Multi-part microtiter plate

Abstract

The invention relates to a microtiter plate (100) comprising: a first module (1) having at least one first row (16, 17) of wells (2) for receiving a sample; and a second module (20, 30) having a further row of wells (21, 31), wherein at least the first module (1) is integrally formed and is fixed to the second module (20, 30) in some way so as to provide a connection enabling material transfer between each well (2, 21, 31) of the first and second modules (1, 20, 30), and wherein the microtiter plate (100) is designed as a multi-part microtiter plate (100).

Description

[0001] MULTI-PART MICROTITER PLATE

[0002] The present invention relates to a multi-part microtiter plate and its assembly.

[0003] Microtiter plates, also commonly called "well plates," are usually manufactured as a single piece. It is possible to selectively control the transfer of substances between the wells using a membrane.

[0004] EP 3 415 607 A1 discloses a microtiter plate as a single-piece monolithic component in which slots for replacing membranes are arranged. This represents a further development in that the membrane can be selectively chosen for the sample in the recesses. However, the insertion variant is particularly challenging with regard to sealing the membrane at its edges. Moreover, the slots must be milled into the component beforehand. The slots in the component, e.g., for mass transfer within a row or mass transfer to an adjacent row, are therefore fixed and cannot be changed.

[0005] The US 2020188913 A1 is also based on the usual principle of a microtiter plate as a single-piece component. A further disadvantage is that the depicted arrangement of the wells does not correspond to any commercially available design.

[0006] In the publication “Construction and Modeling of a Coculture Microplate for Real-Time Measurement of Microbial Interactions”, Charles Jo et al., ASM Journals; mSystems Vol. 8 No. 2, doi: https: / / doi.org / 10.1128 / msystems.00017-21, a multi-part microtiter plate is described. This plate features wells suitable for receiving samples, preventing leakage from the bottom of the well due to sealing issues. To ensure this, however, the component must first be screwed together with a sealing layer and a base plate. A one-piece component with a single well for receiving a sample is therefore not shown in this version. This highly relevant design solution from 2023 allows for free and sample-specific positioning of the membrane and, at the same time, greater design flexibility in the composition of the microtiter plate.However, the concept requires extensive work steps to achieve a seal of the entire structure, meaning that the concept only offers advantages on a laboratory scale and is unsuitable for application-specific mass production due to the numerous assembly steps. Based on the aforementioned problem, the object of the present invention is to provide a microtiter plate that satisfactorily solves the aforementioned problems and has a design with few components, making it particularly suitable for mass production.

[0007] The present invention solves the aforementioned problem by means of a microtiter plate with the features of claim 1.

[0008] A multi-part microtiter plate according to the invention comprises a first component with at least one first row of wells, preferably at least two rows of wells. As is usual with microtiter plates, the wells can be filled with different samples. The samples typically vary in their composition. The wells of the first row preferably do not have a connection for mass transport with the wells of the second row. However, the wells of at least one row of wells, preferably the wells of both rows of wells, each have at least one edge opening, preferably a single edge opening, to form a connection for mass transport.

[0009] Furthermore, the microtiter plate according to the invention comprises a second component, which is provided with at least one further row of wells, in particular with the same number of wells spaced equally apart as in the first component. One or more further rows of wells may also be provided in the component.

[0010] The recesses in the second row of building blocks can be identical to the recesses in the adjacent row of the first building block. Alternatively, however, it is also possible for the recesses to have not just one, but two or more openings at the edges to form a connection for material transport.

[0011] According to the invention, at least the first component is formed in one piece. This one-piece construction may, but need not, include connecting elements for fixing it to the adjacent second component. For example, clamping or locking elements can be formed as part of the one-piece component. However, mechanical connecting elements, e.g., made of a different material than the first component, can also be provided for connecting several components. These can be, for example, one or more connecting screws that are not part of the one-piece component. The one-piece construction can also be achieved, in particular, by a material-bonded connection of several component segments. However, it is especially preferred if the one-piece construction of the component is achieved by a monolithic design. For example, the component can be manufactured as a monolithic block by injection molding.

[0012] Preferably, the second component can also be made in one piece.

[0013] The first building block is connected to the second building block by a fixation forming a connection for mass transport, preferably a channel with a membrane located therein, between a recess of the first and the second building block.

[0014] The single-piece construction of the first and preferably also the second component enables particularly quick and easy assembly of the multi-part microtiter plate. Sealing planes are only required in the area of ​​the respective mass transport connection.

[0015] This significantly reduces the risk of leakage compared to other multi-part microtiter plate designs and considerably simplifies the assembly and, if necessary, disassembly steps for cleaning such a microtiter plate. Therefore, the microtiter plate described above can be mass-produced with just a few steps.

