Thermally Conductive Microplates

Abstract

A thermally conductive microplate made of a thermoplastic material comprises a microplate body (150) with at least 96 wells (151) arranged in the microplate body (150), the microplate body (150) having a flat microplate bottom (154), each well having at least one well wall (152) and a planar well bottom (153) with a bottom thickness of up to 1000 μm aligned with a well bottom surface (200) common to all well bottoms (153). A method for manufacturing the thermally conductive microplate is also disclosed. The microplate body (150) is preferably arranged in a frame carrier (300), in particular by welding, gluing or riveting. The upright thermally conductive microplate with high thermal conductivity is optimized for the automated processing of analytical and synthetic methods that are temperature sensitive and based on temperature changes.

Description

[Technical field]

[0001] The present invention relates to a thermally conductive microplate and a process for manufacturing the same. [Background technology]

[0002] Microplates, also called microtiter plates, are consumable test materials for investigating the biological or / and physicochemical properties of substances, mixtures of substances, chemical or biological systems, especially utilized in pharmaceutical or crop protection research. Microplates are generally made of plastic and typically contain isolated wells (also known as cavities) arranged in rows and columns in the form of a matrix. Standard microplate dimensions are standardized by ANSI standards (ANSI / SLAS1-2004, ANSI / SLAS2-2004, ANSI / SLAS3-2004, ANSI / SLAS4-2004, and ANSI / SLAS6-2004) as recommended by the Society for Laboratory Automation and Screening. Thermally sensitive and temperature change-based analytical and synthetic methods such as PCR (polymerase chain reaction, chain extension reaction) methods, thermophoresis, for example in the development of active ingredients in the pharmaceutical industry, especially microscale thermophoresis, cellular thermal shift assay (CETSA), chemical synthesis, bioassays, storage, diagnostics, or microscopic FISH (fluorescence in situ hybridization), require uniform and controllable process parameters. During the PCR process, the genetic material is replicated, which is achieved by multiple cycles of polymerase. In thermophoresis, proteins or small molecules are analyzed together with biological samples such as proteins under the action of temperature. In cellular thermal shift assay (CETSA), the interaction between an active ingredient and a target protein is quantified.

[0003] The corresponding methods are typically carried out in very small volumes in individual wells of a microplate placed in a thermocycler or another suitable analytical device by performing the desired number of cycles or method steps, respectively, in a series of heating and / or cooling steps, allowing any desired test method, such as, for example, fluorescence and / or luminescence. Summary of the Invention

[0004] Thermally stable microtiter plates have been used for many years for many reactions that are thermally sensitive and based on temperature changes, including qPCR. There are many commercially available microplate types that have uneven bottoms or structures, which prevent them from uniformly conducting heat from heating and / or cooling hotplates. Many of these microplates have special formats and cannot be used with standard devices.

[0005] In particular, the use of standard advanced format microplates, i.e., microplates with multiple wells, together with hotplates or water baths for heating and / or cooling, allows only end-point analysis, especially for thermally sensitive PCR methods, and therefore real-time PCR reactions, in which the PCR reaction is measured or quantified after each cycle, cannot be performed on such devices.

[0006] Reliable and accurate thermal methods for samples in microplates require precise application of process parameters that are uniform across the entire microplate. Thus, a thermally conductive microplate must not only have a large number of wells, but also feature high and uniform thermal conductivity and stability. A microplate is said to be "thermally conductive" in the context of the present invention if it allows rapid heat transfer from a hotplate to the microplate with maximum uniformity across all well bottoms.

[0007] The provided microplate is intended to allow for automated handling, in particular for moving the hot microplate between heating blocks within a measurement device (e.g., as illustrated diagrammatically in FIG. 15), thereby maintaining as much dimensional stability of the microplate as possible throughout handling.

[0008] This objective was achieved by providing a microplate that features a uniform bottom thickness and a high degree of flatness across all well bottoms that are as thin as possible.

[0009] Providing well bases with high flatness and uniform bottom thickness has proven to be particularly difficult, firstly, due to the relatively large number of wells in a given microplate format, and secondly, due to the thin well bases required for many applications. Similarly, it is difficult to provide microplates with well bases that have uniform densification of the bottom material across all of the well bases.

[0010] This problem has been solved by a method for manufacturing a thermally conductive microplate made of a thermoplastic material as claimed in claim 1.

[0011] The present invention further provides a thermally conductive microplate made of a thermoplastic material as claimed in claim 10.

[0012] Particular embodiments will become apparent from the claims dependent on claim 1 or 10.

[0013] In the microplate of the present invention, the wells are arranged in a microplate body, which forms well walls and well bottoms, with each well wall being fused to a well opening at an upward direction and each well being closed by a well bottom at an opposite downward side of the microplate body. The microplate body integrally forms wells formed from the well walls and well bottoms, which are aligned in a well bottom plane to form a continuous bottom element (also referred to as the microplate bottom or microplate body bottom).

[0014] In the context of the present invention, the "bottom thickness" BT in the context of this application corresponds to the bottom thickness as defined in the ANSI standard of the Society for Laboratory Automation and Screening for the elevation of the well bottom, i.e. the average thickness of all well bottoms in a single microplate, i.e. in the present invention in a single microplate body as illustrated in Figure 6B. The bottom thickness is reported as a nominal value [ASNI_SLAS_6, https: / / www.slas.org / SLAS / assets / File / public / standards / ASNI_SLAS_6-WellBottomElevation.pdf].

[0015] To ensure uniform thermal conductivity across the microplate, it is important that the bottom thickness has a small degree of variation across the microplate body. This is characterized by the following parameters according to the Society for Laboratory Automation and Screening ANSI standard for well bottom height: - Well Bottom Elevation Variation (WBEV) is the maximum allowable variance from highest to lowest WBE values ​​in a single microplate. WBEV is typically stated as the maximum. (See ASNI_SLAS_6-WellBottomElevation Figure 2.) - Intra-Well Bottom Elevation Variation (IWBEV) is the range of distances (max-min) from a reference point (A) to any point on the inside bottom surface of a single well. IWBEV is typically reported as the maximum (ASNI_SLAS_6-WellBottomElevation, see Figure 3); - Well Depth (WD): The distance from the maximum protrusion of each individual well to any point on the inside bottom surface of the well. WD is typically stated as a nominal value including tolerances (ASNI_SLAS_6-WellBottomElevation See Figure 4).

