EP4245415A1

EP4245415A1 - Sample assay apparatus, sample assay module arrangement and method of manufacturing the sample assay apparatus

Info

Publication number: EP4245415A1
Application number: EP22162110.5A
Authority: EP
Inventors: Günther KNEBEL
Original assignee: Scienion GmbH
Current assignee: Scienion GmbH
Priority date: 2022-03-15
Filing date: 2022-03-15
Publication date: 2023-09-20

Abstract

A sample assay apparatus 100 for accommodating a plurality of samples, comprises a well film component 10 extending along a main film plane and being shaped for providing a plurality of sample wells 11 deepening in a direction perpendicular to the main film plane, and a carrier device 20 being arranged for supporting the well film component 10 and comprising a circumferential carrier frame 21 with an internal frame opening 22, wherein the well film component 10 contacts the carrier frame 21, wherein the carrier device 20 further comprises a supporting grid 23 with grid webs 24 surrounding grid openings 25, the supporting grid 23 is arranged in the internal frame opening 22 in connection with the carrier frame 21 and the supporting grid 23 extends parallel to the main film plane, the well film component 10 is fixedly connected to the carrier frame 21, and the well film component 10 is supported by the grid webs 24. Furthermore, a sample assay module arrangement and a method of manufacturing the sample assay apparatus 100 are described.

Description

Field of the invention

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.

Background of the invention

In the present specification, reference is made to the following prior art illustrating the technical background of the invention, in particular relating to test plates, in particular micro or nano titer plates.

Reaction plates (test chips or test plates, in particular micro or nano titer plates) are generally known tools for processing liquid samples. 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. With the development of high throughput techniques, the sample well volumes have been decreased and the packing density of the vessels has been increased.
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]).
As an alternative to injection moulding, [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. However, the wall thickness reduction is limited as a stable plane arrangement of the carrier tape on the frame is required. Furthermore, 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].

Objective of the invention

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. In particular, compared to conventional techniques, 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. According to a further aspect, 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. Furthermore, the method of manufacturing the sample assay apparatus is to be executed with reduced complexity and costs.

Summary of the invention

The above objectives are solved by 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.
According to a first general aspect of the invention, the above objective is solved by 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.
According to the invention, 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. Preferably, if 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.
According to a second general aspect of the invention, 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.
According to a third general aspect of the invention, the above objective is solved by 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. Preferably, the at least two sample assay apparatuses are separate modules. Optionally, 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. Optionally, 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.
According to a fourth general aspect of the invention, 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. Particularly preferred, 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. Alternatively, the well film component and the carrier device can be integrally formed so that they are connected to each other.
Generally, 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. Preferably, the carrier frame is a self-supporting, shape-retentive component. Preferably, the sample assay apparatus is dimensioned like a conventional test plate, in particular with a standardized size, which is adapted to laboratory equipment.
Preferably, 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. Particularly preferred, 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. Preferably, a centre to centre distance of neighbouring sample wells is equal or less than 2,25 mm, e. g. approximately 1,5 mm.
Advantageously, compared with conventional reactions plates, 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. Preferably, 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. Preferably, the supporting grid is formed such that a plurality of sample wells (sub-array of sample wells) is arranged in each grid opening.
Preferably, 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 µm to 3 mm. With a practical example, the grid webs have an approximately rectangular cross-section of 2 mm ^∗ 1,2 mm.
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.
Preferably, 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 invention provides the following further advantages. 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.
Furthermore, advantages for coupling the sample assay apparatus with available equipment and for replacing available test plates are obtained. In particular, 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.
Advantageously, 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.
According to a preferred embodiment of the invention, 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. Advantageously, the film carrying surface facilitates the reliable coupling of the well film component with the carrier frame. Particularly preferred, 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.
According to a further preferred embodiment of the invention, 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. Advantageously, 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.
Alternatively, the well film component may comprise a single well array comprising an arrangement, e. g. matrix arrangement of the sample wells. In this case, 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. This embodiment may have advantages for providing a sample assay module arrangement.
Particularly preferred, 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, and the lower profile surface faces to the bottom side of the sample array apparatus. Advantageously, the graduated frame profile facilitates a modular coupling of multiple sample assay apparatuses as a stack. Optionally, the upper profile surfaces may include stacking cams being arranged for carrying the lower profile surface of a stacked carrier frame.
If, according to another preferred embodiment of the invention, 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.
Advantageously, multiple types of connections of the well film component with the carrier device are available. Preferably, 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. These 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.
If the well film component is connected to the carrier device via the adhesive connection, at least one of 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. Advantageously, 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.
Further advantages of the invention are obtained by the following features of the well film component which can be provided alone or in combination or sub-combination. Preferably, the well film component can be a deep-drawn, thermoformed, injection molded or injection compression molded component. These manufacturing methods have advantages in terms of obtaining thin wall materials of the well film component and reducing costs of manufacturing. Alternatively or additionally, the well film component may have a film thickness in a range from 20 µm to 1000 µm, in particular in a range from 50 µm to 800 µm. With a thickness below 50 µm, in particular below 20 µm, the stability of the well film component may be impaired. With a thickness above 800 µm, in particular above 1000 µm, disadvantages resulting from an increased thermal mass may be caused. Alternatively or additionally, 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. Alternatively or additionally, the wells have a conus shape with a flat well bottom, e. g. as disclosed in [5] or [6]. Alternatively or additionally, the well film component has a well bottom film thickness in a range from 100 µm to 500 µm. Advantageously, this thickness range facilitates a fast temperature setting of the sample at the well bottom and a monitoring of the sample.
If, according to a further particularly preferred embodiment of the invention, 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. In particular, microscopic and/or spectroscopic measurements can be executed at the sample(s) in the sample well(s).
According to a further preferred embodiment of the invention, 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. With the multilayer structure, advantages for adapting the well film component to particular functions can be obtained. As an example, 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.
Further advantages of the invention are obtained by the following features of the carrier frame which can be provided alone or in combination or sub-combination. Preferably, 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. Alternatively or additionally, the carrier frame is reinforced with at least one of glass fibers, glass balls and an inorganic powder. Alternatively or additionally, the carrier frame is an integral, monolithic component. Advantageously, both features provide an increased mechanical stability of the sample assay apparatus.
Preferably, 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.
For plural applications, 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. Alternatively, 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.
According to further advantageous embodiments 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. Advantageously, 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. Advantageously, pre-filled parts can be inspected prior or after assembly of the sample assay apparatus.
Features disclosed in the context of the 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 aforementioned aspects and inventive and preferred features, in particular with regard to the manufacturing of the sample assay apparatus, therefore also apply for the apparatus. The preferred embodiments, variants and features of the invention described above are combinable with one another as desired.

