Cell-culture insert for cultivating cells

Abstract

The invention relates to a cell-culture insert for cultivating cells, comprising: a sidewall (7), which encloses a cavity (11) and has an inner face (8), that delimits the cavity (11), and an outer face (9); preferably wherein the sidewall (7) forms a hollow cylinder and / or the cavity (11) substantially surrounds, in a hollow-cylindrical manner, a base, designed as a membrane (14), and an attachment element (18); wherein the membrane (14) is frictionally and / or form-fittingly attached to the inner face (8) of the sidewall (7) by means of the attachment element (18).

Description

[0001] Cell culture insert for culturing cells

[0002] The invention relates to a cell culture insert for culturing cells according to claim 1.

[0003] Cell culture inserts of the type in question are regularly used in well plates. The well plate contains several wells for holding liquid. The wells are usually molded into the well plate. Each well has a bottom, a surrounding wall extending from it, and a rim that encloses the surrounding wall at the top. The rim defines the access opening at the front of the well.

[0004] Liquid is added to the wells of the well plate. This liquid serves as a nutrient medium for the cells that are grown at the bottom of the well or at the bottom of a cell culture insert placed in the well. The nutrient medium is added to the well using a pipette and changed regularly.

[0005] Cell culture inserts of the type in question are used to grow cells on the membrane-like base of the cell culture inserts. Hanging the cell culture inserts into the wells is usually done by at least one support arm extending laterally from the upper opening edge of the respective cell culture insert. Cultivating cells in the hanging insert at a relatively large distance from the bottom of the well allows for the addition of sufficient nutrient fluid into the well and around the cell culture insert.

[0006] However, there are also cultivation methods in which the cell culture inserts are to be placed on a support. For this purpose, it is known to provide support feet projecting downwards at the edge of the side wall, in addition to or as an alternative to a support arm. These feet allow the cell culture insert to be placed securely on a support with a small, even distance between the base and the support. The base of the cell culture insert is usually designed as a microporous membrane. The membrane enables exchange with the nutrient liquid beneath the base of the insert when the cell culture insert is placed in a well of a well plate filled with nutrient liquid. Membranes for cell culture inserts can be made of plastic, such as PTFE, PE, PET, MCE and / or PC. Collagen membranes are also increasingly being used.Collagen is a structural protein of the extracellular matrix and is found, for example, in human and animal skin, bones, muscles, tendons, cartilage, and connective tissue. Structural proteins are proteins that primarily serve as structural materials in the tissues or cells of living organisms. Collagen is the most abundant protein in humans and animals, accounting for 25% to 30% of human and animal protein.

[0007] One possible application of collagen membranes is the cultivation of both adherent and non-adherent cells, primary cells, stem cells, and cell lines, as well as the construction of tissue structures. A cell-seeded collagen membrane can be directly embedded to create a histological section, and staining of the collagen membrane is also possible. The collagen membrane is permeable to nutrients, which enables further applications, such as culturing cells for the construction of skin models or conducting transmembrane transport studies.

[0008] In the prior art on which the invention is based (DE 20 2017 003 978 U1), the cell culture insert has a side wall enclosing a cylindrical cavity. The membrane is disc-shaped and has a diameter essentially corresponding to the outer diameter of the side wall. To create a connection between the side wall and the membrane, the side wall is glued to the membrane at the end face.

[0009] When using membranes made of a biological material, such as collagen, gaps can develop between the membrane and the sidewall if the membrane is damaged by the adhesive and / or the bonding process, which can cause the membrane to partially detach from the sidewall. Furthermore, the mechanical properties and permeability of the membrane can be negatively affected in some places by the adhesive. It is also important to ensure that the adhesive and bonding process used are non-toxic to the cells, which can negatively impact cell growth.

[0010] Alternatively, it is also known from the prior art to bond the membrane to the sidewall by a material fit. For this purpose, the sidewall can be made, at least in sections, of a material, such as plastic, that has a lower softening temperature than the membrane. Heating the material can liquefy it and penetrate the pores of the membrane, creating undercuts. After the material cools and hardens, a positive connection is formed between the sidewall and the membrane.

[0011] High temperatures are required to create a positive connection between the sidewall and the membrane by softening the sidewall material. It has been shown that a membrane made of or containing collagen can be damaged by the high temperatures required, which can negatively impact cell growth.

[0012] The underlying teaching is the problem of creating a cell culture insert that enables an easy-to-establish connection between the side wall and the membrane while simultaneously ensuring a reliable connection between the membrane and the side wall. The object of the invention is also to ensure that the membrane is held flat in the cell culture insert at all times to prevent bulging or sagging of the membrane. The above-identified problem is solved in a cell culture insert with the features of claim 1. Preferred embodiments and further developments are the subject of the subclaims directed to the cell culture insert.