[0016] Further advantageous embodiments of the invention are the subject of the dependent claims.

[0017] The recesses of the second building block differ from the shape and / or design of the recesses of the first building block. In particular, the recesses of the second building block have two, preferably opposing, interfaces for supplying and removing substances through semipermeable membranes into the respective adjacent building blocks and their recesses. These interfaces influence the shape and design of the recesses of the second building block in contrast to the first building block.

[0018] Furthermore, the microtiter plate can have a sequence of at least three fluidically interconnected wells, each containing at least three detachably connected building blocks, wherein the sequence is formed by at least the first and second building blocks. The second building block can have a well for forming two connections for mass transport to the two adjacent building blocks. In contrast, the first building block can have a well for forming only one connection for mass transport to the adjacent second building block.

[0019] The next adjacent building block can be designed as a first building block, a second building block, or a further building block with a recess for forming one or more connections.

[0020] It is advantageous if membranes, preferably semipermeable membranes, are arranged between the recesses of the two building blocks, particularly along the interface between the two building blocks. Preferably, one membrane is arranged per connection.

[0021] Particularly advantageous for sequential separation is the arrangement of a first membrane along the first junction of the second building block with an adjacent first or second building block, and a second membrane along the second junction of the second building block with an adjacent first or second building block, wherein the first membrane has a different permeability than the second membrane. Especially if both the first and second membranes are semipermeable, the first membrane can exhibit a different selective permeability than the second membrane. This enables selective separation, e.g., based on ion charge, size exclusion, hydrophilicity, or similar properties.

[0022] It is advantageous if the fixing is designed as a removable fixation, such that the components are fixed in a way that allows for disassembly. This enables the components of the microtiter plate to be cleaned particularly efficiently after use and reused.

[0023] Alternatively, the fixation can be permanent, preferably as a material-bonded connection, and particularly preferably as an adhesive fixation. This variant is especially preferred for single-use applications, as material-bonded connections with a higher degree of tightness against medium leakage from the samples within the wells, and especially also against mass transport between the wells, can be achieved.

[0024] Sealing elements, preferably sealing rings, especially O-rings, can be provided at the respective connections between two components. The sealing rings can be directly attached to one of the two components by injection molding to form the connection. Alternatively or additionally, the membranes can also be attached to the components by injection molding.

[0025] The fixing can be achieved by two or more corresponding clamping, plug-in, or locking elements that are integrally attached to the building blocks. Such plug-in elements can be designed as a projection and a corresponding recess.

[0026] The modules can be fixed to the microtiter plate alternatively or additionally by at least one, preferably a maximum of two, shaft-shaped mechanical fasteners, preferably a screw with at least a segmented or fully threaded shaft, a threaded rod, a pin, a press sleeve, a slotted sleeve, and / or a bolt. The fasteners pass through a rod guide channel and thereby connect all modules to one another.

[0027] The fixing can be carried out on both sides at the ends of the rows with the recesses to ensure an even distribution of the contact pressure and thus an evenly divided sealing plane.

[0028] Furthermore, it is advantageous, for maintaining a uniform pipetting distance, if the distance of a well to the adjacent wells of a row is constant for all wells of at least one component and preferably of the entire microtiter plate.

[0029] It is advantageous if a medium-tight channel is formed along an interface between two building blocks, serving as the connection for mass transport between two wells of the two adjacent building blocks. The medium-tightness enables lossless mass transport between the two wells. The microtiter plate preferably has several of these channels arranged parallel to each other.

[0030] The channels arranged between the two components have, particularly along the aforementioned interface, several membranes, preferably several semipermeable membranes. Preferably, only one membrane is provided per channel. This allows for selective mass transport, whereby one or more components of the sample in a well are retained in the well by the membrane, while other components can pass through the membrane, in particular by diffusing through it.

[0031] A particular advantage of the aforementioned design is that the channel membranes are configured differently and preferably exhibit varying permeability to one or more components of a sample. This allows the selectivity to be individually adjusted for each channel by selecting a specific membrane. Simultaneously, the individually equipped channels are sealed along a common sealing plane.

[0032] The installation of the individually selected channels can be automated, for example by a placement machine, whereby the selection can also be automated by a preset computer program or by artificial intelligence. A pre-positioning aid, such as a comb with spaces for the membranes or similar, can be used to hold the membranes during placement.

[0033] At least one of the components, preferably all components of the microtiter plate, are advantageously monolithic. All components can particularly preferably be made of the same material, e.g., an injection-moldable plastic. Particularly preferably, this can be a transparent plastic, so that enhanced optical detection or analysis of the samples within the well is possible. The components within the scope of this application are not the aforementioned mechanical fasteners, such as screws, nuts, and the like.

