Cell avidity analysis device

Abstract

The invention is directed to a cell avidity analysis cassette (1). The cassette comprises a sample holder (2), preferably a sample holder in the form of a sample plate (20). The sample holder (2) comprises at least a first flow channel (51) extending between a first channel inlet (51A) and a first channel outlet (51B). The cassette (1) further comprises a casing (3) for holding the sample holder (2) therewithin. The cassette (1) is arranged to hold the sample holder (2) in a substantially hermetically sealed manner within the casing (3). Preferably, said casing (3) can be arranged to be substantially hermetically sealed and / or the cassette (1) can be arranged to provide one or multiple substantially hermetical sealings between the casing (3) and the sample holder (2). Further, the casing (3) is arranged to be opened, for instance to enable temporarily removing the sample holder (2) from the casing (3) and / or to enable putting the sample holder (2) back into the casing (3). Furthermore, the casing (3) is arranged to be closed again, in particular in a manner such that the cassette (1) holds the sample holder (2) in the substantially hermetically sealed manner within the casing (3).

Description

[0001] Title: Cell avidity analysis device

[0002] TECHNICAL FIELD

[0003] The invention relates to a cell avidity analysis device.

[0004] BACKGROUND

[0005] In cell avidity analysis, which for instance may be performed to facilitate cell therapy drug development, the overall cellular binding strength, i.e. the cell avidity, is often analysed in vitro by applying a force to bound cells, e.g. effector cells bound to target cells. An in vitro cell avidity analysis may for example be performed in order to provide a relatively relevant prediction reflecting an in vivo interaction between effector cells, for instance T cells, and target cells, in particular target antigens or immune cells. It will be appreciated that analysing the cell avidity for different effector cells, which are provided with different candidate receptors, can allow one to compare different effector cells. Implementing cell avidity analysis at a relatively early stage of cell therapy drug development may thus facilitate relatively early identification of relatively good lead candidates, which thereby may accelerate the development process and / or make the development more time and / or cost effective.

[0006] In cell avidity analysis processes, control over fluids and cells to be analysed and / or control over interaction and / or incubation time may be of high importance. For example, in order to obtain reproducible results, it may be important to tightly control incubation time and / or other parameters. Known methods for handling samples usually tend to require elaborate manipulation, in particular in manners requiring relatively much manual labour.

[0007] Cell avidity analyses may predict cellular responses relatively well, and may drive relatively good and / or relatively well informed decisions at relatively early stages of drug selection and may improve clinical outcomes. And, although there are already processes and devices to perform cell avidity analysis, there still is a desire for devices and / or methods for further improving cell avidity analysis.

[0008] It is an object of the present invention to provide a novel cell avidity analysis device, in particular one wherein samples can be analysed relatively precisely and / or wherein multiple, preferably relatively many, samples can be analysed simultaneously and / or in relative hight throughput format. SUMMARY OF THE INVENTION

[0009] The present disclosure provides for a new and improved device for cell avidity analysis.

[0010] In particular, the present invention provides for a cell avidity analysis cassette according to claim 1 .

[0011] The cell avidity analysis cassette comprises a sample holder, preferably a sample holder in the form of a sample plate, wherein the sample holder comprises at least a first flow channel, which may also be referred to as a so-called well, wherein said first flow channel extends between a first channel inlet and a first channel outlet. The cassette further comprises a casing, which may also be referred to as a so-called enclosure, for holding the sample holder therewithin. The cassette is arranged to hold the sample holder in a substantially hermetically sealed manner within the casing. Said casing is arranged to be opened and to be closed again, in particular in a manner in which it can hold the sample holder again in a substantially hermetically sealed manner. It will be appreciated that the sample holder can be removably placed within the casing, at least in embodiments.

[0012] By arranging the casing such that it can be opened and closed, it can be enabled that the sample holder can be temporarily removed from the casing and / or can be put back into the casing, in particular in a substantially hermetically sealed manner.

[0013] In advantageous embodiments, the casing may namely be arranged to be substantially hermetically sealed. For example, the casing may comprise at least a first casing part and a second casing part, which can be substantially hermetically sealed to each other. Alternatively or additionally, the cassette may be arranged to provide one or multiple substantially hermetical sealings between the casing and the sample holder, for example between the sample holder and one of multiple casing parts, in particular between the sample holder and a casing part forming a cover or lid.

[0014] Keeping the sample holder, and thus a sample held by said sample holder, substantially hermetically locked within the cassette may for example counteract that the sample can become contaminated. On the other hand, it may, additionally or alternatively, counteract that sample cells, in particular target cells, may unintentionally spread outside of the sample holder and / or outside of the cassette. For example, the sealing may counteract evaporation of a liquid held in a respective flow channel, for example during incubation, in particular incubation of biological material, such as cells, which may be part of the sample. As another example, the sealing may counteract the forming of aerosols, for instance during centrifugation in a centrifuge unit. As yet another example, the sealing may counteract spilling of sample material, for instance biological sample material, when one accidently drops the cassette.

