Thermal block for housing and temperature-controlled at least one laboratory sample container, method for forming it, and simulation method.

Abstract

The present invention relates to a thermal block for containing and temperature-regulating at least one laboratory sample container in a laboratory temperature-regulating container, particularly a PCR thermal cycler, the thermal block being formed using additive manufacturing methods using materials including metal. The present invention further relates to a method for forming the thermal block and a computer-implemented method for simulating the physical properties of a thermal block to be formed in accordance with the present invention.

Description

[Technical Field]

[0001] The present invention relates to a thermal block for regulating the temperature of at least one laboratory sample container, particularly a number of laboratory sample containers, within a laboratory temperature control device, especially a PCR thermal cycler. The present invention further relates to a method for forming a thermal block and a computer-implemented method for simulating the physical properties of a thermal block to be formed according to the present invention. [Background technology]

[0002] This type of thermal block is used in thermal cyclers specifically designed for PCR (polymerase chain reaction). A thermal cycler is a laboratory temperature control device in which a liquid sample is heated or cooled to a predetermined temperature level within a temperature cycle. A Peltier element is usually used for temperature control, and this Peltier element is thermally coupled to the underside of the block. In this case, one temperature cycle consists of at least two temperature stages, usually two or three in the case of PCR, which are adjusted according to a predetermined protocol and maintained for a desired period. To obtain the desired result, especially to double DNA or DNA sequences, the temperature cycle is repeated many times in sequence. In the case of PCR, typical temperature levels for the temperature cycle are 55°C, 70°C, and 95°C. The optimal temperature level for a specific doubling reaction may deviate from the three temperature values ​​mentioned above. The optimal temperature level is determined by the formation of a temperature gradient within the thermal block, so a change in temperature level occurs within the thermal block simultaneously. The optimal temperature level, for example in the case of PCR, is the temperature that, in combination with other necessary optimal temperature levels, yields the maximum yield of replicated product.

[0003] The efficiency of a thermal cycler or thermal block is assessed, in particular, by its accuracy in maintaining temperature levels. For example, when multiple identical samples are simultaneously temperature-controlled within a thermal block, each in a separate laboratory sample container, it is often desirable that the same temperature be precisely maintained, especially for the same duration, in each laboratory sample container, such as the appropriate sample compartment of a PCR plate. In achieving this goal, it is necessary that, given the thermal or cooling output of the temperature control device operating within the thermal block, a temperature distribution as homogeneous as possible is simultaneously achieved within the thermal block. A known source of temperature heterogeneity within a thermal block is the lateral edge regions of the thermal block, which are more strongly exposed to ambient temperature from the sides than the center of the block. When a thermal block is temperature-controlled from below in a planar manner by a Peltier element, the temperature measured in the sample compartments of the edge regions will deviate from the temperature measured in the sample compartment at the center of the block. Therefore, some thermal cycler manufacturers operate with additional temperature control devices located within the edge region, attempting to compensate for ambient effects with these devices. This, in turn, incurs corresponding additional costs for the formation and maintenance of the thermal cycler in question.

[0004] Good temperature homogeneity is further achieved when the necessary heat flow is enabled throughout all areas of the thermal block, and efficient temperature control is facilitated, especially within the edge regions of the thermal block. Furthermore, the influence of ambient temperature is reduced when the thermal block has the highest possible intrinsic heat capacity. These requirements are met by a solid metal thermal block, typically made of aluminum, in which the sample container housing and other desired external shapes are formed by machining. The solid structure of this type of block results in high intrinsic heat capacity and homogeneity. On the other hand, high intrinsic heat capacity also results in slow changes in temperature levels and, consequently, longer overall process durations and higher energy consumption for the cyclic temperature control program performed by the thermal block. Therefore, machining further limits the possibilities for optimizing the block structure.

[0005] An alternative method for forming a silver block involves first forming a sample container housing by electroplating, and then soldering this housing to a silver base plate in another step. The result is a more functional, material-saving block structure. Rapid temperature changes can be achieved with this type of silver block, as the applicant of this application desired within a reasonable timeframe. However, this type of formation is relatively complicated, as many of the forming steps are particularly prone to errors.

[0006] Another requirement for a thermal block is sufficient mechanical load resistance. Thermal cyclers typically use a pressing plate, which presses the sample container from above into the sample container housing and against the thermal block. This ensures that each sample container is in complete contact with the inside of its respective sample container housing, thereby enabling homogeneous temperature control of all samples housed in the thermal block. [Overview of the project] [Problems that the invention aims to solve]

[0007] The object of the present invention is to provide an efficient thermal block having a temperature distribution as homogeneous as possible, and a method for forming and optimizing it. [Means for solving the problem]

[0008] The present invention solves these problems by a thermal block as described in claim 1, a method for forming the same as described in claim 13, and a method for calculating an appropriate shape structure for a thermal block as described in claim 15.

[0009] Within the scope of the development work for this invention, it was surprisingly discovered that not only the requirements for the thermal properties of the thermal block, but also the necessary mechanical load resistance of the thermal block, can be achieved by the additive manufacturing method. Thermal blocks formed by the additive manufacturing method offer advantages, as the integrated construction method can be combined with a material-saving construction method, and furthermore, they provide sufficient mechanical load resistance as required.

[0010] In the context of this invention, “integrally joined” or “integrally joined” means that two sections of a thermal block that are integrally / integrally joined to each other are formed using a metal-containing material by a single additive manufacturing method. In particular when formed integrally in this way, these sections are not formed separately as joining parts and then joined by joining—particularly in other method steps. The integral formation of components is generally known as the integral method, in contrast to the formation of components by joining various joining partners, which is known as the differential method.

[0011] Additive manufacturing methods often involve processing fine-grained material from layer to layer. Based on the resulting surface and volumetric structures, thermal blocks formed by additive manufacturing are always uniquely distinguishable from thermal blocks formed by non-additive methods, such as cutting, galvanic, or casting.

[0012] Preferably, selective laser melting (SLM) is used as an additive manufacturing method for forming the thermal block. Similarly, electron beam melting is used as an additive manufacturing method for forming the thermal block.

[0013] In selective laser melting (SLM), a laser is used to locally melt a material (metal, mixed material) in powder form. The laser is computer-controlled and directed onto points on a plane filled with powder, defined by a 3D model. This process begins by distributing 3D-CAD database data into layer models, with layers having thicknesses between, for example, 10 and 100 micrometers, creating a 2D model for each layer. The database format is the conventional STL database, which is generally used for layer-based 3D printing or stereolithography technologies. This database is then loaded by a software packet for database preparation, assigning parameters, values, and potentially support structures as machine data. This machine data is then implemented by an SLM machine to create the product, i.e., a thermal block. In selective laser melting, a thin layer of atomized fine metal powder is uniformly distributed onto a base plate, usually metal, using a coating mechanism, while the base plate moves in the vertical (Z) axis direction. This is done in a chamber with a strictly controlled inert gas atmosphere. This model is created layer by layer. Each 2D disk of the part geometry is melted along with the layer below it by selectively melting the powder inside each layer using a continuous or pulsating high-power laser beam. The laser energy is strong enough to allow complete melting (welding) of the particles to form a solid metal. This process is repeated layer by layer until the part is formed. Within the chamber area are a material discharge platform, a construction platform and a rake member, the rake member which moves new powder across the construction platform. A commercial SLM machine suitable for forming a thermal block according to the present invention or for carrying out the forming method according to the present invention is available from EOS GmbH, Electro Optical System, 82152 Kryling, Germany.In that case, the company refers to the SLM used as DMLS (Direct Metal Laser Sintering).

[0014] In actual literature, the concept of "selective laser sintering" is sometimes used synonymously with the concept of "selective laser melting." Sintering is a process of shaping a solid material by compressing it with heat and / or pressure without melting it completely into a liquid. Selective laser melting generally assumes that granular material is completely melted. Within the scope of this specification, the two concepts are used synonymously to represent the same method unless it is clearly indicated otherwise; in this case, the concepts of SLM and SLS represent methods in which fine-grained material is partially or completely melted to ensure integrity, and therefore the integral structure of the thermal block to be formed. However, it is also possible and effective for a method of forming a thermal block according to the present invention to have one or more steps, during which a thermal block that is not yet fully formed or not yet completely shaped is treated at a high temperature in each formation step, thereby achieving partial or nearly complete melting of the thermal block or at least some sections of the thermal block. In particular, the degree of heating can be used to adjust or control the porosity of the material of the resulting thermal block.

[0015] Preferably, the thermal block has one, more, or more sample container housings, which are formed by joining them together using an additive manufacturing method with a metal-containing material and / or integrally joining them with a base section or base plate. Preferably, the method for forming the thermal block includes the step of forming one, more, or more sample container housings integrally by joining them together using an additive manufacturing method and / or integrally joining them with a base section or base plate. Integral formation by an additive method is particularly effective when the sample container housings stand freely on the base section or base plate and are therefore not supported by each other. This is because integral formation prevents individual material heterogeneity from occurring in the transition region between the base section and the sample container housings, which can be achieved, for example, in a two-step formation method in which the base section and sample container housings are first formed separately as components and then joined together. Due to the homogeneous material transfer in the case of integral formation, the heat transfer properties of the thermal block correspond particularly reliably to the properties of a model, such as those determined in advance by a simulation method.

[0016] The sample container housing is used to enable heat exchange between the temperature control device and each sample contained in the sample containers typically placed within the sample container housing in the application of a thermal block. For this purpose, each sample container housing has an interior with a contact section, through which the sample containers placed within the housing are in contact. Since the largest possible heat exchange area is desirable for temperature control as quickly as possible, and therefore for controlled heating or cooling to the target temperature, the contact section must be as large as possible. On the other hand, the investigations that form the basis of this invention have revealed that the heating of the sample container increases proportionally to the temperature control rate only when, and only to the extent that, the interior of the sample container opposite the contact portion is also in contact with the liquid sample, where "opposing" specifically means perpendicular to the surface of the contact section. Heat flow is most efficient when perpendicular to the container wall, and therefore the container wall is generally formed as thin as possible. The study also considered that thermal blockers typically use a typical filling height within the sample container, which is usually much lower than the maximum filling capacity of the sample container. In PCR, samples with volumes of 25 μl, 70 μl, 100 μl, and 150 μl are often used. This lower portion of the contact section (the inner side of the sample container opposite to it, which is in contact with the liquid sample at this containment position) is also referred to here as the filling height section, while the upper portion of the contact section (the inner side of the sample container opposite to it, which is not in contact with the liquid sample at this containment position) is referred to as the section from the contact section.