[0013] According to the invention, the cell culture insert has a side wall that encloses a cavity and has an inner side delimiting the cavity and an outer side. It is preferably provided that the side wall forms a hollow cylinder and / or surrounds the cavity essentially in the shape of a hollow cylinder. The cell culture insert further has a base designed as a membrane and a fastening element, wherein the membrane is fastened to the inner side of the side wall in a force-fitting and / or form-fitting manner by means of the fastening element. The force-fitting and / or form-fitting fastening of the membrane to the inner side of the side wall by means of the fastening element enables particularly simple handling and easy assembly of the cell culture insert. The cell culture insert can therefore be manufactured particularly cost-effectively.Due to the force-fitting and / or form-fitting fastening of the membrane to the inside of the side wall, it is not necessary for the fastening element to project beyond the side wall in the radial direction, which means that the installation space requirement of the cell culture insert can be kept low.

[0014] The membrane can be attached to the side wall using the fastening element in a variety of ways, as explained below. It can be particularly useful if the membrane is arranged in the cavity of the side wall. When the cell culture insert is assembled, the membrane is then shielded radially by the side wall, preventing unintentional damage to the membrane.

[0015] It is particularly advantageous if the membrane has an outer shape that complements the design of the inside of the side wall. The membrane can then be positioned relative to the side wall in a particularly simple manner. The simple manufacture of the membrane is of great importance for cost reasons. For this purpose, the membrane can be designed as a cylinder, cylindrical, or disc-shaped. Separating a correspondingly shaped membrane from a rectangular template, for example, is then possible in a particularly simple manner, particularly mechanically, for example by means of a punching process.

[0016] The membrane can, in particular, have a radially outer edge portion. In the assembled state of the cell culture insert, the edge portion is preferably arranged between the inner side of the side wall and an outer side of the fastening element.

[0017] Alternatively or additionally, the membrane can be arranged in the assembled state at least substantially at the level of a floor edge delimiting the cavity at the front.

[0018] A broader range of applications for the membrane can be achieved if the membrane is made of at least one organic material. Particularly preferably, the membrane is made of collagen. The membrane then exhibits biocompatible properties and thus enables a wide variety of possible applications, which are mentioned as examples in the introduction to the description.

[0019] In an alternative embodiment, the membrane can be made of a material that cannot be bonded to the side wall. This can be the case, for example, with materials that are particularly temperature-sensitive and whose mechanical properties and permeability can be negatively affected by correspondingly high temperatures. This also applies to materials whose mechanical properties and permeability can be negatively affected by the use of suitable adhesives. The arrangement and design of the fastening element is of great importance for the simple formation of a connection between the membrane and the side wall. For example, it is possible for the fastening element to be arranged at least partially in the cavity, thereby achieving a compact structure for the cell culture insert.Alternatively or additionally, the fastening element can protrude outwards beyond the side wall and thus specify a minimum distance between the side wall of the cell culture insert and a surrounding wall of a well of the well plate.

[0020] Reliable fastening of the membrane to the sidewall can be achieved by applying a radially outward pressing force to the sidewall. Alternatively or additionally, the fastening element can form a press fit with the sidewall. The term "press fit" generally refers to the fact that the maximum inner dimension of the receiving component is always smaller than the minimum outer dimension of the received component. Press fits can be manufactured cost-effectively and simultaneously represent a secure and defined connection type.

[0021] The costs of the cell culture insert can be further reduced if the fastening element is designed as a hollow cylinder, preferably with a rectangular or conical longitudinal section. Compared to a disc-shaped or cylindrical fastening element, material savings can be achieved in this way. To minimize the complexity of the cell culture insert, it is alternatively or additionally provided that the fastening element is formed as a single piece.

[0022] A particularly strong connection between the fastening element and the side wall can be achieved if the fastening element has a roughened surface on one outer side.

[0023] For secure attachment of the membrane to the side wall, it is particularly useful if the fastening element has an outer diameter that is larger than the diameter of the membrane. It is also useful for a secure and defined contact of the membrane against the fastening element if the fastening element, alternatively or additionally, has an inner diameter that is smaller than the diameter of the membrane.

[0024] For secure attachment of the membrane to the sidewall, the mechanical stability of the sidewall and the fastening element is crucial. A particularly stable and cost-effective fastening element can be achieved if the fastening element is made of polypropylene, polyethylene, polystyrene, and / or polylactic acid. The fastening element can then also be disposed of cost-effectively.