[0015] Additionally, or alternatively, the casing may enable that, for instance after it has been used in a cell avidity analysis, the sample holder may be relatively safely disposed of, in particular in a manner in which the sample holder can be neatly contained such as to counteract that sample cells, in particular target cells, may unintentionally spread outside of the sample holder and / or outside of the cassette.

[0016] In embodiments, the cassette, preferably its casing, can be arranged, such that it provides protections against unauthorised access to the sample holder held within the casing. This may for instance counteract that one may tamper with the sample holder. It may for example also counteract that the cassette may accidentally open, for example when one accidentally drops the cassette, thereby thus counteracting that sample material, which may be potentially harmful biological sample material, may accidently spread.

[0017] Advantageously, the casing may comprise at least two casing parts, for example at least a first casing part and a second casing part. For example, the first casing part may be a part forming a container or a main housing part for the sample holder, whereas the second casing part may be a lid or a cover. The cassette, preferably its casing, may then comprises one or multiple locks or locking mechanisms, preferably internal locking mechanisms, for releasably locking the first casing part with respect to the second casing part, which may protect against unauthorized access.

[0018] In advantageous embodiments, the releasably locking of the second casing part with respect to the first casing part may be in a substantially hermetically sealing manner, for instance in a manner in which the first casing part, if any, is substantially hermetically sealed to the second casing part, if any.

[0019] Alternatively, or additionally, the sample holder may be substantially hermetically sealed to the casing, for instance to its second part, if any. For example in order to further counteract tampering, the number of locks or locking mechanisms may be at least two, preferably at least three, and may more preferably comprise at least four locks or locking mechanisms. In particular, the cassette may comprise at least two, preferably at least three, more preferably at least four locks or locking mechanisms in the form of releasable snap locks, such as for instance so-called click fingers. Preferably, the multiple snap locks may be positioned at such locations that it can be prevented, or at least counteracted to a certain extent, that a person can click them all open simultaneously with one hand only. By doing so, it can be counteracted that a person unlocks all snap locks with one hand and opens the cassette using also his or her other hand. A substantially manual opening may thus be prevented or least counteracted, thereby for instance counteracting accidents.

[0020] Although snap locks may be advantageous, alternative, or additional, other locks or locking mechanism are possible as well. For example, one or multiple locks or locking mechanisms may comprise one or multiple components such as latches, clips, or electronic locks that respond only to a designated tool or key.

[0021] Advantageously, the dimensions, in particular outer dimensions, of the casing may correspond to respective dimensions of the ANSI SLAS standards. This can be highly advantageous, for example as the cassette may then be compatible with standard components arranged to be compatible with microplates conforming to the ANSI SLAS standards, such as for example a lab centrifuge unit arranged to be compatible with microplates conforming to the ANSI SLAS standards.

[0022] Alternatively or additionally, the dimensions of the sample holder may correspond to respective dimensions of the ANSI SLAS standards. For example, the locations of the inlets and outlets may correspond to the positions of wells of a microplate conforming to the ANSI SLAS standards.

[0023] By providing the sample holder with multiple flow channels, in particular multiple flow channels of substantially similar design and / or substantially similar dimensions, wherein each one of said multiple flow channels extends between their respective channel inlet and their respective channel outlet, multiple samples may be handled simultaneously. For example, by centrifuging a single cassette with a sample holder having multiple flow channels, multiple samples may be subjected to a centrifugal force simultaneously.

[0024] The multiple flow channels may be arranged in an array. The array, when seen from above, may comprises multiple columns, for instance twelve columns, preferably wherein the distance between the virtual central axes of two adjacent columns is 9 mm, 4.5 mm or 2.25 mm.

[0025] Additionally or alternatively, the array, when seen from above, may comprise multiple rows, for instance eight rows, preferably wherein the distance between the virtual central axes of two adjacent rows is 9 mm, 4.5 mm or 2.25 mm.

[0026] Additionally or alternatively, the locations of the flow channels of the array and / or the locations of their channel inlets and / or the locations of the channel outlets, when seen from above, may correspond to the locations of wells of a so-called microplate, especially a 96-well microplate, a 384-well microplate or a 1536-well microplate, preferably that of a microplate conforming to the ANSI SLAS standards, especially a 96-well, 384-well or 1536-well microplate conforming to the ANSI SLAS standards.

[0027] Advantageously, the sample holder, at least below at least a part of the respective flow channel and / or at least above a part, preferably the same part, of the respective flow channel, may be transparent to predefined electromagnetic radiation, preferably light, more preferably visible light. For example, the entire sample holder may be made of a substantially transparent material, preferably a substantially transparent plastic material, more preferably a polymer, yet more preferably a cyclic olefin polymer (COP). However, other suitable materials may be used as well.

[0028] Other advantageous embodiments according to the invention are described in the following claims.

