Fluidic device for investigating biological samples and fluidic device assembly

Abstract

The present invention refers to a fluidic device (1) for investigating biological samples (S), comprising (i) a support (10) which has an upper surface (10a) that is configured to carry a biological sample (S) for preparation, incubation and / or investigation, and (ii) a lid assembly (20) which has a lid (30) and a gasket (21) and which is removably mounted or mountable to the upper surface (10a) of the support (10), wherein in a mounted state the lid (30) is attached to the upper surface (10a) of the support (10) with the gasket (21) therebetween to thereby form a surrounded, closable or closed inner or sample space (10i). The fluidic device assembly comprises a fluidic device (1) and plural interchangeably and removably mountable lid assemblies (20) with appropriate configurations.

Description

[0001] FLUIDIC DEVICE FOR INVESTIGATING BIOLOGICAL SAMPLES AND FLUIDIC DEVICE ASSEMBLY

[0002] Description

[0003] The present invention refers to a fluidic device for investigating biological samples and to a fluidic device assembly.

[0004] Nowadays, in the field of investigating biological samples, so-called fluidic devices are used for preparing biological samples in a particular investigation environment and for carrying out the investigations as such.

[0005] However, such known fluidic devices have a rigid and strict configuration, thereby suffering from the drawback of requiring devices which are designed to a respective portion of the preparation and investigation process, namely in order to cover plural or the entirety of required processes.

[0006] It is an object underlying the present invention to suggest an improved fluidic device and a fluidic device assembly that have a higher degree of flexibility from an application point of view.

[0007] The object underlying the present invention is achieved by a fluidic device according to independent claim 1 by a fluidic device assembly according to independent claim 7. Preferred embodiments of the present invention are defined in the respective dependent claims.

[0008] According to a first aspect of the present invention, a fluidic device is proposed which comprises a support that has an upper surface and an opposing lower surface and that is configured to carry a biological sample for investigation. In addition, a lid assembly is part of the fluidic device. The lid assembly comprises a lid and a gasket The lid assembly is removably mounted or mountable to the upper surface of the support. By this configuration, a higher degree of flexibility from the application point of view is achieved.

[0009] The fluidic device according to the present invention is particularly designed for investigating biological samples and / or specimens. The samples and / or specimens may be biological cells or parts or combinations thereof, tissues or parts thereof, parts all assemblies from bacteria or fungi, sections of superordinate samples or the like.

[0010] In a mounted state, the lid is attached to the upper surface of the support with the gasket therebetween. Thereby a closable or closed inner and / or sample space may be formed, in the interior of which a sample and / or an investigation medium, still or flow, may be comprised and surrounded.

[0011] The lid may be or may comprise a lid frame.

[0012] The lid frame or lid plate may have or may be formed as a plate, in particular with a lower surface and an upper surface and / or it may have one or plural supply holes for medium exchange and / or for ventilation.

[0013] In a mounted state of the lid to the upper surface of the support a sample preparation configuration may be formed in the inner space or sample space.

[0014] Alternatively or additionally, the lid may be or may comprise one or plural bottom layers - for instance a bottom channel layer and a bottom frame layer - which may be mounted or mountable to a lower surface of a lid frame or the lid frame - for instance in a stacked manner - and between the lower surface of the lid frame and the gasket

[0015] In particular and as can be seen in a top view, in a mounted state the one or plural bottom layers of the lid may follow or essentially follow an outer circumference of the lower surface of the lid frame and in particular leaving an inner portion of the lower surface of the lid frame open, uncovered or unoccupied.

[0016] In a mounted state of the lid to the upper surface of the support in particular a flow cell configuration may be formed in the inner space or sample space.

[0017] Further alternatively or additionally, the lid may be or may comprise one or plural top layers - in particular a top channel layer and a top frame layer - which may be mounted or mountable to an upper surface of a lid frame or the lid frame.