[0025] In order to reduce the variety of materials, it is particularly advantageous if the fastening element is made of the same, in particular biocompatible, material as the side wall of the cell culture insert.

[0026] A particularly reliable connection between the fastening element and the side wall can be achieved if the side wall forms a hollow truncated cone. Alternatively or additionally, the side wall can surround the cavity essentially in the shape of a hollow truncated cone. The cavity is then preferably designed as a truncated cone and / or frustoconical.

[0027] The fastening element is preferably formed on an outer side complementary to a portion of the side wall delimiting the cavity, in particular the inner side of the side wall. The fastening element is in particular pressed onto the side wall. A press fit is preferably provided between the side wall and the fastening element.

[0028] The inner side of the side wall preferably has a stop surface against which the membrane rests when fastened. To secure the membrane to the side wall in a particularly reliable manner, according to a preferred teaching of the invention, a preferably circumferential stop is formed on the inner side of the side wall for securing the membrane, the fastening element is pressed onto the stop, and the fastening element holds the membrane or presses it against the stop.

[0029] The membrane preferably has a top side and a bottom side, with the membrane preferably only abutting the stop with a portion of its top side. The membrane can abut the fastening element with a portion of its bottom side. The membrane is then held between the fastening element and the stop, particularly in the axial direction, and is thus fastened to the inside of the side wall in a form-fitting and / or force-fitting manner.

[0030] Alternatively, it is also possible for the membrane to rest with its top side against the stop and with its bottom side against the fastening element, whereby the membrane is held force-fitting and / or form-fitting between the fastening element and the side wall. The outer side of the side wall can have an external thread for connection to the fastening element, which engages with an internal thread on an inner side of the fastening element when the cell culture insert is assembled. To attach the membrane to the side wall, it is then easy to place the fastening element onto the side wall and screw it directly to it. Alternatively, it is also possible for the inner side of the side wall to have an internal thread and the fastening element to have an external thread on an outer side, which engages or can be brought into engagement with the internal thread of the side wall.

[0031] A particularly expedient design of the side wall is one in which the stop is formed by a recess on the inside of the side wall and has two stop surfaces arranged at an angle, in particular at right angles, to one another, preferably circumferentially. It is particularly advantageous if one stop surface extends at least substantially in the radial direction and in the circumferential direction, and the other stop surface extends at least substantially in the axial direction and in the circumferential direction. In this way, a simple arrangement of the membrane within the cavity relative to the side wall and a simple arrangement of the membrane between the fastening element and the side wall can be realized.

[0032] A permanently flat arrangement of the membrane in the attached state of the cell culture insert without buckling of the membrane can be ensured if the membrane rests against one stop surface and is spaced from the other stop surface. It is particularly advantageous if the membrane rests against the stop surface running essentially in the radial and circumferential directions and is spaced from the stop surface running essentially in the axial and circumferential directions. The membrane, in particular the outer edge of the membrane, is then at least partially spaced from the inside of the side wall. If, for example, contact of the membrane with nutrient liquid causes the membrane to expand, in particular in the radial direction, the membrane can expand in the radial direction until the membrane rests completely against the inside of the outer wall without the membrane buckling occurring.Accordingly, the distance between the inside of the side wall and the diaphragm can be precisely adjusted to ensure that the diaphragm remains radially free from warping at all times. The diaphragm then rests with its underside against the fastening element and its upper side against the stop, and is fixed in a first axial direction and in a radial direction by the stop, and in a second axial direction by the fastening element.

[0033] A particularly expedient design of the cell culture insert according to the invention is one in which the stop has at least one recess on the stop surface extending substantially in the axial direction and in the circumferential direction, and the fastening element has at least one complementary projection on an outer side, and in which the recess and the projection engage or form a positive connection when fastened. In this way, a particularly secure connection between the side wall and the fastening element can be achieved. By snapping the projection into the recess, the correct positioning of the fastening element relative to the side wall can be easily checked, for example visually or by a sudden drop in the force required to create the connection.In this way, the operational safety of the cell culture insert can be increased and unintentional detachment of the fastening element from the side wall can be reliably prevented.

[0034] Alternatively or additionally, it is also possible for the stop to have at least one recess on the stop surface extending substantially in the radial direction and in the circumferential direction, and for the fastening element to have at least one projection on an end face, and for the projection to engage at least partially in the recess and deform the membrane in the axial direction, thereby creating a radial tension on the membrane in order to further promote a wrinkle-free and smooth plane.