[0029] BRIEF DESCRIPTION OF THE DRAWINGS

[0030] By way of example only, embodiments of the present invention will now be described with reference to the accompanying schematic drawings in which:

[0031] Fig. 1 shows a schematical exploded view of an exemplary embodiment of a cell avidity analysis cassette according to the invention; and

[0032] Fig. 2 shows a schematical cross-sectional view of a detail of a sample holder of the cassette of Fig. 1 .

[0033] DETAILED DESCRIPTION OF EMBODIMENTS It is noted that the figures show merely a preferred embodiment according to the invention. In the figures, the same reference numbers and symbols refer to equal or corresponding parts.

[0034] The figures are intended for illustrative purposes only, and do not serve as restriction of the scope of the protection as laid down by the claims.

[0035] It will be readily understood that the components of the embodiments as generally described in the present disclosure and illustrated in the appended figures could be arranged and designed in a wide variety of different configurations. Thus, also the following more detailed description of various embodiments, as represented in the figures, is not intended to limit the scope of the present disclosure but is merely representative of various embodiments. While the various aspects of the embodiments are presented in drawings, the drawings are not necessarily drawn to scale unless specifically indicated.

[0036] The described embodiments are to be considered in all respects only as illustrative and not restrictive. The scope of the present disclosure is, therefore, indicated by the appended claims rather than by this detailed description. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

[0037] Reference throughout this specification to features, advantages, or similar language does not imply that all of the features and advantages that may be realized with the present disclosure should be or are in any single example of the present disclosure. Rather, language referring to the features and advantages is understood to mean that a specific feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the present disclosure. Thus, discussions of the features and advantages, and similar language, throughout this specification may, but do not necessarily, refer to the same example.

[0038] Furthermore, the described features, advantages, and characteristics of the present disclosure may be combined in any suitable manner in one or more embodiments. One skilled in the relevant art will recognize, in light of the description herein, that the present disclosure may be practiced without one or more of the specific features or advantages of a particular embodiment. In other instances, additional features and advantages may be recognized in certain embodiments that may not be present in all embodiments of the present disclosure. Reference throughout this specification to "one embodiment", "an embodiment", “an exemplary embodiment”, or similar language means that a particular feature, structure, or characteristic described in connection with the indicated embodiment is included in at least one embodiment of the present disclosure. Thus, the phrases "in one embodiment", "in an embodiment", “in and exemplary embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.

[0039] Fig. 1 shows an exemplary embodiment of a cell avidity analysis cassette 1.

[0040] The cassette 1 comprises a sample holder 2. Preferably, as is the case in the here shown exemplary embodiment, the sample holder 2 can be in the form of a sample plate 20, which for example may be build up out of multiple components or parts.

[0041] The sample holder 2 comprises multiple flow channels 51 , 52, 53, each extending between a respective channel inlet 51A, 52A, 53A and a respective channel outlet 51 B, 52B, 53B. All channel inlets 51 A, 52a, 53A and all channel outlets 51 B, 52B, 53B are preferably provided at the same side, in particular at the upper side 20A, of the sample plate 20.

[0042] Although the here shown exemplary embodiment comprises forty eight flow channels 51 , 52, 53, alternative embodiments may have another number of flow channels, for example 192 or 768 channels, such that the combined number of inlets and outlets together may for example be 384 or 1536. By having a combined number of 96, 384 or 1536 inlets and outlets, the combined number of inlets and outlets may correspond to the number of wells of a 96-well, 384-well or a 1536-well microplate, preferably that of a 96-well, 384-well or 1536-well microplate conforming to the ANSI SLAS standards. It will be appreciated that the locations of the channel inlets and the locations of the channel outlets, when seen from above, may correspond to the locations of the wells of a so-called microplate, preferably that of a microplate conforming to the ANSI SLAS standards.

[0043] When seen from above, the multiple flow channels 51 , 52, 53 can thus be arranged in an array comprising for instance twelve columns of inlets and outlets, preferably wherein the distance between the virtual central axes of two adjacent columns, i.e. the distance between the virtual central axes 51A’ of an inlet 51A and an adjacent outlet, is 9 mm, 4.5 mm or 2.25 mm. Additionally, or alternatively, when seen from above, the array may also comprise multiple rows, for instance eight rows, preferably wherein the distance between the virtual central axes of two adjacent rows can be 9 mm, 4.5 mm or 2.25 mm, and preferably correspond to the distance between the virtual central axes of an inlet and an adjacent outlet.

[0044] In embodiments, dimensions, in particular outer dimensions, of the sample plate 20 may correspond to respective dimensions of the ANSI SLAS standards. For example, the dimensions of the sample plate 20 corresponding to respective dimensions of the ANSI SLAS standards may comprises one or multiple dimensions regarding the length of the footprint of the sample plate 20 and / or one or multiple dimensions regarding the width of the footprint of the sample plate 20.