[0018] In particular in a mounted state, the one or plural top layers of the lid may - in particular in a top and / or plan view - essentially follow an outer circumference upper surface of the lid frame leaving an inner portion of the upper surface of the lid frame open, uncovered or unoccupied.

[0019] In a mounted state of the lid to the upper surface of the support in particular a flow cell configuration with an additional upper or top immersion reservoir may be formed on top and it may in particular be configured for microscopy applications configured to receive an immersion fluid. The lid frame may fulfill at least one of the following properties:

[0020] - it may be or comprise a thin layer of a thickness in the range of 0.1 mm to 0.2 mm and in particular of the thickness of about 0.17 mm,

[0021] - it may be chemically inert or it may comprise a chemically inert material,

[0022] - it may be made of or may comprise a glass or glass material,

[0023] - it may be optically transparent or it may comprise an optically transparent material, in particular in the visual range,

[0024] - it may be or may comprise a standardized microscopy cover glass.

[0025] The support may fulfill at least one of the following properties:

[0026] - it may be chemically inert or it may comprise a chemically inert material,

[0027] - it may be made of or may comprise a glass or glass material,

[0028] - it may be optically transparent or it may comprise an optically transparent material, in particular in the visual range,

[0029] - it may be or may comprise a standardized microscopy glass slide.

[0030] The present invention further relates to a fluidic device assembly which comprises the present invention’s fluidic device and which has plural lid assemblies which are interchangeably and removably mountable to the underlying support of the device assembly and which are otherwise defined according to the present invention and as described above.

[0031] 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.

[0032] Figure 1 is a cross-sectional view of an embodiment of the present invention’s fluidic device having a lid assembly of a first kind, thereby yielding a configuration or assembly in particular suitable for sample or specimen configuration and / or preparation.

[0033] Figure 2 is a cross-sectional view of an embodiment of the present invention’s fluidic device having a lid assembly of a second kind, thereby yielding a flow cell configuration or space.

[0034] Figure 3 is a cross-sectional view of an embodiment of the present invention’s fluidic device having a lid assembly of a third kind, thereby yielding a flow cell configuration or space with an upper immersion reservoir formed on top and configured for immersion microscopy applications.

[0035] Figure 4 is a cross-sectional view describing the application of an embodiment of the fluidic device formed according to the present invention as a flow cell and arranged within a superordinate investigation assembly.

[0036] Figure 5 is a top view describing an embodiment of the present invention’s fluidic device assembled within a flow cell or flow chamber in connection with a bottom channel layer.

[0037] In the following, embodiments and the technical background of the present invention are presented in detail by taking reference to accompanying figures 1 to 5. 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.

[0038] 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.

[0039] 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 1 to 3:

[0040] As shown in the figures 1 to 3 in general, cross-sectional views of embodiment of the present invention’s fluidic device 1 having a lid assembly 20 of first to third kinds are presented, thereby yielding (i) a space for sample configuration and / or preparation, (ii) a flow cell configuration and / or space, and (iii) a flow cell configuration and / or space with an upper immersion reservoir 37 formed on top and configured for immersion microscopy applications, respectively.

[0041] The fluidic device 1 according to the present invention is particularly designed for preparing, configuring and / or investigating biological samples S or specimens S. The samples S or specimens S may be biological cells or parts or combinations thereof, tissues or parts thereof, parts of assemblies from bacteria or fungi, sections of superordinate samples or the like.

[0042] The fluidic device 1 according to an embodiment of the present invention may comprise a support 10 which has an upper surface 10a and an opposing lower surface 10b and that is configured to receive, carry and / support one or plural biological samples S or specimens S for preparation, configuration, incubation and / or investigation.

[0043] In addition, a lid assembly 20 is part of the fluidic device 1. The lid assembly may comprise (i) a lid 30 that may have various designs and (ii) a gasket 21.

[0044] The lid assembly 20 is removably mounted or mountable to the upper surface 10a of the support 10.

