Multiple specimen carrier and / or investigation assembly and method of using the same

Abstract

The present invention refers to a multiple specimen carrier and / or investigation assembly (1), comprising: a sample and / or specimen carrier (10), a removably attachable sample and / or specimen frame (20) which is removably attachable to an upper surface (10a) of the sample and / or specimen carrier (10), and a removably attachable reaction frame (30) which is removably attachable to the upper surface (10a) of the sample and / or specimen carrier (10). At a given instance of time at most one of the removably attachable sample and / or specimen frame (20) and of the removably attachable reaction frame (30) may be attachable or may be attached to the upper surface (10a) of the sample and / or specimen carrier (10).

Description

[0001] MULTIPLE SPECIMEN CARRIER AND / OR INVESTIGATION ASSEMBLY AND

[0002] METHOD OF USING THE SAME

[0003] Description

[0004] The present invention refers to a multiple sample carrier and / or investigation assembly and to a method of using a multiple sample carrier and / or investigation assembly.

[0005] In particular, the present invention relates to means and methods for applying multiple and / or different biological specimens or cell samples onto and / or into a single reaction slide as a primary specimen carrier, e.g. for spatial analysis in order to thereby reduce variability of reagent applications and / or reaction conditions and to increase or improve comparability and reproducibility.

[0006] Nowadays, the investigation of multiple biological samples under consideration of spatial aspects and of aspects of vicinity and neighborhood becomes increasingly important.

[0007] Common investigation designs involve comparable fixed and rigid configurations, that do not allow a fast and flexible change and adaptation of an underlying spatial configuration and / or of investigation conditions.

[0008] It is an object underlying the present invention to suggest a multiple sample carrier and / or investigation assembly and a method of using the same, that offer a high degree of flexibility and reliability of investigations designs without increasing the underlying configurations’ complexity.

[0009] The object underlying the present invention is achieved by a multiple sample carrier and / or investigation assembly according to independent claim 1 and by a method of using a multiple sample carrier and / or investigation assembly according to independent claim 12. Preferred embodiments of the present invention are defined in the respective dependent claims.

[0010] According to a first aspect of the present invention, a multiple specimen carrier and / or investigation assembly 1 is proposed, which comprises:

[0011] - a sample and / or specimen carrier,

[0012] - a removably attachable sample and / or specimen frame which is removably attachable to an upper surface of the sample and / or specimen carrier, and a removably attachable reaction frame which is removably attachable to the upper surface of the sample and / or specimen carrier 10.

[0013] At a given instance of time at most one of the removably attachable sample and / or specimen frame and of the removably attachable reaction frame is attachable or attached to the upper surface of the sample and / or specimen carrier. In other words, during the application, only one or at most one of the sample and / or specimen frame and of the reaction frame shall be attached to the sample and / or specimen carrier.

[0014] In an embodiment of the present invention, the sample and / or specimen carrier may comprise an upper surface that may be configured to receive, to have attached, to carry and / or to support one or plural samples or specimens thereon at least in a designated sample and / or investigation area of the upper surface of the sample and / or specimen carrier, in particular in consideration of one or plural wells, chambers or compartments, defined in or on the upper surface of the sample and / or specimen carrier.

[0015] The removably attachable sample and / or specimen frame may comprise:

[0016] - a grid portion that is configured to define plural wells in a grid-like and / or in a web-like manner, in particular in relation to the upper surface of the sample and / or specimen carrier and / or to a or its designated sample and / or investigation area,

[0017] - a rim portion 2 Or that in particular may have a planar and / or rectangular shape and / or that may define and / or surround an inner sample space (20s) and / or the grid portion of the removably attachable sample and / or specimen frame at an outer circumference of the grid portion of the removably attachable sample and / or specimen frame, and / or

[0018] - a lower surface defined by lower surfaces of the grid portion and / or of the rim portion.

[0019] Additionally or alternatively, the removably attachable sample and / or specimen frame may directly or indirectly be removably attachable with its lower surface to a or to the upper surface of the sample and / or specimen carrier and in particular to a or to the designated sample and / or investigation area of the upper surface of the sample and / or specimen carrier. In the assembly according to the present invention, the removably attachable reaction frame may comprise a rim portion, which in particular may have a planar and / or rectangular shape and / or that may define and / or surround an inner reaction space of the removably attachable reaction frame.

[0020] According to a further alternative and advantageous embodiment of the present invention’s assembly, (i) a rim portion or the rim portion of the removably attachable reaction frame and / or an inner reaction space or the inner reaction space of the removably attachable reaction frame on the one hand and (ii) a rim portion or the rim portion of the removably attachable sample and / or specimen frame and / or an inner sample space or the inner sample of the removably attachable sample and / or specimen frame may coincide and / or are be congruent with respect to each other, in particular with respect to a or to the designated sample and / or investigation area of the upper surface of the primary sample and / or specimen carrier.

[0021] According to another advantageous embodiment of the present invention’s assembly, the removably attachable reaction frame may comprise:

[0022] - a grid portion

[0023] - that is surrounded by a or by the rim portion of the removably attachable reaction frame at an outer circumference of the grid portion of the removably attachable reaction frame, and / or

[0024] - that is configured to define within a or within the inner reaction space of the rim portion of the removably attachable reaction frame a single well or plural wells in a grid-like or in a web-like manner, in particular in relation to the upper surface of the sample and / or specimen carrier and / or to a or to its designated sample and / or investigation area, in particular in coincidence and / or congruence with respect to the plural wells of the removably attachable sample and / or specimen frame and / or with respect to the well portions the designated sample and / or investigation area of the upper surface of the primary sample and / or specimen carrier, and

[0025] - a lower surface defined by lower surfaces of the grid portion and / or of the rim portion of the removably attachable reaction frame.

[0026] The reaction frame can have a lower number of wells or framed wells than the specimen frame and up to the same number of framed wells as the specimen frame. The minimal number of wells within the reaction frame is one and it is or may be independent from the number of wells within the specimen frame. In other embodiments, the reaction frame may have a larger number of wells or framed wells than the specimen frame.

[0027] The wells or framed wells may of the reaction frame and of the specimen frame may be in lateral alignment, partially or completely.

[0028] The wells or framed wells may of the reaction frame and / or of the specimen frame may be formed - in a plan view of top view (e.g. in a z or -z direction and / or onto the xy plane in the accompanying figures) - of a rectangular shape, a round shape, an oval shape, a circular shape and / or an elliptical shape.

[0029] The removably attachable reaction frame may be removably attachable with a or with its lower surface directly or indirectly to the upper surface of the sample and / or specimen carrier and in particular to a or to the designated sample and / or investigation area of the upper surface of the sample and / or specimen carrier.