[0016] Thus, it is already known that plastic injection molding methods can be used to manufacture microplates, however, with these methods it is usually not possible to establish the required low bottom thickness with the required flatness and uniform bottom thickness and / or uniform densification of the material.

[0017] Particularly for this reason, so-called composite microplates have been developed, which have a two-part structure and in particular consist of a frame forming the connections with the well walls and a rigid transparent bottom element glued or welded to one end of the end face of the well walls (see, for example, DE 101 09 704 B4). Also known are composite microplates in which the part constituting the well bottom and part of the well walls is made from a thermally conductive material and a frame carrier, while the remaining part of the well walls is made from a thermally insulating material (see WO 2009 / 030908 A2). Such composite microplates are complex from a manufacturing point of view and may be subject to leakage.

[0018] DE Utility Model No. 20 2007 003 536 U1 discloses providing microplates by plastic injection compression molding. Microplates produced in this way also have undesirable irregularities, especially in the sprue area.

[0019] The technical problem underlying the present invention is therefore to provide a thermally conductive microplate and a method for producing same which meets the above mentioned requirements, in particular a thermally conductive microplate which is characterised by an extremely high degree of flatness and uniform bottom thickness, in particular a uniform densification of material within the well bottoms, in particular within all well bottoms, and thus in particular a thermally conductive microplate which is suitable for use in PCR methods, in particular qPCR and real-time PCR methods, thermophoresis methods, synthesis methods, CETSA methods and / or FISH methods.

[0020] For the required form stability, the microplate body is placed on a fixed frame carrier, in particular by welding, gluing or riveting, in other words the microplate of the invention is of two-part type.

[0021] The present invention solves the underlying technical problem by providing the teachings herein, in particular the teachings of the independent claims and the accompanying specification.

[0022] The present invention relates to a method of manufacturing a thermally conductive microplate from a thermoplastic material comprising a microplate body having a microplate bottom and at least 96 wells disposed in the microplate body, each well being defined by a well wall and a planar well bottom, the microplate bottom being flat, all well bottoms being aligned in a well bottom plane, the microplate body between the well bottom plane and the microplate bottom having a bottom thickness of 1000 μm or less, a) providing a liquefied thermoplastic material; b) performing an injection compression molding process in an injection compression molding machine including an injection unit having a conveying screw and an embossing die suitable for forming a thermally conductive microplate body by introducing a first portion of the liquefied thermoplastic material through the conveying screw under a first injection pressure into the at least partially opened embossing die and closing the embossing die while applying a closing pressure to the thermoplastic material; c) then carrying out an injection molding process by introducing a second portion of the liquefied thermoplastic material into the closed embossing die through a conveying screw under a second injection pressure; d) obtaining a microplate body.

[0023] The present invention also relates to a thermally conductive microplate produced or producible by the method of the present invention.

[0024] The present invention also relates to a thermally conductive microplate made from a thermoplastic material comprising a microplate body having a microplate bottom and at least 96 wells disposed in the microplate body, each well being defined by well walls and a planar well bottom, the microplate bottom being flat, all bowl bottoms being aligned in the well bottom plane, and the microplate body between the well bottom plane and the microplate bottom having a bottom thickness of 1000 μm or less.

[0025] The microplates of the present invention, by combining a thin bottom and a fixed frame carrier, are suitable for carrying out reactions carried out at different precisely set temperatures in a device that includes multiple heating blocks connected by a transport system for rapidly heating and cooling the microplates by moving the microplates between the heating blocks. For example, these microplates may be used to carry out quantitative polymerase chain reactions (qPCR), without being limited to this application.

[0026] In certain embodiments, the thermally conductive microplate, or microplate body, is prepared by the following method: a) providing a liquefied thermoplastic material; b) performing an injection compression molding process in an injection compression molding machine including an injection unit having a conveying screw and an embossing die suitable for forming a microplate body by introducing a first portion of the liquefied thermoplastic material through the conveying screw under a first injection pressure into the at least partially opened embossing die and closing the embossing die while applying a closing pressure to the thermoplastic material; c) then carrying out an injection molding process by introducing a second portion of the liquefied thermoplastic material into the closed embossing die through a conveying screw under a second injection pressure; d) obtaining a microplate body.

[0027] The present invention therefore provides teachings that result in a thermally conductive microplate, which, due to its mode of manufacture, is advantageously characterized in particular by a high degree of flatness of the well bottom and / or a uniform bottom thickness and / or a uniform densification of the material. The thermally conductive microplate provided according to the present invention is notable for a particularly high uniformity in terms of the flatness of the well bottom, the bottom thickness of the well bottom and the densification of the material in the area of ​​the well bottom. This uniformity in terms of the flatness and thickness of the well bottom as well as the densification of the material in the well bottom is preferably extended over the entire thermally conductive microplate, in particular over the entire area of ​​the microplate body where the well bottom is present.

[0028] The well bottoms are preferably in the form of flat bottoms. The well bottoms of all wells are collectively aligned in a planar well bottom plane, forming a continuous bottom element which is generally planar and flat. Both the well bottoms and the well walls are integral parts of the microplate body and are therefore advantageously in the form of a single piece, thus avoiding problems associated with the two-piece well structures of the prior art. More preferably, the microplate body accordingly has a continuous bottom element forming the bottoms of all wells, which bottom element has a thickness of 1000 μm or less and is planar.

[0029] A particular feature of the thermally conductive microplate of the present invention is that the microplate body is provided with a special two-step manufacturing process, in particular by forming it by using an injection compression molding step in an injection compression molding machine and a subsequent injection molding step carried out in the same injection compression molding machine, which procedure provides a very flat, uniform thickness and uniformly densified well bottom.

[0030] The injection compression molding machine used according to the invention is characterized in that it has an embossing die and an injection unit formed with at least one conveying screw for introducing, in particular injecting, the liquefied thermoplastic material into the embossing die. The embossing die is three-dimensionally formed so as to be able to form the desired microplate body.

[0031] Thus, in a first method step a), a liquefied thermoplastic material is provided, a first portion of which, in particular the main first portion, is introduced, in particular injected, in an injection compression molding machine, into a partially open embossing die under a first injection pressure in a subsequent method step b). The embossing die has at least two die parts which surround, or rather form, a cavity or hollow space, which is adjustable by a relative movement of the at least two die parts relative to one another. When the embossing die is in the open state, the at least two die parts define a relatively large cavity into which the liquefied thermoplastic material is introduced, such that during and / or after this introduction, the at least two die parts can be moved relative to one another to compress the liquefied plastic. Accordingly, after the introduction, the embossing die is closed, and a closing pressure is applied to the thermoplastic material present in the embossing die, which solidifies the thermoplastic material. In the subsequent method step c) according to the invention, in an injection molding step under a second injection pressure, a second portion of the liquefied thermoplastic material still present in the injection unit, in particular in the conveying screw, is introduced into the closed embossing die. Opening the embossing die after method step b) is not envisaged either before or during method step c).