[0045] In a mounted state, the lid 30 is attached to the upper surface 10a of the support 10 with the gasket 21 therebetween. Thereby a surrounded, closable or closed inner and / or sample space lOi may be formed, in the interior of which a sample S and / or an investigation medium 10m, still or flow, may be comprised and7or may be surrounded.

[0046] The lid 30 may be or may comprises a lid frame 31 or a lid plate 31.

[0047] The lid frame 31 or lid plate 31 may be formed as a plate, in particular with a lower surface 31b and an upper surface 31a and / or it may have one or plural supply holes 32 for medium exchange and / or for ventilation.

[0048] In a mounted state of the lid 30 to the upper surface 10a of the support 10, a sample preparation configuration may be formed in the inner space lOi or sample space lOi. This may be used for a final preparation of the sample S to be investigated.

[0049] Alternatively or additionally, the lid 30 may be or may comprise one or plural bottom layers 33, 34 - for instance a bottom channel layer 33 and a bottom frame layer 34 - which may be mounted or mountable to a lower surface 31b of a lid frame 31 or the lid frame 31 - for instance in a stacked manner - and between the lower surface 31b of the lid frame 31 and the gasket 21.

[0050] In particular and as can be seen in a plan view or top view, in a mounted state the one or plural bottom layers 33 and 34 of the lid 30 may follow or essentially follow an outer circumference of the lower surface 31b of the lid frame 31 and in particular leaving an inner portion of the lower surface 31b of the lid frame 31 open, uncovered and / or unoccupied.

[0051] In a mounted state of the lid 30 to the upper surface 10a of the support 10, in particular a flow cell configuration may be formed in the inner space lOi or sample space lOi.

[0052] Further alternatively or additionally, the lid 30 may be or may comprises one or plural top layers 35, 36 - in particular a top channel layer 35 and a top frame layer 36 - which may be mounted or mountable to an upper surface 31a of a or the lid frame 31.

[0053] In particular and as can be seen in a plan view or top view, in a mounted state the one or plural top layers 35, 36 of the lid 30 may essentially follow an outer circumference upper surface 31a of the lid frame 31 leaving an inner portion of the upper surface 31a of the lid frame 31 open, uncovered or unoccupied.

[0054] In a mounted state of the lid 30 to the upper surface 10a of the support 10 in particular a flow cell configuration with an additional upper or top immersion reservoir 37 or immersion pool 37 may be formed on top and it may in particular be configured for microscopy applications configured to receive an immersion fluid 37f within said immersion pool 37 or immersion reservoir 37.

[0055] The lid frame 31 may fulfill at least one of the following properties:

[0056] - it may be or comprise a thin layer of a thickness in the range of 0.1 mm to 0.2 mm and in particular of the thickness of about 0.17 mm,

[0057] - it may be chemically inert and / or it may comprise one or plural chemically inert materials,

[0058] - it may be made of or may comprise a glass or glass material,

[0059] - it may be optically transparent and / or it may comprise one or plural optically transparent materials, in particular in the visual range,

[0060] - it may be or may comprises a standardized microscopy cover glass.

[0061] The support 10 may fulfill at least one of the following properties:

[0062] - it may be chemically inert and / or it may comprise one or plural chemically inert materials,

[0063] - it may be made of or may comprise a glass or glass material,

[0064] - it may be optically transparent and / or it may comprise one or plural optically transparent materials, in particular in the visual range,

[0065] - it may be or may comprise a standardized microscopy glass slide.

[0066] According to an embodiment of the present invention, the proposed fluidic device assembly may comprise an embodiment of the present invention’s fluidic device 1, but it has or may have plural lid assemblies 20 which are interchangeably and / or removably mountable to the underlying support 10 of the device assembly 1 and which are or may be otherwise formed and configured as described above. Figure 5 is a top view describing an embodiment of the present invention’s fluidic device 1 assembled with a flow cell lOi in a superordinate distribution plate 50 forming - in cooperation with the support 10 and the lid assembly 20 - a flow chamber assembly, namely on the basis of a micro injection molding body 51 and in connection with a bottom channel layer 33, the latter e.g. formed by the injection molding body 51.