[0034] Furthermore, it is advantageous if at least one of the building blocks, preferably all building blocks, are made of a single-use material. Such single use can preferably be achieved by using a coated cardboard material for the building block and / or by using a plastic material for the building block that exhibits irreversible deformability or irreversible shape changes, e.g., through swelling, at temperatures below 121 °C and / or under the influence of steam.

[0035] At least one of the components, preferably all components except for the mechanical fasteners, can alternatively be made of a material that is dimensionally stable at temperatures above 121 °C, steam-resistant, and / or gamma-ray-resistant. This variant allows for multiple uses, particularly through CIP (clean in place) cleaning and / or gamma-ray sterilization.

[0036] The first module can advantageously be designed such that, in combination with two adjacent modules, it has two parallel interfaces, each with several parallel, medium-dense channels for the transfer of at least one component of a sample between the wells of the first module and the adjacent modules. This allows the first module to be coupled to an adjacent module in two different directions, so that the modular microtiter plate is constructed by connecting the first modules in series.

[0037] The microtiter plate can advantageously have sealing points which are arranged exclusively along the interfaces between each two adjacent building blocks, each with at least one series of depressions.

[0038] To allow for comparability of the individual wells and, when filled, of the "microbiological habitats" at the same fill levels, the wells of the building blocks have a circular cross-section, and preferably all wells have a uniform diameter in the cross-sectional area. The circular cross-section can be particularly pronounced near the filling opening of the well. In the deeper area, the cross-section may deviate from this due to the shape of the connections.

[0039] The microtiter plate can also have additional wells, preferably arranged at the edge, without a connection for mass transport with a membrane as a reservoir for evaporation compensation.

[0040] Furthermore, according to the invention, a method for assembling a microtiter plate according to the invention comprises the following steps:

[0041] Step a: Providing and selecting the building blocks for assembling the microtiter plate, comprising the two building blocks of the microtiter plate according to the invention, preferably by injection molding the building blocks; Step b: Specifying a data set regarding a position between exactly two wells of two adjacent building blocks and a specification for the membrane provided for this position, preferably by specifying the membrane thickness and / or the membrane material;

[0042] Step c: Inserting the membrane into the position between the recesses of the two building blocks based on the given data set for the position and specification of the membrane;

[0043] Step d: Assembling the building blocks to form the microtiter plate and

[0044] Step e: Fixing the building blocks.

[0045] Advantageous embodiments of the method according to the invention are the subject of the features described below.

[0046] It is advantageous if several of the membranes used along an interface between two components have different specifications, preferably consisting of different membrane materials. For example, a membrane at one interface can be made of a different membrane material than another membrane located along the interface in an adjacent channel.

[0047] This allows these different specifications to be defined by the dataset in step b) and taken into account when inserted in step c). For example, if certain prior information about several samples and / or their composition is available, the equipment of the microtiter plate with the membranes for a set of different samples, which are used to fill a series of wells, can be considered when creating and using the dataset in step b).

[0048] The procedure may, as part of the provision in step a), include the specification of a further data set regarding the type of building blocks, preferably regarding the number of rows of depressions and / or the design of the depressions.

[0049] Particularly advantageous in the context of specifying this additional data set is the selection of building blocks in step a). This allows for the automated selection of building blocks for assembling the microtiter plate, e.g., a marginal segment as a building block of the microtiter plate, a double-row central segment as a building block of the microtiter plate, a single-row central segment as a building block of the microtiter plate, or the like.

[0050] The selection of the component sequence and the choice of the membrane as variable elements of the microtiter plate thus complement each other through the two data sets to form a logical assembly concept, enabling fully automated assembly with short cycle times and high production throughput. This is advantageous, for example, in assembly under aseptic conditions, as it eliminates the need for human intervention and the additional sterilization of the microtiter plate before packaging.

[0051] For the beneficial reuse of the microtiter plate and to reduce the waste generated, which depending on the sample can be toxic, radioactive, biohazardous, or the like, it is advantageous if the burden of special waste can be eliminated through appropriate cleaning. However, the membrane, which is usually intended for single use only, presents a problem. Single-use concepts therefore discard the entire microtiter plate.

[0052] Within the scope of the present invention, the provision of the two building blocks in step a) can, however, be carried out by disassembling an existing microtiter plate, wherein the membrane is removed along the interface of the two building blocks and wherein the building blocks are cleaned by a cleaning process, in particular a CIP cleaning.

[0053] A microtiter plate according to the present application can, in a preferred embodiment, be composed of at least four building blocks, two with two edge-side building blocks and two middle building blocks, wherein each building block has at least 5, preferably 6-8 wells and preferably arranged side by side in a row.