[0032] The second part of the liquefied thermoplastic material is preferably introduced into the embossing die via an injection nozzle arranged at the embossing die end of the conveying screw and a conveying screw provided with a corresponding receiving channel in the embossing die. The second part of the liquefied thermoplastic material introduced in this way reaches the injection site of the thermoplastic material from method step b) already present inside the embossing die, which results in the flattening of the irregularities formed at this point and / or a uniform densification of the bottom material. Thus, a particular feature of the microplate body produced according to the invention is that it is produced in one piece in a two-stage method having an injection compression molding method step and an injection molding method step, and its well bottoms formed by the bottom elements have a particularly high degree of flatness. This is because, in particular, the injection molding method step carried out after the injection compression molding method step removes the irregularities of the bottom elements and well bottoms of the molded parts produced in method step b) by the plastic subsequently injected in method step c). Thus, the microplate body has the particular feature of having extremely flat, uniformly thick and uniformly densified bottom elements, and therefore extremely flat well bottoms, all lying in one plane, and without (any) function-inhibiting irregularities, bumps or other artifacts around the injection site, also referred to herein as sprue. The microplate body has an extremely high uniformity, in particular with regard to the thickness of the well bottoms. The high uniformity of the flatness of the well bottoms provided according to the invention allows a particularly high uniform heat transfer, which leads to particularly reliable and accurate reactions. The thermally conductive microplate of the invention is therefore particularly suitable as a PCR microplate, in particular as a qPCR microplate (quantitative PCR). In an advantageous manner, the thermally conductive microplate of the invention allows the reactions carried out in the wells to be evaluated by a camera. In particular, the thermally conductive microplate of the invention allows the PCR reactions carried out in the wells to be evaluated by a camera after each cycle, thus allowing real-time PCR.

[0033] The microplate body is preferably placed, in particular welded, glued or riveted, in a frame carrier, which achieves better transport and handling stability despite the thin base.

[0034] The thermally conductive microplates of the present invention are particularly suitable for automation, high throughput screening, and high throughput diagnostics.

[0035] In a preferred embodiment, the thermally conductive microplate of the present invention is a PCR microplate.

[0036] It is preferable to optimize the thermal conductivity of the microplate body across its bottom thickness.

[0037] In a preferred embodiment of the present invention, the microplate body has a bottom thickness (BT) of 20 to 900 μm, in particular 20 to 800 μm, in particular 20 to 600 μm, in particular 20 to 550 μm, in particular 20 to 500 μm, in particular 20 to 450 μm, in particular 20 to 400 μm, in particular 20 to 350 μm, in particular 20 to 300 μm, in particular 20 to 250 μm, in particular 20 to 200 μm, in particular 20 to 190 μm.

[0038] In a particularly preferred embodiment, the microplate body has a bottom thickness BT of 300 μm or less.

[0039] By using the described manufacturing method it is possible to achieve particularly small variations (WBEV, the well bottom height variation) of less than 0.15 mm over the entire area of ​​the microplate body.

[0040] Using the described manufacturing method it is possible to achieve an average inner well bottom height variation (IWBEV) of the microplate body of less than 0.05 mm.

[0041] The microplate of the present invention meets the requirements of the ANSI standard of the Society for Laboratory Automation and Screening [https: / / www.slas.org / SLAS / assets / File / public / standards / ASNI_SLAS_6-WellBottomElevation.pdf].

[0042] The low bottom thickness makes it possible to use thermoplastic materials with a thermal conductivity of 0.1 to 0.8 W / mK, measured by the method according to Horst Czichos (ed.) [Die Grundlagen der Ingenieurwissenschaften, D Werkstoffe, Warmeleitfahigkeit von Werkstoffen [The Fundamentals of Engineering, D Materials, Thermal conductivity of materials], 31st edition, Springer, 2000, ISBN 3-540-66882-9, pD 54.].

[0043] In many biological testing methods utilizing microplates, the prior art has been to seal the microplate in the form of a disposable article with a sealing film after introducing reactants into the wells. This transparent thin sealing film may be made of polycarbonate, polypropylene, cycloolefin or other polymeric materials as known in the art, or may form a multi-layer film made of two or more transparent materials with the desired barrier properties. The sealing can be achieved by welding the sealing film to the body of the disposable article. Experiments have shown that the use of thermoplastic materials containing a medium that enhances thermal conductivity makes it difficult to achieve sealing by traditional welding methods.

[0044] More preferably, the thermoplastic material does not include media that enhance thermal conductivity, such as conductive carbon black or thermally conductive ceramic fillers.

[0045] The required thermal conductivity is achieved by the structure of the microplate, in particular the thinness of the bottom part.

[0046] More preferably, the thermoplastic material is stable to at least 120°C.

[0047] In a particularly preferred embodiment, the thermoplastic material is polypropylene and / or COC (cycloolefin copolymer) and / or polystyrene, in particular polypropylene.

[0048] In a particularly preferred embodiment, the thermoplastic material does not bind to any proteins and / or nucleic acids.

[0049] In a preferred embodiment, a thermoplastic material is used that allows for impermeable sealing of the fabricated microplates with commercially available microtiter plate sealing films or adhesive tapes to protect the well contents from escape, contamination and evaporation during assay processing, incubation or storage.

[0050] In particularly preferred embodiments of the invention, the microplate has at least 96, preferably 384, 1536 or 3456, more preferably 1536 wells, in a format established according to the ANSI standard of the Society for Laboratory Automation and Screening for well positions in microplates (e.g., ANSI / SLAS 4-2004 - https: / / www.slas.org / SLAS / assets / File / public / standards / ANSI_SLAS_4-2004_WellPositions.pdf).

[0051] In a particularly preferred embodiment the well walls have a thickness of 300 to 800 μm, in particular 400 to 700 μm, especially 500 to 600 μm.

[0052] In particularly preferred embodiments of the invention, the wells, viewed in cross-section, are round, square or rectangular.

