EP4245415A1 - Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes - Google Patents

Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes Download PDF

Info

Publication number
EP4245415A1
EP4245415A1 EP22162110.5A EP22162110A EP4245415A1 EP 4245415 A1 EP4245415 A1 EP 4245415A1 EP 22162110 A EP22162110 A EP 22162110A EP 4245415 A1 EP4245415 A1 EP 4245415A1
Authority
EP
European Patent Office
Prior art keywords
well
film component
sample assay
sample
grid
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.)
Withdrawn
Application number
EP22162110.5A
Other languages
English (en)
French (fr)
Inventor
Günther KNEBEL
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.)
Scienion GmbH
Original Assignee
Scienion GmbH
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 Scienion GmbH filed Critical Scienion GmbH
Priority to EP22162110.5A priority Critical patent/EP4245415A1/de
Publication of EP4245415A1 publication Critical patent/EP4245415A1/de
Withdrawn legal-status Critical Current

Links

Images

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/52—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
    • B01L9/523—Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips for multisample carriers, e.g. used for microtitration plates
    • 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—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
    • B01L3/50853—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates with covers or lids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02—Adapting objects or devices to another
    • B01L2200/025—Align devices or objects to ensure defined positions relative to each other
    • 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
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater

Definitions

  • the invention relates to a sample assay apparatus for accommodating a plurality of samples, in particular a sample assay apparatus comprising a well film component having sample wells and a carrier device supporting the well film component. Furthermore, the invention relates to a sample assay reaction apparatus, comprising the sample assay apparatus and a tempering device, and to a sample assay module arrangement, comprising at least two sample assay apparatuses. Furthermore, the invention relates to a method of manufacturing the sample assay apparatus. Applications of the invention are available e. g. in chemistry and biochemistry, in particular for processing biological samples, e. g. for executing PCR reactions. According to a particular example, the invention relates to a test plate, e. g. with 1536 wells, for High Speed RT-PCR in Single Cell Applications.
  • Reaction plates test chips or test plates, in particular micro or nano titer plates
  • a reaction plate has a plane array of sample wells, which usually are arranged with a standardized matrix format which is matched to processing and monitoring equipment, like droplet dispensing machines, temperature setting units and microscopes.
  • processing and monitoring equipment like droplet dispensing machines, temperature setting units and microscopes.
  • Reaction plates usually are made of plastic materials by injection moulding with low costs (see e. g. [1] to [3]).
  • a plastic plate with a matrix arrangement of wells is provided, e. g. with the size of microscope slide.
  • the sample wells are formed by injection moulding. This technique has multiple disadvantages resulting from the injection moulding of the sample wells. Injection moulding requires relatively thick walls of the sample wells, resulting in a low sample well volume and a high thermal mass.
  • Usual reaction plates allow setting of a plate temperature, e. g. for isothermal PCR reactions. However, as the high thermal mass requires long cooling or heating periods, they have limits when fast temperature cycles are required, e. g. for more complex PCR reactions (see e. g. [3]).
  • [4] proposes manufacturing a reaction plate made by embossing sample wells in a plastic carrier tape and mounting the tape on a frame.
  • This technique allows a reduction of the wall thickness.
  • the wall thickness reduction is limited as a stable plane arrangement of the carrier tape on the frame is required.
  • the technique of [4] may have disadvantages in terms of reliability in practical use, limited capability of modular coupling, costs and creating complex sample well shapes, as described e. g. in [5] or [6].
  • the objective of the invention is to provide an improved sample assay apparatus for accommodating and/or processing a plurality of samples, an improved sample assay reaction apparatus including the sample assay apparatus, an improved sample assay module arrangement of at least two sample assay apparatuses and an improved method of manufacturing the sample assay apparatus, wherein disadvantages of conventional techniques are avoided.