Brief description of the drawings

Further details and advantages of the invention are described with reference to the attached drawings, which schematically show in

Figures 1 and 2:: illustrations of an embodiment of a sample assay apparatus according to the invention before and after assembling;
Figures 3 to 6:: details of a carrier device of the sample assay apparatus according to preferred embodiments of the invention;
Figure 7:: embodiments of sample assay module arrangements according to the invention;
Figure 8:: a view on the bottom side of a sample assay apparatus according to another embodiment of the invention; and

Figures 9 and 10: embodiments of a sample assay reaction apparatus according to the invention.

Description of preferred embodiments

Features of preferred embodiments of the invention are described in the following with reference to features of the sample assay apparatus, the sample assay module arrangement and the sample assay reaction apparatus and the manufacturing thereof. Details of using these devices, e. g. for executing PCR or other reactions, including depositing samples and processing liquids in the sample wells and executing reactions, are not described as far as they are known per se from prior art techniques.
Exemplary reference is made to embodiments of the invention, wherein 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 µm, connected by a common top surface with a maximum thickness of 1000 µm 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). It is emphasized that the invention is not restricted to these examples, but alternatively can be implemented with a sample assay apparatus having a modified configuration. For example, 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.
According to Figures 1 and 2, 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. about 127,8 mm ^∗ 85,5 mm with a centre to centre distance between neighbouring sample wells 11 of about 1,5 mm and a distance between the well arrays 12 (width of the plane sheet section 13 between the well arrays 12) of about 6,5 mm. The sample wells 11 (not shown in detail) 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.
Furthermore, 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. Furthermore, 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 µm. 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). For creating the completed sample assay apparatus 100 as shown in Figure 2, 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. As a result, the well film component 10 is supported with a plane extension by the carrier device 20. Optionally, 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. At the crossing points of the grid webs 24, material bulges 24A are formed which improve the mechanical stability of the supporting grid 23. Furthermore, in case of manufacturing the carrier device 20 by injection molding, 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.
As shown with the embodiment of Figure 4, 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 µm to 1 mm, preferably 100 µm to 500 µm. When the well film component is bonded with an adhesive to the carrier device 20, 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.
Figures 7A and 7B illustrate embodiments of sample assay module arrangements 300. As shown in Figure 7A, 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. With the illustrated design, 768 sample wells can be provided per sample assay apparatus 100.1, 100.2. In the complete sample assay module arrangement 300, 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). For these application, e. g. the common support or the tempering device is dimensioned such that multiple modules can be accommodated side by side.
According to the alternative of Figure 7B, 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 bottom side of a sample assay apparatus 100, e. g. according to one of the sample assay apparatuses of Figure 7B, is shown in Figure 8. With this embodiment, 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. Preferably, the cut-outs 29 are aligned with the grid openings 25 at the ends of the carrier frame 21. With the illustrated example, 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.
An embodiment of a sample assay reaction apparatus 200 according to the invention is illustrated in Figures 9 and 10. 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. For illustrative purposes, 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.
The features of the invention disclosed in the above description, the drawings and the claims can be of significance individually, in combination or sub-combination for the implementation of the invention in its different embodiments.