[0067] On the one hand, and as can be seen in the top view of figure 5, in a top portion of the distribution plate 50 based on the molding body 51 immersion pool 37 or immersion reservoir 37 is formed. The immersion pool 37 or immersion reservoir 37 is connected to an immersion fluid supply channel 52 for having supplied the immersion fluid 37f into the immersion pool 37 or immersion reservoir 37 as well as an immersion fluid removal channel 53 for exhausting the immersion fluid 37f from the immersion pool 37 or immersion reservoir 37.

[0068] In addition, figure 5 also demonstrates formed in the micro injection molding body 51 of the distribution plate 50 the provision of a vertical inlet section 54 for buffer / reagent supply into an underlying flow cell lOi, namely in connection with a funnel portion / geometry 55 for generating homogenous pressure distribution at inlet section 54. A respective connection is realized by vertical inlets 57 for a reagent / buffer 10m which are connected by a channel 56.

[0069] On the other hand, reagent / buffer 10m or investigation medium 10m can be removed from the flow cell lOi by a vertical outlet section 58 for exhausting reagent / buffer 10m from the flow cell lOi, also by using an outlet channel 60 for the waste of reagent / buffer 10m.

[0070] Eventually, figure 4 is a cross-sectional side view describing the application of an embodiment of the fluidic device 1 formed according to the present invention as a flow cell lOi and formed by and / or arranged within an superordinate investigation assembly 100.

[0071] In particular, the configuration as shown in figure 5 is applied herein, i.e. by using the distribution plate 50 having the micro injection molding body 51 forming the bottom channel layer 33 for realizing the flow cell lOi.

[0072] The fluidic device 1 and in particular the lid assembly 20 in combination with the distribution plate 50 are arranged and supported by a clamping mechanism 65, in particular in order to apply a sealing force, wherein the clamping mechanism 65 comprises an upper portion 65a and a lower portion 65b as a counterpart (the latter for instance formed as an aluminum enclosure), namely for receiving, supporting and fixing therebetween the combination of the fluidic device 1 with its lid assembly 20 applied to the support 10 and the distribution plate 50.

[0073] Via a high precision adapter 66 and by using a sealing ring 67, a tubing or capillary 68 is connected through the lower portion 65b to the vertical channel 54 for supplying reagent / buffer 10m to the flow cell lOi and the sample S or specimen S attached to the upper surface 10a of the support within the inner space lOi or flow cell lOi.

[0074] The distribution plate 50, the support 10, and the lid assembly 20 in a mounted state are embraced by an enclosure 70, which might be formed as a conventional injection molding component. The enclosure 70 might have an upper part 71 and a lower part 72, both parts 71, 72 may be connected via a click connection. The upper part 71 of the enclosure and 70 may have an overlapping edge 73 for guaranteeing that the immersion fluid 37f gets into contact with the upper surface 31a of the lid plate 31, which therefore might have advantageously hydrophilic properties, for instance by an appropriate coating or any other suitable treatment.

[0075] Figure 4 also demonstrates the provision of a microscope 80 with its objective 81 or objective lens 81 being inserted into an opening 82 of the enclosure 70 and its upper part 71.

[0076] These and further aspects of the present invention will also be described in detail in the following passages:

[0077] The present invention inter alia refers (i) to enclosed fluidics devices 1 with an inter-changeable lid assembly 20 for imaging specimens S from tissues and / or cell samples and / or (ii) to concepts and designs for fluidics devices 1 that are configured to deliver reagents 10m to specimens S of tissue and / or cell samples inter alia for imaging applications.

[0078] Embodiments of the proposed concepts and designs allow the usage of standard microscope slides with 1 mm thickness (or other values of thickness) as primary sample and / or specimen carriers for tissue and / or cell samples, in particular for imaging on immersion microscopy setups and / or for other microscopy setups.