[0017] It has been shown that, when a sample container is positioned within the sample container housing of a thermal block according to specifications, it is not necessary to design the height of the contact section to be greater than the typical filling height of the sample container for the purpose of rapid heat transfer. Furthermore, it has been shown that for efficient heat transfer, it is preferable to connect the filling height section to the lower side (first side) of the base section or base plate of the thermal block using a sufficiently large heat transfer cross-section, which is achieved by a sufficiently large material thickness, particularly of the filling height section of the sample container housing, and especially the lower terminal section. The section from which the sample container is positioned does not efficiently contribute to the temperature control of the sample placed in the sample container, and therefore, in principle, the temperature control of this section can be omitted. At the same time, it has been shown that it is preferable to keep the dimensions of the sample container housing within the section small, thereby avoiding unnecessary temperature control in this dimensional area—and consequently unnecessary energy consumption and extension of the temperature control period—or, in other words, eliminating the parasitic heat capacity of the sample container housing.

[0018] The thermal block preferably has a base section on which one or more sample container housings are arranged and particularly integrally connected. The base section is preferably a plate section of the thermal block, or more particularly a plate that is substantially rectangular in shape and particularly flat. The height of the plate is preferably less than the height of the sample container housings. The plate section has an upper and a lower side. This plate is also referred to as the base plate.

[0019] The sample container accommodation part is preferably arranged in rows and columns, particularly in a rectangular grid arrangement, in which case the center of the rotationally symmetric sample container accommodation part, preferably centered on the vertical longitudinal axis, is located at the intersection of the grid. The rectangular grid arrangement is herein particularly referred to as a grid, and the grid is regularly constructed from grid cells having the same rectangular, particularly square, basic shape. The grid arrangement preferably corresponds to the SBS standard, which will be further described below. The number of sample container accommodation parts (and / or the preferred grid arrangement) can also be 8 (2x4), 16 (2x8 or 4x4), 32 (4x8) or 64 (8x8 or 4x16). The grid arrangement can further correspond to a partial area of the SBS-compliant grid arrangement, for example, half of the SBS grid arrangement having 8x12 grid points, and thus has 48 grid points. The grid arrangement and the sample container accommodation part are preferably arranged and particularly shaped such that, for example, as described below, standard sample containers can be arranged within the sample container accommodation part. The grid arrangement does not necessarily have to be rectangular, and particularly the geometric arrangement of the individual grid cells does not have to be rectangular. In principle, it can correspond to a structured or unstructured grid.

[0020] Typical sample containers are particularly suitable for PCR. Many are disposable plastic containers. It can be an individual container with or without a cover cap, or a multi-container, particularly a microtiter plate. The latter is preferably suitable for PCR and is in this case referred to as a PCR plate.

[0021] Individual containers typically have a maximum packing volume of 0.1 ml, 0.2 ml, or 0.5 ml, and in principle, packing volumes between 10 μl and 2 ml are possible. Preferably, the packing volume is between 10 μl and 200 μl. Individual containers for placement in a thermal block preferably have lateral outer walls (and inner walls as well), which extend in a conical shape, thereby allowing for haphazard insertion into and removal from the thermal block and enabling efficient heat transfer within this region. This region has a contact section specifically for heat transfer. The bottom of the individual containers can selectively have the following shapes: F-bottom (flat bottom), C-bottom (flat bottom with minimal chamfered corners), V-bottom (bottoms that approach each other in a conical shape), and U-bottom (U-shaped recess).

[0022] Multi-well containers, especially microtiter plates or PCR plates, are preferably standard sample containers. This type of microtiter plate or PCR plate has many small recesses (cavities, wells in English) insulated from each other in rows and columns, resulting in a rectangular grid arrangement. The exact dimensions (length x width x height) are 127.76 mm x 85.48 mm x 14.35 mm according to the ANSI standard based on the recommendations of the Society for Biomolecular Screening (SBS) (SBS standard "ANSI / SBS4-2004"). Microtiter plates or PCR plates can have various formats based on standards, all on the same bottom surface, and some have variable heights (number of recesses, grid arrangement, typical filling volume in ml): 6.2 x 3, 2 - 5; 12.3 x 4, 2 - 4; 24.4 x 6, 0.5 - 3; 48.6 x 8, 0.5 - 1.5; 96.8 x 12, 0.1 - 0.3; 384.16 x 24, 0.03 - 0.1; 1536.32 x 48, 0.005 - 0.015; 3456.48 x 72, 0.001 - 0.005. Other formats not based on standards can also be used. The recesses for accommodation in the thermal block also preferably have side outer walls (and inner walls), which extend in a conical shape, so that insertion and removal into the thermal block are possible without problems and efficient heat transfer can be carried out in this area. This area has a contact section especially for heat transfer. The bottom of the recess can selectively have particularly the following shapes: F-bottom (flat bottom), C-bottom (flat bottom with minimally chamfered corners), V-bottom (bottoms converging conically towards each other), and U-bottom (U-shaped recess).

[0023] Within the scope of this invention, the terms "up" and "down" generally refer to the direction of gravity. This is because the sample containers are filled with liquid samples according to the specifications, and since this requires horizontal storage of the base section, the central longitudinal axis of each sample container housing is oriented vertically. The front or anterior side of the thermal block is the side that faces forward into the laboratory container when the thermal block is incorporated into the laboratory container, particularly into a PCR thermal cycler, and is particularly directed forward towards the user when the user is working in front of the laboratory equipment. The rear or posterior side of the thermal block is the side that faces backward into the laboratory equipment when the thermal block is incorporated into the laboratory equipment, particularly into a PCR thermal cycler, and is particularly directed backward away from the user when the user is working in front of the laboratory equipment. Similarly, the “left side” and “right side” of a thermal block are determined from the user’s perspective, positioned in front of a laboratory instrument with a thermal block installed according to the specifications, and viewed from “left to right.” The lower side of the thermal block or its components is also referred to as the first side, and the upper side of the thermal block or its components, opposite to this side, is also referred to as the second side.

[0024] The base section or base plate is preferably formed with at least one of the morphological features listed below, and is particularly formed additively. It is effective if at least one sample container housing is formed in the additive manufacturing method, particularly without interruption of this formation method. However, it is also possible and effective for the base section or base plate to be formed separately by an additive formation direction or by other formation methods, for example by casting, cutting or galvanic methods.

[0025] The base plate has a first plate side arranged to be thermally coupled to one or more temperature control devices, and a second plate side facing the first plate side, the second plate side preferably integrally coupled to a plurality of sample container housings for accommodating and temperature-controlling a plurality of laboratory sample containers. The first plate side is preferably planar and has at least one transition cross-sectional area, which is the transition area between the base plate and at least one sample container housing. The base plate has at least one opening and / or at least one cutout and / or at least one protruding section, in which case the latter may protrude from the planar first or second side. This type of variation from the purely planar side of the plate may be provided when it is used for a desired heat distribution, in particular when it is used for a homogeneous temperature distribution in a sample container housing, especially for equal temperature control of the contact sections of the sample container housing.

[0026] The base plates preferably have a length l, width b, and height h, each perpendicular to the other, and can be oriented according to x / l, y / b, and z / h, to further explain along the Cartesian coordinate axes x, y, and z. The length and width of the base plates are preferably dimensionally designed such that a standard sample container can be placed in a suitable sample container housing above the base plate. Preferred dimensions for the length are between 50 mm and 260 mm, or between 60 mm and 160 mm; preferred dimensions for the width are between 40 mm and 180 mm, or between 60 mm and 120 mm; preferred dimensions for the height are between 1.0 mm and 15.0 mm, or between 0.3 mm and 0.8 mm. The length, width, and / or height are measured such that any lateral projections, which may exist, of the substantially rectangular base plate are not taken into account, or the dimensions are measured such that they are determined as the maximum spread of the base plate along the x-axis (to measure l), as the maximum spread of the base plate along the y-axis (to measure b), or as the maximum spread of the base plate along the z-axis (to measure h).

[0027] Preferably, the thermal block has one, more or more sample container housings, which are joined together using an additive manufacturing method with a metal-containing material and / or integrally joined to a base section or base plate. Preferably, the method for forming the thermal block includes the step of forming one, more or more sample container housings by integrally joining them together using an additive manufacturing method and / or integrally joining them to a base section or base plate.

[0028] Preferably, the thermal block has a plurality (two or more) or a large number (six or more) of sample containers, which are arranged in particular along a plane that extends parallel to the first planar side of the base plate of the thermal block. Preferably, the circular openings of the sample container housing, provided at the upper end of the sample container housing, are all preferably parallel to the first planar side of the base plate of the thermal block. Preferably, the sample container housing is arranged in a rectangular grid having rows and columns.

[0029] The sample container housing is preferably formed with at least one of the following morphological features, and is particularly formed additively. Preferably, at least one sample container housing is formed in an additive manufacturing method, particularly integrally and / or without interruption of the formation method. Preferably, at least two sample container housings are formed in an additive manufacturing method, particularly integrally and / or without interruption of the formation method. Preferably, the base section, particularly the base plate and at least one sample container housing are formed integrally and / or without interruption of the formation method by an additive manufacturing method.

[0030] However, it is also possible and effective for at least one sample container housing to be formed separately by additive manufacturing or other forming methods, such as casting, cutting, or galvanic methods. The sample container housings can be formed individually or as a group of multiple sample containers, or all sample container housings can be formed in common as a single integrated component. In this case, preferably, at least one sample container housing is joined to the base section after its formation—individually, in groups, or as a whole component. It is possible and effective for the base section to be joined to at least one separately formed sample container housing by additive forming. In this case, it is possible for the material of at least one sample container housing to be melted, followed by the joining of a first material layer of the base section, and the base section to be constructed sequentially thereafter. It is also possible and effective for at least one sample container housing to be joined to a separately formed base section by additive forming.

[0031] The sample container housing preferably has an internal volume used to house a sample container section. By housing the sample container section of the sample container within its housing position, contact is formed between the sample container and the sample container housing. This contact is made via the contact surfaces of the contact sections of the sample container housing. The internal volume is preferably surrounded by at least one housing wall and more particularly defined by at least one housing wall or the inside of the sample container housing. The housing wall can be functionally divided into two or more wall sections.

[0032] The sample container housing preferably has a central longitudinal axis A, along which the sample container housing extends. The longitudinal axis A preferably extends perpendicularly to the base section or base plate, preferably to a second planar side or a planar section of the second side. The sample container housing is preferably formed rotationally symmetric with respect to this longitudinal axis A—this is common in the prior art. However, it is also possible and effective for the sample container housing to be preferably formed rotationally asymmetric with respect to this longitudinal axis A.

[0033] The sample container housing preferably has a lower terminal section through which the sample container housing is connected, particularly integrally, to the base section or base plate. This lower terminal section may be a volumetric region located below the wall section of the sample container housing, particularly the base section of the sample container housing, or it may be a surface. This surface, which is a component of the lower terminal section and similarly forms a transitional cross-sectional area or connection between the sample container housing and the base section or base plate, is preferably circular, but may have other shapes. This lower terminal section may be defined by not including a contact section and not being complete or a fractional portion.