Claims

Sample assay apparatus (100), being configured for accommodating a plurality of samples, comprising
- a well film component (10) extending along a main film plane and being shaped for providing a plurality of sample wells (11) deepening in a direction perpendicular to the main film plane, and

- a carrier device (20) being arranged for supporting the well film component (10) and comprising a circumferential carrier frame (21) with an internal frame opening (22), wherein the well film component (10) contacts the carrier frame (21),
characterized in that

- the carrier device (20) further comprises a supporting grid (23) with grid webs (24) surrounding grid openings (25), wherein the supporting grid (23) is arranged in the internal frame opening (22) in connection with the carrier frame (21) and the supporting grid (23) extends parallel to the main film plane,

- the well film component (10) is fixedly connected to the carrier frame (21), and

- the well film component (10) is supported by the grid webs (24).
Sample assay apparatus according to claim 1, wherein
- the carrier frame (21) has a circumferential film carrying surface (26), and

- the well film component (10) is fully or partially connected with the film carrying surface (26).
Sample assay apparatus according to one of the foregoing claims, wherein
- the well film component (10) comprises an arrangement of multiple well arrays (12), where the sample wells (11) are provided, and plane film sections (13) extending between the well arrays (12), and

- the well film component (10) is supported by the grid webs (24) along the plane film sections (13), wherein

- the well arrays (12) protrude through the grid openings (25) surrounded by the grid webs (24).
Sample assay apparatus according to one of the foregoing claims, wherein
- the carrier frame (21, 21A) has a graduated frame profile (27, 27A) with upper profile surfaces (27.1, 27.1A) and lower profile surfaces (27.2, 27.2A), and

- shapes of the upper and lower profile surfaces (27.1, 27.1A, 27.2, 27.2A) are matched to each other so that the carrier frame (21) can be stacked with a neighboring carrier frame (21A) of another sample assay apparatus with the lower profile surface (27.2) resting on the upper profile surface (27.1A) of the neighboring carrier frame (10A).
Sample assay apparatus according to one of the foregoing claims, wherein
- the well film component (10) is fully or partially connected to the grid webs (24).
Sample assay apparatus according to one of the foregoing claims, wherein
- the well film component (10) is connected to the carrier device (20) via a riveted connection, a bonding connection, an adhesive connection or a combination of at least two of the listed connection methods.
Sample assay apparatus according to claim 6, wherein
- the well film component (10) is connected to the carrier device (20) via the adhesive connection, and

- at least one of the carrier frame (21) and the grid webs (24) have recesses (28) being open towards the well film component (10), wherein the recesses (28) are arranged for accommodating excess adhesive of the adhesive connection.
Sample assay apparatus according to one of the foregoing claims, comprising at least one of the features
- the well film component (10) is a deep-drawn, thermoformed, injection molded or injection compression molded component,

- the well film component (10) has a film thickness in a range from 20 µm to 1000 µm, in particular in a range from 50 µm to 800 µm,

- the well film component (10) is a thermoplastic component, in particular made of at least one of PP, PET, PC, COC and COP,

- the sample wells (11) have a conus shape with a flat well bottom,

- the well film component (10) has a well bottom film thickness in a range from 100 µm to 500 µm.
Sample assay apparatus according to one of the foregoing claims, wherein
- the well film component (10) is made of a transparent, in particular optically clear plastic.
Sample assay apparatus according to one of the claims 1 to 8, wherein
- the well film component (10) 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.
Sample assay apparatus according to one of the foregoing claims, comprising at least one of the features
- the carrier frame (21) is made of at least one of PS, PET, PC, COC and COP,

- the carrier frame (21) is reinforced with at least one of glass fibers, glass balls and an inorganic powder, and

- the carrier frame (21) is an integral, monolithic component.
Sample assay apparatus according to one of the foregoing claims, wherein
- the grid webs (24) and grid openings (25) of the supporting grid (23) are dimensioned and shaped such that the grid openings (25) are capable of accommodating a tempering device (210), in particular a heating and/or cooling device, in particular at least one PCR thermocycler block.
Sample assay apparatus according to one of the foregoing claims, further comprising
- a cover film covering the well film component (10).
Sample assay reaction apparatus (200), comprising
- the sample assay apparatus (100) according to one of the foregoing claims, and

- a tempering device (210), in particular a heating and/or cooling device, in particular at least one PCR thermocycler block.
Sample assay module arrangement (300), comprising
- at least two sample assay apparatuses (100) according to one of the foregoing claims, wherein

- the at least two sample assay apparatuses (100) are arranged side by side with an extension parallel to the main film plane.
Method of manufacturing the sample assay apparatus (100) according to one of the claims 1 to 14, comprising the steps of
- forming the well film component (10) including the sample wells (11) by shaping a deformable film,

- forming the carrier device (20) with the circumferential carrier frame (21) and the supporting grid (23) arranged in the internal frame opening (22) of the carrier frame (21), and

- connecting the well film component (10) and the carrier device (20), so that the well film component (10) is supported by the carrier device (20).
Method according to claim 16, wherein
- at least one of the carrier device (20) and the well film component (10) is made by injection molding, injection compression molding, deep-drawn process, thermoforming or a combination of these processes.
Method according to claim 16, wherein
- the well film component (10) and the carrier device (20) are formed separately from each other and connected subsequently, or

- the well film component (10) and the carrier device (20) are integrally formed so that they are connected to each other.