[0045] As can be seen relatively well in Fig. 2, which shows a schematical cross-sectional view of a detail of the sample holder 2 of the cassette 1 of Fig. 1 , the sample holder 2, which may preferably thus be in the form of a sample plate 20, can comprise a flat base plate 21 , for instance substantially made of COP (cyclic olefin polymer) or another suitable polymer, another suitable plastic, or any other suitable material. The sample holder 2 may further comprise one or multiple top parts 22 attached to the upper side of the flat base plate 21. Preferably, the top part 22 or top parts may be made substantially of the same material as the material of the base plate 21 , and may for example also be made at substantially of COP.

[0046] One or multiple regions 211 of the upper side of the base plate 21 may form at least a part of a respective bottom of a respective one of the one or multiple flow channels 51. The top part 22 may then define at least part of a respective ceiling 221 of a respective one of the multiple flow channels 51 , and may preferably also form at least part of the respective channel inlet 51 A and at least part of the respective channel outlet 51 B.

[0047] The sample holder 2, at least below at least a part of the respective flow channel 51 , 52, 53 and / or at least above a part, of the respective flow channel 61 , 62, 63, and preferably both below and above the same part of the flow channel, may be transparent to predefined electromagnetic radiation, preferably light, more preferably visible light. This may facilitate imaging samples within the respective flow channel, for example by means of a microscope or other imaging device.

[0048] Actually, in embodiments, substantially the entire sample holder 2 may be made of substantially transparent material. Further, at least a part of the ceiling 221 , and preferably the entire ceiling 221 , of the flow channel 51 may extend substantially parallel to at least a respective portion of an upper surface 228 of the sample holder 2 located above said at least part of the ceiling 221 and substantially parallel to at least a respective portion of a lower surface 218 of the sample holder 2 located below said at least part of the ceiling 221 .

[0049] The sample holder 2 may define a first optical distance to be measured in a direction perpendicular to said at least part of the ceiling 221 of the flow channel 51 , and which first optical distance is to be measured from said upper surface 228 of the sample holder 2 to said ceiling 221.

[0050] The sample holder 2, when the flow channel 52 is filled with an aqueous medium 100, as is the case in Fig. 2 defines a second optical distance to be measured, in a direction perpendicular to said at least part of the ceiling 221 of the flow channel 51 , from said lower surface 218 to said ceiling 221. The refractive index of the aqueous medium may be in the range of n = 1.20 to n = 1.46 or may be considered as n = 1.33 ±10%.

[0051] Preferably, the refractive index of said aqueous medium may be about n = 1.33.

[0052] It may be advantageous when said first optical distance substantially equals said second optical distance. This may for example enable that cells, or other sample material, present on or against said ceiling 221 can relatively simply be observed from either the top side or the bottom side, for instance without substantially adjusting an imaging device or its optics, such as a microscope or the like.

[0053] It is noted that said first optical distance substantially equalling said second optical distance may be considered as that they do not differ more than 400 pm, preferably not more than 200 pm, yet more preferably not more than 100 pm.

[0054] The sample holder 2 may be provided with a least one first abutment surface for facilitating positioning the sample holder 2 with respect to an imaging device in a first position of the sample holder 2. For example, the first abutment surface may be formed by the upper surface 228 of the top part 22 of the sample holder 2.

[0055] The sample holder 2 may further be provided with at least one second abutment surface 61 , 62, 63 for facilitating positioning the sample holder 2 with respect to the imaging device in a second position of the sample holder 2 which is an upside-down with respect to its first position. Said one or more second abutment surfaces 61 , 62, 63 may preferably be formed by one or multiple uncovered portions of the lower surface 229 of said same top part 22. The base plate 21 may thereto be provided with recesses or the like, as can be seen in Fig. 1 , which may enable that the lower side 229 of the top part 22 can locally be left free. This is, at the locations of said one or multiple second abutment surfaces 61 , 62, 63, the top part 22 is locally not covered by the base plate 21. Preferably, this is done at at least three positions 61 , 62, 63, in particular ones which are located relative to each other in a triangular formation, thereby facilitating that the sample holder 2 can be supported relatively stable in its upside-down position by positioning it on said at least three positions positioned in a triangular shape.

[0056] Advantageously, both the first abutment surface and the one or multiple second abutment surfaces may thus be formed by respective surfaces of the same part, in particular by respective surfaces the top part 22. Since said top part 22 may define the wall 221 which during an avidity experiment may be used to hold the cells thereto, and since it may be advantageous to for instance neatly control the distance from optical element of an imaging device to said wall 221 , in particular to make relatively good images, it can be advantageous to use the top part 22 for providing the first and / or second abutments surfaces, preferably both the first and second abutment surfaces.