[0034] The sample container housing preferably has a wall section, which is located substantially or largely above the lower terminal section. The sample container housing preferably has an upper terminal section, which is particularly an opening section, located particularly above the wall section. This wall section is preferably shaped conically, in which case the cone tapers from top to bottom. The wall section can be defined in particular as a section of the sample container along the longitudinal axis A that defines the internal volume of the sample container housing, and its interior is conical. The lower terminal section can particularly include a section of the sample container housing that also defines the internal volume of the sample container housing, and its interior is not conical. The wall section is preferably shaped as a hollow cone section extending rotationally symmetrically around the axis of rotation A (longitudinal axis A). This allows for easy insertion and removal of a complementary conical sample container.

[0035] The wall section preferably has a first lower wall section which forms part of the contact section, in particular a section below the contact section, and is located above the lower terminal section and in particular below the second upper wall section when viewed in particular along the longitudinal axis A. The lower wall section is preferably a filling height section. The wall section preferably has at least one second upper wall section which does not include any components of the contact section. The upper wall section is preferably a section. The lower wall section can be defined by having a greater thickness than the upper wall section. The aforementioned thicknesses do not need to be constant along each wall section. Preferably, the thickness of the lower wall section increases as the distance to the lower terminal section decreases when viewed in particular along the longitudinal axis A. The lower wall section may be the base section of the sample container housing, and the base section has a cross section which widens downward or in the direction of the lower terminal region or widens when viewed perpendicular to the longitudinal axis A. This widening allows for greater heat flow, particularly between the base section and the sample container housing, and further supports the positioning of the sample container housing relative to the base section. The lower wall section can become a component of the base section.

[0036] The sample container housing preferably has an upper terminal section which is connected to a wall section, and more particularly integrally connected. The upper terminal section is preferably an opening section which has an upward-facing, preferably circular, opening through which the sample container is introduced into the sample container housing.

[0037] The height of the lower end section can be between 0.0 and 5.0 mm, preferably between 0.0 and 3.0 mm, and more preferably between 0.0 and 1.5 mm.

[0038] The height of the wall section can be between 0.0 and 15.0 mm, preferably between 0.0 and 10.0 mm, and more preferably between 0.0 and 8.0 mm.

[0039] The height of the first wall section of the wall section can be between 0.0 and 15.0 mm, preferably between 0.0 and 10.0 mm, and preferably between 0.0 and 8.0 mm.

[0040] The height of the second wall section of the wall section can be between 0.0 and 15.0 mm, preferably between 0.0 and 10.0 mm, and preferably between 0.0 and 8.0 mm. The height of the second section can be greater than, less than, or the same as the height of the first section.

[0041] The height of the upper end section can be between 0.0 and 5.0 mm, preferably between 0.0 and 3.0 mm, and more preferably between 0.0 and 1.5 mm.

[0042] The height can be any of the values ​​mentioned above, or at least less than or greater than them, while each of the other values ​​can be excluded, or all of the values ​​mentioned above can be excluded.

[0043] In conventional thermal blocks, all sample container compartments, or in the case of milled thermal blocks, all block sections having sample container compartments, are equally formed, and in particular equally molded, and arranged in the base section in the same shape. Additive manufacturing methods make it possible for each section of a sample container compartment to be individually formed and in particular as required. Additive manufacturing methods also make it possible for each sample container compartment to be individually formed as required, or for a given group of sample container compartments to be individually formed and in particular molded, so that the sample container compartments within the same group have the same shape and / or are arranged in the base section in the same shape. "Individually formed" means that the sample container compartments are molded differently from other sample container compartments and / or are arranged in the base section with a base section that is molded differently from other sample container compartments, or that one group of sample container compartments is molded differently from other groups of sample container compartments and / or is arranged in the base section with a base section that is molded differently from other groups of sample container compartments.

[0044] In particular, when multiple sample container housings are arranged side by side, especially within a rectangular grid arrangement, the following preferred configurations arise: Preferably, the sample container compartments on the edge side are molded differently from the sample container compartments that are not on the edge side, and in particular, differently from the sample container compartments within the central inner region of the sample container compartment arrangement. Preferably, sample container compartments positioned at the corners of the arrangement are molded differently from the sample container compartments on the edge side and / or the non-edge side. Being on the edge side means being located at the edge of the base section, particularly a rectangular base plate, and therefore having fewer adjacent sample container compartments within the central inner region of the sample container compartment arrangement than a sample container compartment located in the center rather than on the edge side. Preferably, the lower end section of the sample container compartment on the edge side is molded differently from the lower end section of the sample container compartment on the non-edge side, and in particular, differently from the lower end section of the sample container compartment within the inner region of the sample container compartment arrangement. Preferably, the lower end section of the sample container housing positioned within the corner of the arrangement is molded differently from the lower end section of the sample container housing on the edge side and / or the lower end section of the sample container housing on the non-edge side. Preferably, the wall sections of the sample container on the edge side are molded differently from the wall sections of the sample container container on the non-edge side, and in particular differently from the wall sections of the sample container container within the internal region of the sample container container arrangement. Preferably, the wall sections of the sample container container located at the corners of the arrangement are molded differently from the wall sections of the sample container container on the edge side and / or the wall sections of the sample container container on the non-edge side. Due to the different morphologies, the heat flow or heat capacity of the thermal block is affected according to its position within the thermal block.

[0045] Preferably, the lower terminal section of the sample container housing on the edge side has a larger volume or dimensions than the lower terminal section of the sample container housing on the non-edge side, and in particular has a larger volume or dimensions than the lower terminal portion of the sample container housing within the internal region of the sample container housing arrangement. Preferably, the lower terminal section of the sample container housing positioned at the corner of the arrangement has a larger volume or dimensions than the lower terminal section of the sample container housing on the edge side and / or the lower terminal section of the sample container housing on the non-edge side. In this configuration, the edge region is generally affected by a much lower ambient temperature, and in particular within the edge region of the thermal block, the heat flow into the sample container housing and the heat capacity are configured to be different.

[0046] The lower terminal sections of one, more, or all sample container compartments are preferably molded to widen downwards, at least partially, starting from the upper section of the sample container compartment, particularly the wall section, and extending to the base section. The base section thus defined allows for greater heat flow between the sample container compartment and the wall section, thereby allowing the sample container compartment with the base section to be heated more rapidly than the sample container compartment without the base section. Furthermore, the base section reinforces the position of the sample container compartment within the base section against mechanical forces.

[0047] The base section is preferably formed in a conical shape, in which case the vertical cross-sections extending through the longitudinal axis A, particularly the vertical cross-sections extending through the longitudinal axis A on the outside of the base section, can be formed as straight lines, but they can also be formed as non-straight lines, particularly concave.

[0048] The sample container housing is preferably cup-shaped, that is, in this case the sample container housing is formed like a cup with an upward-facing opening.

[0049] One, multiple, or all of the sample containers of a thermal block can be connected to the base section only by its wall section or lower end section, and there are no connecting sections that extend horizontally above the base section—and especially below the upper end section—to connect adjacent sample containers. This type of sample container is also referred to as standing without support.

[0050] Within the upper terminal section, multiple or all of the sample container housings can be joined by a perforated plate, in which case the sample container housings, their upper terminal sections, or their openings can be positioned within the holes of the perforated plate, respectively.

[0051] A sample container housing of this type cannot be said to stand without support, because it is supported by one (or more) connecting members, in this case, perforated plates.

[0052] Preferably, the thermal block has a base section and a sample container section, in which case at least one sample container housing is located within the latter. The base section and / or sample container section are preferably substantially rectangular in shape, since the base section may have the shape of a rectangular plate, and the sample container housing of the sample container section may form a substantially rectangular region. The base section and the sample container section may be joined to each other, particularly substantially within a transition region, which may be formed as a plane—referred to as a transition plane—or as a plate-shaped transition region, for example, by various sample container housings beginning at various heights in the base section. Furthermore, it is possible for the thermal block to lack a base section and be formed by sample container sections, where the sample container sections are joined by connecting sections, particularly by connecting sections extending horizontally between adjacent sample container sections and joining them, and particularly by connecting sections extending horizontally between adjacent lower end sections and / or wall sections and / or upper end sections and joining them. These connecting sections can, in particular, be components of a grid network or at least one perforated plate that joins the sample container sections, through which the sample container sections extend and are joined. However, the aforementioned connecting sections can also be provided when the thermal block has a base section.

[0053] The sample container section has at least one or more connecting sections that connect adjacent sample container housings. These connecting sections are particularly those that extend horizontally between adjacent sample container housings and connect them, and particularly those that extend horizontally between the lower end sections and / or wall sections and / or upper end sections of adjacent sample container housings and connect them. These connecting sections can be, in particular, components of a grid network or at least one perforated plate that connects the sample container housings, through which the sample container housings extend and are connected. However, the connecting sections described above can also be provided when the thermal block has a base section.

[0054] In particular, when multiple sample container compartments are arranged side by side, and especially when adjacent sample container compartments are arranged in a rectangular grid, the following preferred configurations arise:

[0055] At least one, or exactly one, connecting section may be provided between directly adjacent sample container compartments, particularly between multiple or all directly adjacent sample container compartments. Within the rectangular grid of sample container compartments, two consecutive sample container compartments within one row of the grid are directly adjacent, and two consecutive sample container compartments within one column of the grid are directly adjacent. However, at least one, or exactly one, connecting section may also be provided between diagonally adjacent sample container compartments, particularly between multiple or all diagonally adjacent sample container compartments. If another sample container compartment exists between two sample container compartments, the first two sample container compartments are not considered adjacent.

[0056] A space can be provided between the connecting section and the base section that joins adjacent sample container housings, particularly in the plane formed by the longitudinal axis of the sample container housing, and therefore especially below the connecting section. This connecting section cannot be directly connected to the base section—it is indirectly connected to the base section via the sample container housing. In this case, the connecting section contributes to the cooling of the sample container housing through the convection of ambient air flowing around the connecting section. Therefore, this connecting section or structure is suitable for cooling hotter sample container housings and improving homogeneity within the thermal block. Structural parameters that determine the optimal heat extraction are the thickness of the connecting section or structure and the spacing of the connecting section or structure relative to the base section or base plate, especially the minimum spacing, the dimensions of the connecting section and / or surface. Another use of the connecting section or structure between sample container housings is that it can provide the necessary stability and strength to the components in individual cases. In this case, the connecting section or structure can be designed to be as far away as possible from the center of gravity of the components, and therefore smaller and / or thinner. Another advantage here is that the thermal effects on the small structure are relatively small. The heat must first flow through the sample containment, and therefore the structure is heated last.

