WO2025237604A1 - Plaque de microtitration en plusieurs parties - Google Patents

Plaque de microtitration en plusieurs parties

Info

Publication number
WO2025237604A1
WO2025237604A1 PCT/EP2025/060105 EP2025060105W WO2025237604A1 WO 2025237604 A1 WO2025237604 A1 WO 2025237604A1 EP 2025060105 W EP2025060105 W EP 2025060105W WO 2025237604 A1 WO2025237604 A1 WO 2025237604A1
Authority
WO
WIPO (PCT)
Prior art keywords
microtiter plate
building blocks
plate according
recesses
component
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2025/060105
Other languages
German (de)
English (en)
Inventor
Lukas SCHWYTER
Rolf KÜMMERLI
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zurich Universitaet Institut fuer Medizinische Virologie
Original Assignee
Zurich Universitaet Institut fuer Medizinische Virologie
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zurich Universitaet Institut fuer Medizinische Virologie filed Critical Zurich Universitaet Institut fuer Medizinische Virologie
Publication of WO2025237604A1 publication Critical patent/WO2025237604A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/028—Modular arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/126—Paper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/508—Rigid containers without fluid transport within
    • B01L3/5085—Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates
    • B01L3/50855—Rigid containers without fluid transport within for multiple samples, e.g. microtitration plates using modular assemblies of strips or of individual wells