[0057] It is advantageous if least a part of the ceiling 221 of the flow channel 51 is formed as a so-called functionalised wall surface 22T. For instance, at least a part of the ceiling 221 may thereto be provided with a functionalisation layer 222. Preferably, the functionalised wall surface 22T can be arranged for facilitating the attachment of cells, such as for example target cells or effector cells, thereto. This may facilitate that the cells, in particular target cells can adhere to the ceiling 221.

[0058] It is also possible that at least a part of the ceiling of the flow channel 51 , 52, 53 is already provided with cellular objects, preferably biological cells, such as for example target cells.

[0059] Furthermore, at least a part of the bottom 212 of the flow channel 51 , 52, 53 can at least partly be provided with an adhesion prevention layer 213 or a so-called anti-fouling coating 213, which may counteract that cellular objects, or at least certain cellular objects, may attach to at least said part of the bottom 212. It is also possible that not only said part of the bottom or said bottom, but substantially all wall surfaces defining the flow channel but the functionalised wall surface 22T, are provided with such an adhesion prevention layer 213 or anti-fouling coating 213. It is noted that the cell avidity analysis cassette 1 does not only comprise the sample holder 2, but further also comprises a casing 3 for holding the sample holder 2 therewithin. The cassette 1 is arranged to hold the sample holder 2 in a substantially hermetically sealed manner within the casing 3.

[0060] Preferably, said casing 3 can be arranged to be substantially hermetically sealed, for example by means of a seal provided between a first casing part 31 and a second casing part 32.

[0061] Alternatively, or additionally, the cassette 1 can be arranged to provide one or multiple substantially hermetical sealings between the casing 3 and the sample holder 2. For example, an inner side of a casing part 32 to which the inlets and outlets face, may be provided with one or multiple seals, which may also counteract that there may be cross-contamination between different flow channels.

[0062] It is noted that the casing 3 is arranged to be opened, for instance to enable temporarily removing the sample holder 2 from the casing 3 and / or to enable putting the sample holder 2 back into the casing 3. As such, the sample holder may for instance be positioned outside the casing 3 in order to make one or multiple images of at least a respective part of one or multiple samples provided in one or multiple respective flow channels.

[0063] It is noted that the casing 3 further is arranged to be closed again, in particular in a manner such that the cassette 1 holds the sample holder 2 again in the substantially hermetically sealed manner within the casing 3, when said sample holder 2 is placed back in case it had been temporarily removed from the casing 3 before.

[0064] The cassette 1 , preferably its casing 3, can provide protections against unauthorised or accidental access to the sample holder 2 held within the casing 3 to at least a certain extent. For example thereto, the cassette 1 , in particular its casing 3, may comprise one or multiple locks 4 or locking mechanisms 4, preferably internal locking mechanisms, for releasably locking the first casing part 31 with respect to the second casing part 32.

[0065] As can be seen in the exemplary embodiment shown in Fig. 1 , the cassette 1 may comprise at least two, preferably at least three, more preferably at least four locks or locking mechanisms in the form of releasable snap locks 40, such as for instance so-called click fingers. Preferably, the multiple snap locks 40 can be positioned at such locations that it can be prevented, or at least complicated, that a person can click them all open simultaneously with one hand only.

[0066] In the here shown embodiment, each snap lock 40 comprises two engaging elements 41 , 42 for engaging each other in an interlocking manner, wherein one 41 of the two engaging elements is provided at, on and / or in the first casing part 31 and the other one 42 is provided at, on and / or in the second casing part 32. For example, one of the two engaging element 41 , 42 is formed as a protrusion (preferably in the form of a barb, which may comprise a stop / lock surface and a run-on surface) and the other formed as a corresponding recess (not shown in Fig. 1), which may comprise a corresponding stop surface for engaging a stop surface or the like of said protrusion. One 41 of them, for instance the one formed as a protrusion, may be provided at, on or in a resilient element 410, said resilient element for instance being in the form of a resilient arm or a resilient wall part.

[0067] The resilient element 410 may be arranged to be deflected in order to release the interlocking. Preferably, the snap lock 40, in particular its resilient element 410, may be arranged for engagement by a respective tool, for instance by means of providing it with a respective anchor point 411 or the like.

[0068] It is noted that the cassette 1 can be arranged such that, in a closed state of the casing 3, the casing 3, preferably the other one 32 of the two casing parts than the one 31 which is provided with the resilient element 410, covers the resilient element 410 to such an extent that it is at least substantially prevented that a barehanded person can deflect said resilient element 410 to such extent that the interlocking can be released.