[0057] Furthermore, it is possible and effective to avoid providing a gap between the connecting section and the base section that join adjacent sample container compartments, particularly in the plane below the connecting section, formed by the longitudinal axis of the sample container compartment. The connecting section can be directly connected to the base section. In this case, the connecting section is also used to heat or temperature control the sample container compartment using a temperature control device. This can be applied to multiple, many, or all connecting sections of a sample container compartment or thermal block. This arrangement has the effect of guiding heat from the hotter gaps to the sample container compartment, thus improving homogeneity. The structural parameters here are the thickness of the connecting section, its dimensions, and / or the general shape of its surface and mounting, for example, chamfering with a variable diameter and triangulation with a variable angle.

[0058] The wall sections of the sample container housing, particularly the lower and / or upper wall sections, may have different thicknesses. The material thickness of the sample container housing can be individually increased: individual variations in material thickness, when correctly selected, have a positive effect on the homogeneity and speed of the thermal block. The individual thicknesses of the wall sections, the dimensions of the sample container housing, and / or the surface are optimizable structural parameters of the thermal block.

[0059] The connecting section that joins adjacent sample container housings can be web-shaped, particularly plate-shaped. The plate is characterized by its thickness, outer contour, and main plane, the main plane of which can extend horizontally and therefore parallel to the xy plane, or perpendicular to the xy plane and parallel to the z axis. The thickness and outer contour are optimizable structural parameters of the thermal block.

[0060] The joint section may have one or more cutouts and / or openings and / or protrusions, or it may be lattice-shaped and / or porous. In this way, the thermal properties of the joint section are regulated.

[0061] The use of one or more base sections for the sample container housing and / or the use of connecting sections between adjacent sample container housings, as well as the changes in structural parameters that define the structure of the thermal block, realize the following progressive idea: using additive manufacturing methods, the material is constructed only where it has a positive effect on heat conduction between the temperature control device and the sample. Additional structures to ensure mechanical robustness and stability, and structures used for sealing between the thermal block, temperature control device and surroundings, may be exceptions here.

[0062] The sample container compartment has an internal volume that extends from the inside of the bottom wall of the sample container compartment to its opening over a section along the longitudinal axis A. This section is referred to as the depth of the sample container compartment. Preferably, the opening of the sample container compartment of the thermal block is located in a common plane, and preferably multiple or all sample container compartments have equal depth. However, it is also possible and effective for the depth of one or more sample container compartments, particularly the edge-side sample container compartments, to be greater than that of the non-edge-side sample container compartments. The internal volume of a sample container compartment with greater depth can extend particularly deeper and particularly into the base section. This can improve heat transfer in the edge region and enhance homogeneity. The depth of the sample container compartment is an optimizeable structural parameter of the thermal block.

[0063] It is possible and effective for the base section or base plate to have regions with different thicknesses. By positioning additional material on the base plate as desired, the local heat capacity can be adjusted, improving the homogeneity of the thermal block. Similarly, the heat capacity can be further reduced by locally cutting out parts of the base section or base plate. This can improve speed and homogeneity. The thickness and outer contour of the regions with varying thicknesses are optimizable structural parameters of the thermal block.

[0064] The thermal block preferably has a housing frame and / or a sealing frame that encircles the thermal block, particularly with respect to the base plate or parallel to the xy plane. Depending on the design of the additive manufacturing method, the sealing frame / housing frame can also be combined with the base plate to further reduce the heat capacity.

[0065] The temperature control device is preferably positioned between the thermal block and the cooling body, and these components are pressed together by fastening means, particularly screws. By additive manufacturing methods, support structures, particularly lattice structures, are further integrated without complexity, positioned above the base section or base plate, and can extend particularly between the base section and the plane of the opening of the sample container housing, and absorb the bonding forces when the aforementioned components are fixed.

[0066] The complex structure of the thermal block is realized by additive manufacturing. Preferably, the thermal block has at least one or more base plates, each having a planar lower side and at least one or more sample container sections. The sample container sections may have one or more cutouts and / or openings and / or protrusions between the sample container compartments, or may be porous. One or more or each sample container compartment may have one or more cutouts and / or openings and / or protrusions, or may be porous. In this way, the thermal conductivity properties of the bonded sections are adjusted.

[0067] Preferably, the thermal block is characterized by being formed using an additive manufacturing method, such that the base section and at least one sample container housing are formed by an additive manufacturing method, preferably integrally.

[0068] Additive manufacturing methods allow for the formation of thermal blocks—which typically exist virtually as data models—from a desired direction, and the additional formation does not necessarily have to begin from the lower end of the thermal block. By rotating the virtual model and determining the horizontal formation layer of the additional formation from the rotated position, it is possible, in principle, to form the thermal block from a direction other than from its bottom to its top. For example, a thermal block can be formed from its top to its bottom, from its left to its right, or from its front to its back. The choice of formation direction depends on the efficiency with which the formation can be carried out, and in some cases, on the fact that the desired structure of the thermal block can only be formed from a predetermined direction.

[0069] Preferably, the thermal block is characterized in that the base section of the thermal block is first formed by an additive manufacturing method, and then at least one sample container housing is formed by an additive manufacturing method, and in particular, the additive manufacturing method is formed without interruption between the formation of the base section and the formation of at least one sample container housing—particularly the first layer.

[0070] However, initially, at least one sample container housing is manufactured by an additive manufacturing method. It is also possible and effective that the thermal block is formed by an additive manufacturing method, such that the base section of the thermal block is formed by an additive manufacturing method, without any interruption of the additive manufacturing method between the formation of at least one sample container housing and the formation of the base section—particularly the first layer.

[0071] It is effective that at least one sample container housing and / or base section is formed in an additive manufacturing method, particularly without interruption of the forming method. However, it is also possible and effective that at least one sample container housing and / or base section be formed separately by an additive manufacturing method or other forming method, for example, by a casting method, a cutting method or a galvanic method.

[0072] The sample container compartments can be formed individually, in groups of multiple sample container compartments, or all sample container compartments can be formed as a single integrated component. In this case, it is effective if at least one sample container compartment is joined to the base section after its formation—individually, in groups, or as a whole component. Preferably, the base section is joined to at least one sample container compartment by additional formation. In this case, it is possible that the material of at least one sample container compartment is melted, thereby joining a first material layer of the base section, and then the base section is constructed sequentially.

[0073] Laboratory equipment with a thermal block is preferably a (PCR) thermal cycler. It is also possible for the laboratory equipment with a thermal block to be a thermal mixer. The thermal block and / or the laboratory equipment with a thermal block can be part of a laboratory automation system, particularly a laboratory pipetting automation system for high-flow processing of liquid samples (Liquid Handling Automat).

[0074] A thermal cycler is an instrument capable of sequentially adjusting at least one sample to predetermined temperatures over time and maintaining it at these temperature levels for a predetermined period. This temperature control sequence is periodic; that is, a predetermined temperature cycle, and therefore a sequence of at least two temperature levels, is repeatedly performed. This method is particularly used to carry out polymerase chain reactions (PCR). In this context, a thermal cycler is often also referred to as a PCR block. A thermal cycler, and more particularly a thermal cycler apparatus, preferably has a thermal block. The thermal block is a sample holder made of a heat-conducting material, generally a material containing metal or a metal, particularly aluminum or silver. The sample holder has a contact side, which contacts at least one heating / cooling device of the thermal cycler, particularly a Peltier element. A thermal cycler, particularly a thermal cycler processing unit, has a closed-loop control unit comprising at least one closed-loop control circuit, to which at least one heating / cooling device is associated as an operating member and at least one temperature measuring device is associated as a measuring member. The temperature of the temperature stages is controlled in a closed loop using the closed-loop control unit. The cooling body of the thermal cycler, particularly a thermal cycler processing unit, is used to cool sections of the thermal cycler, particularly the Peltier element. The thermal cycler, particularly a thermal cycler processing unit, may have other heating and / or cooling members. Preferably, the thermal cycler, particularly a thermal cycler processing unit, has a timing device, which allows control of temporal parameters that regulate the temperature cycle.

[0075] A thermal mixer, also called a "thermal mixing device," is used to move temperature-controlled samples, particularly for mixing laboratory samples having multiple components. A thermal mixer, and especially its processing apparatus, can be configured to perform oscillating motion. A thermal mixer, and especially its processing apparatus, has a drive device that drives the motion, a timing device that can control temporal parameters that regulate the mixing process, and a closed-loop control device that comprises at least one heating / cooling device and at least one closed-loop control circuit, to which at least one heating / cooling device is associated as an operating member and at least one temperature measuring device is associated as a measuring member. The instrument-controlled processing of at least one laboratory sample corresponds to the mixing process in a thermal mixer, and at least one sample undergoes this mixing process.

[0076] The thermal block preferably has a housing for a temperature sensor. The temperature sensor is preferably positioned above the base plate of the thermal block so that the temperature acting on the sensor during operation of the thermal block is more or less equivalent to the temperature inside the sample. In conventionally constructed thermal blocks, the temperature sensor is generally in direct thermal contact with the base plate or positioned directly on the base plate; thereby, the target temperature at the sensor is generally achieved much faster than the temperature inside the sample, so a periodic delay may have to be considered in some cases.

[0077] The homogeneity of a thermal block can be tested in various ways. One possibility is to attach a calibrated temperature sensor to various positioned sample container compartments of the thermal block and determine the homogeneity during operation of the thermal block, for example, as the standard deviation of the mean temperature in the thermal block. Another possibility is to perform the same PCR reaction in various positioned sample container compartments of the thermal block and determine the yield of replicated product in each sample container. Yet another possibility is to determine homogeneity using a simulation method, in which the temperature distribution of the thermal block formed according to the present invention is calculated using a data model of the thermal block formed according to the present invention. A suitable method for determining the homogeneity of the temperature distribution of a thermal block is described in Eppendorf APPLICATION NOTE No. 244 of December 2011, which can be obtained via www.eppendorf.de.

[0078] The rate of temperature control of a thermal block can be determined by determining how long a desired temperature rise persists within the thermal block at a known constant heating output, or by determining the temperature difference that occurs when the thermal block is heated for a predetermined period at a known constant heating output. A suitable method for determining the rate of temperature control of a thermal block is described in Eppendorf Application Note No. 274, which can be obtained via www.eppendorf.de.

[0079] The additional formation of the thermal block starts from a fine-grained material, which preferably contains a metal, preferably aluminum, silver, or titanium. Ceramic materials are also possible. Non-metallic or other materials, such as silicon carbide, carbon, or graphite, are also possible.

[0080] The present invention also relates to a method for forming a thermal block, which is used to house and regulate the temperature of laboratory sample containers in laboratory temperature control equipment, particularly in PCR thermal cyclers, and preferably comprises the step of forming a thermal block using an additive manufacturing method based on metal-containing granules.