[0030] The primary sample and / or specimen carrier may at least one of:

[0031] - be formed as a plate or with a plate-like and / or planar shape,

[0032] - be formed with a planar upper surface and / or a planar lower surface,

[0033] - have a rectangular shape,

[0034] - have a thickness in the range of about 75 pm to about 250 pm, preferably in a range up to 190 pm and more preferably in a range up to 170 pm, or a thickness in the range of about 0,75 mm to about 1,50 mm,

[0035] - be chemically inert, in particular at its surfaces or at portions thereof,

[0036] - be bio-compatible, in particular at its surfaces or at portions thereof,

[0037] - comprise at or on its surfaces or at or on portions thereof a coating for initiating, enhancing and / or improving attachment, maintenance, growth and / or cultivation of a sample or specimen, in particular based on at least one of poly-lysine, amino-silane, and collagen, be optically transparent, in particular in the visual range, be formed of or comprises at least one of a glass material and a plastic material, and

[0038] - be formed as a slide or glass slide for microscopic applications.

[0039] The removably attachable sample and / or specimen frame may at least one of:

[0040] - be made from or with at least one of ceramic materials, plastic materials, and metal materials,

[0041] - have hydrophobic or hydrophilic surfaces or surfaces with mixed or well-designed hydrophobicity in order to achieve a predetermined meniscus of an underlying medium, in particular in horizontal or slightly convex form or shape,

[0042] - comprise a sealing material on its lower surface, in particular from or comprising a biocompatible material, for either suppressing any or defining a predetermined exchange of fluid and / or of bio-material between directly adjacent wells or compartments in a state in which the sample and / or specimen frame is attached to the sample and / or specimen carrier, and

[0043] - comprise a pressurizing mechanism or a mechanical coupling to a pressurizing mechanism for controllably exerting a pressing force of the sample and / or specimen frame against the sample and / or specimen carrier.

[0044] The removably attachable reaction frame may at least one of:

[0045] - be made from or with at least one of ceramic materials and plastic materials,

[0046] - have hydrophobic or hydrophilic surfaces or surfaces with mixed or well-designed hydrophobicity in order to achieve a predetermined meniscus of an underlying medium, in particular in horizontal or slightly convex form or shape,

[0047] - comprise a sealing material on its lower surface, in particular from or comprising a biocompatible material, for either suppressing any or defining a predetermined exchange of fluid and / or of bio-material between directly adjacent wells or compartments in a state in which the sample and / or specimen frame is attached to the sample and / or specimen carrier, and - comprise a pressurizing mechanism or a mechanical coupling to a pressurizing mechanism for controllably exerting a pressing force of the sample and / or specimen frame against the sample and / or specimen carrier.

[0048] In a plan or top view in a direction onto parallel upper surfaces of the sample and / or specimen frame and / or the reaction frame, the sample and / or specimen frame and the reaction frame may have a coinciding and / or congruent shape with respect to their rim portions and / or their grid portions and / or with respect to a designated sample and / or investigation area of the sample / specimen carrier and / or a configuration of its wells.

[0049] The assembly according to the present invention may be formed as a kit, as an add-on kit, or as a retrofit kit

[0050] The present invention further relates to a method of using a multiple specimen carrier and / or investigation assembly.

[0051] Such a method may be realized as a method or in a method of preparing a sample and / or specimen carrier for investigation and / or as a method or in a method of investigating a sample and / or specimen carrier, in particular in a process of spatial omics.

[0052] Within such a method, in a preceding step the assembly’s sample and / or specimen frame may be attached with its lower surface to and / or immobilized on an upper surface of the assembly’s sample and / or specimen carrier, thereby defining one or plural wells.

[0053] According to a preferred embodiment and in particular in a step following a step or the step of attaching and / or immobilizing - one or plural samples and / or specimens may be provided by supplying, seeding, growing and / or cultivating in one or plural of the wells, in particular with attachment and / or immobilization to the upper surface of the sample and / or specimen carrier and / or under supply and / or presence of predetermined incubation media, reagents and / or drugs.

[0054] Furthermore and in particular in a step following a step or the step of providing one or plural samples and / or specimens - the one or plural samples and / or specimens may be fixed to the upper surface of the sample and / or specimen carrier and / or any incubation media present may be removed, in particular via aspiration. In addition and also in particular in a step following a step or the step of fixing the one or plural samples and / or specimens and / or a step or the step of removing incubation media, the one or plural samples and / or specimens maybe dried.

[0055] Also in particular in a step following a step or the step of drying the one or plural samples and / or specimens, the assembly’s sample and / or specimen frame may be removed and the assembly’s reaction frame may be attached and / or be immobilized to the upper surface of the sample and / or specimen carrier, in particular in coincidence and / or congruence with (i) the removed sample and / or specimen frame’s former position and / or orientation and / or in coincidence and / or congruence with (ii) the designated sample and / or investigation area of the primary sample / specimen carrier and / or its wells or well portions.

[0056] In particular in a step following a step or the step of drying and / or a step or the step of attaching the assembly’s reaction frame the thereby prepared sample and / or specimen carrier may either be objected to an investigation process directly and / or immediately, in particular in a or to a process of spatial analysis, or it may be stored under cool, cooling and / or freezing conditions before commencing such an investigation process.

[0057] These and further details, advantages and features of the present invention will be described based on embodiments of the invention and by taking reference to the accompanying figures.

[0058] Figure 1A is a schematic plan view on an embodiment of a primary sample and / or specimen carrier or sample slide underlying an embodiment of the present invention’s multiple sample / specimen carrier and / or investigation assembly.

[0059] Figure IB is a schematic side view of the configuration as shown in figure 1A.

[0060] Figure 2A is a schematic plan view on an embodiment of the primary sample and / or specimen carrier or sample slide having attached on its upper surface a removable or removably attachable cell or sample / specimen frame.

[0061] Figure 2B is a schematic and cross-sectional side view of the configuration as shown in figure 2A, along the section line or plane B-B as indicated in figure 2 A.

[0062] Figure 3A is a schematic plan view on the configuration of figure 2A after having formed plural specimens or samples in the wells or well portions of the configuration. Figure 3B is a schematic and cross-sectional side view of the configuration as shown in figure 3 A, along the section line or plane B-B as indicated in figure 3 A.

[0063] Figure 4A is a schematic plan view on the configuration of figure 3A after having removed the removable or removably attachable cell or sample / specimen frame with the plural specimens or samples maintained in the portions of the wells.

[0064] Figure 4B is a schematic and cross-sectional side view of the configuration as shown in figure 4A, along the section line or plane B-B as indicated in figure 4A.