[0069] For example, the cassette 1 may be arranged such that, in a closed state of the casing 3, the casing 3, preferably by means of the other one 32 of the two casing parts than the one 31 which is provided with the resilient element 410, covers the resilient element 410 to such extent that it lets free only one or multiple areas 310 having a respective width W310 and / or a respective height H310 which not exceeds 1.5 cm, preferably not exceeding 12 mm, more preferably not exceeding 10 mm, yet more preferably not exceeding 8 mm. For example, the respective casing part 32, may thereto be provided with one or more openings 320, in particular in the form of one or more recesses, which may keep only said one or multiple areas 310 uncovered. Advantageously, dimensions, in particular outer dimensions, of the casing 3 can correspond to respective dimensions of the ANSI SLAS standards. Preferably, said dimensions of the casing 3 corresponding to respective dimensions of the ANSI SLAS standards comprise at least one of: (i) one or multiple dimensions regarding the length L3 of the footprint of the casing 3; (ii) one or multiple dimensions regarding the width W3 of the footprint of the casing 3; and (iii) one or multiple dimensions regarding one or multiple flanges 30 of the casing 3, if any. Preferably, the one or multiple flanges, if any, is / are provided at the first casing part 31 , yet more preferably at a lower end of said first casing part 31.

[0070] As can be seen in Fig. 1 , at least in embodiments, the outside of the casing 3, when seen from above, can be of a substantially rectangular design. Said substantially rectangular casing 3 may nevertheless not be entirely rotationally symmetrical about a virtual upstanding axis extending transverse to the footprint of the casing 3. For example, the casing 3 may be provided with a deviation 39, such as for instance a protrusion or indentation 39A. Preferably, as is the case in the here shown exemplary embodiment, the indentation 39A may be in the form of for instance a so-called corner notch 39A’, in particular one which is similar to the ones often present at corners of so-called microplates. Such or other deviation 39 can thus cause that the substantially rectangular casing is not rotationally symmetrical, when seen from above. This may for example help orienting the cassette 1 , the casing 3 and / or the sample holder 2.

[0071] Additionally, or alternatively, the first casing part 31 and the second casing part 32 may be arranged such that they only fit onto each other in one position, for instance by providing them with corresponding shapes which may include one or more corresponding protrusions and / or indentations. This may also apply to the sample holder, which in embodiments may also be provided with a such a deviation, in particular an indentation, more in particular a corner notch (which is not the case in the embodiment shown in Fig. 1).

[0072] In embodiments, the cassette 1 may be arranged such that the casing 3 can house the sample holder 2 in at least two positions, i.e. a first position in which the upper side 2A of the sample holder 2 faces up, as is the case in Fig. 1 , and a second position in which the upper side 2A faces down, The cassette 1 may then be arranged such that it can hold the sample holder 2 in a substantially hermetically sealed manner within the casing 3 in both said first position and said second position. The cassette 1 may for example be in a cell avidity analysis apparatus, for example an apparatus which comprises a centrifuge unit for centrifuging the sample holder 2 and which further comprises an imaging device, such as a microscope device or the like, for imaging at least a first section of the sample holder 2, preferably said first section being formed by a section of a respective flow channel 51 , 52, 53 of said sample holder 2.

[0073] For example to allow such apparatus to identify the cell avidity analysis cassette 1 and / or one or more samples held therein, said cassette 1 may be provided with at least one identification tag. The identification tag may for example be in the form of a transponder, more preferably in the form of a RFID tag, such as for example a UHF RFID tag.

[0074] The invention is not restricted to the embodiments described herein. It will be understood that many variants are possible.

[0075] Other such variants will be obvious for the person skilled in the art and are considered to lie within the scope of the invention as formulated in the following claims.

Claims

CLAIMS1. Cell avidity analysis cassette (1), comprising a sample holder (2), preferably a sample holder in the form of a sample plate (20), wherein the sample holder (2) comprises at least a first flow channel (51) extending between a first channel inlet (51 A) and a first channel outlet (51 B), the cassette (1) further comprising a casing (3) for holding the sample holder (2) therewithin, wherein the cassette (1) is arranged to hold the sample holder (2) in a substantially hermetically sealed manner within the casing (3), preferably said casing (3) being arranged to be substantially hermetically sealed and / or the cassette (1) being arranged to provide one or multiple substantially hermetical sealings between the casing (3) and the sample holder (2), wherein said casing (3) is arranged to be opened, for instance to enable temporarily removing the sample holder (2) from the casing (3) and / or to enable putting the sample holder (2) back into the casing (3), and wherein said casing (3) further is arranged to be closed again, in particular in a manner such that the cassette (1) holds the sample holder (2) in the substantially hermetically sealed manner within the casing (3).

2. Cell avidity analysis cassette (1) according to claim 1 , wherein the cassette, preferably its casing, is arranged, such that it provides protections against unauthorised access to the sample holder (2) held within the casing (3).

3. Cell avidity analysis cassette (1) according to anyone of the preceding claims, wherein the casing (3) comprises a first casing part (31) and a second casing part (32), wherein the cassette (1), preferably its casing (3), comprises one or multiple locks (4) or locking mechanisms (4), preferably internal locking mechanisms, for releasably locking the first casing part (31) with respect to the second casing part (32),preferably wherein said releasably locking of the second casing part with respect to the first casing part is in a substantially hermetically sealing manner, for instance in a manner in which the first casing part (31), if any, is substantially hermetically sealed to the second casing part (32), if any, and / or in which the sample holder (2) is substantially hermetically sealed to the casing (3), for instance to its second part (32), if any.