[0081] The present invention also relates to a method (hereinafter also referred to as a "simulation method") for calculating the shape structure of a thermal block, the thermal block being used to house and temperature control laboratory sample containers in laboratory temperature control equipment, particularly PCR thermal cyclers, and being formed by a computer-controlled additive manufacturing method dependent on at least one structural parameter, wherein the shape structure of the thermal block is defined by at least one structural parameter and comprises the following steps:

[0082] *Change at least one structural parameter; *Implement a simulation method to simulate the heat flow through at least one section of the thermal block according to at least one structural parameter; *According to the simulation method, at least one structural parameter is selected to define the thermal block to be formed, and in particular, this at least one structural parameter is then provided for the additional formation of the thus structurally defined thermal block.

[0083] Suitable structural parameters for implementing the simulation method are included in the following description of the invention, or can be directly derived from the description of preferred structural forms of the thermal block. The simulation method can be implemented using commercially available software, such as Finite-Elemente-Software. ANSYS from Ansys Inc. of Pennsylvania, USA, is particularly suitable.

[0084] In a preferred embodiment, the thermal block is characterized by being formed by the following forming method; a preferred embodiment of the method according to the present invention for forming a thermal block also features the same steps: - Preferably, the base section or base plate is formed using additive manufacturing or other methods; -In order to integrally bond the fine-grained material to be further processed with the base section or base plate, at least one sample container housing is additionally formed above the base section or base plate, particularly by melting the top layer of the base section or base plate, in which case the top layer of the base section or base plate preferably has or consists of the same material. -Selective step: *Before the additional forming step: Form a stack complex by coupling a temperature control device, particularly a Peltier element, provided for use with the thermal block to be formed, to a base section or base plate, and preferably also to a cooling body, *then: Measure the homogeneity of the temperature distribution on the base section or base plate, in which case this homogeneity is the result of the individual forms of the temperature control device, particularly the Peltier element, particularly the homogeneity of heat transfer across its surface, particularly the result of individually forming and / or attaching cooling bodies to one or more temperature control devices, particularly temperature control This is a result of individually thermally coupling the device to the base section or base plate using a heat-conducting medium, such as a graphite heat transfer pad, and is a result of electronic control and / or voltage supply of the temperature control device by a control device, and is a result of the spatial arrangement of the temperature control device coupled to the base section or base plate with respect to one or more components of the laboratory apparatus, particularly the thermal cycler (these components may be the frame into which the base section is fitted), when the thermal block (or base section and temperature control device) is arranged within the laboratory apparatus as specified.

[0085] It is possible and effective for a thermal block to be further processed after it has been formed by an additive manufacturing method, or further processed within the framework of the forming method. Possible and preferred post-processing steps are, in particular, independent of or in combination with each other:

[0086] * Heating or cooling a thermal block formed by an additive manufacturing method, particularly above the melting point of the material; *The thermal blocks formed using additive manufacturing methods are coated, particularly by immersion baths or sprays; *The thermal blocks formed by additive manufacturing methods are subjected to cutting, particularly milling and polishing;

[0087] This type of post-processing step smooths the following surfaces in particular: surfaces having surface porosity or roughness as recognized by the additive manufacturing method; the underside of the base section or base plate to improve thermal contact with the temperature control device, particularly the Peltier element; and the inside of the sample container housing to improve thermal contact with the sample container, particularly its outside.

[0088] The thermal block according to the present invention can be characterized by its formation characteristics. Insofar as the method according to the present invention for forming a thermal block is described by one or more steps within the framework of the present invention, these steps are considered to be features that easily describe the thermal block structurally, if these steps structurally characterize the thermal block. The additive manufacturing of the thermal block or its components characterizes the thermal block, because this thermal block has porosity of its surface and / or volume by this particular type of formation.

[0089] A method according to the present invention for forming a thermal block is described in particular by steps of this method within the framework of this specification. To the extent that a thermal block is described within the framework of this specification by structural features, for example, by a support structure located above a base section provided between adjacent sample container housings, steps of a method according to the present invention for forming a thermal block are derived directly therefrom, for example, a method for forming a thermal block having the step of additionally forming the support structure described above together with the sample container housings.

[0090] Other preferred embodiments of the thermal block according to the present invention and the method for forming the same according to the present invention will be made apparent from the following description of embodiments, which is associated with the drawings and their description. Identical components in embodiments are characterized by substantially the same reference numerals unless otherwise described or the context differs. [Brief explanation of the drawing]

[0091] [Figure 1] Figure 1 schematically shows an embodiment of the method according to the present invention for forming a thermal block according to the present invention, based on a first embodiment. [Figure 2a] Figure 2a shows a thermal block according to the present invention reproduced using camera perspective, based on the first embodiment. [Figure 2b] Figure 2b shows a thermal block according to the present invention reproduced using camera perspective, based on a second embodiment. [Figure 3a] Figure 3a shows the thermal block based on Figure 2b, positioned within the frame of the thermal cycler. [Figure 3b] Figure 3b shows the thermal block from Figure 2b, positioned within the frame, from a diagonal front view and a diagonal rear view. [Figure 4a] Figure 4a shows a perspective view of a part of the thermal block according to the present invention, based on a second embodiment. [Figure 4b]Figure 4b shows a perspective view of a part of the thermal block according to the present invention, based on a third embodiment. [Figure 4c] Figure 4c shows a front view of a portion of the thermal block according to the present invention, based on a fourth embodiment. [Figure 4d] Figure 4d shows a front view of a portion of the thermal block according to the present invention, based on a fifth embodiment. [Figure 5a] Figure 5a shows a perspective view of a part of the thermal block according to the present invention, based on the sixth embodiment. [Figure 5b] Figure 5b shows a perspective view of a part of the thermal block according to the present invention, based on the seventh embodiment. [Figure 6a] Figure 6a shows a side cross-sectional view of a part of the thermal block according to the present invention, based on the eighth embodiment. [Figure 6b] Figure 6b shows a lateral cross-section of a portion of the thermal block according to the present invention, based on the ninth embodiment. [Figure 7a] Figure 7a shows a side cross-sectional view of a part of the thermal block according to the present invention, based on a second embodiment. [Figure 7b] Figure 7b shows a lateral cross-section of a portion of the thermal block according to the present invention, based on a third embodiment. [Figure 8a] Figure 8a shows a perspective view of a portion of the thermal block according to the present invention, based on a tenth embodiment, in which case this portion is used as a model for implementing an example of a method for simulating or calculating the shape structure of the thermal block according to the present invention. [Figure 8b] Figure 8b shows a calculated thermal image, which is a lateral cross-sectional view of a portion of the thermal block shown in Figure 8a and the heat distribution present therein, the heat distribution which occurs in an example of the method according to the present invention for simulating or calculating the shape structure of the thermal block. [Figure 9a]Figure 9a shows a calculated thermal image, which is a lateral cross-sectional view of a portion of the thermal block according to the present invention based on the 11th embodiment, and the heat distribution present therein, which occurs in an example of a method according to the present invention for simulating or calculating the shape structure of the thermal block. [Figure 9b] Figure 9b shows a calculated thermal image, which is a lateral cross-sectional view of a portion of the thermal block according to the present invention based on the twelfth embodiment, and the heat distribution present therein, which occurs in an example of the method according to the present invention for simulating or calculating the shape structure of the thermal block. [Figure 10a] Figure 10a schematically illustrates a method for forming a thermal block based on an example. [Figure 10b] Figure 10b schematically illustrates a method for calculating the shape structure of a thermal block based on an example. [Modes for carrying out the invention]

[0092] Figure 1 schematically shows an embodiment of Method 100 according to the present invention for forming a thermal block 1 according to the present invention. In this method, selective laser melting (SLM) is used as an additive manufacturing method for forming the thermal block. In this case, a laser beam 5 is used to locally melt a material 6 in powder form, such as fine aluminum granules, in particular EOS aluminum AlSi10Mg. In this case, the instrument EOS M290, obtained from Electro Optical Systems GmbH, EOSGmbH, 82152 Kryling, Germany, can be used. In this case, the laser is computer-controlled and directed onto a point predetermined by a 3D model of the powder-filled plane 6.

[0093] The process begins by distributing 3D-CAD data files into a layered model, for example, where each layer has a thickness between 10 and 100 micrometers (not shown), in which case a 2D image of each layer is formed. This data file format is the conventional STL data file, used for many layer-based 3D printing or stereolithography technologies. In this case, the data file is loaded by a software packet for data file preprocessing, which specifies parameters, values, and possibly support structures as mechanical data. This mechanical data is then implemented by an SLM machine to form the thermal block, which is the product.

[0094] In method 100, described here as an example, a thin layer of atomized fine metal powder is uniformly distributed as a powder-filled layer 6, usually metal, onto a base plate (not shown) using a coating mechanism, and the base plate moves along the vertical (Z) axis. This is preferably done in a chamber (not shown), which has a particularly tightly controlled inert gas atmosphere. The laser and / or base plate is moved laterally in the xy plane, thereby generating the section of the thermal block to be formed in this plane. The thermal block is formed layer by layer. Each 2D disk in a subgeometric arrangement is melted by selective melting using a continuous or pulsating high-power laser beam, along with the powder inside each layer and the layer located beneath it. The laser energy is preferably strong enough to allow for complete melting (welding) of the powder, thereby forming a solid metal. This process is repeated layer by layer until a part is formed. Within the chamber region are a material output platform (not shown), a construction platform (not shown), and a rake member (shown in the illustration), the rake member which moves new powder across the construction platform.

[0095] As shown in Figure 1, first in step A, the base section 2 is machined, and in particular, additively formed. This base section 2 is, in this case, a rectangular, flat base plate 2. The base section can also be prepared as a pre-formed component, for example, as a cast and / or milled component. In steps B and C, sample container sections 3, each having sample container housings 4 arranged to stand freely side by side, are sequentially and layer by layer additively formed. All sample container housings 4 are molded in principle identically in the first embodiment of the thermal block 1. In this case, when visually inspecting the sample container housings or base plate of the thermal block shown in this embodiment, surface granulation or roughness due to the additive manufacturing method can be detected. In step D, the thermal block 1 is formed, but residual material 7 in powder form is still present between—and within—the sample container housings 4 in the rectangular region of the sample container section 3. In step E, the residual material 7 is removed, and the additively formed thermal blocks 1 exist individually.

[0096] In another step F, the thermal block 1 can be further post-processed. Preferably, the underside of the base plate is smoothed, for example by milling, and similarly preferably, the inside of the hollow conical section of the sample container housing 4 is smoothed.

[0097] The commercial SLM machine used to form the thermal block made of aluminum alloy, as shown in the examples, is a so-called EOS M290, and the initial material in powder form is EOS aluminum AlSi10Mg.