[0054] Along each connection between two wells, an individual membrane is always arranged. Thus, the different configurations of the adjacent membranes allow not only for changes in the composition of the medium in the wells, but also for changes in the separation performance by varying the membrane of the microtiter plate, e.g., in size or polarity. Each module can have specific fixing channels for the insertion of screws or similar fasteners, allowing the modules to be connected by mechanical means, particularly by screwing. These fixing channels are spatially separated from the wells in the module.

[0055] The depressions preferably have flat bottoms, wherein the depression is particularly preferably designed as cylindrical circular cylindrical walls and the flat bottoms as flat cylindrical end surfaces.

[0056] The recesses of each building block are spaced apart from one another. Furthermore, additional recesses can be arranged, preferably laterally to the rows of recesses; these recesses do not allow for mass exchange with an adjacent recess and serve as solvent reservoirs to protect against evaporation.

[0057] Individual connections can also be provided without a membrane. For example, two interconnected depressions can be used to define a larger intake volume. Up to 12 depressions can also be interconnected.

[0058] The microtiter plate can be used as part of automated sampling and / or sample delivery.

[0059] The fluid-tight connection between two building blocks can be ensured via an O-ring seal.

[0060] Further advantages, features, and details of the invention will become apparent from the following description, in which an embodiment of the invention is explained in more detail with reference to the accompanying drawings. Those skilled in the art will expediently consider the features disclosed in the drawing, the description, and the claims individually and combine them into meaningful further combinations. In particular, there are numerous possibilities for modifying and further developing the multi-part microtiter plate according to the invention within the scope of the present invention. The drawings show:

[0061] Fig. 1 Top view of a first component of a microtiter plate according to the invention;

[0062] Fig. 2 Bottom view of the building block of Fig. 1; Fig. 3 Side view of the building block of Figs. 1 and 2;

[0063] Fig. 4 Side view of a first interface of the component of Fig. 1-3;

[0064] Fig. 5 Side view of a second interface of the component of Fig. 1-4;

[0065] Fig. 6 Top view of a second component of the microtiter plate according to the invention;

[0066] Fig. 7 Ground view of the building block of Fig. 6;

[0067] Fig. 8 Side view of the building block of Figs. 6 and 7;

[0068] Fig. 9 Side view of a first interface of the component of Fig. 6-8;

[0069] Fig. 10 Side view of a second interface of the component of Fig. 6-9;

[0070] Fig. 11 Perspective view of the microtiter plate; and

[0071] Fig. 12 Schematic diagram of the operation of the microtiter plate.

[0072] A microtiter plate, often also called a "well plate" in technical jargon, is typically used in plant and pharmaceutical research and serves, among other things, to examine liquid samples, e.g., biological samples, which can be analyzed for their composition, individual components, especially their concentration, their biological activity, and / or their reaction with other substances. A typical examination involves analysis using an optical sensor, e.g., a photometer, preferably with regard to absorption and / or transmission. The examination of the liquid sample can be carried out as part of a high-throughput screening sequence of numerous samples, especially interactions of microorganisms, such as bacteria. The use and basic construction of microtiter plates are known to those skilled in the art.

[0073] Fig. 1-5 reveals a building block 1 for the construction of a multi-part microtiter plate 100. Identical connecting elements, components or segments are described with the same reference numerals.

[0074] The component 1 has one side with two interfaces 3 and 8, at which the component can be connected to further components 1, 20 and 30. In the illustrated embodiment, the connection between the components 1, 20 and 30 is a clamping or snap-fit ​​connection. They have a mounting direction A, preferably a plug-in direction, which in the embodiment of Fig. 1-10 also represents the longitudinal extent of the microtiter plate.

[0075] The component 1 has two adjacent rows 16 and 17 of recesses 2. The recesses 2 of such a microtiter plate 100 are designed as cylindrical recesses. The rows 16 and 17 are arranged parallel to each other and, in particular, perpendicular to the mounting direction A.

[0076] All recesses 2 of the building block 1 are essentially identical in design. Each such cylindrical recess 2 has a terminal opening 10 for introducing a sample, in particular a liquid sample.

[0077] Each of the recesses 2 also has a peripheral through-opening 12, which is arranged in the cylindrical surface of the recess 2. The through-opening 12 has a peripheral sealing surface 4, which is provided either by the component 1 itself or by a sealing element, e.g., a sealing ring. The sealing surface 4 is designed such that when the respective two identical sides are coupled to form an interface 3 or 8, a medium-tight channel is created.

[0078] A membrane 25 is arranged in the microtiter plate 100 on the same plane as an interface 3 or 8 with two adjacent sides of two coupled modules 1, forming a medium-tight channel. The function of the membrane 25 will be discussed later. The membrane 25 extends over the entire cross-section of the channel.