  • the sample assay apparatus is to be capable of providing sample wells with a reduced wall thickness, an improved wall thickness to vessel volume ratio, reduced thermal mass, a high packing density, and an increased stability and reliability.
  • the sample assay apparatus is to be capable of facilitating fast temperature setting, in particular thermocycling, and/or modular coupling of multiple sample assay apparatuses.
  • the method of manufacturing the sample assay apparatus is to be executed with reduced complexity and costs.
  • a sample assay apparatus a sample assay reaction apparatus, a sample assay module arrangement of at least two sample assay apparatuses and/or a method of manufacturing the sample assay apparatus, comprising the features of the independent claims.
  • Advantageous embodiments and applications of the invention are defined in the dependent claims.
  • a sample assay apparatus (or: test plate), being configured for accommodating and in particular processing a plurality of samples, comprising a well film component extending along a main film plane and being shaped for providing a plurality of sample wells (or: reaction vessels, compartments) deepening in a direction perpendicular to the main film plane, and a carrier device being arranged for supporting the well film component and comprising a circumferential carrier frame with an internal frame opening, wherein the well film component contacts the carrier frame.
  • the carrier device further comprises a supporting grid with grid webs surrounding grid openings, wherein the supporting grid is arranged in the internal frame opening in connection with the carrier frame and the supporting grid extends parallel to the main film plane, the well film component is fixedly connected to the carrier frame, and the well film component is supported by the grid webs.
  • the carrier device is made of plastics
  • the supporting grid is coupled to the carrier frame by injection molding. Accordingly, the carrier frame and the supporting grid preferably provide the carrier device as a monolithic, integral component.
  • the above objective is solved by the sample assay reaction apparatus according to the first general aspect of the invention or an embodiment thereof, and a tempering device, in particular a heating and/or cooling device, in particular at least one PCR thermocycler block.
  • a sample assay module arrangement comprising at least two sample assay apparatuses according to the first general aspect of the invention or an embodiment thereof, wherein the at least two sample assay apparatuses are arranged side by side with an extension parallel to the main film plane.
  • the at least two sample assay apparatuses are separate modules.
  • the at least two sample assay apparatuses may be connected via at least one connecting component between adjacent frame sections of the carrier frames thereof.
  • the sample assay apparatuses of the sample assay module arrangement can be provided with a common well film component, which is arranged on all (sub-)frames of the sample assay apparatuses.
  • the above objective is solved by a method of manufacturing the sample assay apparatus according to the first general aspect of the invention or an embodiment thereof, comprising the steps of forming the well film component including the wells by shaping a deformable film, forming the carrier device with the circumferential carrier frame and the supporting grid arranged in the internal frame opening of the carrier frame, and connecting the well film component and the carrier device, so that the well film component is supported by the carrier device.
  • Shaping the deformable film may comprise thermo-forming a plane film material or creating the deformed film, e. g. by injection molding or by 3D printing.
  • At least one of the carrier device and the well film component is made by injection molding, injection compression molding, deep-drawn process, thermoforming or a combination of these processes.
  • the well film component and the carrier device can be formed separately from each other and connected subsequently.
  • the well film component and the carrier device can be integrally formed so that they are connected to each other.
  • the sample assay apparatus is a plate-shaped substrate with receptacles for a plurality of separately accommodated samples. Despite of the light-weight composition of the frame-shaped carrier device and the well film component, the sample assay apparatus is called a plate. Due to the rigid carrier device, the sample assay apparatus has a stability like a conventional test plate.
  • the carrier frame is a self-supporting, shape-retentive component.
  • the sample assay apparatus is dimensioned like a conventional test plate, in particular with a standardized size, which is adapted to laboratory equipment.
  • the well film component is a flexible film (or: foil) sheet, particularly preferred providing a continuous sheet material (sheet material without holes).
  • the film sheet comprises plane sheet sections and the plurality of sample wells extending perpendicular to the plane sheet sections.