[0035] It is also possible for the stop to be formed by a clamping projection on the inside of the side wall. The clamping projection can be conical in longitudinal section and / or form a circumferential stop surface against which the membrane rests, in particular with its underside. The stop surface runs in particular transversely to the radial and / or axial direction. In this way, a fold- and warping-free arrangement of the membrane can be realized. At the same time, a reliable force-locking connection can be formed between the fastening element and the stop on the clamping projection or additionally in the radial direction on the inside of the side wall.

[0036] It is also possible for the circumferential stop surface, formed transversely to the radial direction, to have at least one recess and for the fastening element to have at least one complementary projection on an outer side. When fastened, the projection can engage in the recess, thus forming a positive connection. In this way, a particularly secure connection between the side wall and the fastening element can be achieved. By snapping the projection into the recess, the correct positioning of the fastening element relative to the side wall can be easily checked, for example visually or by a sudden drop in the force required to create the connection.

[0037] In order to ensure that the nutrient liquid can penetrate into the cavity of the cell culture insert exclusively through the membrane, a suitable embodiment of the cell culture device provides that the fastening element and / or the stop of the side wall have grooves or a sealing lip, whereby a particularly reliable seal is formed between the fastening element and the side wall.

[0038] Reusability of individual components of the cell culture insert is achieved by detaching the fastening element and the membrane from the side wall. This also makes it possible to replace the membrane, thus adapting the cell culture insert to the specific application. The force-fitting and / or form-fitting fastening of the membrane to the inside of the side wall eliminates the need to remove adhesive residue from the side wall and / or the membrane, thus facilitating the removal of the membrane from the side wall and its replacement.

[0039] To easily detach the membrane from the side wall, the fastening element can be provided with at least one externally accessible recess for removal using a tool. In this way, an optimized force flow to the fastening element can be generated or a lever arm can be created, whereby the fastening element can be detached from the side wall in a particularly simple manner. In an alternative embodiment, the fastening element is ferromagnetic for removal using a magnetic device. With the help of a magnet, for example a permanent magnet or an electromagnet, a force can be exerted on the fastening element, by which the fastening element can be detached from the side wall.Alternatively, it is also possible for the fastening element to have at least one projection projecting radially inward from an inner side of the fastening element, with an externally accessible recess for removal by means of a tool. The projection can be spaced from an edge of the inner side of the fastening element.

[0040] The assembly of the cell culture insert can be further simplified if the fastening element is made up of several parts, preferably two parts, and the membrane is clamped between parts of the fastening element. For example, the fastening element can be formed from two hollow cylindrical elements between which the membrane is clamped. It is possible, for example, for the two parts of the fastening element to be connected to one another in such a way that the membrane is clamped between the two parts and the two fastening elements and the membrane are fixed relative to one another. In this way, a pre-assembled functional unit consisting of the fastening element and the membrane is created. The functional unit consisting of the membrane and the fastening element can then be connected to the side wall in a single assembly movement.

[0041] Alternatively, it is also possible to design the fastening element in several parts, preferably in two parts, with the membrane being clamped between at least one part of the fastening element and the side wall. For example, the fastening element can consist of two identically designed elements which, when placed against one another in the circumferential direction, essentially form a hollow cylinder. It is also possible for the individual parts of the fastening element to be connectable to one another, for example by being latched together and / or connected in a form-fitting manner. By using two fastening elements, it is possible to divide the membrane into an area accessible to cells and an area inaccessible to cells, or to treat areas of the membrane differently and use them for subsequent comparative tests.

[0042] A particularly preferred design is one in which the fastening element has a support device arranged beneath the membrane. The support device provides stiffening of the fastening element, particularly in the radial direction. The support device can rest against the underside of the membrane, thereby preventing the membrane from buckling or sagging in the axial direction.

[0043] To securely position the cell culture insert on a base, especially a corrugated plate, at least three support elements can be attached to the underside of the fastening element for securely positioning the cell culture insert and for removing the fastening element. It is then possible, for example, to provide different fastening elements with differently designed support elements for cell culture inserts, so that a fastening element with appropriate support elements can be selected depending on the application.

[0044] The cell culture insert according to the invention enables a modular design in which a side wall can be combined with different membranes and / or different fastening elements in a particularly simple manner. This makes the cell culture insert versatile and can be easily and cost-effectively adapted to the specific application by selecting a suitable membrane and fastening element.

[0045] The cell culture insert is particularly easy to assemble. The membrane is first connected to the fastening element or placed against the stop on the side wall. The fastening element can then be inserted into the receiving space defined by the stop and pressed against the stop, thereby securing the membrane, particularly by pressing it, to the inside of the outer wall with a force-fitting and / or positive fit.