[0079] Between the recesses, material protrusions are arranged along the interface 3 or 8, which are designed as additional flexible sealing strips 5, 5'.

[0080] For centering and / or pre-fixing, each building block has 1 corresponding plug-in elements, e.g. projections 7a, 7b, 7a' and 7b' and projection receptacles 9b and 9a'.

[0081] The plug-in elements are arranged along the edge of component 1, beyond the wells 2, which are spaced at a standardized, uniform distance from each other. This allows the wells to be automatically filled using existing high-throughput machines or pipettes with a multi-tip attachment, where the tip spacing is always consistent. Therefore, the microtiter plates can be used in existing laboratory systems.

[0082] The component also features a rod passage channel 6, 6' per edge for the passage of a connecting screw or threaded rod. Other connecting rods, e.g., spring pins with end stop surfaces, e.g., screw heads, can also be guided through the rod passage channel, thus enabling the coupling of several components 2, 20 and / or 30 by a mechanical connecting element.

[0083] A fluidic connection between the two recesses of the same building block, e.g., in the form of a channel, does not exist. This connection is only formed through the connection with another building block.

[0084] The building block 1 , 20, 30 is advantageously constructed in one piece, preferably monolithically, with a bottom segment 11 which preferably forms a closed bottom surface over the entire length and width of the building block 1 , 20, 30.

[0085] On its edge, the building block 1, 20, 30 has a rim 13 which protrudes from an edge surface and is part of the base segment 11. This rim 13 can be used, for example, to guide the microtiter plate within a transport device.

[0086] Another optional component of the microtiter plate 100 is shown in Fig. 6-10. This is an edge component which, with respect to the mounting direction A, is arranged at the beginning and end of a chain of several interconnected components 1, 20, 30. All components preferably have the same width and height, perpendicular to the mounting direction A.

[0087] The edge component 20 shown in Figs. 6-10 also has at least one row of recesses 2, each with a through-opening 12 along the cylindrical surface. The design of the interface side 3, including the sealing surface 4 and the sealing strip 5, is analogous to Figs. 1-5. Parallel to this row runs a second row with recesses 21, which can serve, for example, for receiving a reference sample, for zero adjustment, or for calibration. These recesses are circumferentially closed, i.e., they do not have a through-opening 12.

[0088] The outer edge surface 14 of this edge block 20 is simultaneously the outer edge surface of the microtiter plate 100 according to the invention. It therefore has no interface with an adjacent block. Instead, an edge strip 13 is provided on this outer edge surface, analogous to the lateral edge surface of the block 1.

[0089] The building block 1 is therefore a central building block with the sides of the two interfaces 3 and 8 each, and the edge building block 20 logically only has one side with an interface 3, which is identical in construction to the interface of the central building block.

[0090] The edge block 20 has additional recesses 15 on its edge side, which can be filled with water or any liquid to protect the actual recesses, e.g. the recesses 2, from evaporation.

[0091] However, it is not strictly necessary. The same applies to the row with the recesses 21. All other elements, in particular those on the edge of the row with the recesses 2, for coupling with a central component, are designed analogously to Fig. 1-5.

[0092] Furthermore, a building block 30, shown in Fig. 11, can be provided to implement a multi-reaction and / or diffusion setup. Building block 30 is also a central building block.

[0093] Unlike component 20, component 30 has only a single row of recesses 31. Like component 20, the recess 31 is cylindrical, but it has two through-openings 12 in its cylindrical surface, arranged diametrically opposite each other. Each recess 31 thus forms part of an interface when connected to an adjacent component. The further design of component 30 is analogous to that of component 20 described above.

[0094] In a first embodiment of the invention, the individual building blocks can be made of a single-use material, such as laminated or coated cardboard and / or disposable plastic. As previously described, a custom-selected membrane can be arranged in the channel between the adjacent interfaces of two building blocks. This means that, particularly when choosing semipermeable membranes, the pore size or polarity of the membrane material, for example, can be specifically tailored to the samples filled in the two wells.

[0095] In this case, unlike in the illustrated embodiment, the fixing between the building blocks does not have to be reversible, but can also be formed, for example, by gluing the individual building blocks together, e.g. using an adhesive.

[0096] This allows for the provision of a sample-specific microtiter plate with a plurality of different membranes, in particular with a plurality of different semipermeable membranes, which can be disposed of after use.

[0097] Alternatively or additionally, the number of fluidically connected wells during the assembly of the 100-cell microtiter plate can be varied individually or according to customer requirements. Assembly can be automated.

[0098] In particular, a manageable selection of the three aforementioned components can be used to produce a custom-made microtiter plate. Therefore, large-scale warehousing is not necessary for production.

[0099] The microtiter plate described above can therefore be manufactured industrially in large quantities.