[0065] Figure 5A is a schematic plan view on the configuration of figure 4A after having attached on its upper surface a removable or removably attachable reaction frame according to a first embodiment having no inner grid portion.

[0066] Figure 5B is a schematic and cross-sectional side view of the configuration as shown in figure 5 A, along the section line or plane B-B as indicated in figure 5 A.

[0067] Figure 6A is a schematic and cross-sectional side view of a detail of the configuration as shown in figure 7A or 8A, along the section line or plane B-B as indicated in figure 7A or 8A.

[0068] Figure 6B is a schematic and cross-sectional side view of a detail of the configuration as shown in figure 7A or 8A, along the section line or plane B-B as indicated in figure 7A or 8A, but in a situation where a sealing layer is formed between the upper surface of the primary sample and / or specimen carrier and the removable or removably attachable reaction frame.

[0069] Figure 7A is a schematic plan view on the configuration of figure 4A after having attached on its upper surface a removable or removably attachable reaction frame according to a second embodiment having an inner grid portion that is different from and / or not congruent to the inner grid portion of the removable or removably attachable cell or sample / specimen frame.

[0070] Figure 7B is a schematic and cross-sectional side view of the configuration as shown in figure 7 A, along the section line or plane B-B as indicated in figure 7A. Figure 8A is a schematic plan view on the configuration of figure 4A after having attached on its upper surface a removable or removably attachable reaction frame according to a second embodiment having an inner grid portion that is identical and / or congruent to the inner grid portion of the removable or removably attachable cell or sample / specimen frame.

[0071] Figure 8B is a schematic and cross-sectional side view of the configuration as shown in figure 8A, along the section line or plane B-B as indicated in figure 8A.

[0072] In the following, embodiments and the technical background of the present invention are presented in detail by taking reference to accompanying figures 1A to 8B. Identical or equivalent elements and elements which act identically or equivalently are denoted with the same reference signs. Not in each case of their occurrence a detailed description of the elements and components is repeated.

[0073] The depicted and described features and further properties of the invention’s embodiments can arbitrarily be isolated and recombined without leaving the gist of the present invention.

[0074] In the following and first of all, a preliminary and very general view is taken on the enclosed figures, with a particular focus on figures 1A to 6B:

[0075] Figure 1A is a schematic plan view on an embodiment of a primary sample and / or specimen carrier 10 or sample slide 10 underlying an embodiment of the present invention’s multiple sample / specimen carrier and / or investigation assembly 1. Figure IB is a schematic side view of the configuration as shown in figure 1A. In this case, the primary sample and / or specimen carrier 10 or sample slide 10 has a plate-like configuration in the xy plane with a constant height or thickness in the z direction, a 1stor upper surface 10a, a 2ndor lower surface 10b and a rim lOr or rim portion lOr connecting and / or surrounding the opposing the upper and lower surfaces 10a, 10b.

[0076] Figure 2A is a schematic plan view on an embodiment of the primary sample and / or specimen carrier 10 or sample slide 10 having attached on its upper surface 10a a removable or removably attachable cell or sample / specimen frame 20 with its 2ndor lower surface 20b. The removable or removably attachable cell or sample / specimen frame 20 is attached to and / or defines a designated sample / specimen investigation area 10s on the primary sample and / or specimen carrier 10 or sample slide 10 in which samples S or specimens S are preferably attached or attachable, thereby forming or defining by plural wells 20w of the removable or removably attachable cell or sample / specimen frame 20, the latter given by the cooperation of the grid portion 20g and the rim portion 20r surrounding the grid portion 20g, wells lOw or well portions lOw on the 1stor upper surface 10a of primary sample and / or specimen carrier 10 or sample slide 10 and in particular in its designated sample / specimen investigation area 10s.

[0077] Figure 2B is a schematic and cross-sectional side view of the configuration as shown in figure 2A, along the section line or plane B-B as indicated in figure 2 A.

[0078] Figure 3A is a schematic plan view on the configuration of figure 2A after having formed plural samples S or specimens S in the wells lOw, 20w of the configuration.

[0079] Figure 3B is a schematic and cross-sectional side view of the configuration as shown in figure 3A, along the section line or plane B-B as indicated in figure 3 A.

[0080] Figure 4A is a schematic plan view on the configuration of figure 3A after having removed removable or removably attachable cell or sample / specimen frame 20 with the plural specimens S or samples S maintained in the portions of the wells lOw of the primary sample and / or specimen carrier 10 or sample slide 10.

[0081] Figure 4B is a schematic and cross-sectional side view of the configuration as shown in figure 4A, along the section line or plane B-B as indicated in figure 4A.

[0082] Figure 5A is a schematic plan view on the configuration of figure 4A after having attached on the 1stor upper surface 10a of the underlying primary sample and / or specimen carrier 10 or sample slide 10a removable or removably attachable reaction frame 30, namely with its 2ndor lower surface 30b and according to a first embodiment in which the removable or removably attachable reaction frame 30 has no inner grid portion 30g, but is essentially formed by an outer rim portion 3 Or, thereby offering a single and superordinate well 30w, e.g. as a common reaction space for the entirety of samples S or specimens S distributed over the plurality of well portions lOw of the of the designated sample and / or investigation area 10s of sample / specimen carrier 10.

[0083] Figure 5B is a schematic and cross-sectional side view of the configuration as shown in figure 5A, along the section line or plane B-B as indicated in figure 5 A.

[0084] Alternatively and as exemplified in figures 7A to 8B demonstrating second and third embodiments, the removable or removably attachable reaction frame 30 may comprise an inner grid portion 30g in order to define a particular arrangement of a plurality of well defining portions 30w, which may also be referred to as wells 30w of the removable or removably attachable reaction frame 30.

[0085] In this regard, figure 7A gives a schematic plan view on the configuration of figure 4A after having attached on its upper surface a removable or removably attachable reaction frame 30 according to the second embodiment having an inner grid portion 30g that is different from and / or not congruent to the inner grid portion 20g of the removable or removably attachable cell or sample / specimen frame 20.

[0086] Figure 7B is a schematic and cross-sectional side view of the configuration as shown in figure 7A, along the section line or plane B-B as indicated in figure 7A.

[0087] Further alternatively, figure 8A presents a schematic plan view on the configuration of figure 4A after having attached on its upper surface a removable or removably attachable reaction frame 30 according to a second embodiment having an inner grid portion 30g that is identical and / or congruent to the inner grid portion 20g of the removable or removably attachable cell or sample / specimen frame 20.

[0088] In a similar manner, figure 8B is a schematic and cross-sectional side view of the configuration as shown in figure 8A, along the section line or plane B-B as indicated in figure 8A.