[0046] The invention also relates to a device for cultivating cells with a well plate and a cell culture insert according to one of claims 1 to 16.

[0047] In the following, the invention will now be explained in more detail with reference to a drawing which merely represents a preferred embodiment.

[0048] The drawing shows

[0049] Fig. 1 shows a perspective view of a device according to the invention for cultivating cells with a well plate with several, here a total of twenty-four, wells for receiving liquid, and with several, here a total of four, cell culture inserts according to the invention,

[0050] Fig. 2 in a perspective view obliquely from above a cell culture insert according to the invention from Fig. 1 ,

[0051] Fig. 3 in perspective view obliquely from below the cell culture insert according to the invention from Fig. 2,

[0052] Fig. 4 the cell culture insert from Fig. 2 in a longitudinal section,

[0053] Fig. 5 shows a perspective view of a longitudinal section of the side wall and the fastening element from Fig. 4 in a first embodiment,

[0054] Fig. 6 shows a perspective view of a longitudinal section of the side wall and the fastening element from Fig. 4 in a further embodiment, Fig. 7 shows a perspective view of a longitudinal section of the side wall and the fastening element from Fig. 4 in a further embodiment,

[0055] Fig. 8 is a longitudinal section of the side wall and the fastening element of Fig. 4 in a further embodiment,

[0056] Fig. 9 shows a longitudinal section of a cell culture insert according to the invention from Fig. 1 according to a further embodiment,

[0057] Fig. 10 shows a longitudinal section of a cell culture insert according to the invention from Fig. 1 according to a further embodiment,

[0058] Fig. 11 shows a perspective view obliquely from below of the cell culture insert from Fig. 2 in a further embodiment with a fastening element which has two removal elements,

[0059] Fig. 12 shows a perspective view obliquely from below of the cell culture insert from Fig. 2 in a further embodiment with a fastening element having a support device,

[0060] Fig. 13 in a perspective view obliquely from above the fastening element from Fig. 12 and

[0061] Fig. 14 shows a perspective view obliquely from below of the cell culture insert from Fig. 2 in a further embodiment with a fastening element which has support elements.

[0062] Fig. 1 shows a particularly preferred embodiment of a device for culturing cells. This device comprises a well plate 1 made of thermoplastic material. The well plate 1 contains several wells 2, here a total of twenty-four, for receiving liquid. The well plate 1 has an upper side 3 extending over part of its surface, on which the identification numbers are located, as shown in Fig. 1. The wells 2 are integrally formed into the well plate 1. In the spaces between wells 2, the upper side 3 is recessed so that the lateral walls 4 of the wells 2 can be seen there, as they are freely accessible.

[0063] Each well 2 has a bottom section (not shown in detail in Fig. 1), from which the upstanding, circumferential lateral wall 4 extends to a top edge 5. In Fig. 1, it is clearly visible on the right of the empty wells 2 that each well 2 has a specific lateral inner dimension in a plane parallel to the bottom section and a specific inner height in the direction perpendicular to the bottom section. In the illustrated embodiment, the wells 2 are cylindrical, so that the lateral inner dimensions are conclusively defined by a specific inner diameter. Non-circular wells 2 have more complex lateral inner dimensions. Fig. 1 shows a cell culture insert 6 in each of the wells 2 with the alphanumeric numbering A1, A2, B1 and B2.

[0064] The cell culture insert 6 according to the invention has, as shown for example in Fig. 2 and Fig. 3, a side wall 7 with an inner side 8 and an outer side 9, which extends essentially along an insert axis 10 and completely surrounds it, whereby the inner side 8 of the side wall 7 delimits a cavity 11. In the embodiment shown in the figures and thus preferred, the side wall 7 forms a hollow cylinder and surrounds the cavity 11 essentially in a hollow cylinder. The side wall 7 extends from an upper front opening delimited by an opening edge 12 along the insert axis 10 to a lower front opening delimited by a bottom edge 13. In the region of the bottom opening, a base formed by a membrane 14 is arranged, which is connected to the side wall 7.The bottom, designed as a membrane 14, defines a cell culture chamber 15 in the axial direction on one side, which is radially delimited by the side wall 7 and in which cell growth takes place. Starting from the bottom, designed as a membrane 14, the cell culture chamber 15 extends axially to the opening defined by the opening edge 12.

[0065] The term "axial" in this case always refers to the insert axis 10. The same applies to the terms "radial" and "circumferential direction," which in this case also always refer to the insert axis 10.