  • the side of the well film component, where the samples wells are open, e. g. for sample supply or monitoring purposes, is called upper side of the sample array apparatus, while the opposite side, where the sample wells are closed by the bottoms thereof, is called bottom side of the sample array apparatus.
  • the plane sheet sections provide the film material between and around the sample wells in the main film plane.
  • the extensions of the plane sheet sections are determined by the arrangement and distribution of the sample wells along the well film component. Larger plane sheet sections are provided along the outer border of the well film component for a support by the carrier frame and between arrays of sample wells for a support by the grid webs. Between individual sample wells within an array of sample wells, the plane sheet sections may be substantially narrower. Due to the improved mechanical stability of the sample array apparatus, the sample wells can be provided with an improved wall thickness to vessel volume ratio.
  • the sample wells preferably provide at least one well array, wherein the sample wells are arranged as a matrix with straight rows and columns.
  • the at least one well array has a standardized matrix format, e. g. with 8 ⁇ 12 sample wells on a rectangular area of approximately 16 mm ⁇ 24 mm or 32 ⁇ 48 sample wells on a rectangular area of approximately 70 mm ⁇ 100 mm.
  • a centre to centre distance of neighbouring sample wells is equal or less than 2,25 mm, e. g. approximately 1,5 mm.
  • the provision of the supporting grid allows the creation of the well film component with a reduced material thickness, in particular a reduced thickness of the sample well walls, while keeping a sufficient mechanical stability of the well film component.
  • the plane sheet sections of the well film component or even sections between neighbouring sample wells are carried by the carrier frame and the supporting grid while the sample wells protrude though the grid openings.
  • the supporting grid is formed such that a plurality of sample wells (sub-array of sample wells) is arranged in each grid opening.
  • the grid webs of the supporting grid are straight rod-like elements, e. g. with a rectangular cross-section, which are arranged such that the grid openings have a rectangular shape.
  • the grid webs preferably have a cross-sectional dimension in a range from 800 ⁇ m to 3 mm. With a practical example, the grid webs have an approximately rectangular cross-section of 2 mm ⁇ 1,2 mm.
  • the well film component Due to the reduced material thickness, the well film component has a reduced overall mass, compared with conventional reactions plates, resulting in a low heat capacity (low thermal mass) and a capability of fast and precise temperature changes, while keeping the stability of the test plate.
  • the sample wells are exposed in the grid openings towards the bottom side.
  • the sample wells can be brought into direct contact with the tempering device, in particular an actively heating or cooling part thereof, further facilitating fast temperature setting, in particular thermocycling.
  • the test plate can be produced pretty inexpensive by thermoforming. A large variety of suitable thermoplastic materials with low DNA binding is available, thus providing particular advantages for PCR reaction applications of the test plate.
  • the sample assay apparatus allows an optimization and adaptation of mechanical stability through variation in film and/or grid web thicknesses.
  • the well film component allows a simple positioning of the test plate by vacuum during filling the sample wells.
  • the sample assay apparatus has a reduced number of disposable parts. It is cheaper and more efficient, allowing a higher throughput of test plate applications.
  • a funnel shape of the sample wells can be converted into a test plate format for e. g. 1536 wells, and the funnel can be made by thermoforming (e. g. with a film thickness of less than 1 mm), while there is no more a need for injection molding.
  • the shape of the sample assay apparatus can be matched to available centrifuge adapters, in particular for a test plate format for 1536 wells, instead of e. g. 4 ⁇ 384 wells in current techniques, and allows a less labor-intensive handling.
  • the combination of the low thermal mass of the inventive test plate and the supporting grid in particular with the arrangement of the individual 96-well arrays, makes it possible to reliably dip into the sample assay apparatus from below with a PCR block (see below) and make the test plate accessible for largely automated processing.
  • This grid structure then also enables scalability for larger formats, e.g. 1536 wells.
  • the carrier frame has a circumferential film carrying surface parallel to the main film plane, and the well film component is fully or partially connected with the film carrying surface.