[0053] In a particularly preferred embodiment of the invention, the thermally conductive microplate has at least 96, in particular 384, in particular 1536 wells and has length and width dimensions according to the ANSI standards of the Society for Laboratory Automation and Screening (ANSI / SLAS 1-2004, ANSI / SLAS 2-2004, ANSI / SLAS 3-2004 and / or ANSI / SLAS 4-2004).

[0054] In a particularly preferred embodiment the microplate body has a height of 1 to 8 mm, in particular 2 to 5 mm, in particular 3.3 mm.

[0055] In a particularly preferred embodiment, the wells each have an internal volume of 10 μl or less, in particular 0.3 to 6 μl, in particular 0.5 to 4 μl, in particular 4 μl or 1 μl.

[0056] In a particularly preferred embodiment, the microplate body is arranged, in particular welded, glued or riveted, in particular riveted, on a frame carrier. The microplate body arranged on the frame carrier together form a microplate for the purposes of the present invention.

[0057] In a particularly preferred embodiment, the frame carrier is manufactured from polycarbonate or polystyrene.

[0058] The microplate body and / or the frame carrier may be transparent or may be opaquely colored accordingly. In particular, for application to measuring devices with visual evaluation, opaquely colored microplates are preferred. In a particularly preferred embodiment, the thermally conductive microplate is opaquely colored black or white.

[0059] In a particularly preferred embodiment of the invention, the frame carrier of the thermally conductive microplate of the invention together with the microplate body has dimensions as defined in the ANSI standards of the Society for Laboratory Automation and Screening [ANSI / SLAS Microplate Standards - https: / / www.slas.org / education / ansi-slas-microplate-standards / ; ANSI SLAS 1-2004(R2012); footprint dimensions, ANSI SLAS 2-2004(R2012); height dimensions, ANSI SLAS 3-2004(R2012); flange exterior bottom dimensions, ANSI SLAS 4-2004(R2012); well position, ANSI SLAS 6-2012; well bottom height].

[0060] In a particularly preferred embodiment of the invention, the thermally conductive microplate has length and width dimensions according to the ANSI standards of the Society for Laboratory Automation and Screening (ANSI / SLAS 1-2004, ANSI / SLAS 2-2004, ANSI / SLAS 3-2004 and / or ANSI / SLAS 4-2004), in particular 127.76 mm length by 85.48 mm width.

[0061] In a particularly preferred embodiment, the frame carrier of the thermally conductive microplate of the present invention has a height of 10.4 mm.

[0062] In a particularly preferred variant of the invention, the frame carrier is rectangular.

[0063] The microplate of the present invention can be provided by the manufacturing method of the present invention, in which in step b) an injection compression molding step is carried out in an injection compression molding machine by introducing a first portion of a liquefied thermoplastic material into an at least partially opened embossing die through a conveying screw under a first injection pressure and closing the embossing die while applying a closing pressure to the thermoplastic material.

[0064] In the context of the present invention, "an at least partially apertured embossing die" in step b) preferably means an offset of the embossing die caused by the aperture (Figure 2), experience has shown that the optimal offset is 0.1-0.8 mm, preferably 0.3-0.6 mm, preferably 0.5 mm, but this is preferably elucidated or confirmed experimentally.

[0065] In a particularly preferred embodiment of the method, the first injection pressure provided in method step b) is higher than the second injection pressure provided in method step c).

[0066] In a further preferred embodiment, the first injection pressure provided in method step b), in particular the higher first injection pressure provided in method step b) and the second injection pressure provided in method step c) are applied for a shorter duration than the second injection pressure provided in method step c).

[0067] In a particularly preferred embodiment, the first injection pressure is between 700 and 1100 bar, in particular between 750 and 1000 bar, in particular between 750 and 950 bar, in particular between 750 and 900 bar, in particular 900 bar.

[0068] In a particularly preferred embodiment, the first injection pressure is applied for a period of 0.1 to 10 seconds, in particular 0.1 to 9 seconds, in particular 0.1 to 5 seconds, in particular 0.1 to 2 seconds, in particular 0.25 seconds.

[0069] In a particularly preferred embodiment, the first portion of the liquefied thermoplastic material is introduced into the embossing die in method step b) at a speed of 100 mm / s.

[0070] In a particularly preferred embodiment, the second injection pressure is between 200 and 700 bar, in particular between 250 and 700 bar, in particular between 300 and 700 bar, in particular 500 bar.

[0071] In a particularly preferred embodiment, the second injection pressure is applied for a period of from 10 to 30 seconds, in particular from 11 to 30 seconds, in particular from 12 to 28 seconds, in particular from 14 to 25 seconds.

[0072] In a particularly preferred embodiment, a method for producing a thermally conductive microplate according to the invention is provided, in which the injection molding step envisaged in method step c) is carried out in at least two stages, in particular with different injection pressures, in particular with a first second injection pressure and a second second injection pressure. In this embodiment, the first second injection pressure is higher than the second second injection pressure, in particular twice as high. The first second injection pressure is higher than the second injection pressure in the preferred embodiment and is preferably applied over a period of 4 to 13 seconds, in particular 7 to 11 seconds, in particular 9 seconds, and the second injection pressure is preferably applied over a period of 2 to 8 seconds, in particular 4 to 6 seconds, in particular 5 seconds, the total period being preferably 10 to 30 seconds, in particular 12 to 28 seconds, in particular 14 to 25 seconds.

[0073] In a particularly preferred embodiment of the method the closing pressure is between 600 and 1000 kN, in particular between 700 and 900 kN, in particular 800 kN.

[0074] In a particularly preferred embodiment, a method for producing a thermally conductive microplate of the invention is provided, in which the closing pressure is maintained until the embossing die is opened and a thermally conductive microplate is obtained, in particular for the duration of method step c).

[0075] In a particularly preferred embodiment, a method of manufacturing a thermally conductive microplate of the present invention is provided, wherein the thermoplastic material is stable at least to 120°C.

[0076] In a particularly preferred embodiment, a method for producing a thermally conductive microplate of the invention is provided, wherein the thermoplastic material is polypropylene and / or cycloolefin polymer (COP) and / or COC (cycloolefin copolymer) and / or polystyrene, in particular polypropylene.

[0077] In a particularly preferred embodiment of the present invention, a method of manufacturing a thermally conductive microplate of the present invention is provided, wherein a mass of the first portion of liquefied thermoplastic material is greater than a mass of the second portion of liquefied thermoplastic material.