[0079] Separate flow cell lid assemblies 20 are proposed with different configurations to be attached to standard microscope slides in order to form an enclosed flow cell cavity lOi for delivering reagents to tissue and / or cell samples S. The proposed designs permit sequential assembly of different lids 30 with the same tissue or cell attached as samples or specimens S to standard microscope slides for different applications, e.g. sample preparation, staining, transcript reagent delivery and imaging, protein reagent delivery and imaging.

[0080] Figures 1 to 3 demonstrate the present invention’s concept of multiple lid configurations or assemblies that are or may be configured to match standard microscope slides, e.g. with a 1 mm thickness.

[0081] In particular, figure 3 exemplifies the present invention’s concept of a fully assembled flow cell lOi. The bottom is a standard thickness slide 10 with tissue S or cell S attached on its top surface 10a. The top portion is formed by a flow cell lid assembly 20 with an immersion reservoir 37 on its top. An immersion objective lens 81 may image the tissue S or cell samples S from upright position from the top.

[0082] Figure 4 demonstrates a concept design of a fully assembled flow cell lOi from figures 1 to 3 in a superordinate investigation assembly or device 100.

[0083] Figure 5 elucidates a concept design of a bottom channel layer 33 for reagent delivery to a flow chamber lOi.

[0084] The present invention inter alia refers to a fluidic device 1 - in particular for investigating biological samples S or specimens S. The fluidic device 1 may comprise (i) a support 10 which has an upper surface 10a that is configured to receive, carry and / or support a biological sample S or specimen S for preparation, incubation and / or investigation, and (ii) a lid assembly 20 which has a lid 30 and a gasket 21 and which is removably mounted or mountable to the upper surface 10a of the support 10, wherein in a mounted state the lid 30 is attached to the upper surface 10a of the support 10 with the gasket 21 therebetween to thereby form a surrounded, closable or closed inner or sample space lOi. A fluidic device assembly according to the present invention comprises a fluidic device 1 and plural interchangeably and removably mountable lid assemblies 20 with appropriate configurations. List of Reference Signs

[0085] 1 fluidic device

[0086] 10 support, primary sample and / or specimen carrier

[0087] 10a upper surface of the support 10

[0088] 10b lower surface of the support 10 lOi inner space, sample space, flow cell

[0089] 10m investigation medium, reagent, buffer

[0090] 20 lid assembly

[0091] 21 gasket

[0092] 30 lid

[0093] 31 lid frame, lid plate

[0094] 31a upper surface of the lid frame / plate 31

[0095] 31b lower surface of the lid frame / plate 31

[0096] 31m fiducial mark

[0097] 32 supply hole of the lid frame / plate 31

[0098] 33 bottom layer of the lid frame 31, bottom channel layer

[0099] 34 bottom layer of the lid frame 31, bottom frame layer

[0100] 35 top layer of the lid frame 31, top channel layer

[0101] 36 top layer of the lid frame 31, top frame layer

[0102] 37 immersion pool, immersion reservoir

[0103] 37f immersion fluid

[0104] 50 (microstructure) distribution plate

[0105] 51 micro injection molding body

[0106] 52 immersion fluid supply channel

[0107] 53 immersion fluid removal channel

[0108] 54 (vertical) inlet section for buffer / reagent supply into flow cell lOi

[0109] 55 funnel portion / geometry for generating homogenous pressure distribution and at inlet section 54

[0110] 56 channel connecting reagent / buffer inlet

[0111] 57 (vertical) inlet for reagent / buffer 10m 58 (vertical) outlet section for exhausting reagent / buffer 10m from flow cell lOi

[0112] 59 (vertical) waste outlet for reagent / buffer 10m

[0113] 60 outlet channel for waste (reagent / buffer 10m)

[0114] 65 clamping mechanism (in particular to apply sealing force)