Definitions

  • the present invention relates to a multi-part microtiter plate and its assembly.
  • 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.
  • 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.
  • the insertion method is particularly challenging with regard to sealing the membrane at its edges.
  • 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.
  • 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.
  • the object of the present invention is to provide a microtiter plate which satisfactorily solves the aforementioned problems and has a structure with few components, so that it can be manufactured in particular as a mass-production-suitable variant.
  • the present invention solves the aforementioned problem by means of a microtiter plate with the features of claim 1.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • the first component is formed in one piece.
  • This one-piece construction may, but need not, include connecting means for fixing it to the adjacent second component.
  • clamping or locking elements may be formed as part of the one-piece component.
  • mechanical connecting means e.g., made of a different material than the first component, may also be provided for connecting several components. These could, for example, be one or more connecting screws.
  • These components are not part of the single-piece building block.
  • the single-piece nature can also be achieved, in particular, by the material-bonded connection of several building block segments. However, it is especially preferred if the single-piece nature of the building block is achieved through a monolithic design.
  • the building block can be manufactured as a monolithic block by injection molding.
  • the second component can also be made in one piece.
  • 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.
  • 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.
  • microtiter plate described above can be mass-produced with just a few steps.
  • the recesses of the second building block differ from the shape and/or design of the recesses of the first building block.
  • 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.
  • 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 building block and the second building block.
  • the said second building block can
  • the first building block has a depression for the formation of two connections for mass transport to the two adjacent building blocks.
  • the first building block may have a depression for the formation of only one connection for mass transport to the adjacent second building block.
  • 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.
  • membranes preferably semipermeable membranes
  • membranes are arranged between the recesses of the two building blocks, particularly along the interface between the two building blocks.
  • one membrane is arranged per connection.
  • first membrane along the first junction of the second building block with an adjacent first or second building block
  • second membrane along the second junction of the second building block with an adjacent first or second building block
  • the first membrane has a different permeability than the second membrane.
  • 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 the like.
  • the fixing is designed as a releasable fixation, such that the components are fixed in a removable manner. This allows the components of the microtiter plate to be cleaned particularly efficiently after use and reused.
  • 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.
  • Sealing elements preferably sealing rings, especially O-rings, can be provided in the area of the respective connections between two components.
  • the sealing rings can be directly attached to one of the two components using an injection molding process. Components for forming the connection are attached. Alternatively or additionally, the membranes can also be attached to the components using injection molding.
  • the fixing can be achieved by two or more corresponding clamping, plug-in, or locking elements that are integrally attached to the building blocks.
  • plug-in elements can be designed as a projection and a corresponding recess.
  • 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.
  • 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.
  • 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.
  • 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 diffuse through it.
  • 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.
  • the installation of 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.
  • At least one of the components 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 in the scope of this application are not the aforementioned mechanical fasteners, such as screws, nuts, and the like.
  • At least one of the 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.
  • At least one of the building blocks can alternatively be made of a material that is dimensionally stable at more than 121 °C, steam-stable and/or gamma-ray-stable. It must be made of material. This variant allows for multiple uses, especially through CIP (clean in place) cleaning and/or gamma ray sterilization.
  • 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.
  • 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.
  • 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.
  • 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.
  • a method for assembling a microtiter plate according to the invention comprises the following steps:
  • 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 Specification of a data set relating to a position between exactly two recesses of two adjacent building blocks and a specification of the membrane provided for this position, preferably by specifying the membrane thickness and/or the membrane material;
  • 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;
  • Step d Assembling the building blocks to form the microtiter plate
  • Step e Fixing the building blocks.
  • a membrane at one interface can be made of a different membrane material than another membrane located along the interface in an adjacent channel.
  • step b) 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).
  • 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.
  • step a Particularly advantageous in the context of specifying this additional data set is the selection of building blocks in step a).
  • This allows the data set to be used for this purpose.
  • an automated selection of building blocks for assembling the microtiter plate e.g. a marginal segment as a building block of the microtiter plate or a double-row middle segment as a building block of the microtiter plate or a single-row middle segment as a building block of the microtiter plate or the like.
  • the selection of the component sequence and the choice of the membrane as variable elements of the microtiter plate are thus complemented by 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.
  • 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.
  • 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.
  • each building block can have specific fixing channels for the insertion of screws or similar fasteners, allowing the building blocks to be connected by mechanical means, in particular by screwing. These fixing channels are spatially separate from the recesses in the building block.
  • 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.
  • each building block is 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.
  • Individual connections can also be provided without a membrane.
  • two interconnected depressions can be used to define a larger intake volume. Up to 12 depressions can also be interconnected.
  • the microtiter plate can be used as part of automated sampling and/or sample delivery.
  • the fluid-tight connection between two building blocks can be ensured via an O-ring seal.
  • Fig. 1 Top view of a first component of a microtiter plate according to the invention
  • FIG. 2 Ground view of the building block of Fig. 1 ;
  • Fig. 3 Side view of the building block of Figs. 1 and 2;
  • FIG. 4 Side view of a first interface of the component of Fig. 1-3;
  • FIG. 5 Side view of a second interface of the component of Fig. 1-4;
  • FIG. 6 Top view of a second component of the microtiter plate according to the invention.
  • FIG. 7 Ground view of the building block of Fig. 6;
  • FIG. 8 Side view of the building block of Figs. 6 and 7;
  • FIG. 9 Side view of a first interface of the component of Fig. 6-8;
  • FIG. 10 Side view of a second interface of the component of Fig. 6-9;
  • FIG. 11 Perspective view of the microtiter plate
  • Fig. 12 Schematic diagram of the operation of the microtiter plate.
  • 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 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.
  • 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.
  • the building block 1 has one side with two interfaces 3 and 8, at which the building block can be connected to further building blocks 1, 20 and 30.
  • the connection between components 1, 20, and 30 is achieved via a clamping or snap-fit connection.
  • They have a mounting direction A, preferably a plug-in direction, which in the embodiment of Figs. 1-10 simultaneously represents the longitudinal extent of the microtiter plate.
  • 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.
  • 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.
  • 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.
  • a membrane 25 whose function will be discussed later, 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 membrane 25 extends over the entire cross-section of the channel.
  • material protrusions are arranged along the interface 3 or 8, which are designed as additional flexible sealing strips 5, 5'.
  • each building block has 1 corresponding plug-in elements, e.g. projections 7a, 7b, 7a' and 7b' and projection receptacles 9b and 9a'.
  • the plug-in elements are arranged along the edge of the building block 1 beyond the recesses 2, which have a standardized, equal distance from each other. This means that the recesses – or “wells” – cannot be machined with existing machines. High-throughput, automatically fillable or with pipettes featuring a multi-tip attachment where the tip spacing is always consistent. This allows the microtiter plates to be used in existing laboratory systems.
  • the building block also features a rod guide 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, such as screw heads, can also be guided through the rod guide channel, thus enabling the coupling of several building blocks 2, 20 and/or 30 by a mechanical connecting element.
  • 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.
  • 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.
  • the building block 1, 20, 30 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.
  • FIG. 6-10 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.
  • the edge component 20 shown in Fig. 6-10 also has at least one series of recesses 2, each of which has 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 Fig. 1-5. Parallel to this row runs a second row with recesses 21, which can be used, for example, for holding a reference sample, for zero adjustment, or for calibration. These recesses are closed on all sides, i.e., they have no through-opening 12.
  • 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.
  • 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.
  • 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.
  • 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.
  • component 30 has only a single row of recesses 31.
  • 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.
  • the individual building blocks can be made from a single-use material, such as laminated or coated cardboard and/or
  • the device is made of disposable plastic.
  • a custom-selected membrane can be positioned in the channel between the adjacent interfaces of two components. This means that, particularly when choosing semipermeable membranes, factors such as pore size or polarity of the membrane material must be specifically tailored to the samples filled in the two wells.
  • 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.
  • 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.
  • 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.
  • microtiter plate described above can therefore be manufactured industrially in large quantities.
  • one or more, in particular all, of the building blocks 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.
  • This modular microtiter plate design is reusable, particularly multiple times. It is suitable, for example, for experimental laboratories at universities.
  • the membrane should ideally be replaced after each experiment. Nevertheless, the waste to be disposed of can be limited to the membrane itself.
  • the additional building blocks and mechanical connecting elements for fixing them can be used multiple times and, by disassembly, also in a different configuration of building blocks and/or by replacing the semipermeable membrane between building blocks 2, 20, 30.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • a set of wells can be connected by a channel and a permeable membrane.
  • the setup can be used for chemical detection, signal transmission, and/or data 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.
  • 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.
  • this configuration can also enable chemical sensing, signal transduction, and/or the exchange of metabolic products without direct physical contact.
  • 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.
  • 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.
  • each component can be dishwasher-safe and steam-sterilised or autoclaved at 121 °C.
  • certain or all components of the microtiter plates can be sterilized by steam, so that all parts (except the membranes) can be reused.
  • the microtiter plate especially in its reusable version, makes it possible to minimize waste and costs for users and to reduce the ecological footprint.
  • the building blocks are preferably manufactured by injection molding and are also preferably fixed together with a small number of mechanical connecting elements and with just a few steps, using only two mechanical connecting elements, particularly preferably two screws or two threaded rods.
  • 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.
  • 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.
  • 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.
  • 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.
  • the customer can choose from three or more different modules and any membrane properties.
  • microtiter plate enables chemical detection, signal transmission and the exchange of metabolites between two or more wells without direct physical contact.
  • 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.