  • the circumferential film carrying surface is a plane section of the carrier frame facing to the upper side of the test plate.
  • the film carrying surface facilitates the reliable coupling of the well film component with the carrier frame.
  • the well film component is coupled with the carrier frame exclusively via the film carrying surface. Thus, bending or folding of the well film component, in particular at the outer border plane sheet sections can be avoided.
  • the well film component comprises an arrangement of multiple well arrays, where the sample wells are provided, and plane film sections extending between the well arrays, and the well film component is supported by the grid webs along the plane film sections, wherein the well arrays protrude through the grid openings surrounded by the grid webs, in particular to the bottom side of the sample array apparatus.
  • one well array may be arranged in each of the grid openings.
  • the grid webs surrounding one of the well arrays provide a plane support of the well array.
  • the well film component may comprise a single well array comprising an arrangement, e. g. matrix arrangement of the sample wells.
  • plane film sections are provided around the single well array only, and the well film component is supported by the grid webs between the sample wells of the well array. Groups of sample wells protrude through the grid openings surrounded by the grid webs.
  • the carrier frame has a graduated frame profile with upper profile surfaces and lower profile surfaces, and shapes of the upper and lower profile surfaces are matched to each other so that the carrier frame can be stacked with a neighboring carrier frame of another sample assay apparatus with the lower profile surface resting on the upper profile surface of the neighboring carrier frame, preferably in a form-fitting manner.
  • the upper profile surface faces to the upper side
  • the lower profile surface faces to the bottom side of the sample array apparatus.
  • the graduated frame profile facilitates a modular coupling of multiple sample assay apparatuses as a stack.
  • the upper profile surfaces may include stacking cams being arranged for carrying the lower profile surface of a stacked carrier frame.
  • the well film component is fully or partially connected to the grid webs, the stability of the sample array apparatus and the provision of a plane well film component can be improved in an advantageous manner.
  • connections of the well film component with the carrier device are available.
  • the well film component may be connected to the carrier device via a riveted connection, a bonding connection, an adhesive connection or a combination of at least two of the listed connection methods.
  • connection methods have particular advantages in terms of reliability of fixing the well component to the carrier device and easy execution in manufacturing the sample array apparatus.
  • the riveted connection or a clamping connection may have advantages over solvent or adhesive based connections or thermal bonding as the well film component or the samples cannot be influenced by the riveted or clamping connections.
  • the carrier frame and the grid webs may have recesses being open towards the well film component, wherein the recesses are arranged for accommodating excess adhesive of the adhesive connection.
  • the recesses may comprise grooves extending along the lengths of the carrier frame or grid web surfaces, or they may comprise multiple recess sections, e. g. arrangements of groove shaped recesses or pits in the respective surfaces.
  • the recesses facilitate a plane, aligned connection of the well film component with the carrier device. Deviations from the plane shape or unintended protrusions on the bottom side of the sample wells which could be created by excess adhesive are avoided as any possible excess adhesive is introduced into the recesses.
  • the well film component can be a deep-drawn, thermoformed, injection molded or injection compression molded component.
  • the well film component may have a film thickness in a range from 20 ⁇ m to 1000 ⁇ m, in particular in a range from 50 ⁇ m to 800 ⁇ m. With a thickness below 50 ⁇ m, in particular below 20 ⁇ m, the stability of the well film component may be impaired.
  • the well film component is a thermoplastic component, in particular made of at least one of PP, PET, PC, COC and COP. These materials have advantages in terms of the formability and stability during thermocycling. PP and COP are particularly preferred as it has a low protein binding capability.
  • the wells have a conus shape with a flat well bottom, e. g. as disclosed in [5] or [6].
  • the well film component has a well bottom film thickness in a range from 100 ⁇ m to 500 ⁇ m.
  • this thickness range facilitates a fast temperature setting of the sample at the well bottom and a monitoring of the sample.