[0089] The wells 30w of the removable or removably attachable reaction frame 30 may therefore coincide or may be congruent or aligned with the wells 20w of the former removable or removably attachable cell or sample / specimen frame 20 and / or with the well portions lOw of the primary sample and / or specimen carrier 10 or sample slide 10, namely as shown in the third embodiment of figures 8A, and 8B.

[0090] Figure 6A is a schematic and cross-sectional side view of a detail of the configuration as shown in figure 7A or 8A, along the section line or plane B-B as indicated in figure 7A or 8A.

[0091] Figure 6B is a schematic and cross-sectional side view of a detail of the configuration as shown in figure 7A or 8A, along the section line or plane B-B as indicated in figure 7A or 8A, but in a situation where a sealing layer 40 is formed between the upper surface 10a of the primary sample and / or specimen carrier 10 and 2ndor lower surface 30b of the removable or removably attachable reaction frame 30.

[0092] As shown in the figures 1A to 8B in general, a multiple specimen carrier and / or investigation assembly 1 according to the present invention comprises: a sample and / or specimen carrier 10,

[0093] - a removably attachable sample and / or specimen frame 20 which is removably attachable to an upper surface 10a of the sample and / or specimen carrier 10, and

[0094] - a removably attachable reaction frame 30 which is removably attachable to the upper surface 10a of the sample and / or specimen carrier 10.

[0095] In particular, at a given instance of time at most one of the removably attachable sample and / or specimen frame 20 and of the removably attachable reaction frame 30 is attachable or attached to the upper surface 10a of the primary sample and / or specimen carrier 10. In other words, during the application, only one of the of the sample and / or specimen frame 20 and of the reaction frame 30 shall be attached to the sample and / or specimen carrier 10.

[0096] According to one aspect of the present invention, the focus may be set on the first frame 20 as a removably attachable cell or sample / specimen frame 20, e.g. to enable and perform the seed of cells or to immobilize cells such as PMBCs, so that many cell chambers can harbor (a) different cells (different lines, cells from different sources or patients etc.), (b) different growth conditions, or (c) different treatments.

[0097] After fixing the cells or in general samples / specimens at the position of the wells 20w within the first frame 20, the first frame 20 is removed and a second frame 30, also referred to as a removable or removably attachable reaction chamber frame 30 or reaction frame 30, is fixed to the sample slide 10.

[0098] The reaction frame 30 may contain only a single well 30w - as show for the first embodiment of figures 5A and 5B - that covers all cells or in general samples / specimens S immobilized on the slide 10.

[0099] Therefore, the architecture of the second frame 30 or reaction frame 30 allows that all cells or samples / specimens S undergo the same reaction, e.g. MC, protein detection, other.

[0100] Variations of this architecture may be applied: The first frame 20 or removably attachable frame 20 may be sealed to the glass slide 10 by a porous membrane so that the sealing 40 is not completely tight and substances, protuberances of cells, e.g. axons, or even cells can diffuse or migrate from one well to another.

[0101] The sizes of the pores define what can diffuse or migrate between individual wells.

[0102] It may be that the porous membrane 40 is only available between defined wells 20w, 30w and not between all wells 20w, 30w so that multiple interactions can be analyzed in a defined way using MC or protein detection assays.

[0103] The reaction frame 30 may have also more than a single well 30w to analyze the samples by different probe sets or antibody sets, e.g. as shown for the second and third embodiments demonstrated in figures 7A to 8B.

[0104] In an embodiment of the present invention, the sample and / or specimen carrier 10 may comprise an upper surface 10a that may be configured to receive, to have attached, to carry and / or to support one or plural samples S or specimens S thereon at least in a designated sample and / or investigation area 10s of the upper surface 10a of the sample and / or specimen carrier 10, in particular in consideration of one or plural wells lOw, chambers lOw or compartments lOw, defined in or on the upper surface 10a of the sample and / or specimen carrier 10.

[0105] The removably attachable sample and / or specimen frame 20 may comprise:

[0106] - a grid portion 20g that is configured to define plural wells 20w in a grid-like web-like manner, in particular in relation to the upper surface 10a of the sample and / or specimen carrier 10 or its designated area 10s,

[0107] - a rim portion 2 Or surrounding the grid portion 20g at an outer circumference of the grid portion 20g, and / or

[0108] - a lower surface 20b defined by lower surfaces 20gb, 20rb of the grid portion 20g and / or of the rim portion 2 Or.

[0109] Additionally or alternatively, the removably attachable sample and / or specimen frame 20 may directly or indirectly be removably attachable or attached with its lower surface 20b to an upper surface 10a or to the upper surface 10a of the primary sample and / or specimen carrier 10 and in particular to a designated sample and / or investigation area 10s of the upper surface 10a of the sample and / or specimen carrier 10.

[0110] In another alternative or additional embodiment of the assembly 1 according to present invention, the removably attachable reaction frame 30 may comprise a rim portion 30r, that in particular may have a planar and / or a rectangular shape and / or that may define and / or surround an inner reaction space 30s of the removably attachable reaction frame 30.

[0111] Additionally or alternatively, (i) a rim portion 3 Or or the rim portion 3 Or of the removably attachable reaction frame 30 and / or an inner reaction space 30s or the inner reaction space 30s of the removably attachable reaction frame 30 on the one hand and (ii) a rim portion 2 Or or the rim portion 20r of the removably attachable sample and / or specimen frame 20 and / or an inner sample space 20s or the inner sample space 20s of the removably attachable sample and / or specimen frame 20 may coincide and / or may be congruent with respect to each other, in particular with respect to a or to the designated sample and / or specimen investigation area 10s of the upper surface 10a of the primary sample and / or specimen carrier 10.

[0112] According to an embodiment of the present invention’s assembly 1, the removably attachable reaction frame 30 may further comprise a grid portion 30g.

[0113] Said grid portion 30g of the removably attachable reaction frame 30 may be surrounded by the rim portion 3 Or of the removably attachable reaction frame 30 at an outer circumference of the grid portion 30g of the removably attachable reaction frame 30.

[0114] Additionally or alternatively, said grid portion 30g of the removably attachable reaction frame 30 may be configured to define within the inner reaction space 30s of the rim portion 30r of the removably attachable reaction frame 30 a single well 30w or plural wells 30w in a grid-like or in a web-like manner, in particular in coincidence and / or congruence with respect to the plural wells 20w of the removably attachable sample and / or specimen frame 20 and / or with respect to the well portions lOw the designated sample and / or investigation area 10s of the upper surface 10a of the primary sample and / or specimen carrier 10.