[0098] Figure 2a reproduces a photograph of an additively formed thermal block 11, which in principle corresponds to the shape of thermal block 1. The thermal block 11 has an additively formed flat rectangular base plate 12, which is raised in layers by an additive method to obtain a sample container housing section 14 integrally coupled with the base plate 12. The base plate 12 has 12 holes 12a, which extend through the base plate perpendicular to the main plane of the base plate 12. These holes are used to accommodate fixing screws. The holes 12a can be formed by additive manufacturing or by post-processing the additively formed thermal block using drilling.

[0099] Each sample container housing 14 is molded identically. They have a cup shape. The bottom of each cup is formed by a base plate 12. The cup wall is hollow cone-shaped. The hollow cone is open and widens upward (in the positive z direction). The hollow cone is formed rotationally symmetric with respect to an axis A perpendicular to the main plane of the base plate 12. Axis A extends along the hollow cone through its center of symmetry. The openings of all sample container housings 14 are all located in the same plane. This is a standard arrangement to accommodate standard-compliant microtiter plates or PCR plates. Refer to the SBS standard described above. However, the height of the sample container housings can, in principle, vary, and in particular, two, more, or all of the openings of the sample container housings 14 may be at different heights.

[0100] The thermal block 11 has a total of 96 sample container compartments, which are arranged in a regular rectangular grid. Each grid cell in this grid is square. This grid arrangement corresponds to the grid arrangement of 96 microtiter plates based on the SBS standard ANSI SLAS1-2004(R2012) (see section 4.1 and Figure 1 therein, which has 8 columns and 12 rows).

[0101] Figures 2a and 2b each show line L, with Cartesian coordinates shown relative to it, where the z-axis extends parallel to line L at its position. Because the representations in Figures 2a, 2b (and 3a) are based on photographs, the axes A of the sample container housing appear not to be parallel to each other, but this is actually the case. The representations in Figures 2a, 2b, and 3a are not isometric.

[0102] Figure 2b is a photographic reproduction of the additively formed thermal block 21. The thermal block 21 has additively formed, flat, rectangular base plates 22, which are raised from layer to layer in an additive manner to obtain a sample container housing section 24 integrally bonded with the base plates 22. The main plane of the base plates 22 extends parallel to the xy plane in the figure.

[0103] The thermal block 21 has additional structures 22a, 22b, 22c, and 23a compared to the thermal block 11, which are additionally formed within the same formation process as the thermal block 21. The base plate 22 has additional structures 22a, 22b, and 22c: the base plate has an upward-extending web 22a that encircles all of the sample container housings. This, together with the upper side of the base plate 22, forms a chamber in which all of the sample container housings 24 are positioned. Furthermore, the upper side of the base plate 22 has reinforcing structures 22b and 22c, which are used to fix the thermal block 21 in the mounting position of the thermal cycler (see Figure 3b) and absorb and distribute the fixing force onto the base plate when the base plate is screwed and / or clamped to a base, for example, a cooling body of a Peltier element (not shown) to be placed below the base plate. The reinforcing shape extending upward from the base plate is formed in a cross shape (viewed in the xy plane) and has a hole in its center, which extends through the base plate perpendicular to the main plane of the base plate 22. These holes are used to accommodate fixing screws. These holes can be formed by additional formation or by post-processing an additionally formed thermal block by drilling.

[0104] One, more, or all of the above-described additional structures can, in principle, be provided in each thermal block according to the present invention.

[0105] Each sample container housing section 24 is molded identically. Its shape corresponds to the sample container housing section 14 in Figure 2a. Unlike the thermal block 11, the thermal block 21 has a reinforcing structure 23a, which is formed additionally or integrally with the sample container section (23) and especially integrally with the base plate 22, so as to be completely above the base plate and in direct contact without the base plate.

[0106] The reinforcing structure 23a has a total of 172 connecting webs, through which each sample container accommodating part 14 is integrally connected to at least one adjacent sample container accommodating part 14. Among these 172 connecting webs, 8 * 11 = 88 extend parallel to the x-axis or the first longitudinal side of the base plate respectively, and among these 172 connecting webs, 7 * 12 = 84 extend parallel to the y-axis or the second longitudinal side of the base plate respectively. A total of 2 * 8 + 2 * 10 = 36 edge-side sample container accommodating parts in the grid arrangement are integrally connected to the adjacent sample container accommodating parts through two connecting webs respectively, and the 6 * 10 = 60 sample container accommodating parts located inside the grid arrangement are integrally connected to the adjacent sample container accommodating parts through four connecting webs respectively.

[0107] Starting from a thermal block having a total of n * m sample container accommodating parts arranged in a rectangular grid consisting of n rows and m columns, the preferred arrangement of the connecting webs of the reinforcing structure 23a of this embodiment is abstracted as follows: This reinforcing structure has a total of n * (m - 1) + (n - 1) * m connecting webs, through which each sample container accommodating part is integrally connected to at least one adjacent sample container accommodating part. Among these n * (m - 1) + (n - 1) * m connecting webs, the number n * (m - 1) connecting webs extend parallel to the x-axis or the first longitudinal side of the base plate respectively, and among these 172 connecting webs, the number (n - 1) * m extend parallel to the y-axis or the second longitudinal side of the base plate respectively. A total of 2 * n + 2 * (m - 1) edge-side sample container accommodating parts are integrally connected to the adjacent sample container accommodating parts through two connecting webs respectively, and the (n - 2) *The sample container housing located inside (m-2) is integrally connected to the adjacent sample container housing via four bonding webs. For the thermal blocks fully shown in Figures 2b and 3a, n=8 and m=12, respectively.

[0108] The bonding webs of the reinforcing structure 23a (Figures 2b and 3b) can be formed and positioned as shown in more detail, for example, in Figures 4a and 7a. Alternatively, they can be formed and positioned as shown more precisely, respectively, in Figures 4b, 4c, 4d, and 7b. The bonding webs of the reinforcing structure are positioned here parallel to the x and y axes, but can also be positioned in alternative and / or additional configurations, for example, parallel to lines having angles different from 90° with respect to the x or y axis, particularly 45° (also referred to as “diagonal arrangement”).

[0109] Figure 3a shows the thermal block 21, based on Figure 2b, located within the frame 29 of the thermal cycler.

[0110] Figure 3b shows the same thermal cycler 80 twice in perspective views, once from the front at an angle and once from the rear at an angle. In the front view shown on the left, the thermal block 91 is visible, and this thermal block is located within frame 99, which corresponds to frame 29 shown in Figure 3a. The oscillating cover of the thermal cycler is shown in an open state in the front view, and closed in the rear view.

[0111] The thermal cycler 80 shown in Figure 3c has a swingable cover 82, which has a cover grip 81 that is swingably positioned on the cover 82, which the user can use to open / close and lock / unlock the cover 82.

[0112] In the fully locked state, the heat-sensitive pressure plate 83 located within the cover applies pressure to one or more sample containers located within the sample container housing of the thermal block 84. The thermal blocks illustrated in the examples are all sufficiently stable to withstand pressure without damage throughout their entire lifespan.

[0113] As the thermal block 84, each of the thermal blocks according to the present invention, as described in the illustrated embodiment, can be used. The thermal block 84 is in planar contact with the Peltier element on its underside (invisible). The underside of the Peltier element is also in thermal contact with a metal cooling body or other cooling chamber, thereby allowing the heat generated by the Peltier element during temperature control (closed-loop controlled heating / cooling) to dissipate to the surroundings. To ensure uniform thermal contact of the heat-transmitting surfaces of the heat-transmitting medium and / or components placed between the thermal block 84, the Peltier element, the cooling body, and optionally between them, the thermal block 84, the Peltier element, the cooling body, and optionally between them, are pressed against each other by a fixing system, which imposes permanent pressure on the thermal block 84. All thermal blocks shown in the embodiment are sufficiently stable to withstand this permanent pressure without damage for the duration of their lifespan.

[0114] The thermal cycler 80 is controlled by an electronic control device (not shown). This control device includes, in particular, a microprocessor and control software (not shown). The thermal cycler has various interfaces for energy supply or data exchange: Ethernet® 85, Net 86, mode switch 87, CANout 88, CANin 89. A maintenance flap 91 and a type plate 92 are also shown. The thermal cycler 80 is operable and, in particular, programmable by a user via a user interface device, which here has an operating field 90 with a touchscreen and operating members. The thermal cycler is programmed by the user via parameter adjustment, or a suitable program stored in the control device's memory is selected by the user to automatically implement a desired temperature control protocol. In this type of temperature control protocol, the thermal block 84 of the thermal cycler 80 is temperature-controlled sequentially or periodically according to a temperature cycle. This type of temperature control protocol is used, in particular, to carry out the replication of substances in liquid solutions, especially for polymerase chain reaction (PCR). In this case, individual containers or—accordingly—sample plates (microtiter plates or PCR plates) can be placed in one, more or all of the sample container compartments of the thermal block, and these contain a predetermined volume of liquid solution (or various kinds of solutions). The thermal cycler can be driven in such a way that each of these individual containers or each of these sample container compartments is temperature-controlled to as uniform a temperature as possible during each temperature step of the temperature control cycle. The thermal block according to the present invention is preferably molded and formed such that each of its sample container compartments is temperature-controlled to as uniform a temperature as possible during each temperature step of the temperature control cycle. To this end, in particular, integral formation of the thermal block and especially its special form having a reinforcing structure or a temperature control structure are used.

[0115] The reinforcing structure is a structure of the thermal block that mechanically stabilizes the thermal block. The temperature control structure is a structure of the thermal block that achieves or optimizes desired heat transfer or a desired temperature distribution within the thermal block or within the sample container placed therein. The reinforcing structure can also be used as a temperature control structure, and vice versa. The reinforcing structure or the temperature control structure can be uniquely determined by structural parameters. In this way, the structural parameters and the shape of the thermal block can be determined or optimized in the simulation method or method for calculating the shape structure of the thermal block 84 according to the present invention.

[0116] Figure 4a shows a perspective view of a portion of the thermal block 21. Within the region marked with the symbol "1," a bonding section or bonding web 25 of the reinforcing structure 23a is visible, connecting two adjacent sample container housings 24 to each other and forming an integral part of them. One or more of these bonding webs 25 are used as both reinforcing and temperature-regulating structures. Simulation methods have revealed that heat can be distributed, particularly between adjacent sample containers, using the bonding webs 25. These bonding webs are not directly bonded to the base plate. They draw heat from the sample container housings through heat exchange with the surroundings. This effect increases with the surface size of the bonding web. Therefore, these bonding webs are suitable for cooling hotter sample container housings and improving temperature homogeneity within the thermal block. Optimal structural parameters for optimal heat transfer, particularly optimal heat extraction, are the thickness of the bonding webs and the minimum spacing of the structures relative to the base plate.

