incorporated | Microplate for performing crystallography studies and methods for making and using such microplates |
| WO2004018105A1 (en) * | 2002-08-20 | 2004-03-04 | Quanta Biotech Limited | Thermal engine for a thermocycler with interchangeable sample block |
-
2005
- 2005-09-14 DE DE200510044021 patent/DE102005044021A1/en not_active Withdrawn
-
2006
- 2006-08-08 WO PCT/EP2006/007814 patent/WO2007031158A1/en not_active Ceased
- 2006-08-08 EP EP06763011A patent/EP1924361A1/en not_active Withdrawn
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5061630A (en) * | 1988-05-13 | 1991-10-29 | Agrogen Foundation, Seyffer & Co. & Ulrich C. Knopf | Laboratory apparatus for optional temperature-controlled heating and cooling |
| EP0611598A2 (en) * | 1993-02-16 | 1994-08-24 | The Perkin-Elmer Corporation | In situ PCR amplification system |
| US5459300A (en) * | 1993-03-03 | 1995-10-17 | Kasman; David H. | Microplate heater for providing uniform heating regardless of the geometry of the microplates |
| US20020114734A1 (en) * | 1996-05-09 | 2002-08-22 | Pantoliano Michael W. | Microplate thermal shift assay apparatus for ligand development and multi-variable protein chemistry optimization |
| DE19646115A1 (en) * | 1996-11-08 | 1998-05-14 | Eppendorf Geraetebau Netheler | Temperature control block with temperature control devices |
| US20020141905A1 (en) * | 2001-03-19 | 2002-10-03 | Corning Incorporated | Microplate for performing crystallography studies and methods for making and using such microplates |
| WO2004018105A1 (en) * | 2002-08-20 | 2004-03-04 | Quanta Biotech Limited | Thermal engine for a thermocycler with interchangeable sample block |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1924361A1 (en) | 2008-05-28 |
| DE102005044021A1 (en) | 2007-03-15 |
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