[0100] Alternatively, one or more, in particular all, of the components can also be made of a cleanable, in particular CIP-capable, water vapor and / or gamma radiation resistant material, preferably of a suitable plastic or of metal, such as stainless steel.

[0101] This modular microtiter plate variant can be reused, and in particular, reused multiple times. It is suitable, for example, for experimental laboratories at universities. The membrane, however, should preferably be replaced after each experiment. Nevertheless, the waste to be disposed of can be limited to the membrane itself. The other modules and the mechanical fasteners used to fix them can be reused multiple times and, by disassembly, can also be used in a different configuration of modules and / or by replacing the semipermeable membrane between modules 2, 20, and 30.

[0102] Regardless of the material, the multi-part microtiter plate offers the possibility of equipping it with a variety of different selected semipermeable membranes between two rows of adjacent wells.

[0103] Figure 12 illustrates the operation of the microtiter plate in variants a) and b). Wells 2 and 31 are separated by selected membranes that allow differential diffusion of substances, thereby preferably, and optionally selectively, keeping bacteria, ions, germs, or other substances apart. The plate is closed on each side with a screw, threaded connection, or similar device to facilitate quick assembly.

[0104] A modular microtiter plate with permeable membranes thus enables the cultivation of several bacterial species in spatial separation and simultaneously allows interaction through diffusible connections.

[0105] The microtiter plate described above can have standardized dimensions, e.g., exactly 72 wells. This makes the microtiter plate compatible with standard devices such as multimode plate readers. It can also be configured with exactly 12, exactly 48, exactly 96, exactly 284, or exactly 288 wells.

[0106] The shape of the wells and the overall shape of the microtiter plate correspond to the shapes and dimensions of classic 96-well microtiter plates. This simplifies integration into existing systems, as no modifications are required.

[0107] The wells are preferably designed as cylindrical wells. This preferred well shape of the microtiter plate according to the invention enables a preferred biological growth dynamic during the assembly of the building blocks.

[0108] Depending on requirements, the customer can choose from various modules and membrane properties. For example, a set of wells can be connected by a channel and a permeable membrane. This setup can enable, for instance, chemical detection, signal transmission, and / or the exchange of metabolites between two or more wells without direct physical contact. This allows, for example, the investigation of complex interactions between multiple pathogens and host factors.

[0109] Thus, the microtiter plate enables the use of robot-assisted manufacturing and / or automated systems for the high-throughput investigation of a large number of combinations, preferably for microorganisms. The microtiter plate also allows two bacterial species to be cultivated spatially separated from one another while maintaining their ability to interact via diffusible compounds. Each pair of wells is connected by a channel 12 containing a permeable membrane 25. In addition to the aforementioned mass transfer, this configuration can also enable chemical sensing, signal transduction, and / or the exchange of metabolic products without direct physical contact.

[0110] The microtiter plate therefore provides a platform for investigating pairwise microbial interactions using high-throughput methods. The growth, relative fitness, secretion of compounds, and potentially also the gene expression of each competing species can be measured or qualitatively monitored using the microtiter plate, preferably via optical density, fluorescence measurements, or other methods.

[0111] The microtiter plate can be assembled quickly and easily. The individual components can be easily slotted together or, preferably, clicked into place, ensuring a secure seal. Once assembled, two screws are used to securely fasten the structure, providing additional stability. However, it is also possible that the snap-fit ​​connection is self-supporting and no additional screws are necessary.

[0112] Ideally, each component can be dishwasher-safe and steam-sterilised or autoclaved at 121 °C.

[0113] In particular, certain or all components of the microtiter plates can be sterilized by steam, so that all parts (except the membranes) can be reused.

[0114] Moreover, the microtiter plate, especially in its reusable version, allows users to minimize waste and costs and reduce their ecological footprint. The components are preferably manufactured using injection molding and are also preferably fixed together with a small number of mechanical fasteners and in just a few steps, using only two mechanical fasteners, most preferably two screws or two threaded rods.

[0115] This simultaneously reduces the reject rate during manufacturing and the number of sealing points in the microtiter plate assembly. These sealing points are located exclusively between two components, specifically only at the interfaces between two adjacent and abutting components in a single assembly direction, and not within a single component.

[0116] In particular, the design allows for the creation of a standard 96-well microtiter plate, preferably with commercially available standard dimensions. This ensures that the microtiter plate fits into standard instruments, especially standard optical analysis devices such as multimode plate readers.

[0117] Furthermore, the first building block 1 described above can be varied with other building blocks which differ from the recesses 2 in terms of the shape and design of the depressions.

[0118] The modular microtiter plate described above, with its membranes, enables the cultivation of several bacterial species in spatial separation and simultaneously allows preferential interaction through diffusible sample-specific compounds.