[0115] Additionally or alternatively, said grid portion 30g of the removably attachable reaction frame 30 may comprise a lower surface 30b defined by lower surfaces 30gb, 30rb of the grid portion 30g and / or of the rim portion 30r of the removably attachable reaction frame 30. The removably attachable reaction frame 30 may be removably attachable with its lower surface 30b directly or indirectly to the upper surface 10a of the sample and / or specimen carrier 10 and in particular to the designated sample and / or investigation area 10s of the upper surface 10a of the sample and / or specimen carrier 10.

[0116] The sample and / or specimen carrier 10 may at least one of:

[0117] - be formed as a plate, or with a plate-like and / or planar shape

[0118] - be formed with a planar upper surface 10a and / or a planar lower surface 10b,

[0119] - have a rectangular shape,

[0120] - have a thickness in the range of about 75 pm to about 250 pm, preferably in a range up to 190 pm and more preferably in a range up to 170 pm, or a thickness in the range of about 0,75 mm to about 1,50 mm,

[0121] - be chemically inert, in particular atits surfaces 10a, 10b, lOr or atportions 10s thereof,

[0122] - be bio-compatible, in particular at its surfaces 10a, 10b, lOr or atportions thereof,

[0123] - comprise at or on its surfaces 10a, 10b, lOr or at or on portions thereof a coating for initiating, enhancing and / or improving attachment, maintenance, growth and / or cultivation of a sample S or specimen S, in particular based on at least one of poly-lysine, amino-silane, and collagen,

[0124] - be optically transparent, in particular in the visual range,

[0125] - be formed of or comprises at least one of a glass material and a plastic material, and

[0126] - be formed as a slide or glass slide 10’ for microscopic applications.

[0127] The removably attachable sample and / or specimen frame 20 may at least one of:

[0128] - be made from or with at least one of ceramic materials and plastic materials,

[0129] - have hydrophobic or hydrophilic surfaces or surfaces with mixed or well-designed hydrophobicity in order to achieve a predetermined meniscus of an underlying medium, in particular in horizontal or slightly convex form or shape,

[0130] - comprise a sealing material 40 on its lower surface 20b, in particular from or comprising a biocompatible material, for either suppressing any or defining a predetermined exchange of fluid and / or of bio-material between directly adjacent wells 20w or compartments in a state in which the sample and / or specimen frame 20 is attached to the sample and / or specimen carrier 10, and

[0131] - comprise a pressurizing mechanism or a mechanical coupling to a pressurizing mechanism for controllably exerting a pressing force of the sample and / or specimen frame 20 against the sample and / or specimen carrier 10.

[0132] The removably attachable reaction frame 30 may at least one of:

[0133] - be made from or with at least one of ceramic materials and plastic materials,

[0134] - have hydrophobic or hydrophilic surfaces or surfaces with mixed or well-designed hydrophobicity in order to achieve a predetermined meniscus of an underlying medium, in particular in horizontal or slightly convex form or shape,

[0135] - comprise a sealing material on its lower surface 30b, in particular from or comprising a biocompatible material, for either suppressing any or defining a predetermined exchange of fluid and / or of bio-material between directly adjacent wells 30w or compartments in a state in which the sample and / or specimen frame 30 is attached to the sample and / or specimen carrier 10, and

[0136] - comprise a pressurizing mechanism or a mechanical coupling to a pressurizing mechanism for controllably exerting a pressing force of the sample and / or specimen frame 30 against the sample and / or specimen carrier 10.

[0137] In a plan or top view in a direction onto parallel upper surfaces 20a, 30a of the sample and / or specimen frame 20 and / or the reaction frame 30, the sample and / or specimen frame 20 and the reaction frame 30 may have a coinciding and / or congruent shape with respect to their rim portions 20r, 30r and / or their grid portions 20g, 30g and / or with respect to a designated sample and / or investigation area 10s of the sample / specimen carrier 10 and / or a configuration of its wells lOw.

[0138] The assembly 1 according to the present invention may be formed as a kit, as an add-on kit, or as a retrofit kit

[0139] The present invention’s method of using a multiple specimen carrier and / or investigation assembly 1 may be realized as a method or in a method of preparing a sample and / or specimen carrier 10 for investigation and / or as a method or in a method of investigating a sample and / or specimen carrier 10, in particular in a process of spatial omics.

[0140] Within such a method, in a preceding step the assembly’s 1 sample and / or specimen frame 20 may be attached with its lower surface 20b to and / or immobilized on an upper surface 10a of the assembly’s sample and / or specimen carrier 10, thereby defining one or plural wells lOw, 20w.

[0141] In particular in a step following a step or the step of attaching and / or immobilizing - one or plural samples S and / or specimens S may be provided by supplying, seeding, growing and / or cultivating in one or plural of the wells lOw, 20w, in particular with attachment and / or immobilization to the upper surface 10a of the sample and / or specimen carrier 10 and / or under supply and / or presence of predetermined incubation media, reagents and / or drugs.

[0142] Furthermore and also in particular in a step following a step or the step of providing one or plural samples S and / or specimens S - the one or plural samples S and / or specimens S may be fixed to the upper surface 10a of the sample and / or specimen carrier 10 and / or any incubation media present may be removed, in particular via aspiration.

[0143] In addition and also in particular in a step following a step or the step of fixing the one or plural samples S and / or specimens S and / or a step or the step of removing incubation media, the one or plural samples S and / or specimens S maybe dried.

[0144] Also in particular in a step following a step or the step of drying the one or plural samples S and / or specimens S, the assembly’s sample and / or specimen frame 20 may be removed and the assembly’s reaction frame 30 may be attached and immobilized to the upper surface 10a of the sample and / or specimen carrier 10, in particular in coincidence and / or congruence with (i) the removed sample and / or specimen frame’s 20 former position and / or orientation and / or (ii) the designated sample and / or investigation area 10s of the sample / specimen carrier 10 and / or its wells lOw.

[0145] In particular in a step following a step or the step of drying and / or a step of attaching the assembly’s reaction frame 30 the thereby prepared sample and / or specimen carrier 10 may either be objected to an investigation process directly and immediately, in particular a process of spatial analysis, or stored under freezing conditions before commencing such an investigation process.

[0146] These and further aspects of the present invention will also be described in detail in the following passages:

[0147] The present invention inter alia defines means and methods for applying multiple and / or different biological specimens S or cell samples S onto and / or into a single reaction slide 10’ as a primary specimen carrier 10 e.g. for spatial analysis in order to thereby reduce variability of reagent applications and / or reaction conditions and to increase or improve comparability and reproducibility.

[0148] In the context of the present invention, microscopic and / or spatial analysis is performed on microscopic slides 10’ serving as an embodiment for general primary sample or specimen carriers 10.