[0078] In a particularly preferred embodiment of the present invention, a method for producing a thermally conductive microplate of the present invention is provided, in which 40% by weight to 90% by weight, in particular 50% by weight to 80% by weight, in particular 60% by weight to 70% by weight, based on the total mass of the liquefied thermoplastic material produced in method steps (b) and (c), is produced as a first portion and 10% by weight to 60% by weight, in particular 20% by weight to 50% by weight, in particular 30% by weight to 40% by weight, is produced as a second portion of thermoplastic material.

[0079] In a particularly preferred embodiment, the first portion of liquefied thermoplastic material produced according to method step b) is between 50% and 80% by weight, in particular between 60% and 70% by weight, and the second portion of liquefied thermoplastic material produced according to method step c) is between 20% and 50% by weight, in particular between 30% and 40% by weight (in each case based on the total mass of the thermoplastic material introduced). In a particularly preferred embodiment, a method for producing a thermally conductive microplate according to the invention is provided, in which the mass ratio of the first portion of liquefied thermoplastic material to the second portion of liquefied thermoplastic material is 0.5 to 2.5, in particular 1 to 2, in particular 2 to 1 for the first portion to the second portion.

[0080] In a particularly preferred embodiment of the invention, the method of method step b) is carried out as a gate method, in particular as a needle valve gate method.

[0081] In a particularly preferred embodiment of the invention, the method of method step c) is carried out as a gate method, in particular as a needle valve gate method.

[0082] In a particularly preferred embodiment of the invention, the method of method steps b) and c) is carried out as a gate method, in particular as a needle valve gate method.

[0083] In a particularly preferred embodiment of the invention, the injection compression molding machine used according to the invention comprises at least one injection unit and at least one embossing die, the injection unit in particular comprising at least one plasticizing cylinder and a rotatable conveying screw, the end of the conveying screw facing the embossing die having an injection nozzle constituting the transition to the embossing die. The injection unit and the embossing die may be temperature controllable, in particular temperature induced, and may have different temperatures.

[0084] In a particularly preferred embodiment of the invention, the embossing die used in accordance with the invention comprises at least two die parts defining cavities for forming the thermally conductive microplate of the invention of variable volume, a first die part defining the bottom region of the thermally conductive microplate and a second die part movable relative to the first die part, in particular in a normal direction thereto, and having a number of embossed core elements corresponding to the number of wells.

[0085] In the context of the present invention, "sprue" is understood to mean the location within the body of the microplate where the liquefied thermoplastic material is introduced into the embossing die by the injection nozzle of the injection compression molding machine.

[0086] In the context of the present invention, "sink marks" are understood to mean depressions in the body of the microplate which result in a reduction in bottom thickness, densification and / or unevenness, especially in the region of the well bottom.

[0087] In the context of the present invention, "thermal conductivity" is understood to mean the property of a material to conduct heat within the material without mass transfer.

[0088] In the context of the present invention, the term "and / or" is understood to mean that all elements of the group associated with the term "and / or" are present both together in any combination, both cumulatively and alternatively. By way of example, the term "A, B and / or C" means the disclosure of: i) (A or B or C), or ii) (A and B), or iii) (A and C), or iv) (B and C), or v) (A and B and C), or vi) (A and B or C), or vii) (A or B and C), or viii) (A and C or B).

[0089] Further preferred embodiments of the invention are the subject matter of the dependent claims.

[0090] List of symbols 1. Injection compression molding machine 11 Injection unit 111 Plasticizing Cylinder 112 Conveying screw 113 Injection Nozzle 12 Embossing Die 121 / 122 Die parts 13 Cavities / Volume 14 Thermoplastic materials / melts 15 Thermally conductive microplates 150 Microplate Body 151 wells 152 Well Wall 153 Well bottom 154 Bottom element / Bottom of microplate body / Bottom of microplate 155 sprue 16 Offset related to embossing die opening 50 Intermediate element of die part 122 having embossed core element 51 End element of die part 122 60 Embossed Core Elements 200 well flat bottom 300 Frame Carrier 301 Rivet WBE - Well Bottom Height WD-Well Depth ECTP - External clearance to bottom of plate WBW - Well bottom width BT-Bottom thickness IWBEV - Inner Well Bottom Height Variation 400 Heating element for melting plastic 500 Hot Plate 501 Cover Plate 600 / 600' Camera 601 Lighting

[0091] The invention will be elucidated in detail by the following examples and the corresponding figures. [Brief description of the drawings]