[0119] Depending on requirements, the customer can choose from three or more different modules and any membrane properties.

[0120] The design of the microtiter plate enables chemical detection, signal transmission and the exchange of metabolites between two or more wells without direct physical contact.

[0121] This allows, for example, the investigation of complex interactions between multiple pathogens and host factors.

[0122] Furthermore, the design of the microtiter plate 100 enables the use of robots / automated systems to investigate a large number of combinations using a high-throughput method.

[0123] The invention is not limited to the previously mentioned embodiment. 1 building block

[0124] 2. In-depth study

[0125] 3 Interface

[0126] 4 Sealing surface

[0127] 5 Sealing strip

[0128] 5' Sealing strip

[0129] 6 rod feedthrough channel

[0130] 6' rod feedthrough channel

[0131] 7a advantage

[0132] 7b advantage

[0133] 7a' advantage

[0134] 7b' lead

[0135] 8 Interface

[0136] 9a Protrusion shot

[0137] 9b Forward shot

[0138] 10 Opening

[0139] 11 Floor segment

[0140] 12 Passage opening

[0141] 13 Edge strip

[0142] 14 Outer edge surface

[0143] 15 In-depth study

[0144] 16th row

[0145] 17th row

[0146] 20 building blocks

[0147] 21 In-depth study

[0148] 25 Membran

[0149] 30 building blocks

[0150] 31 In-depth study

[0151] 100 microtiter plate

[0152] A Mounting direction

Claims

Patent claims 1. Microtiter plate (100), comprising a first building block (1 ) with at least a first row (16, 17) of wells (2) for receiving a sample and a second building block (20, 30) with a further row of wells (21 , 31 ), wherein at least the first building block (1 ) is formed in one piece and is connected to the second building block (20, 30) by a fixation forming a connection for mass transport between each well (2, 21 , 31 ) of the first and the second building block (1 , 20, 30) and wherein the microtiter plate (100) is formed as a multi-part microtiter plate (100).

2. Microtiter plate according to one of the preceding claims, characterized in that the recesses (31 ) of the second component (30) differ from the shape and / or design of the recesses (2) of the first component (1 ).

3. Microtiter plate according to claim 2, characterized in that the microtiter plate has a sequence of three fluidically interconnected wells (2, 31, 21) of at least three detachably connected building blocks (1, 30, 20), wherein the sequence is formed at least by a first building block (1) according to claim 1 and a second building block (30) according to claim 2, wherein the second building block (30) according to claim 2 has a well (31) for forming two connections for mass transport to the two adjacent building blocks (1, 20, 30).

4. Microtiter plate according to one of the preceding claims, characterized in that membranes (25), preferably semipermeable membranes, are arranged between the recesses (2, 21, 31) of the two building blocks (1, 20, 30), in particular along the interface (3, 8).

5. Microtiter plate according to one of the preceding claims 3 and 4, characterized in that a first membrane (25) is arranged along the first connection of the second component (30) with an adjacent first or second component (2, 20) and that a second membrane (25) is arranged along the second connection of the second component (30) with an adjacent first or second component (2, 20) and that the first membrane (25) has a different material permeability than the second membrane (25).

6. Microtiter plate according to one of the preceding claims, characterized in that the first component (1) has at least two rows (16, 17) of depressions (2) for receiving a sample.

7. Microtiter plate according to one of the preceding claims, characterized in that the fixation is designed as a releasable fixation, such that the building blocks (1 , 20, 30) are fixed in a disassemblable manner.

8. Microtiter plate according to one of the preceding claims 1-6, characterized in that the fixation is designed as an inseparable fixation, preferably as a material-bonded connection, particularly preferably as an adhesive fixation.

9. Microtiter plate according to one of the preceding claims, characterized in that the fixing is realized by two mutually corresponding clamping, plugging or locking means (7a, 7b, 7a', 7b', 9a, 9b) arranged integrally on the building blocks (1 , 20, 30).

10. Microtiter plate according to one of the preceding claims, characterized in that the fixing of the building blocks (1 , 20, 30) to form the microtiter plate (100) is effected by at least one, preferably a maximum of two, shaft-shaped mechanical connecting means, preferably one screw with at least segmental threaded shaft, one threaded rod, one pin, one press sleeve, one slotted sleeve and / or one bolt, which is passed through a rod passage channel (6, 6') and connects all building blocks (1 , 20, 30) together.

11. Microtiter plate according to one of the preceding claims, characterized in that the fixing, preferably by the shaft-shaped mechanical connecting means, is carried out on both sides at the ends of the rows (16, 17) with the recesses (2).

12. Microtiter plate according to one of the preceding claims, characterized in that the distance of a well (2) to the adjacent wells (2) of a row (16, 17) is constant for all wells (2) of the component (1 , 20, 30).