[0117] Another use of these bonding webs between the sample container housings is that they provide the necessary stability and strength to the thermal block. The bonding webs 25 are located as far away as possible from the center of gravity of the thermal block and can therefore be designed to be smaller and / or thinner. Another advantage here is that the thermal impact of the small bonding webs is relatively small. Heat must first flow through the sample container housings and therefore heat the bonding webs 25 last.

[0118] When designing for manufacturing, it is preferable to ensure that the geometric arrangement of overhangs provides a construction angle that is acceptable for 3D printing (typically an angle > 30-45°).

[0119] Figure 4b shows a perspective view of a portion of the thermal block 21', which is constructed similarly to the thermal block 21, except for the shape and position of the bonding web. There, within the region marked by the symbol "2", the bonding web 26 of the bonding section or reinforcing structure 23a is visible, which connects two adjacent sample container housings 24 to each other and is integrally formed with them. One or more of these bonding webs 26 are used as reinforcing webs and simultaneously as temperature-regulating webs.

[0120] The bonding web 26 between the sample container housings 24 is also bonded to the base plate 22. This has the effect of guiding heat from the hotter gap to the sample container housing, thus increasing temperature homogeneity. The structural parameters here are the thickness of the bond and the general shape (chamfered with a variable diameter and angular / triangular with a variable angle: see bonding web 26' in Figure 4c and bonding web 26'' in Figure 4d).

[0121] Figure 5a shows a perspective view of a portion of the thermal block 31. The sample container housing sections 24a, 24b, 24c, 24d, 24e, and 24f of the thermal block 31 have base sections 27 in the corner sections (24a), the edge sections (24b, 24c, 24d, 24e), and the inner sections (24f), and each is formed differently. In particular, the base section 27 of the corner section 24a has larger dimensions than the base section 27 of the edge sections (24b, 24c, 24d, 24e) and the inner section (24f). Specifically, the base section 27 of the edge section 24b, 24c, 24d, and 24e has larger dimensions than the base section 27 of the inner section 24f. This is specifically obtained by the bending radius of the base section when viewed in a plane perpendicular to the xy-plane, and it is greater for the sample container housing 24a located at the corner than for the other sample container housings not located at the corner. One of the four corner regions of the thermal block is shown, but all are formed similarly. Possible structural parameters for optimization on a simulation basis are, in particular, the dimensions and / or the bending radius of one base section or multiple or all base sections.

[0122] Figure 5b is a perspective view of a portion of the thermal block according to the present invention based on the seventh embodiment. Here, instead of a base section, the thickness of the substantially hollow conical sample container housing is varied. In particular, the sample container housings located at the corners have a greater thickness than those located at the edges 24b', 24c', 24d' and the sample container housing 24f' located inside. Specifically, the sample container housings 24b, 24c, 24d, and 24e located at the edges have a greater thickness than the sample container housing 24f located inside. By individually increasing the thickness of the sample container housings, and thereby individually changing the heat flow, a positive effect can be given to the homogeneity and speed of the thermal block. Possible structural parameters for optimization on a simulation basis are, in particular, the thickness of the individual, multiple, or all sample container housings of the thermal block.

[0123] Figure 6a shows a lateral cross-section of a portion of the thermal block according to the present invention, based on the eighth embodiment. In particular, a section of the base plate 42 and especially the sample container section 44 are visible, into which a conical sample container 49 (or a sample container having at least a conical section of its outer wall) is inserted, and the sample container is in thermal-physical contact with the inside of the sample container container section 40. In particular, the lower terminal section or base section 44a and the hollow conical upper wall section 44b are shown. The sample container container section 40 has a smaller thickness within the upper wall section 44b than within the lower terminal section or base section 44a, and here the internal volume of the sample container container section 44 also extends into its base section. The sample container container section 44 is formed rotationally symmetric with respect to the longitudinal axis A. The height and thickness mentioned above are structural parameters.

[0124] Figure 6b shows a lateral cross-section of a portion of the thermal block according to the present invention, based on the ninth embodiment. In particular, a section of the base plate 52 and especially a sample container housing 54 are visible, into which a conical sample container 49 can be inserted, thereby bringing the sample container into thermal-physical contact with the cylindrical interior of the sample container housing 40. The sample container housing 50 is formed here rotationally symmetric with respect to the longitudinal axis A. In particular, a lower terminal section or base section 54a and a hollow conical upper wall section 54b are shown. The sample container housing 40 has a smaller thickness in the upper wall section 54b than in the lower terminal section or base section 54a, and here again the internal volume of the sample container housing 54 extends into the base section.

[0125] The sample container housing section 54 has at least two regions 54b', 54'' with different material thicknesses within the upper wall section 54b, so that there are a total of three characteristic wall subsections of the wall: within the base section 54a, the lower wall subsection 54_1 is recognizable, and it has a material thickness that is generally greater than the other wall subsections 54_2, 54_3 on average along the longitudinal axis A. The material thickness of the central wall subsection 54_2 is substantially constant here and is smaller than the material thickness in the lower wall subsection 54_1 but greater than the thickness in the upper wall subsection 54_3. The transitions between the outer wall subsections are preferably edgeless, but may be stepped and / or edged. Inward, the wall subsections follow an open conical shape that extends continuously upward in the longitudinal direction. These wall subsections serve the purpose of a common filling height section, and wall subsection 54_3 serves the purpose of a section from which, as described much above,

[0126] Figure 7a shows a lateral cross-sectional view of a portion of a thermal block 21 having a base plate 22 and a sample container housing 24. The bonding web 25 connects adjacent sample container housings 24 and is integrally bonded to them by additive manufacturing. The bonding web 25 is not directly bonded to the base plate 22, but rather is separated from the base plate by a space 25'. The overall height of the sample container housing 24 is H, the height of the lower wall section 24a is h1, the height of the upper wall section 24b is h2, the maximum height of the bonding web 25 is h3, and the minimum height of the bonding web 25 is h4. These heights are measured along the longitudinal axis A, respectively. The thickness of the bonding web is measured perpendicular to the plane of the bonding web 25, here along the y-axis. The bonding web 25 transitions to the outer wall of the adjacent sample container housing 24 without edges, and the thickness of the bonding web 25 changes, particularly within this transition region—but not only there—and can increase, in particular there. The height and thickness mentioned above are structural parameters. Preferably, h3 >= 0.5 * H, especially h3 <= H, preferably h4 = 0.5. * h3 (this value preferably has a range of ±5% of h3), h3 <= 0.5 * H, h3 <= 0.3 * H, h3 >= 0.1 * H. The upper edge of the bonded web preferably extends in or parallel to plane B below it, and the opening of the sample container housing 24 of the thermal block is also located in that plane. The main plane (and therefore the two largest faces) of the bonded web 25 extends perpendicular to the main plane of the base plate 22, here parallel to plane zx or (not shown in Figure 7a) plane zy. The lower edge of the bonded web rises from two sides along the x-axis toward the centerline C of the bonded web, which extends parallel to the longitudinal axis A. Two sections of this lower edge, extending toward each other, meet at an angle α, in which case preferably 90° <= α <= 180°, preferably 110° <= α <= 160°. The height, thickness and angle α described above are structural parameters.

[0127] Figure 7b shows a lateral cross-sectional view of a portion of a thermal block 21 having a base plate 22 and a sample container housing 24. A bonding web 26 connects adjacent sample container housings 24 and is integrally bonded to them based on additive formation; the bonding web is further directly and integrally bonded to the base plate 22. The overall height of the sample container housing 24 is H, the height of the lower wall section 24a is h1, the height of the upper wall section 24n is h2, the maximum height of the bonding web 26 is h3, and the minimum height of the bonding web 26 is h4. These heights are measured along the longitudinal axis A, respectively. The thickness of the bonding web is measured perpendicular to the plane of the bonding web 26, here along the y-axis. The bonding web 26 transitions, each without edges, to the outer wall of the adjacent sample container housing 24 and / or to the base plate 22, and the thickness of the bonding web 26 changes, particularly within this transition region—but not necessarily only there—and increases there in particular. The height and thickness listed here are structural parameters. Preferably, h3 >= 0.5 * H, especially h3 <= H, preferably h4 = 0.5. * h3 (this value preferably has a range of ±5% of h3), h3 <= 0.5 * H, h3 <= 0.3 * H, h3 >= 0.1 *H. The lower edge of the bonded web preferably extends in contact with the upper side of the base plate 22. The main faces (and therefore the two largest faces) of the bonded web 26 extend perpendicular to the main plane of the base plate 22, here parallel to plane zx or (not shown in Figure 7a) plane zy. The bonded web here has space between the upper edge of the bonded web 26 and plane B. The upper edge of the bonded web descends from two sides along the x-axis toward the centerline C of the bonded web, which extends parallel to the longitudinal axis A. Two sections of this upper edge that extend toward each other meet at an angle α, in which case preferably 90° <= α <= 180°, preferably 110° <= α <= 160°. The height, thickness and angle α listed here are structural parameters.

[0128] Figure 8a shows a perspective view of a portion of the thermal block 101 according to the present invention, based on a tenth embodiment, in which case this portion is used to carry out an example method for simulating or calculating the shape structure of the thermal block according to the present invention. These calculations were performed here using ANSYS versions 2019R1 and 2019R2. The figure shows the initially air-filled unit cells (boundary boxes) used in the calculations within the internal region of the grid-shaped sample container housing of the thermal block - the structure of the unit cells preferably differs within the edge region. The shape of the metal sample container housing 103 is shown here to resemble that of the thermal block 1, in which case the sample container housing is joined by a plate 106 extending upward parallel to the base plate 102, the plate itself being a perforated plate, and the opening of the sample container housing communicates with the holes within its perforations. Assumed to be implemented for carrying out a method for simulating or calculating the shape structure of a thermal block according to the present invention, the following assumptions are given: a conical plastic container is placed inside a sample container housing, and the plastic container is in physical and thermal contact with the inside of the sample container housing. The plastic container is filled with water to a predetermined filling height. A constant heat flow having 5,208 W acts on the underside of the base plate.

[0129] Figure 8b shows a calculated thermal image, which in a lateral cross-sectional view shows a portion of the thermal block 101 based on Figure 8a and the heat distribution present therein, the heat distribution occurring in an exemplary method according to the present invention for simulating or calculating the shape structure of the thermal block. It can be seen that a broad spread of maximum temperature occurs parallel to the plane xy within the lower terminal region b1. Therefore, a metal base section can be provided in this region to increase or maximize the temperature control rate. Section b2 located above the water surface is similarly heated significantly (the empty section): however, since no sample is placed there, this heat is not utilized. However, the empty section must be temperature controlled each time. Therefore, preferably, the dimensions of the sample container housing are reduced or minimized within the empty section. This can be done by reducing the material thickness, or by locally thinning or making this section porous, as already shown. This reduces the "parasitic" heat capacity of the thermal block, thereby allowing the thermal block to be temperature controlled more quickly.