[0092] [Figure 1] An injection compression molding machine (1) is shown with an injection unit (11) and an embossing die (12) containing unmolten thermoplastic material (14) in the injection unit. The conveying screw (112) is in a starting position and the embossing die is in a slightly open state, as can be seen from the offset (16) between the intermediate element (50) having the embossing core element (60) movable in relative terms and the end elements (51) of the die parts (122) that define the volume (13) formed by the well walls. [Diagram 2] Shown is an injection compression molding machine (1) in which a thermoplastic material (14) is injected at a first injection pressure into a cavity (13) of an embossing die (12) through an injection nozzle (113). A conveying screw now moves towards the injection nozzle. The thermoplastic material (14) is melted (plasticized) by heat and friction in the area of ​​the heating element (400) of the conveying screw. [Diagram 3] The injection compression molding machine (1) is shown with the embossing die (12) closed and with closing pressure being applied, as can be seen by the fact that the middle element (50) of the die part (122), which defines the volume formed by the well walls, is moving relative to the end element (51) of the die part (122). [Figure 4] An injection compression molding machine (1) is shown in which a conveying screw (112) introduces additional thermoplastic material (14) into the closed embossing die (12) while applying a second injection pressure. [Diagram 5] It is shown that the embossing die (12) is opened to obtain a microplate body (150). [Figure 6A] A schematic diagram of a microplate (15) in a side view is shown, including a microplate body (150) disposed on a frame carrier (300). [Figure 6B] FIG. 6B shows an enlarged portion of FIG. 6A highlighting the main quality parameters of the microplate (15) of the present invention. [Figure 7] A 3D scan of the surface of the microplate body (150) shows no sink marks in the area of ​​the sprue (155) and therefore no depressions that would result in a bottom thickness, reduced densification, or unevenness at the bottom of the wells, which is particularly flat at the bottom compared to microplates other than the present invention that have depressions that would result in a bottom thickness, reduced densification, or unevenness at the bottom of the wells. [Figure 8] 3D scan of the surface of a microplate not manufactured according to the present invention (injection compression molding method) that has sink marks in the area of ​​the sprue (155) and has an uneven bottom compared to the thermally conductive microplate body of the present invention. [Figure 9] A photograph of the surface of a microplate body (150) manufactured according to the present invention is shown, which has no obvious sink marks in the area of ​​the sprue (155) and has a particularly flat bottom compared to a microplate not manufactured according to the present invention. [Figure 10] Photograph of the surface of a microplate (injection compression molding method) not manufactured according to the present invention, which has visible sink marks (155) in the area of ​​the sprue and an uneven bottom compared to the microplate body (150) manufactured according to the present invention. [Figure 11A]1 shows a 3D top view of a thermally conductive microplate (15) of the present invention having 1536 wells (151), in which the microplate body (150) is riveted in a frame carrier 300. [Figure 11B] 3D bottom oblique view of a thermally conductive microplate (15) of the present invention having 1536 wells (151), in which the microplate body (150) is riveted in a frame carrier 300, is shown. [Figure 12A] 1 shows a cross-sectional structure of a thermography experiment using a microplate of the present invention. [Figure 12B] 1 shows an image of the experimental setup taken from above by a FLIR 645sc (LWIR) thermographic camera, where position SP1 indicates a well in a microplate. [Figure 13] Shown are detailed images of measurements carried out in wells (151) at different temperatures of 60°C, 80°C and 95°C, as well as a color scale for comparison. [Figure 14] 1 shows the heating curve and reproducibility of the microplate (15) of the present invention in the process of heating from 60° C. to 95° C. over time. [Figure 15] A schematic diagram of such a measurement device is shown, which comprises three PCR blocks B1-B3 for rapid heating and cooling of a microplate. [Figure 16] Plots of measurements recorded with an sCMOS camera with a 35 mm F1.6 C-mount objective are shown, showing uniform amplification across the plate. Figures 17A and 17B, as well as Figure 18, show white light interferometry topography measurements of plates produced by injection compression molding and by the described method of the present invention. [Figure 17A] 4 shows an image of the interference signal by a CCD sensor of the measuring device. [Figure 17B] 4 shows an image of the interference signal by a CCD sensor of the measuring device. [Figure 18] The corresponding elevation of the plate at various measurement points on the profiles Pa and Pb is shown. [Figure 19A] 4 shows white light interferometry around the injection site in each case for plates produced by injection compression molding or by the method of the invention described. [Figure 19B] 4 shows white light interferometry around the injection site in each case for plates produced by injection compression molding or by the method of the invention described. [Figure 20] The corresponding bump at the site of ejection is shown. [Figure 21A] 1 shows white light interferometry of flatness within the wells for plates produced by injection compression molding or by the method of the invention as described. [Figure 21B] 1 shows white light interferometry of flatness within the wells for plates produced by injection compression molding or by the method of the invention as described. [Figure 22] The corresponding profile measurements of flatness within the well are shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0093] The method for producing a thermally conductive microplate (15) described below is carried out in an injection compression molding machine (1) comprising an injection unit (11) with a conveying screw (112) rotatable in a plasticizing cylinder (111) mounted on a heating element (400) and with an injection nozzle (113) at the end of the conveying screw facing an embossing die (12). The injection compression molding machine further comprises an embossing die (12) formed from at least two die parts (121 / 122) movable relative to each other and forming a cavity (13) into which a liquefied thermoplastic material (14) is introduced, in which a thermally conductive microplate is formed. One of the die parts (121) defines the bottom of the well and the other die part defines the volume (122) formed by the well walls (see also the structure of the injection compression molding machine in FIG. 1).

[0094] The method of the present invention will now be described in detail with reference to the accompanying drawings and specific exemplary configurations.

[0095] The use of all examples or exemplary language (e.g., "etc.") provided herein is intended merely to further clarify the invention and does not limit the scope of the invention unless specifically stated otherwise.

[0096] The present invention includes all modifications and equivalents of the subject matter specifically recited in the appended claims to the extent permitted under current law.In addition, the disclosure encompasses any combination of the elements described above in all possible variations thereof unless otherwise indicated herein or clearly contradicted by context.

[0097] In a first method step a), polypropylene was provided in liquefied form as melt (14). In a second method step b), the embossing die (12) was provided in a semi-open state (Figure 1), the embossing die was opened by 0.5 mm, a first portion of the liquefied polypropylene, i.e. 15 g (67% by weight or about twice the first portion), was introduced into the cavity of the embossing die (13) with a first injection pressure of 900 bar for a period of 0.25 seconds by means of a conveying screw (112) moving over 87% of the distance towards the injection nozzle required for injection (Figure 2), and the embossing die was closed to apply a closing pressure of 800 kN (Figure 3). In the subsequent method step c), a two-stage injection molding process is carried out with a first second injection pressure of 500 bar for 9 seconds, then a second second injection pressure of 250 bar for 5 seconds, i.e. a total of 14 seconds, in which the second portion of the liquefied polypropylene, i.e. 7.5 g (33% by weight), is introduced into the closed embossing die (in the closed state, the embossing die opens by 0.3 mm) by means of a conveying screw (in this case, the conveying screw moves over the remaining 13% of the distance required for injection) (Figure 4). The embossing die is opened after the liquefied polypropylene has solidified, and in method step d), the microplate body (150) of the thermally conductive microplate (15) of the invention is obtained (Figure 5). The produced microplate body (150) is fixed by rivets (301) in a frame carrier (300) produced from polycarbonate.

[0098] In summary, the manufactured microplate has the following characteristics: number of wells: 1536 wells; WBE=7.4 mm; WD=3 mm; WBW=1.2 mm; BT=0.3 mm; ECTP=7.1 mm; microplate body material: polypropylene; frame carrier material: polycarbonate.

[0099] FIG. 6A shows a thermally conductive microplate (15) obtained according to the invention. It shows wells (151) arranged in a microplate body (150) with well walls (152) whose individual well bottoms (153) lie in a formed well bottom plane (200) and the microplate bottom (154) is flat. Each well is formed in cross section from a circular well wall (152) which opens upwards at the well opening and is closed and bounded on the opposite lower side by a planar well bottom (153). The microplate body (150) is fixed in a frame carrier (300) by rivets (301). FIG. 6B shows an enlarged portion of FIG. 6A, specifying the main quality parameters of the microplate (15) of the invention. Measuring the surface of the entire plate or the plate cross section from the bottom by a surface measuring device with a confocal distance sensor and determining the height profile by individual measurement lines showed that injection compression molding induces bending of the plate of less than 0.1 mm. This low degree of bending was not achieved in the case of the microplate samples produced by standard manufacturing methods (bending of more than 0.3 mm).