[0066] The base, designed as a membrane 14, can rest against the side wall 7 at the front end and delimit it at the front end. In the present case, the side wall 7 projects beyond the base, designed as a membrane 14, in the axial direction, as shown by way of example in Fig. 4.

[0067] On the outer side 9 of the side wall 7, a plurality of downwardly projecting feet 16 are arranged (Fig. 2), exactly three in the figures, with which the side wall 7 can be placed securely against tipping on a base with a small, uniform distance between the base, designed as a membrane 14, and the base, as shown in Fig. 1 with reference to the wells 2 numbered B1 and B2. Extending from the side wall 7 is an outwardly projecting support arm 17 (Fig. 2), which can be placed on the corrugated plate 1 in the edge region of a well 2, as also shown in Fig. 1 with reference to the wells 2 numbered A1 and A2.

[0068] From Fig. 4 to Fig. 7, it can be seen that the cell culture insert 6 according to the invention has a fastening element 18, wherein the membrane 14 is fastened to the inner side 8 of the side wall 7 by means of the fastening element 18 in a force-fitting and / or form-fitting manner. The membrane 14 is preferably arranged entirely within the cavity 11.

[0069] The term "force-locking" in this case means that movement between the two fastening partners, in this case between the membrane 14 and the inner side 8 of the side wall 7, is prevented by static friction. Force-locking fastenings require a normal force acting on the connecting surfaces of the fastening partners. Mutual relative movement of the fastening partners is prevented as long as the counterforce caused by static friction is not exceeded.

[0070] In the present case, it is preferably provided that the normal force acting between the membrane 14 and the side wall 7 is generated by a positive and / or non-positive connection between the fastening element 18 and the side wall 7. It is preferably provided that the fastening element 18 is in direct positive and / or non-positive engagement with the side wall 7, in particular with the inner side 8 of the side wall 7.

[0071] The term "positively secured" refers to the blocking or obstruction of relative movement between the fastening components, in this case between the membrane 14 and the inner side 8 of the side wall 7, through structural details. A positive connection can block relative movement in one or more directions or dimensions. A positive connection can be achieved, for example, by the interlocking of the fastening components or by the interlocking of one of the fastening components with another component.

[0072] It is preferably provided that the fastening element 18 engages directly with the side wall 7, in particular the inner side 8 of the side wall 7, in a form-fitting and / or force-fitting manner such that the membrane 18 is fastened in a form-fitting manner to the inner side 8 of the side wall 7. A form-fitting fastening of the membrane 14 to the inner side 8 of the inner wall 7 is particularly suitable for dimensionally stable membranes 14. The form-fitting fastening of the membrane 14 can also be advantageous if a particularly large radial expansion of the membrane 14 is to be enabled, as already described in detail above.

[0073] The membrane 14 is, as shown in the figures, designed as a cylinder, cylindrical, or disc-shaped. Other configurations of the membrane 14 are also possible, for example, a square or rectangular base area perpendicular to the insertion axis 10, so that a shape of the membrane 14 adapted to the respective application can be used.

[0074] The membrane 14 is preferably formed in one piece. However, it is also possible for the membrane 14 to be multi-part or consist of several individual components.

[0075] The membrane 14 may have a thickness of 5 pm to 500 pm, preferably of 10 pm to 200 pm, more preferably of at least substantially 100 pm.

[0076] The term "thickness" in this case refers to the extension of the membrane 14 along the insert axis 10 in the attached state. Furthermore, the term "thickness" refers in particular to the dry membrane 14 before the membrane 14 comes into contact with nutrient fluid or the like.

[0077] Alternatively, the membrane 14 can also be made as a fabric. The membrane 14 formed as a fabric can have a thickness of 10 μm to 1000 μm, preferably 20 μm to 500 μm, more preferably at least substantially 250 μm.

[0078] The membrane 14 preferably has an outer edge portion 14A. The edge portion 14A is particularly circumferentially formed and preferably completely surrounds the membrane 14 in the radial direction relative to the insert axis 10.

[0079] In the fastened state, the edge portion 14A is preferably arranged between the inner side 8 of the side wall 7 and an outer side of the fastening element 18, as shown in Fig. 4 to Fig. 10.

[0080] The membrane 14 preferably has an upper side 20 and a lower side 21, which, in the fastened state, are arranged at least substantially transversely, in particular perpendicularly, to the insertion axis 10. As Figs. 4 to 10 further show, the membrane 14 rests with the upper side 20 or the lower side 21 of the membrane 14, in particular the edge portion 14A, against the inner side 8 of the side wall 7 and with the other component of the upper side 20 and lower side 21 against the fastening element 18.