[0130] Figure 9a shows a calculated thermal image, which in a lateral cross-sectional view shows a portion of the thermal block 111 according to the present invention based on the 11th embodiment and the heat distribution present therein, which occurs in an exemplary method according to the present invention for simulating or calculating the shape structure of the thermal block. The sample container housing 113 and its thermal image are similar to those in Figures 8a and 8b. A thermosensor 114, which is used by an electronic open-loop or closed-loop control device for measurement within the framework of temperature control, is here directly positioned on the base plate 112 at position P0. Figure 9b shows a modified arrangement of the thermal block 112' compared to Figure 9a, in which, as an additional structure, the base 115 is formed as a vertical bulge projecting upward from the base plate 112'. By comparison with the resulting thermal image, it becomes clear that the upper side of the base 115 bulges out from the region of maximum temperature and communicates with a region that is not heated as strongly, and the temperature of that region is rather similar to the temperature inside the water sample s. In this type of configuration, more reliable and accurate electronic closed-loop temperature control is achieved. A thermosensor 114', which is used by an electronic open-loop or closed-loop control device for measurement within the framework of temperature control, is located on the base 115 at position P1 above the base plate in Figure 9b.

[0131] The sample container housing and reinforcing or temperature control structures of the example given above can be combined even within a single thermal block. Other preferred features of the thermal block n according to the present invention, which are not shown herein and can be combined or separate, are as follows: a. Stepped depth of the sample container compartment: The sample container compartment on the edge side may have a different depth compared to the sample container compartment located on the inside. This one or more depths can be a structural parameter. b. Increasing the thickness of the base plate individually: By layering and positioning additional materials on the base plate, local heat capacity can be adjusted to improve homogeneity. To this end, the base plate has at least two different plate regions, each having a different (constant or average) plate region thickness. The size (volume, surface area) and plate region thickness of the plate region can be structural parameters. c. Individual cutouts in the base plate: By locally cutting out parts of the base plate, the amount of heat can be further reduced. This can improve speed and homogeneity. For this purpose, the base section or base plate has at least one, two, more, or more cutouts. These may each have different (constant or average) cutout depths. The size (volume, surface area) and depth of the cutouts can be structural parameters. d. The design flexibility of the additive method allows the thermal block's sealing frame / encompassing frame to be combined with the base plate to further reduce its heat capacity. e. Reduction of thermal effects of the fixing structure, fixing sleeve-fixing web / fixing base by absorbing bonding forces through the provision of a lattice structure that is optimally positioned or distributed on the base plate. The fixing structure is used in particular to fix thermal blocks within a thermal cycler.

[0132] Figure 10a schematically illustrates a method for forming a thermal block to house and temperature-control laboratory sample containers within a laboratory temperature control device, particularly within a PCR thermal cycler, and the method comprises the following steps: • A thermal block is formed using an additive manufacturing method (201); The thermal block formed by the additive manufacturing method is post-treated by a post-treatment method, particularly by heating, coating, polishing and / or cutting (202).

[0133] Figure 10b schematically illustrates a method for calculating the shape and structure of a thermal block, which is used to house and regulate the temperature of laboratory sample containers within laboratory temperature control devices, particularly PCR thermal cyclers, and can be formed by additive manufacturing methods. In this case, the shape and structure of the thermal block can be defined by structural parameters based on the examples, and the examples have the following steps: • Change at least one structural parameter (301); • Implement a simulation method to simulate the heat flow through at least one section of a thermal block according to at least one structural parameter (302); • To add-on the structurally defined thermal block in this manner, at least one structural parameter is selected according to the simulation method (303).

[0134] Compared to other thermal blocks incorporated within the same thermal cycler or other commercially available thermal cyclers (manufacturer: Eppendorf AG, Germany), the speed advantage (maximum heating or cooling rate) of the 3D-printed thermal block 21 ("MC X50 3D-Block") is as follows in comparative experiments: [Table 1] This disclosure also includes the following aspects: [Aspect 1] In a thermal block for accommodating and temperature-regulating at least one laboratory sample container within a laboratory temperature control device, particularly within a PCR thermal cycler, A thermal block characterized in that it is formed using a material containing metal and an additive manufacturing method. [Aspect 2] A thermal block according to embodiment 1, having a number of sample container housing sections formed by an additive manufacturing method for housing and temperature-regulating a large number of laboratory sample containers. [Aspect 3] A thermal block according to embodiment 1 or 2, having a base plate, wherein the first plate side of the base plate is arranged to be thermally coupled to a temperature control device, and the second plate side facing the first plate side is integrally coupled to a plurality of sample container housings formed by an additive manufacturing method for housing and temperature-controlling a plurality of laboratory sample containers, wherein the plurality of sample container housings are arranged in particular within a rectangular grid. [Aspect 4] A thermal block according to any one of embodiments 1 to 3, having at least one sample container housing formed by an additive manufacturing method, wherein the sample container housing is formed in a cup shape, and in particular in at least a partially hollow cone shape. [Aspect 5] A thermal block according to any one of embodiments 2 to 4, wherein the sample container housing preferably has an opening for housing a laboratory sample container and a base section opposite to the opening, the base section is integrally bonded with a plate section and is formed using an additive manufacturing method, and the volume of the material of the base section decreases upward from the base section. [Aspect 6] A thermal block according to any one of embodiments 1 to 5, having a base section and a sample container housing section coupled thereto, wherein the sample container housing section has an opening for housing a sample container and a wall section disposed between the opening and the base section, the inside of the wall section is arranged to be thermally coupled with a laboratory sample container disposed within the sample container housing section, and in particular the wall section has a lower wall section whose thickness is greater than that of the wall section disposed above it. [Aspect 7] A thermal block according to any one of embodiments 1 to 6, having a base plate extending parallel to a horizontally positioned plane and coupled thereto, wherein at least one, or exactly one, coupling section extending parallel to the plane is provided between at least two adjacent sample container containers, particularly between multiple, or all directly adjacent sample container containers. [Aspect 8] The thermal block according to embodiment 7, wherein a space exists between the bonding section and the base plate, and the bonding section is not directly bonded to the base plate. [Aspect 9] The thermal block according to embodiment 7, wherein there is no space between the bonding section and the base plate, and / or the bonding section is directly bonded to the base plate. [Aspect 10] A thermal block according to any one of embodiments 1 to 9, integrally formed from fine grains containing aluminum or an aluminum alloy using an additive manufacturing method. [Aspect 11] A thermal block according to any one of embodiments 1 to 10, which is formed using an additive manufacturing method and then processed by a post-treatment method, particularly by heating, coating, polishing and / or cutting. [Aspect 12] Laboratory equipment having a thermal block according to any one of embodiments 1 to 11, particularly a PCR thermal cycler. [Aspect 13] A method for forming a thermal block, which involves housing and controlling the temperature of laboratory sample containers within a laboratory temperature control device, particularly within a PCR thermal cycler, A thermal block is formed using an additive manufacturing method. A method having steps. [Aspect 14] A thermal block formed using an additive manufacturing method is post-processed by a post-treatment method, particularly by heating, coating, polishing, and / or cutting. A method for forming a thermal block according to embodiment 13, comprising a step. [Aspect 15] A method for calculating the shape structure of a thermal block, which is used to house and temperature-control a laboratory sample container in a laboratory temperature control apparatus, particularly a PCR thermal cycler, and which can be formed by a computer-controlled additive manufacturing method according to at least one structural parameter, wherein the shape structure of the thermal block is definable by at least one structural parameter, and comprises the following steps: • Change at least one structural parameter; A simulation method is performed to simulate the heat flow through at least one section of the thermal block according to the aforementioned at least one structural parameter; • Select at least one structural parameter according to the simulation method, and then prepare the said at least one structural parameter for the subsequent fabrication of the thus structurally defined thermal block. method.

Claims

1. In a thermal block for accommodating and temperature-regulating at least one laboratory sample container within a laboratory temperature control device, The thermal block has a base plate, the first plate side of the base plate is arranged to be thermally coupled to a temperature control device, and the second plate side opposite the first plate side is integrally coupled to a plurality of sample container housings formed by an additive manufacturing method and integrally coupled to each other for accommodating and temperature-regulating a plurality of laboratory sample containers, and these plurality of sample container housings are arranged within a rectangular grid. A thermal block characterized in that it is formed using a material containing metal and an additive manufacturing method.

2. The thermal block according to claim 1, having at least one sample container housing portion formed by an additive manufacturing method, wherein the sample container housing portion is formed in a cup shape.

3. The thermal block according to claim 1 or 2, wherein the sample container housing section has an opening for housing a laboratory sample container and a base section opposite to the opening, the base section is integrally bonded with a plate section and is formed by an additive manufacturing method, and the volume of the material of the base section decreases upward from the base section.

4. A thermal block according to any one of claims 1 to 3, comprising a base section and a sample container housing section coupled thereto, wherein the sample container housing section has an opening for housing a sample container and a wall section disposed between the opening and the base section, the inside of the wall section is arranged to be thermally coupled with a laboratory sample container disposed within the sample container housing section, and the wall section has a lower wall section whose thickness is greater than that of the wall section disposed above it.

5. A thermal block according to any one of claims 1 to 4, comprising a base plate extending parallel to a horizontally positioned plane and coupled thereto, wherein at least one, or exactly one, coupling section extending parallel to the plane is provided between at least two adjacent sample container containers, between a plurality of, or all directly adjacent sample container containers.

6. The thermal block according to claim 5, wherein a space exists between the bonding section and the base plate, and the bonding section is not directly bonded to the base plate.

7. The thermal block according to claim 5, wherein there is no space between the bonding section and the base plate, and / or the bonding section is directly bonded to the base plate.

8. A thermal block according to any one of claims 1 to 7, integrally formed from fine particles containing aluminum or an aluminum alloy using an additive manufacturing method.

9. A thermal block according to any one of claims 1 to 8, which is formed by an additive manufacturing method and then processed by a post-treatment method.

10. Laboratory apparatus having a thermal block according to any one of claims 1 to 9.

11. A method for forming a thermal block, which involves housing laboratory sample containers within a laboratory temperature control device and controlling their temperature, The thermal block has a base plate, the first plate side of the base plate is arranged to be thermally coupled to a temperature control device, and the second plate side opposite the first plate side is integrally coupled to a plurality of sample container housings formed by an additive manufacturing method for housing and temperature-regulating a plurality of laboratory sample containers, and these plurality of sample container housings are arranged within a rectangular grid. A thermal block is formed using an additive manufacturing method. A method for forming a thermal block having steps.

12. A thermal block formed using an additive manufacturing method is post-processed using a post-processing method. A method for forming a thermal block according to claim 11, comprising the step of [step].

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