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  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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Abstract

L'invention concerne une plaque de microtitration (100) comprenant : un premier module (1) ayant au moins une première rangée (16, 17) de puits (2) pour recevoir un échantillon ; et un second module (20, 30) ayant une autre rangée de puits (21, 31), au moins le premier module (1) étant formé d'un seul tenant et étant fixé au second module (20, 30) de manière à fournir un raccordement permettant le transfert de matériau entre chaque puits (2, 21, 31) des premier et second modules (1, 20, 30), la plaque de microtitration (100) étant conçue sous la forme d'une plaque de microtitration en plusieurs parties (100).
PCT/EP2025/060105 2024-05-17 2025-04-11 Plaque de microtitration en plusieurs parties Pending WO2025237604A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE202024102565.2U DE202024102565U1 (de) 2024-05-17 2024-05-17 Mehrteilige Mikrotiterplatte
DE202024102565.2 2024-05-17

Publications (1)

Publication Number Publication Date
WO2025237604A1 true WO2025237604A1 (fr) 2025-11-20

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PCT/EP2025/060105 Pending WO2025237604A1 (fr) 2024-05-17 2025-04-11 Plaque de microtitration en plusieurs parties

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DE (1) DE202024102565U1 (fr)
WO (1) WO2025237604A1 (fr)

Citations (6)

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US20180015459A1 (en) * 2014-12-18 2018-01-18 Ikerlan, S. Coop. Disposable device for performing plurality of simultaneous biological experiments in fluidic samples
EP3415607A1 (fr) 2016-02-12 2018-12-19 Ginreilab Inc. Instrument multipuits
US20190314812A1 (en) * 2016-05-20 2019-10-17 The University Of Dundee Skin sample culture and membrane test device
US20200188913A1 (en) 2018-12-12 2020-06-18 Wisconsin Alumni Research Foundation Platform And Method For Multi-Variable Screening
EP3115449B1 (fr) * 2015-07-08 2020-09-09 IVTech S.r.l. Plaquette à puits multiples pour cultures cellulaires
US20240058819A1 (en) * 2022-08-18 2024-02-22 Cerillo, Inc. Modular well plate system with a reusable frame

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DE10324397A1 (de) * 2003-05-28 2005-01-20 Hte Ag The High Throughput Experimentation Company Modulares Probenhalterungssystem
WO2005025749A1 (fr) * 2003-09-08 2005-03-24 Irm, Llc Recipients multi-puits, systemes, et procedes d'utilisation
US7553671B2 (en) * 2004-05-25 2009-06-30 Vertex Pharmaceuticals, Inc. Modular test tube rack
US20240060026A1 (en) * 2022-08-18 2024-02-22 Cerillo, Inc. Manufacturable co-culture module

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Publication number Priority date Publication date Assignee Title
US20180015459A1 (en) * 2014-12-18 2018-01-18 Ikerlan, S. Coop. Disposable device for performing plurality of simultaneous biological experiments in fluidic samples
EP3115449B1 (fr) * 2015-07-08 2020-09-09 IVTech S.r.l. Plaquette à puits multiples pour cultures cellulaires
EP3415607A1 (fr) 2016-02-12 2018-12-19 Ginreilab Inc. Instrument multipuits
US20190314812A1 (en) * 2016-05-20 2019-10-17 The University Of Dundee Skin sample culture and membrane test device
US20200188913A1 (en) 2018-12-12 2020-06-18 Wisconsin Alumni Research Foundation Platform And Method For Multi-Variable Screening
US20240058819A1 (en) * 2022-08-18 2024-02-22 Cerillo, Inc. Modular well plate system with a reusable frame

Non-Patent Citations (1)

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Title
CHARLES JO ET AL.: "Construction and Modeling of a Coculture Microplate for Real-Time Measurement of Microbial Interactions", ASM JOURNALS; MSYSTEMS, vol. 8, no. 2, Retrieved from the Internet <URL:https://doi.org/10.1128/msystems.00017-21>

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