[0081] The membrane 14 consists in the present case of at least one organic material, here and preferably of collagen.

[0082] Alternatively, the membrane 14 can be made of a material that cannot be bonded to the side wall 7. This can be the case, for example, with a material that is particularly temperature-sensitive and whose mechanical properties and permeability can be negatively affected by correspondingly high temperatures. Furthermore, materials whose mechanical properties and permeability can be negatively affected by the use of suitable adhesives are also included.

[0083] It is also possible to construct the membrane 14 from a different material, in particular plastic. In this context, reference is made to the introductory remarks.

[0084] In Fig. 4 to Fig. 8, it can be seen that the fastening element 18 is at least partially arranged in the cavity 11. Alternatively or additionally, it is possible for the fastening element 18 to protrude at least partially outwardly beyond the side wall 7 (Fig. 11).

[0085] In the present case, the fastening element 18 is pressed against the inner side 8 of the side wall 7. The fastening element 18 has a pressing force acting radially outward on the inner side 8 of the side wall 7. The fastening element 18 here and preferably forms a press fit with the side wall 7. The fastening element 18 is thus pressed in a particularly simple manner into the opening in the side wall 7 delimited by the bottom edge 13. The fastening element 18 is designed as a hollow cylinder in the present case, although other structural designs, such as a cylindrical or disc-shaped design, are also possible. In the embodiment shown in Fig. 4, the fastening element 18 has a rectangular longitudinal section. Other shaped longitudinal sections are also possible. For example, the fastening element 18 in the embodiment shown in Fig. 5 has a conical longitudinal section.

[0086] In the embodiments shown in the figures and preferred in this respect, the fastening element 18 is formed in one piece. The fastening element 18 has an outer diameter and an inner diameter, wherein the term "outer diameter" here refers to the minimum outer diameter of the fastening element 18 and the term "inner diameter" refers to the maximum inner diameter of the fastening element 18. The outer diameter of the fastening element 18 is, as shown in Fig. 4, larger than the diameter of the membrane 14. The inner diameter of the fastening element 18 is additionally or alternatively smaller than the diameter of the membrane 14. The term "diameter" is clearly defined for disc-shaped or cylindrical membranes 14 and hollow-cylindrical fastening elements 18.If the membrane 14 does not have a circular base and / or the fastening element 18 does not have a circular or annular base, the term "diameter" in this case refers to the maximum extension in the radial direction. The membrane 14 can abut against the fastening element 18 in the axial direction and thus be fixed in an axial direction by the fastening element 18, as shown in Fig. 4.

[0087] In this case, the fastening element 18 comprises or consists of polypropylene, polyethylene, polystyrene, and / or polylactic acid, although a design made of other materials, preferably one or more plastics, is also possible. A low modulus of elasticity can ensure elastic material behavior of the fastening element 18 and a concomitant seal between the fastening element 18 and the side wall 7.

[0088] In order to increase the static friction and / or the sealing between the side wall 7 and the fastening element 18, the fastening element 18 can have a roughened surface on an outer side.

[0089] As shown in particular in Fig. 4, a preferably circumferential stop 19 for fastening the membrane 14 is formed on the inner side 8 of the side wall 7, the fastening element 18 is pressed onto the stop 19 and the fastening element 18 holds or presses the membrane 14, in particular via the edge section 14A, against the stop 19. In the embodiment shown in the figures, it is provided that the fastening element 18 presses the membrane 14 in the axial direction against the side wall 7. The membrane 14, in particular the edge section 14A, is then arranged between the stop 19 and the fastening element 18 and preferably pressed between them.

[0090] The membrane 14 has an upper side 20 and a lower side 21, wherein the membrane 14 preferably rests against the stop 19 exclusively with a portion of its upper side 20. A particularly uniform pressing of the membrane 14 against the stop 19 can be achieved if the membrane 14 preferably rests against the fastening element 18 exclusively with a portion of its lower side 21, as shown in Fig. 4. The stop 19 then fixes the membrane 14 in a first axial direction, wherein the fastening element 18 simultaneously fixes the membrane 14 in the opposite, second axial direction.

[0091] Figs. 4 to 8 show a further special feature of the cell culture insert 6 according to the invention in that the stop 19 is formed by a recess on the inner side 8 of the side wall 7 and has two stop surfaces 22 arranged at an angle, in particular at right angles, to one another, preferably circumferentially, wherein one stop surface 22 extends at least substantially in the radial direction and in the circumferential direction and the other stop surface 22 extends at least substantially in the axial direction and in the circumferential direction. If the two stop surfaces 22 are formed over the entire circumference, it is possible for the membrane 14 to bear with an edge section over its entire circumference against a stop surface 22, whereby a uniform pressing of the membrane 14 can be achieved.