13. Microtiter plate according to one of the preceding claims, characterized in that the microtiter plate (100) has at least one medium-dense channel along an interface (3, 8) between two components (1, 21, 31). between two recesses (2, 21, 31) of the two adjacent building blocks (1, 20, 30), which is formed by connecting two through-openings (12) arranged at the edges in the recesses (2, 21, 31).

14. Microtiter plate according to one of the preceding claims, characterized in that several parallel channels between the recesses (2, 21, 31) of the two building blocks (1, 20, 30), in particular along the interface (3, 8), have membranes (25), preferably semipermeable membranes.

15. Microtiter plate according to claim 14, characterized in that the membranes (25) of the channels are designed differently and particularly preferably have different permeabilities to components of a sample.

16. Microtiter plate according to one of the preceding claims, characterized in that at least one of the building blocks (1 , 20, 30), preferably apart from the mechanical connecting means, all building blocks (1 , 20, 30) of the microtiter plate (100) are monolithic and are particularly preferably made of the same material.

17. Microtiter plate according to one of the preceding claims, characterized in that at least one of the building blocks (1 , 20, 30), preferably all building blocks (1 , 20, 30), are made of a single-use material, preferably coated cardboard and / or plastic, with irreversible deformability or irreversible change in shape, e.g. by swelling, at temperatures below 121 °C and / or under the influence of steam.

18. Microtiter plate according to one of the preceding claims, characterized in that at least one of the components (1 , 20, 30), preferably apart from the mechanical connecting means, all components (1 , 20, 30) are made of material that is dimensionally stable at more than 121 °C, steam-stable and / or gamma-ray-stable.

19. Microtiter plate according to one of the preceding claims, characterized in that the first component (1) is designed such that, in combination with two adjacent components (1, 20, 30), it forms two parallel- has intersecting interfaces (3, 8) with several parallel medium-density channels for the transition of at least one component between the depressions.

20. Microtiter plate according to one of the preceding claims, characterized in that the microtiter plate (100) has sealing points which are arranged exclusively along the interfaces (3, 8) between each two adjacent building blocks (1 , 20, 30) with each having at least one series of recesses (2, 21 , 31 ).

21. Microtiter plate according to one of the preceding claims, characterized in that the recesses (31) of the second component (30) differ from the shape and / or design of the recesses (2) of the first component (1).

22. Microtiter plate according to one of the preceding claims, characterized in that the microtiter plate (100) has a rectangular base and a total, i.e., comprising all building blocks, exactly 12, exactly 48, exactly 72, exactly 96, exactly 284 or exactly 288 wells.

23. Microtiter plate according to one of the preceding claims, characterized in that the components (1 , 20, 30) of the microtiter plate (100) are made of transparent plastic material.

24. Microtiter plate according to one of the preceding claims, characterized in that the membrane (25) and / or sealing means, in particular sealing rings, are bonded along the interface with the first and / or second component, in particular by injection molding.

25. Microtiter plate according to one of the preceding claims, characterized in that the components (1 , 20, 30) are connected to each other via snap connections.

26. Microtiter plate according to one of the preceding claims, characterized in that the recesses (2, 21, 31) of the building blocks (1, 20, 30) have a circular cross-section.

27. Microtiter plate according to one of the preceding claims, characterized in that the microtiter plate (100) has additional, preferably peripheral- laterally arranged, depressions (15) without a connection for mass transport with a membrane as a reservoir for evaporation compensation.

28. Method for assembling a multi-part microtiter plate (100) comprising a plurality of building blocks (1 , 20, 30), in particular according to one of the preceding claims, characterized by the following steps: A selection between a sequence of two, three or more separation steps and determination of the number of fluid-connected wells (2, 21, 31) and building blocks (1, 20, 30); B Selection of the components to be separated and determination of membranes (25) tailored to the separating components from a variety of membranes with different separation characteristics; and / or Selection of membrane (25) from a variety of membranes with different separation characteristics; C. Provide a first building block (1) with at least one first row (16, 17) of depressions (2) for receiving a sample and a second building block (20, 30) with a further row of depressions (21, 31), and D Fixation of the building blocks (1 , 20, 30) to form the microtiter plate (100) by forming the sequence of fluid-connected connections depending on the separation steps selected in step A, wherein a membrane (25) determined or selected in step B is arranged along each connection between the wells (2, 21 , 31 ) of the building blocks (1 , 20, 30).

29. Method according to claim 28, characterized in that the membranes (25) are materially bonded to the building block (1 , 20, 30) by injection molding.

30. Method according to one of the preceding claims, characterized in that in step B a membrane (25) is selected individually for each connection of two recesses (2, 21 , 31 ).

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