[0149] For and during microscopic and / or spatial analysis, the slides 10’ or general carriers 10 shall (i) receive, carry, and / or support one or plural samples S or specimens S in an immobilized manner and (ii) form one or plural reaction wells lOw or chambers lOw for applying probes, antibodies, and / or reagents or the like for a proper incubation of the samples S or specimens S therewith.

[0150] The specimens S or samples S may be biological samples in a broad sense, i.e. the samples S or specimens S may be or comprise one or plural of cells, tissues, and portions, parts, sections, combinations, cultures or other derivatives thereof.

[0151] Investigations of such samples S and in particular cell culture applications are often performed in a comparable manner.

[0152] In this regard and by means of the present invention, one or plural of the following aspects can be considered:

[0153] (i) Drugs can be administered at various concentrations within a single experiment

[0154] (ii) Different sample or specimen types - e.g. different cell types or the like - may be treated with the same drug or the like.

[0155] (iii) Peripheral blood mononuclear cells or PMBCs from various patients may be analyzed in parallel.

[0156] (iv) Various Car-T cells with different gene modifications may be compared.

[0157] (v) Co-culture combinations of different cell combinations or different ratios may be compared.

[0158] (vi) 3D cell culture systems may be analyzed in different wells.

[0159] In order to increase the comparability and / or reproducibility for spatial omics and to minimize e.g. involved pipetting steps, it may be suitable and useful according to the present invention to bring or unite different investigation wells lOw, 20w, 30w or chambers lOw, 20w, 30wor cell wells lOw, 20w, 30w or chambers lOw, 20w, 30w into a single and superordinate reaction chamber.

[0160] The invention solves these issues by providing and / or using a removable sample or specimen chamber 20, cell chamber 20 or chamber template 20 that is substituted by a reaction chamber 30 or reaction chamber template 30 as shown in the sequence of figures 1A to 6B.

[0161] An investigation process according to the present invention may be designed by a processing sequence as follows:

[0162] (1) Taking a primary sample or specimen carrier 10, e.g. a slide 10’, and providing a removable cell sample frame 20 or rCSF 20 and a removable reaction frame 30 or rRF 30.

[0163] (2) The rCSF 20 contains or defines a number of two or a larger number or plurality of wells 20w or chambers 20w for individual sample seeding or cell seeding.

[0164] (3) Immobilizing the rCSF 20 onto the microscopic slide 10.

[0165] (4) Seeding the samples S or cells S into the individual chambers lOw, 20w or wells 10, 20w and - if necessary - cultivate and or treat the cells by drugs.

[0166] (5) Aspirating the media and / or fixing the samples S or cells S onto the upper surface 10a of the primary sample carrier 10 or microscopic slide 10’.

[0167] (6) Drying the fixed samples S, specimens S or cells S. The rCSF 20 can be removed now. At this point, sample carrier 10 with the samples S or cells S thereon may be stored in the cold, e.g. under freezing conditions.

[0168] (7) Immobilizing a rRF 30 onto the microscopic slide 10’.

[0169] (8) Starting and performing an investigation and in particular a spatial analysis.

[0170] A primary sample or specimen carrier 10 according to the present invention may e.g. be formed in consideration of the following aspects and may - in the sense of the present invention - also be referred to as a concrete microscopic slide 10’:

[0171] The primary sample or specimen carrier 10 or microscopic slide 10’ may be made from any kind of transparent material like plastic or glass.

[0172] The thickness of the involved material for the primary sample or specimen carrier 10 may be adapted to underlying optics and may be made by a comparably thin (e.g. 100 pm) or by a comparably thick (e.g. about or above 1 mm) material plate or layer.

[0173] The surface of the material of the primary sample or specimen carrier or microscopic slide may be coated for better attachment of the sample or specimen, e.g. of cells, for instance by having a coating of or comprising e.g. poly-lysine, amino-silane, collagen or others or the like or combinations thereof.

[0174] The size of the microscopic slide 10’ may depend on the concrete application.

[0175] Removable cell sample frame 20 or rCSF 20:

[0176] The rCSF 20 can be made from different materials such as plastics, ceramics etc.

[0177] The involved material may be hydrophilic or hydrophobic and may ideally have a mixed hybrobicity that results in a horizontal or slightly convex meniscus. In this regard, the term "hydrobilic surface” means that water or a general polar solvent may have a tighter contact to the surface when compared to a hydrophobic surface where a droplet is rounded or the other way round: A non-polar solvent does not form a droplet and has a tight contact with a hydrophobic surface.

[0178] The rCSF 20 may define or have more than two wells 20w. The rCSF 20 may define and / or have multiple wells 20w, e.g. of up to 1000 wells, 4 to 500 wells, or 8 to 100 wells. The rCSF 20 may have a sealing 40 at the rims and / or portions of its lower surface 20b of the wells 20w that contact the upper surface 10a of the underlying sample or specimen carrier 10 or microscopic slide 10’.

[0179] The sealing 40 can be made from various materials that must be bio-compatible if cell growth is required.

[0180] The sealing 40 may be configured in order to have no exchange of substances, cells or other materials / substances between individual wells lOw, 20w, 30w.

[0181] In an alternative format, the sealing 40 may not be completely tight, such that substances or even samples, sample portions or cells of defined sizes may diffuse, migrate or be exchanged from one well lOw, 20w, 30wto another in particular in a predetermined and / or selective manner.

[0182] For example, substances that are secreted from a sample or from cells in a given well lOw, 20w, 30w may diffuse from said given well lOw, 20w, 30w to receptor cells located in another and spatially separated well 1 Ow, 2 Ow, 3 Ow.

[0183] For such an alternative, all wells lOw, 20w, 30w or predefined and / or selected wells lOw, 20w, 30w only may be connected to each other.

[0184] The sealing 40 may be further improved by an applied controllable pressure or a removable stickiness to the underlying sample or specimen carrier 10 or microscopic slide 10’.

[0185] The pressure can be applied by various mechanisms, e.g. like a sliding into splint, by clamps and / or by any other method that can result in a removable contact between the sample or specimen carrier 10 or microscopic glass slide 10’ and the rCSF 20.

[0186] Alternatively, the sealing 40 at the rims and / or lower surfaces 20b, 30b of the wells 20w, 30w may have a tight and removable contact to the microscopic slide 10’ by a removable adhesive strip.