[0115] 65a upper portion of clamping mechanism

[0116] 65b lower portion / counterpart of clamping mechanism

[0117] 66 high precision adapter

[0118] 67 sealing ring

[0119] 68 tubing / capillary

[0120] 69 gasket or 2k injection molded sealing or adhesive

[0121] 70 enclosure

[0122] 71 upper part of enclosure 70

[0123] 72 lower part of enclosure 70

[0124] 73 overlapping edge

[0125] 74 laser welding portion

[0126] 80 microscope device

[0127] 81 objective or objective lens of microscope device

[0128] 82 opening in the enclosure for granting access of the objective 81

[0129] 100 (superordinate) investigation assembly

[0130] S biological sample, specimen, cell, cell portion, tissue portion x spatial direction

[0131] X direction of the longitudinal or length extension y spatial direction

[0132] Y direction of the transversal or width extension z spatial direction

[0133] Z direction of the height extension

Claims

Claims1. Fluidic device (1) for investigating biological samples (S),- comprising:- a support (10) which has an upper surface (10a) that is configured to receive, carry and / or support a biological sample (S) for preparation, incubation and / or investigation, and- a lid assembly (20) which has a lid (30) and a gasket (21) and which is removably mounted or mountable to the upper surface (10a) of the support (10),- wherein in a mounted state the lid (30) is attached to the upper surface (10a) of the support (10) with the gasket (21) therebetween to thereby form a surrounded, closable or closed inner and / or sample space (lOi).

2. Fluidic device (1) according to claim 1, wherein:- the lid (30) is or comprises a lid frame (31) that is in particular formed as a plate and / or that has one or plural supply holes (32), and- in a mounted state of the lid (30) to the upper surface (10a) of the support (10) in particular a sample preparation configuration is formed in the inner and / or sample space (lOi).

3. Fluidic device (1) according to any one of the preceding claims, wherein:- the lid (30) is or comprises one or plural bottom layers (33, 34)- which are mounted or mountable to a lower surface (31b) of a or the lid frame (31) and between the lower surface (31b) ofthe lid frame (31) and the gasket (21) and- which in particular in a mounted state and in particular in a top or plan view follow an outer circumference of the lid frame (31) leaving an inner portion of the lower surface (31b) ofthe lid frame (31) unoccupied, and- in a mounted state of the lid (30) to the upper surface (10a) of the support (10) in particular a flow cell configuration is formed in the inner or sample space (lOi).

4. Fluidic device (1) according to any one of the preceding claims, wherein:- the lid (30) is or comprises one or plural top layers (35, 36)- which are mounted or mountable to an upper surface (31a) of a or the lid frame (31) and- which in particular in a mounted state and in particular in a top or plan view follow anouter circumference of the lid frame (31) leaving an inner portion of the upper surface (31a) of the lid frame (31) unoccupied, and- in a mounted state of the lid (30) to the upper surface (10a) of the support (10) in particular a flow cell configuration with an upper immersion reservoir (37) is formed on top in particular configured for microscopy applications configured to receive an immersion fluid (37).

5. Fluidic device (1) according to any one of the preceding claims, wherein the lid frame (31) fulfills at least one of the following properties:- it is or comprises a thin layer of a thickness in the range of 0.1 mm to 0.2 mm and in particular of the thickness of about 0.17 mm,- it is chemically inert,- it is made of or comprises a glass or glass material,- it is optically transparent in the visual range,- it is or comprises a standardized microscopy cover glass.

6. Fluidic device (1) according to any one of the preceding claims, wherein the support (10) fulfills at least one of the following properties:- it is chemically inert,- it is made of or comprises a glass or glass material,- it is optically transparent in the visual range,- it is or comprises a standardized microscopy glass slide.

7. Fluidic device assembly,- comprising a fluidic device (1) according to any one of the preceding claims, and- having plural lid assemblies (20):- which are interchangeably and removably mountable to the underlying support (10) of the device assembly (1) and- which are formed according to any one of claims 1 to 5.

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