[0100] Plate cross sections from the bottom were analyzed to assess bending of individual wells. Measurements showed that injection compression molding resulted in a uniform plate bottom structure with less than 10 μm variation. This uniformity and flatness was not achieved in the case of standard manufacturing microplate samples (>14 μm variation).

[0101] 7 to 10 show the advantages of the method of the present invention for producing a microplate by comparing it with a microplate produced by a conventional injection compression molding method.

[0102] The thermally conductive microplate (15) of the present invention also has a particularly flat microplate bottom (154), especially evident in the area of ​​the sprue (155) in FIG. 7 (microplate of the present invention) as a dark inner circle when compared to that of the standard microplate manufacturing method of FIG. 8. In the area between the sprue and the wells of the microplate, sink marks that cause unevenness are evident in the non-inventive microplates of the sunken morphology (compare FIGS. 7 and 8, especially the area between 4-6 mm (x-axis) and FIGS. 9 and 10, especially the dark area in the area to the right of the sprue).

[0103] The inventive procedure for manufacturing a thermally conductive microplate therefore results in a particularly remarkable bottom (154 / 153) flatness and a particularly uniform bottom thickness of the thermally conductive microplate (15). Figures 11A and 11B show a 3D view of the top and bottom oblique views of a thermally conductive microplate (15) of the invention riveted into a frame carrier (300), said microplate having 1536 wells (151).

[0104] In a further experiment, a microplate of the invention (15) containing empty wells was placed on a hotplate (500), covered with an opaque cover plate (501) except for one well (151 / sp1), and the temperature change at the bottom of the well (153) was recorded and measured using a thermographic camera (600), e.g. a FLIR 645 sc (LWIR) and a light source (601). Figure 12A shows the setup for the thermographic experiment in cross section.

[0105] FIG. 12B shows an image of the experimental setup taken from above by a FLIR 645sc (LWIR) thermographic camera, where position SP1 indicates a well in a microplate.

[0106] FIG. 13 shows detailed images of measurements carried out in wells (151) at different temperatures of 60° C., 80° C. and 95° C., as well as a comparative color scale.

[0107] Figure 14 shows the heating curve and its reproducibility of a microplate (15) of the present invention during heating from 60°C to 95°C over time. The increase in temperature for a nominal 35K temperature jump was 20K in about 2 seconds. This thermal experiment shows that rapid heat transfer from the hotplate to the microplate can be achieved.

[0108] Furthermore, the feasibility of using the microplate of the present invention for real-time PCR was experimentally verified. For example, in a 1536 well white microplate of the invention, the following steps were carried out: For each well of the microplate (15), a mixture of the following solutions was used and pipetted into the well (151):

[0109] [Table 1]

[0110] The microplate (15) was then sealed with a visually transparent permanent adhesive film (Applied Biosystems, 4311971) (not shown), and the microplate (15) was centrifuged and placed into a measurement device for real-time PCR measurement (also called a PC measurement device).

[0111] Figure 15 shows a schematic diagram of such a measurement device, including three PCR blocks B1-B3 for rapid heating and cooling of the microplate according to a procedure protocol by a heating block (500), an imaging station I including a heating block (500) and a transparent hot plate (501) for controlling the temperature of the microplate (15), a light source (401) and an sCMOS camera with a 35 mm F1.6 C-mount objective lens (600'). The microplate (15) moves according to the procedure protocol between the PCR blocks B1-B3 (numbering is arbitrary) and the imaging station I using a transport system, illustrated diagrammatically with horizontal arrows.

[0112] The following procedure protocol was used for the PCR measurement device: after an initial time of 2 min at 95° C., 45 cycles of three temperature steps are repeated, in each case first at 95° C. for 10 s, second at 60° C. for 30 s and third at 72° C. for 5 s. In each cycle, after the third step (72° C.), the plate is irradiated / excited with light of wavelength 539 nm and then the emitted light is recorded / measured at 569 nm.

[0113] Summary of primers / samples used in PCR reactions:

[0114] [Table 2]

[0115] FIG. 16 shows a plot of measurements recorded with an sCMOS camera with a 35 mm F1.6 C-mount objective, showing uniform amplification across the plate.

[0116] The uniform temperature distribution over the plate shows the advantage of the manufacturing method, especially in the area of ​​the sprue.

[0117] Further comparison of 1536-well plate bodies manufactured using different manufacturing methods: A comparison was made of 1536 well plate bodies manufactured by conventional injection compression molding, by standard injection molding, and by the method of the present invention using the mold of FIG.

[0118] For all manufacturing processes, polypropylene was supplied in liquefied form as a melt. The melt was introduced into the mold / compression die cavity (13) with the parameters detailed below. After the liquefied polypropylene solidified, the embossing die was opened to obtain the microplate body.

[0119] To injection-compression mold the plate body, the melt was introduced into the cavity (13) of the embossing die, which was not completely closed, with the following parameters: holding force 950 kN, injection time 0.3 s, switching point 10.61 mm, and injection speed 106.1 mm / s.

[0120] In standard injection molding, the melt is introduced into a mold suitable for the purpose with similar parameters. However, experience shows that the achievable bottom thickness of such plates is at least 0.6 mm, making such plates unsuitable for qPCR experiments due to inadequate heat transfer.

[0121] The plate of the present invention was provided by the method described above.

[0122] Topography measurements of the underside of each plate body were performed at room temperature using a white light interferometer. White light interferometry is a non-contact optical testing method that uses the interference of broadband light (white light) and therefore allows 3D profile measurements of structures with dimensions from a few centimeters to a few micrometers. White light interferometry is frequently used in wafer analysis (quality inspection).

[0123] Each measurement object was placed in a white light interferometer and measured.

[0124] The effective area of ​​the white light interferometer was approximately 80 mm × 120 mm.

[0125] Figures 17A and 17B show the interference signal obtained by the CCD sensor of the measuring device as a function of the position of the measurement object for each individual pixel, while Figure 18 shows the curvature of the corresponding plate at different points of the corresponding reference profiles Pa and Pb derived by a method according to the prior art based on the measurements of the corresponding pixels.

[0126] The plate produced by conventional injection compression molding shows interference signals partially outside the measurement area (gray area, Fig. 17A). The plate shows a general curvature of about 0.35 mm in the measurable area (Fig. 18, profile Pa).