  • the well film component is made of a transparent, in particular optically clear plastic, advantages for optically investigating at least one or preferably all samples in at least one or up to all of the sample wells can be obtained.
  • microscopic and/or spectroscopic measurements can be executed at the sample(s) in the sample well(s).
  • the well film component has a multilayer structure, including multiple plastic layers or multiple metal layers or a combination of at least one plastic layer and one metal layer.
  • the multilayer structure advantages for adapting the well film component to particular functions can be obtained.
  • at least one plastic layer can be provided for obtaining a high mechanical stability of the well film component, while at least one metal layer can be provided for ensuring a high thermal conductivity and heat distribution, or reflection of thermal radiation.
  • the carrier frame is made of plastics, in particular at least one of PS, PET, PC, COC and COP. These materials facilitate the fixation of the well film component. Furthermore, they allow an easy formability for manufacturing the sample assay apparatus and a high stability during thermocycling.
  • the carrier frame is reinforced with at least one of glass fibers, glass balls and an inorganic powder.
  • the carrier frame is an integral, monolithic component.
  • both features provide an increased mechanical stability of the sample assay apparatus.
  • the grid webs and grid openings of the supporting grid are dimensioned and shaped such that the grid openings are capable of accommodating a tempering device, in particular a heating and/or cooling device, in particular at least one PCR thermocycler block, especially a tempering component thereof.
  • Available tempering devices usually have at least one tempering block with a size and shape being adapted to the matrix format of the sample well arrays of available test plates.
  • the tempering block includes at least one of a resistance heater and a Peltier cooler, which are adapted for heating and/or cooling the sample wells, resp..
  • the supporting grid is configured that the at least one tempering block can protrude into the at least one grid opening for a direct contact with the sample wells being arranged in the grid opening.
  • the sample assay apparatus is provided with an empty condition of the sample wells.
  • Samples and/or processing liquids can be supplied by the user/applicant of the sample assay apparatus.
  • the sample assay apparatus can be provided with a pre-filled condition.
  • At least one or preferably all of the sample wells may include a processing liquid.
  • the processing liquid(s) may be selected in dependency on the sample reactions and investigations to be executed.
  • the optionally pre-filled sample assay apparatus (sample assay reaction kit), in particular a pre-filled sample assay apparatus for PCR reactions, can be considered as an independent subject of the invention.
  • the sample assay apparatus can be provided with a cover film covering the well film component.
  • the cover film can be employed for closing at least one or preferably all of the sample vessels at the upper side of the well film component.
  • the cover film creates a simple sealing of the sample vessel(s). It can be provided with an empty test plate, e. g. for keeping a sterile condition before use, or with a pre-filled test plate, e. g. for avoiding a leakage of the sample(s) and/or processing liquid(s).
  • the cover film can be applied to the well film component before or after connecting the well film component with the carrier frame.
  • pre-filled parts can be inspected prior or after assembly of the sample assay apparatus.
  • sample assay apparatus the sample assay reaction apparatus and the sample assay module arrangement or the embodiments thereof also represent preferred features of the inventive method of manufacturing the sample assay apparatus or the embodiments thereof and vice versa.
  • the preferred embodiments, variants and features of the invention described above are combinable with one another as desired.
  • Figures 9 and 10 embodiments of a sample assay reaction apparatus according to the invention.
  • the sample assay apparatus is a test plate which is produced of thermoplastic material and comprises multiple arrays of e. g. 8 ⁇ 12 sample wells (e. g. 16 arrays providing 1536 sample wells), each consisting of an individual low volume nanoliter receptacle with at least one conical side wall and a flat base with a bottom thickness of a maximum of 500 ⁇ m, connected by a common top surface with a maximum thickness of 1000 ⁇ m assembled in the separate carrier frame with dimensions according to the ANSI SLAS 4-2004 format (formerly ANSI / SBS 4-2004, i. e. a nominal plate length of 127.76 mm and a nominal plate width of 85.48 mm).
  • ANSI SLAS 4-2004 format originally ANSI / SBS 4-2004, i. e. a nominal plate length of 127.76 mm and a nominal plate width of 85.48 mm.
  • sample assay apparatus having a modified configuration.