4. Cell avidity analysis cassette (1) according to claim 3, wherein the amount of the one or multiple locks or locking mechanisms is at least two, preferably at least three, more preferably at least four locks or locking mechanisms; and / or wherein the cell avidity analysis cassette (1) comprises at least two, preferably at least three, more preferably at least four locks or locking mechanisms in the form of releasable snap locks (40), such as for instance so-called click fingers, and said multiple snap locks (40) being positioned at such locations that it is prevented that a person can click them all open simultaneously with one hand only.

5. Cell avidity analysis cassette (1) according to claim 3 or 4, wherein the one or multiple locks or locking mechanisms (4) comprise at least one snap lock (40) comprising two engaging elements (41 , 42) for engaging each other in an interlocking manner, one of the two engaging elements being provided at, on and / or in the first casing part (31) and the other one being provided at, on and / or in the second casing part (32), wherein a first one (41) of the two engaging elements is provided at, on and / or in a resilient element (410), said resilient element for instance being in the form of a resilient arm or a resilient wall part, wherein the resilient element (410) is arranged to be deflected in order to release the interlocking, and wherein the cassette (1) is arranged such that, in a closed state of the casing (3), the casing, preferably the other one (32) of the two casing parts than the one (31) which is provided with the resilient element (410), covers the resilient element (410) to such extent that it is at least substantially prevented that a person17 can deflect said resilient element (410) to such extent that the interlocking can be released; and / or wherein the cassette (1) is arranged such that, in a closed state of the casing (3), the casing (3), preferably by means of the other one (32) of the two casing parts than the one (31) which is provided with the resilient element (410), covers the resilient element (410) to such extent that it (3, 32) only lets free one or multiple areas (310) having a width (W310) and / or a height (H310) which not exceeds 1.5 cm, preferably not exceeding 12 mm, more preferably not exceeding 10 mm, yet more preferably not exceeding 8 mm.

6. Cell avidity analysis cassette (1) according to anyone of the preceding claims, wherein dimensions, in particular outer dimensions, of the casing (3) correspond to respective dimensions of the ANSI SLAS standards, preferably wherein said dimensions of the casing corresponding to respective dimensions of the ANSI SLAS standards comprises at least one of: one or multiple dimensions regarding the length (L3) of the footprint of the casing; one or multiple dimensions regarding the width (W3) of the footprint of the casing; and one or multiple dimensions regarding one or multiple flanges (30) of the casing, if any, more preferably wherein said one or multiple flanges, if any, is / are provided at the first casing part (31), yet more preferably at a lower end of said first casing part.

7. Cell avidity analysis cassette (1) according to anyone of the preceding claims, wherein the sample holder (3) comprises multiple flow channels (51 , 52, 53), preferably multiple flow channels (51 , 52, 53) of substantially similar design and / or substantially similar dimensions, wherein each one of said multiple flow channels (51 , 52, 53) extends between their respective channel inlet (51A, 52A, 53A) and their respective channel outlet (51 B, 52B, 53B).

188. Cell avidity analysis cassette (1) according to claim 7, said multiple flow channels (51 , 52, 53) being arranged in an array, wherein the array, when seen from above, comprises multiple columns, for instance twelve columns of inlets and outlets, preferably wherein the distance between the virtual central axes of an inlet and an adjacent outlet is 9 mm, 4.5 mm or 2.25 mm, and / or wherein the array, when seen from above, comprises multiple rows, for instance eight rows, preferably wherein the distance between the virtual central axes of two adjacent rows is 9 mm, 4.5 mm or 2.25 mm, and / or wherein the locations of the flow channels (51 , 52, 53) of the array and / or the locations of their channel inlets and / or the locations of the channel outlets, when seen from above, correspond to the locations of wells of a so-called microplate, especially a 96-well microplate, a 384-well microplate or a 1536-well microplate, preferably that of a microplate conforming to the ANSI SLAS standards, especially a 96-well, 384-well or 1536-well microplate conforming to the ANSI SLAS standards.

9. Cell avidity analysis cassette (1) according to anyone of the preceding claims, wherein the outside of the casing (3), when seen from above, is of substantially rectangular design, wherein said substantially rectangular casing (3) is not rotationally symmetrical about a virtual upstanding axis extending transverse to the footprint of the casing (3), preferably wherein the casing is provided with a deviation (39), such as for instance a protrusion or indentation (39A) , preferably in the form of a so-called corner notch (39A’) which are often present at corners of so-called microplates, said deviation causing that the substantially rectangular casing is not rotationally symmetrical, when seen from above.