[0127] The interference signals of the plate produced by the method of the invention are all within the measurement range (FIG. 17B), and the plate shows an improved flatness of about 0.15 mm (FIG. 18, profile Pb).

[0128] The flatness and curvature can also be further improved in the device according to FIG. 5 by compressing the two-part plate 15 between two hot plates 500, 501 during use at a temperature of 95°C.

[0129] Low plate warping is essential for the qPCR process because it ensures intimate contact between the bottom of the plate and the heat source.

[0130] Measurement for sink marks at injection site: Figures 19A and 19B show white light interferometry measurements around the injection site for plates produced by injection compression molding or by the method of the present invention, respectively, and Figure 20 shows the corresponding profiles at the injection site at corresponding positions Pa and Pb.

[0131] An active area of ​​8 mm x 8 mm was defined for white light interferometry measurements from the underside of the plate around the injection site (Figure 19A, Figure 19B). To obtain reliable qPCR results, all wells must show equal detection power. Significant sink marks at the injection site in qPCR plates manufactured by conventional injection molding lead to uneven contact between the underside of the plate and the heat source. This results in inaccurate or at least delayed qPCR signal intensity.

[0132] Measuring flatness inside a well Figures 21A and 21B show white light interferometry measurements of flatness within the wells for plates made by injection compression molding or by the method of the invention, respectively, and Figure 22 shows the corresponding measured profiles of flatness within the wells against the corresponding reference profiles Pa and Pb.

[0133] For this measurement, a 7 mm x 9 mm cross section was measured from the bottom of each plate. Figures 21A and 21B show white light interferometry measurements of the measured plates.

[0134] The well bottoms of plates produced by the method of the present invention vary by less than 10 μm and are flatter than the well bottoms of plates produced by conventional injection compression molding methods.

[0135] To obtain reliable qPCR results, all wells must show equal power. Significant variations in the well bottoms in plates manufactured by conventional injection compression lead to uneven heat transfer between the plate and the heat source, resulting in inaccurate or at least delayed qPCR signal intensity.

Claims

1. A method for manufacturing a thermally conductive microplate (15) from a thermoplastic material (14), comprising: a microplate body (150) having at least 96 wells (151) arranged therein, the microplate body (150) having a flat microplate bottom (154), each well (151) having at least one well wall (152) and a planar well bottom (153) having a bottom thickness of 1000 μm or less, aligned with a well bottom plane (200) common to all well bottoms (153); a) providing a liquefied thermoplastic material (14); b) performing an injection-compression molding process in an injection-compression molding machine (1) including an injection unit (11) having a conveying screw (112) and an embossing die (12) suitable for forming the microplate body (150), by introducing a first portion of the liquefied thermoplastic material (14) through the conveying screw (112) under a first injection pressure into the at least partially opened embossing die (12), and closing the embossing die (12) while applying a closing pressure to the thermoplastic material (14); c) then carrying out an injection molding process by introducing a second portion of said liquefied thermoplastic material (14) into said closed embossing die (12) via said conveying screw (112) under a second injection pressure; d) obtaining said microplate body (150).

2. 10. The method of claim 1, wherein the first injection pressure is between 700 and 1100 bar.

3. 3. The method of claim 1, wherein the second injection pressure is between 200 and 700 bar.

4. 3. The method of claim 1, wherein the closing pressure is between 600 and 1000 kN.

5. 3. The method of claim 1 or 2, wherein the thermoplastic material (14) is stable at least to 120°C.

6. 3. The method of claim 1 or 2, wherein the thermoplastic material (14) is polypropylene or COC.

7. The method of claim 1 or 2, wherein the thermoplastic material does not include any thermal conductivity enhancing medium.

8. 3. The method according to claim 1 or 2, wherein the microplate body (150) is placed, in particular welded, glued or riveted, on a frame carrier (300).

9. 3. The method according to claim 1 or 2, wherein the mass ratio of the first portion of the liquefied thermoplastic material (14) to the second portion of the liquefied thermoplastic material (14) is 0.5:2.5, in particular 1:2, in particular 2:1, for the first portion to the second portion.

10. A thermally conductive microplate (15) made of a thermoplastic material, comprising: a microplate body (150) having a microplate bottom (154); and at least 96 wells (151) arranged in the microplate body, each well (151) being defined by well walls (152) and a planar well bottom (153), the microplate bottom (154) being flat, all well bottoms (153) being aligned at a well bottom plane (200), and the microplate body (15) between the well bottom plane (200) and the microplate bottom (154) having a bottom thickness of 1000 μm or less.

11. The thermally conductive microplate (15) of claim 10, wherein the thermoplastic material does not include any thermal conductivity enhancing media.

12. 12. The thermally conductive microplate (15) according to claim 10 or 11, wherein the thermoplastic material (14) is polypropylene or COC.

13. 12. A thermally conductive microplate (15) according to claim 10 or 11, wherein the microplate body (150) is arranged, in particular welded, glued or riveted, on a frame carrier (300).

14. The microplate body (150) a. providing a liquefied thermoplastic material (14); b) in an injection-compression molding machine (1) including an injection unit (11) having a conveying screw (112) and an embossing die (12) suitable for forming the thermally conductive microplate body (150), carrying out an injection-compression molding process by introducing a first portion of the liquefied thermoplastic material (14) through the conveying screw (112) under a first injection pressure into the at least partially opened embossing die (12), and closing the embossing die (12) while applying a closing pressure to the thermoplastic material (14); c) then carrying out an injection molding process by introducing a second portion of said liquefied thermoplastic material (14) into said closed embossing die (12) through said conveying screw (112) under a second injection pressure; d. obtaining the thermally conductive microplate body (150).

15. 12. The thermally conductive microplate (15) according to claim 10 or 11, wherein the microplate body (150) and / or the frame carrier (300) are opaque-colored.

16. 12. The thermally conductive microplate (15) according to claim 10 or 11, wherein the thermally conductive microplate body (150) and / or the frame carrier (300) are opaquely colored black or white.

17. A thermally conductive microplate (15) according to claim 10 or 11, wherein the wells (151) each have an internal volume of 10 μl or less, in particular 0.3 to 6 μl, in particular 0.5 to 4 μl, in particular 4 μl, in particular 1 μl.

18. 12. The thermally conductive microplate (15) according to claim 10 or 11, wherein the thermally conductive microplate (15) does not bind to proteins.

19. A thermally conductive microplate (15) according to claim 10 or 11, wherein the thermally conductive microplate has a height of 2 to 5 mm.

Images