  • the sample assay apparatus can be manufactured either by injection molding, injection compression molding, thermoforming or a combination of these processes.
  • the assembly of the test plate to a semi-rigid holder can be executed e. g. by glueing or ultrasonic welding or thermal bonding.
  • Preferred formats of the sample assay apparatus are 96, 384, 784, 1536, 3456, and 6144 sample wells.
  • the sample assay apparatus 100 comprises a well film component 10 extending along a main film plane (x-y) and including a plurality of sample wells 11, which are arranged as plural well arrays 12 each including 8 ⁇ 12 sample wells 11.
  • the portions of the well film component 10 which are not shaped as well arrays 12 are called plane sheet sections 13.
  • the plane sheet sections 13 are provided at the outer border of the well film component 10 and between the well arrays 12.
  • the sample assay apparatus 100 has a size of e. g.
  • the sample wells 11 extend parallel to a direction (z) perpendicular to the main film plane (x-y). The positive z-direction is directed to the upper side of the sample assay apparatus 100, while the opposite direction is directed to the bottom side of the sample assay apparatus 100.
  • the sample wells 11 are formed e. g. as described in [4] or [5] or with a cylindrical or conical hollow shape.
  • the sample assay apparatus 100 comprises a carrier device 20 supporting the well film component 10.
  • the carrier device 20 comprises a circumferential carrier frame 21 parallel to the main film plane (x-y).
  • the carrier frame 21 encloses an internal frame opening 22, which is partitioned by the inventive supporting grid 23 with crossing grid webs 24 into rectangular grid openings 25. Alternatively, other geometries of the grid openings 25, like triangles, can be provided.
  • the carrier frame 21 preferably has a graduated frame profile 27, which is shown with further details in Figure 6 .
  • the plane sheet sections 13 of the well film component 10 between the well arrays 12 and the grid webs 24 are aligned relative to each other such that the plane sheet sections 13 are supported by the grid webs 24 in the assembled state of the sample assay apparatus 100.
  • the carrier frame 21 has an inner section which provides a circumferential strip-shaped film carrying surface 26 (see also Figures 3 , 5 and 6 ).
  • the well film component 10 has a size being matched to the size of the area enclosed by the film carrying surface 26.
  • the plane sheet sections 13 at the outer border of the well film component 10 are fully or partially fixedly connected with the film carrying surface 26 of the carrier frame 21.
  • the well film component 10 is made of a foil, e. g. a PP foil, with a thickness of e. g. 500 ⁇ m.
  • the sample wells 11 are created e. g. by thermoforming, using a heated tool with a shape and arrangement of the well arrays 12 to be created.
  • the carrier frame 21 and the supporting grid 23 are made of e. g. PP as well, e. g. by injection molding as a monolithic component. Alternatively, the carrier frame 21 can be made e. g. by 3D printing.
  • Figure 1 shows the parts of the sample assay apparatus 100 before assembling. While the carrier frame 21 is self-supporting and shape-retentive, the well film component 10 can be spanned with a plane shape using an appropriate auxiliary tool, like a tool frame (not shown).
  • the well film component 10 and the carrier device 20 are bonded to each other. At least the plane sheet sections 13 at the outer border of the well film component 10 are fully or partially bonded to the film carrying surface 26. Preferably, the plane sheet sections 13 between the well arrays 12 are fully or partially bonded to grid webs 24 as well.
  • the well film component 10 is supported with a plane extension by the carrier device 20.
  • a cover film (not shown) can be provided on the upper surface of the well film component 10.
  • Figures 3 to 6 show further details of the carrier device 20, 20A (partially shown), which can be provided alone or in combination.
  • the top view on a part of the carrier device 20 in Figure 3 shows the carrier frame 21 and the grid webs 24 of the supporting grid 23 injection molded to the carrier frame 21.
  • the upper surfaces of the supporting grid 23 are aligned with the film carrying surface 26, so that the well film component (not shown in Figure 3 ) can be fixed in a plane, step-free manner on the film carrying surface 26.
  • material bulges 24A are formed which improve the mechanical stability of the supporting grid 23.
  • the material bulges 24A advantageously provide space for sufficiently large ejector pins.
  • Figure 3 also illustrates stacking cams 27.3, which are described with further details with reference to Figure 6 .
  • recesses 28 are formed as grooves (open channels) in the upper surfaces of the grid webs 24.
  • the recesses 28 longitudinally extend along the grid webs 24 with a depth in a range of e. g. 100 ⁇ m to 1 mm, preferably 100 ⁇ m to 500 ⁇ m.