10. Cell avidity analysis cassette (1) according to anyone of the preceding claims, wherein the sample holder (2) is in the form of a sample plate (20) comprising multiple flow channels (51 , 52, 53) each having their own respective channel inlet (51 A, 52a, 53A) and channel outlet (51 B, 52B, 53B), and19 wherein all channel inlets (51A, 52a, 53A) and all channel outlets (51 B, 52B, 53B) are provided at the same side, preferably at the upper side (20A), of the sample plate (20).

11. Cell avidity analysis cassette (1) according to anyone of the preceding claims, preferably according to claim 10, wherein the cassette (1) is arranged such that the casing (3) can house the sample holder (2) in at least two positions, i.e. a first position in which the upper side (2A) of the sample holder (2) faces up and a second position in which the upper side (2A) faces down, and wherein the cassette (1) is arranged to hold the sample holder (2) in a substantially hermetically sealed manner within the casing (3) in both said first position and said second position.

12. Cell avidity analysis cassette (1) according to anyone of the preceding claims, preferably according to claim 10, wherein the sample holder (2), which preferably is in the form of a sample plate (20), comprises a flat base plate (21) and one or multiple top parts (22) attached to the upper side of the flat base plate (21), wherein one or multiple regions (211 , 212, 213) of the upper side of the base plate (21) form at least a part of a respective bottom of a respective one of the one or multiple flow channels (51 , 52, 53), wherein the top part (22) defines at least part of a respective ceiling of a respective one of the multiple flow channels (51 , 52, 53), and preferably also form at least part of the respective channel inlet (51A, 52A, 53A) and at least part of the respective channel outlet (51 B, 52B, 53B), preferably wherein the sample holder (2) is arranged such that the base plate (21) leaves free one or multiple portions (61 , 62, 63) of the lower side (229) of one or multiple top parts (22) attached to the upper side of the flat base plate (21), more preferably at least at three positions (61 , 62, 63) which are located relative to each other in a triangular formation.

13. Cell avidity analysis cassette (1) according to anyone of the preceding claims,20 wherein at least a part of the ceiling (221), and preferably the entire ceiling, of the flow channel (51) extends substantially parallel to at least a respective portion of an upper surface (228) of the sample holder (2) located above said at least part of the ceiling (221) and substantially parallel to at least a respective portion of a lower surface (218) of the sample holder (2) located below said at least part of the ceiling (221), wherein the sample holder defines a first optical distance, which is to be measured in a direction perpendicular to said at least part of the ceiling (221) of the flow channel, and which is to be measured from said upper surface (228) of the sample holder (2) to said ceiling (221), wherein the sample holder (2), when the flow channel (52) is filled with an aqueous medium (100), preferably one having a refractive index in the range of n = 1.20 to n =1.46, more preferably of about n = 1.33, defines a second optical distance to be measured in a direction perpendicular to said at least part of the ceiling (221) of the flow channel (51), and which is to be measured from said lower surface (218) to said ceiling (221), and wherein said first optical distance substantially equals said second optical distance.

14. Cell avidity analysis cassette (1) according to anyone of the preceding claims, preferably according to claim 13, wherein the sample holder is provided with a least one first abutment surface for facilitating positioning the sample holder with respect to an imaging device in a first position of the sample holder, preferably wherein the at least one first abutment surface is formed by an upper surface (228) of one or multiple top parts (22) attached to the upper side of the base plate (21), and wherein the sample holder is provided with at least one second abutment surface for facilitating positioning the sample holder with respect to the imaging device in a second position of the sample holder which is an upside-down with respect to its first position, preferably wherein the at least one second abutment surface is formed by a respective portion (61 , 62, 63) of the lower side (229) of one or multiple top parts (22) left free by the base plate (21).2115. Cell avidity analysis cassette (1) according to anyone of the preceding claims, wherein the first casing part and the second casing part are arranged such that they only fit onto each other in one position, preferably wherein the cassette (1) is a cassette (1) according to claim 9 and said deviation (39) at least partly causes that the first casing part (31) and the second casing part (32) only fit onto each other in one position; and / or wherein the sample holder, at least below at least a part of the respective flow channel (51 , 52, 53) and / or at least above a part, preferably the same part, of the respective flow channel (61 , 62, 63), is transparent to predefined electromagnetic radiation, preferably light, more preferably visible light; and / or wherein at least a part of a bottom of the flow channel (51 , 52, 53) is at least partly provided with an adhesion prevention layer or a so-called anti-fouling coating; and / or wherein at least a part of a ceiling of the flow channel (51 , 52, 53) is formed as a so-called functionalised wall surface, for instance by providing at least a part of the ceiling with a functionalisation layer, preferably wherein the functionalised wall surface is arranged for facilitating the attachment of cells, such as for example target cells or effector cells, thereto; and / or wherein the at least a part of a ceiling of the flow channel (51 , 52, 53) is provided with cellular objects, preferably biological cells, such as for example target cells or effector cells; and / or wherein the cassette (1) is provided with at least one identification tag, preferably in the form of a transponder, more preferably in the form of a RFID tag, such as for example a UHF RFID tag.

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