[0187] Summarizing all the circumstances as presented above, the present invention inter alia proposes a multiple specimen carrier and / or investigation assembly 1, that comprises a sample and / or specimen carrier 10, a removably attachable sample and / or specimen frame 20 which is removably attachable to an upper surface 10a of the sample and / or specimen carrier 10, and a removably attachable reaction frame 30 which is removably attachable to the upper surface 10a of the sample and / or specimen carrier 10. At a given instance of time at most one of the removably attachable sample and / or specimen frame 20 and of the removably attachable reaction frame 30 is or may be attachable or is or may be attached to the upper surface 10a of the sample and / or specimen carrier 10.

[0188] List of Reference Signs

[0189] 1 multiple sample / specimen carrier and / or investigation assembly or kit

[0190] 10 (primary) sample or specimen carrier, sample slide

[0191] 10’ microscopic (glass) slide

[0192] 10a upper surface of sample / specimen carrier 10

[0193] 10b lower surface of sample / specimen carrier 10 lOr rim, rim portion of sample / specimen carrier 10

[0194] 10s designated sample and / or investigation area of sample / specimen carrier 10 lOw well, well portion of the designated sample and / or investigation area 10s of sample / specimen carrier 10

[0195] 20 (removable / removably attachable) cell or sample / specimen frame, rCSF

[0196] 20a upper surface of (removable) cell or sample / specimen frame 20

[0197] 20b lower surface of (removable) cell or sample / specimen frame 20

[0198] 20g grid or grid portion of (removable) cell or sample / specimen frame 20

[0199] 20ga upper surface portion of grid portion 20g

[0200] 20gb lower surface portion of grid portion 20g

[0201] 2 Or rim or rim portion of (removable) cell or sample / specimen frame 20

[0202] 2 Ora upper surface portion of rim portion 2 Or

[0203] 2 Orb lower surface portion of rim portion 2 Or

[0204] 20s inner sample and / or specimen space of the (removable / removably attachable) cell or sample / specimen frame, rCSF, 20

[0205] 20w well (defining) portion, well

[0206] 30 (removable) reaction (chamber) frame, rRF

[0207] 30a upper surface of (removable) reaction (chamber) frame 30

[0208] 30b lower surface of (removable) reaction (chamber) frame 30

[0209] 30g grid or grid portion of (removable) reaction (chamber) frame 30

[0210] 30ga upper surface portion of grid portion 30g

[0211] 30gb lower surface portion of grid portion 30g

[0212] 3 Or rim or rim portion of (removable) reaction (chamber) frame 30

[0213] 3 Ora upper surface portion of rim portion 3 Or

[0214] 3 Orb lower surface portion of rim portion 3 Or 30s inner reaction space of the (removable) reaction (chamber) frame, rRF, 30 30w well (defining) portion, well

[0215] 40 seal or sealing portion

[0216] 40a upper surface of sealing 40

[0217] 40b lower surface of sealing 40

[0218] B-B plane / line for cross-sectional view

[0219] S sample, specimen x spatial direction

[0220] X direction of longitudinal extension, longitudinal direction y spatial direction

[0221] Y direction of width / transversal extension, width direction z spatial direction

[0222] Z direction of height extension, height direction

Claims

Claims1. Multiple specimen carrier and / or investigation assembly (1), comprising:- a sample and / or specimen carrier (10),- a removably attachable sample and / or specimen frame (20) which is removably attachable to an upper surface (10a) of the sample and / or specimen carrier (10), and- a removably attachable reaction frame (30) which is removably attachable to the upper surface (10a) of the sample and / or specimen carrier (10), wherein in particular at a given instance of time at most one of the removably attachable sample and / or specimen frame (20) and of the removably attachable reaction frame (30) is attachable or is attached to the upper surface (10a) of the sample and / or specimen carrier (10).

2. The assembly (1) according to claim 1, wherein the sample and / or specimen carrier (10) comprises an upper surface (10a) that is configured to receive, to have attached, to carry and / or to support one or plural samples (S) or specimens (S) thereon at least in a designated sample and / or investigation area (10s) of the upper surface (10a) of the sample and / or specimen carrier (10).

3. The assembly (1) according to any one of the preceding claims, wherein the removably attachable sample and / or specimen frame (20) comprises:- a grid portion (20g), that is configured to define plural wells (20w) in a grid-like or in a web-like manner, in particular in relation to the upper surface (10a) of the sample and / or specimen carrier (10) and / or to a or to its designated sample and / or investigation area (10s),- a rim portion (20r), that in particular has a planar and / or rectangular shape and / or that defines and surrounds an inner sample space (20s) and / or the grid portion (20g) of the removably attachable sample and / or specimen frame (20) at an outer circumference of the grid portion (20g) of the removably attachable sample and / or specimen frame (20), and in particular- a lower surface (20b) defined by lower surfaces (20gb, 20rb) of the grid portion (20g) and / or of the rim portion (20r).

4. The assembly (1) according to any one of the preceding claims, wherein the removably attachable sample and / or specimen frame (20) is directly or indirectly removably attachablewith a or with its lower surface (20b) to an upper surface (10a) of the sample and / or specimen carrier (10) and in particular to a or to the designated sample and / or investigation area (10s) of the upper surface (10a) of the sample and / or specimen carrier (10).

5. The assembly (1) according to any one of the preceding claims, wherein the removably attachable reaction frame (30) comprises a rim portion (30r), that in particular has a planar and / or rectangular shape and / or that defines and surrounds an inner reaction space (30s) of the removably attachable reaction frame (30).

6. The assembly (1) according to any one of the preceding claims, wherein (i) a rim portion (30r) or the rim portion (30r) of the removably attachable reaction frame (30) and / or an inner reaction space (30s) or the inner reaction space (30s) of the removably attachable reaction frame (30) on the one hand and (ii) a rim portion (20r) or the rim portion (20r) of the removably attachable sample and / or specimen frame (20) and / or an inner sample space (20s) or the inner sample space (20s) of the removably attachable sample and / or specimen frame (20) coincide and / or are congruent with respect to each other, in particular with respect to a or to the designated sample and / or specimen investigation area (10s) of the upper surface (10a) of the primary sample and / or specimen carrier (10).

7. The assembly (1) according to claim 5 or claim 6 referred back to claim 5, wherein the removably attachable reaction frame (30) comprises:- a grid portion (30g),- that is surrounded by the rim portion (3 Or) of the removably attachable reaction frame (30) at an outer circumference of the grid portion (30g) of the removably attachable reaction frame (30), and / or- that is configured to define within the inner reaction space (30s) of the rim portion (3 Or) of the removably attachable reaction frame (30) a single well (30w) or plural wells (30w) in a grid-like or in a web-like manner, in particular in coincidence and / or congruence with respect to the plural wells (20w) of the removably attachable sample and / or specimen frame (20) and / or with respect to the well portions (lOw) the designated sample and / or investigation area (10s) of the upper surface (10a) of the primary sample and / or specimen carrier (10), and- a lower surface (30b) defined by lower surfaces (30gb, 30rb) of the grid portion (30g) and / or of the rim portion (30r) of the removably attachable reaction frame (30).