  • the recesses 28 accommodate possible excess adhesive.
  • the grooves or other recesses optionally can be provided also in the film carrying surface 26.
  • Figure 5 shows an embodiment of the invention wherein the carrier frame 21 of the carrier device 20 has a T-profile with a long section extending parallel to the main film plane (see Figure 1 ) and a short section extending perpendicular to the main film plane.
  • An upper surface of the long section of the T-profile provides the film carrying surface 26.
  • Figure 6 shows an alternative embodiment of the invention wherein multiple sample assay apparatuses 100, 100A are stacked.
  • the carrier frames 21, 21A of the sample assay apparatuses 100, 100A have the film carrying surfaces 26, 26A and the graduated frame profile 27, 27A with upper profile surfaces 27.1, 27.1A and lower profile surfaces 27.2, 27.2A.
  • the upper profile surfaces 27.1, 27.1A include stacking cams 27.3, 27.3A.
  • the stacking cams 27.3, 27.3A comprise rib-shaped projections, which are arranged such that lower profile surfaces of an upper carrier frame rests on the stacking cams of a lower carrier frame.
  • the stacking cams 27.3, 27.3A have advantages in terms of reducing the thermal contact area between the carrier frames and improved stackability.
  • the upper and lower profile surfaces 27.1, 27.2 of the first, upper sample assay apparatus 100 are arranged such that the carrier frame 21 can be stacked with neighboring carrier frames, e. g. the neighboring carrier frame 21A of the other, lower sample assay apparatus 100A, wherein the lower profile surfaces 27.2 of the upper carrier frame 21 rest on the stacking cams 27.3A of the upper profile surfaces 27.1A of the lower carrier frame 21A and the lower profile surface 27.2A of the lower carrier frame 21A may rest on stacking cams of an upper profile surface of another carrier frame (not shown). Accordingly, multiple sample assay apparatuses can be stacked, e. g. for storing thereof or for cultivating samples in a cultivation environment.
  • FIGS 7A and 7B illustrate embodiments of sample assay module arrangements 300.
  • the sample assay module arrangement 300 comprises two sample assay apparatuses 100.1, 100.2, each with a carrier frame 21.1, 21.2, having a supporting grid (not shown), and with a well film component 11.1, 11.2, as described in particular with reference to Figures 1 and 2 .
  • 768 sample wells can be provided per sample assay apparatus 100.1, 100.2.
  • the carrier frames 21.1, 21.2 are commonly arranged as separate modules, e. g. on a common support or on a tempering device 210 of a sample assay reaction apparatus 200 (see Figures 9 and 10 ).
  • the common support or the tempering device is dimensioned such that multiple modules can be accommodated side by side.
  • the sample assay module arrangement 300 comprises multiple rectangular sample assay apparatuses 100.1, 100.2, 100.3, 100.4, each with a row of four well arrays including 8 ⁇ 12 sample wells.
  • the sample assay apparatuses 100.1, 100.2, 100.3, 100.4 are shown in a separated condition.
  • the carrier frame 21 has multiple, e. g. four cut-outs 29 at the bottom rim of the carrier frame 21, which are arranged for an engagement with a gripper tool for handling the sample assay apparatus 100.
  • the cut-outs 29 are aligned with the grid openings 25 at the ends of the carrier frame 21.
  • the sample assay apparatus 100 has a size of 75 mm ⁇ 12 mm with 384 sample wells 11 in four 96 sample well arrays 12.
  • the sample assay reaction apparatus 200 comprises the sample assay apparatus 100, which is dimensioned e. g. like the sample assay apparatus 100 of Figure 8 and configured like the sample assay apparatus 100 of Figures 1 and 2 , and a tempering device 210.
  • the sample assay apparatus 100 is shown in Figure 9 without the well film component.
  • the tempering device 210 comprises a heating and/or cooling device, like an arrangement of at least one PCR thermocycler block 211 or a contoured temperature setting body, in contact with the well film component 10 including the sample wells 11 (see Figure 10 ) of the sample assay apparatus 100.
  • the surface of the tempering device 210 accommodating the sample assay apparatus 100 is formed complementary to the lower surface of the sample assay apparatus 100, in particular the well film component 10 thereof, so that the well film component 10 and the sample wells 11 can contact the surface in a form-fitting manner.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
EP22162110.5A 2022-03-15 2022-03-15 Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes Withdrawn EP4245415A1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP22162110.5A EP4245415A1 (de) 2022-03-15 2022-03-15 Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP22162110.5A EP4245415A1 (de) 2022-03-15 2022-03-15 Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes

Publications (1)

Publication Number Publication Date
EP4245415A1 true EP4245415A1 (de) 2023-09-20

Family

ID=80781031

Family Applications (1)

Application Number Title Priority Date Filing Date
EP22162110.5A Withdrawn EP4245415A1 (de) 2022-03-15 2022-03-15 Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes

Country Status (1)

Country Link
EP (1) EP4245415A1 (de)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2288233A (en) * 1994-04-06 1995-10-11 Akzo Nobel Nv Microtitre plate.
US20090298718A1 (en) * 2007-12-21 2009-12-03 Paul Winfield Denman Method and device for forming an assembly
GB2494860A (en) * 2011-09-07 2013-03-27 Abgene Ltd An array of PCR wells and an array of caps for such a well array
US20140206079A1 (en) * 2013-01-24 2014-07-24 Sabic Innovative Plastics Ip B.V. Microwell plate
WO2020225420A1 (en) 2019-05-08 2020-11-12 Scienion Ag Assay plate with nano-vessels and sample recovery assembly

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2288233A (en) * 1994-04-06 1995-10-11 Akzo Nobel Nv Microtitre plate.
US20090298718A1 (en) * 2007-12-21 2009-12-03 Paul Winfield Denman Method and device for forming an assembly
GB2494860A (en) * 2011-09-07 2013-03-27 Abgene Ltd An array of PCR wells and an array of caps for such a well array
US20140206079A1 (en) * 2013-01-24 2014-07-24 Sabic Innovative Plastics Ip B.V. Microwell plate
WO2020225420A1 (en) 2019-05-08 2020-11-12 Scienion Ag Assay plate with nano-vessels and sample recovery assembly

Similar Documents

Publication Publication Date Title
EP1945359B1 (de) Probenplatte und verfahren zur verarbeitung von biologischen proben
JP3586448B2 (ja) 改善された薄ウェルマイクロプレートおよびその作製方法
US7005109B2 (en) System for handling liquid samples
US20070212775A1 (en) Microtiter plate, method of manufacturing thereof and kit
US20120276541A1 (en) Microplates, Reaction Modules and Detection Systems
US20090298718A1 (en) Method and device for forming an assembly
WO2002026377A2 (en) Method and apparatus for processing biomolecule arrays
PT1337336T (pt) Placa de reação
US6386219B1 (en) Fluid handling system and method of manufacture
KR20130142999A (ko) 순응형 멀티웰 플레이트
JP2008509387A (ja) マイクロ流体デバイスを流体処理デバイスと接続する装置及び方法
EP1316360B1 (de) Herstellungsmethoden für dünnwandige Mikroplatte
EP1754538A2 (de) Zweiteilige Mikrowellenplatte und Herstellungsverfahren
EP2035144A2 (de) Hochdichte durchlässige träger für screening mit hohem durchsatz
EP4245415A1 (de) Probentestgerät, probentestmodulanordnung und verfahren zur herstellung des probentestgerätes
US20110064630A1 (en) Multi-well improved plate
EP1979094A1 (de) Mikrofilterplatte, herstellungsverfahren dafür und satz
GB2494860A (en) An array of PCR wells and an array of caps for such a well array
CN108816301B (zh) 微流控芯片及其封装方法、微流控芯片封装用封装配件
EP4249117A1 (de) Verbrauchsmaterial zur probenverarbeitung in einem automatisierten analysegerät
FI122208B (fi) Tarvikesarja ja menetelmä biologisten näytteiden prosessoimiseksi ja näytelevy

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN PUBLISHED

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20240321