8. The assembly (1) according to any one of the preceding claims, wherein the removablyattachable reaction frame (30) is removably attachable with a or with its lower surface (30b) directly or indirectly to the upper surface (10a) of the sample and / or specimen carrier (10) and in particular to a or to the designated sample and / or investigation area (10s) of the upper surface (10a) of the primary sample and / or specimen carrier (10).

9. The assembly (1) according to any one of the preceding claims, wherein the primary sample and / or specimen carrier (10) at least one of:- is formed as a plate or with a plate-like and / or planar shape,- is formed with a planar upper surface (10a) and / or a planar lower surface (10b),- has a rectangular shape,- have a thickness in the range of about 75 pm to about 250 pm, preferably in a range up to 190 pm and more preferably in a range up to 170 pm, or a thickness in the range of about 0,75 mm to about 1,50 mm,- is chemically inert, in particular at its surfaces (10a, 10b, lOr) or at portions (10s) thereof,- is bio-compatible, in particular at its surfaces (10a, 10b, lOr) or at portions thereof,- comprises at or on its surfaces (10a, 10b, lOr) or at or on portions thereof a coating for initiating, enhancing and / or improving attachment, maintenance, growth and / or cultivation of a sample (S) or specimen (S), in particular based on at least one of polylysine, amino-silane, and collagen,- is optically transparent, in particular in the visual range,- is formed of or comprises at least one of a glass material and a plastic material, and- is formed as a slide or glass slide (10’) for microscopic applications.

10. The assembly (1) according to any one of the preceding claims, wherein the removably attachable sample and / or specimen frame (20) at least one of:- is made from or with at least one of ceramic materials and plastic materials,- has hydrophobic or hydrophilic surfaces or surfaces with predetermined, mixed and / or well-designed hydrophobicity in order to achieve a predetermined meniscus of an underlying medium, in particular in horizontal or slightly convex form or shape,- comprises a sealing material (40) on its lower surface (20b), in particular from or comprising a bio-compatible material, for either suppressing any or defining a predetermined exchange of fluid and / or of bio-material between directly adjacent wells (20w) or compartments in a state in which the sample and / or specimen frame (20) is attached to the sample and / or specimen carrier (10), and- comprises a pressurizing mechanism or a mechanical coupling to a pressurizing mechanism for controllably exerting a pressing force of the sample and / or specimenframe (20) against the sample and / or specimen carrier (10).

11. The assembly (1) according to any one of the preceding claims, wherein the removably attachable reaction frame (30) at least one of:- is made from or with at least one of ceramic materials and plastic materials,- has hydrophobic or hydrophilic surfaces or surfaces with predetermined, mixed and / or well-designed hydrophobicity in order to achieve a predetermined meniscus of an underlying medium, in particular in horizontal or slightly convex form or shape,- comprises a sealing material on its lower surface (30b), in particular from or comprising a bio-compatible material, for either suppressing any or defining a predetermined exchange of fluid and / or of bio-material between directly adjacent wells (30w) or compartments in a state in which the sample and / or specimen frame (30) is attached to the sample and / or specimen carrier (10), and- comprises a pressurizing mechanism or a mechanical coupling to a pressurizing mechanism for controllably exerting a pressing force of the sample and / or specimen frame (30) against the sample and / or specimen carrier (10).

12. The assembly (1) according to any one of the preceding claims, wherein in a plan view in a direction onto parallel upper surfaces (20a, 30a) of the sample and / or specimen frame (20) and the reaction frame (30), the sample and / or specimen frame (20) and the reaction frame (30) have a coinciding and / or congruent shape with respect to their rim portions (20r, 30r) and / or their grid portions (20g, 30g) and / or with respect to a designated sample and / or investigation area (10s) of the sample / specimen carrier (10) and / or a configuration of its wells (lOw).

13. The assembly (1) according to any one of the preceding claims, which is formed as a kit, as an add-on kit, or as a retrofit kit.

14. Method of using a multiple specimen carrier and / or investigation assembly (1) according to any one of the preceding claims, in particular- in a method of preparing a sample and / or specimen carrier (10) for investigation and / or- in a method of investigating a sample and / or specimen carrier (10), in particular in a process of spatial omics.

15. Method according to claim 14, wherein in a preceding step the assembly’s sample and / or specimen frame (20) is attached with its lower surface (20b) to and / or immobilized on anupper surface (10a) of the assembly’s sample and / or specimen carrier (10), thereby defining one or plural wells (lOw, 20w).

16. Method according to claim 14 or 15, wherein - in particular in a step following a step or the step of attaching and / or immobilizing - one or plural samples (S) and / or specimens (S) are provided by supplying, seeding, growing and / or cultivating in one or plural of the wells (lOw, 20w), in particular with attachment and / or immobilization to the upper surface (10a) of the sample and / or specimen carrier (10) and / or under supply and / or presence of predetermined incubation media, reagents and / or drugs.

17. Method according to any one of claims 14 to 16, wherein - in particular in a step following a step or the step of providing one or plural samples (S) and / or specimens (S) - the one or plural samples (S) and / or specimens (S) are fixed to the upper surface (10a) of the sample and / or specimen carrier (10) and / or any incubation media present is removed, in particular via aspiration.

18. Method according to any one of claims 14 to 16, wherein - in particular in a step following a step or the step of fixing the one or plural samples (S) and / or specimens (S) and / or a step or the step of removing incubation media - the one or plural samples (S) and / or specimens (S) are dried.

19. Method according to any one of claims 14 to 18, wherein - in particular in a step following a step or the step of drying the one or plural samples (S) and / or specimens (S) - the assembly’s sample and / or specimen frame (20) is removed and the assembly’s reaction frame (30) is attached and / or is immobilized to the upper surface (10a) of the sample and / or specimen carrier (10), in particular (i) in coincidence and / or congruence with the removed sample and / or specimen frame’s (20) former position and / or orientation and / or (ii) in coincidence and / or congruence with the designated sample and / or investigation area (10s) of the sample / specimen carrier (10) and / or its wells (lOw) or well portions (lOw).

20. Method according to any one of claims 14 to 19, wherein - in particular in a step following a step or the step of drying and / or a step or the step of attaching the assembly’s reaction frame (30) - the thereby prepared sample and / or specimen carrier (10) is either objected to an investigation process directly and / or immediately, in particular in a or to a process of spatial analysis, or it is stored under cool, cooling and / or freezing conditions before commencing such an investigation process.

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