[0092] As the detailed view of Fig. 5 shows in particular, the membrane 14, in particular the edge section 14A of the membrane 14, rests against one stop surface 22, preferably the stop surface 22 running essentially in the radial direction and in the circumferential direction, and is spaced from the other stop surface 22, preferably the stop surface 22 running essentially in the axial direction and in the circumferential direction. The membrane 14 is then fixed in the axial direction between the fastening element 18 and the stop 19. As can also be seen in the detailed view of Fig. 5, the membrane 14 is spaced apart in the radial direction from the inner side 8 of the side wall 7. If the membrane 14 expands, for example due to contact with a liquid, the membrane 14 can expand in the radial direction without curving in the axial direction.In this way, a uniform, flat clamping of the membrane 14 is made possible, whereby a curvature of the membrane 14 in the axial direction is effectively prevented.

[0093] In order to create a positive connection between the fastening element 18 and the side wall 7, the embodiment shown in Fig. 6 and Fig. 7 provides that the stop 19 has at least one recess 23 on the stop surface 22 running essentially in the axial direction and in the circumferential direction, and the fastening element 18 has at least one complementary projection 24 on an outer side, and that the recess 23 and the projection 24 engage or form a positive connection in the fastened state. In Fig. 6, the stop 19 has exactly one recess 23 on the stop surface 22 running essentially in the axial direction and in the circumferential direction, and the fastening element 18 has a complementary projection 24.

[0094] Fig. 7 shows a further embodiment in which the stop 19 has two recesses 23 on the stop surface 22 extending substantially in the axial direction and in the circumferential direction, and the fastening element 18 has two complementary projections 24. A reverse arrangement is also conceivable, in which the fastening element has a recess 23 and the stop 19 has a complementary projection 24.

[0095] In the embodiment shown in Fig. 8 and thus preferred, the stop 19 has at least one recess 23 on the stop surface 22 running essentially in the radial direction and in the circumferential direction, and the fastening element 18 has at least one projection 24a on one end face, wherein the projection 24a engages at least partially in the recess 23 and braces the membrane 14 in the axial direction. The recess 23 is preferably provided between the stop surface 22 running essentially in the radial direction and in the circumferential direction and the stop surface 22 recess 23 running essentially in the axial direction and in the circumferential direction. In the embodiment shown in Fig. 8, the fastening element 18 has the projection 24a on one end face, which extends essentially in the axial direction.When the cell culture insert 6 is assembled, the projection 24a of the fastening element 18 provides additional axial tension to the membrane 14 in the region of its outer edge, which advantageously further reduces the expansion of the membrane 14 upon contact with the nutrient fluid. In the preferred embodiment shown in Fig. 8, the projection 24a is not complementary to the recess 23. However, it is also possible to design the projection 24a complementary to the recess 23.

[0096] To seal the connection between the fastening element 18 and the stop 19 particularly reliably, the fastening element 18 and / or the stop 19 of the side wall 7 can have grooves or a sealing lip. Corresponding grooves or the sealing lip are preferably formed from a plastic, in particular an elastomer. The grooves or the sealing lip can also be formed from several plastics, in particular copolymers.

[0097] As a further special feature of the cell culture insert 6 according to the invention, the fastening element 18 and the membrane 14 are detachable from the side wall 7, thereby enabling easy replacement of the membrane 14 through a modular design of the cell culture insert 6. The membrane 14 can then be replaced with another membrane 14 adapted to the application in a particularly simple manner.

[0098] In the embodiments of the cell culture insert 6 shown in Fig. 3 to Fig. 8, the fastening element 18 can be pushed or pressed into the bottom opening of the side wall 7 delimited by the bottom edge 13 for assembly purposes.

[0099] Fig. 9 and Fig. 10 each show a longitudinal section of a cell culture insert 6 according to a respective further embodiment. The further embodiments differ from the embodiments shown in Fig. 3 to Fig. 8 in particular in that the fastening element 18 and / or the membrane 14 can be pushed or pressed into the opening in the side wall 7 delimited by the opening edge 12 for assembly purposes. In particular, the fastening element 18 can be pushed or pressed together with the membrane 14 into the opening delimited by the opening edge 12 for assembly purposes.

[0100] In the embodiments shown in Figs. 9 and 10, the side wall 7 is preferably formed, at least in sections, as a hollow truncated cone. In particular, the side wall 7 or a section of the side wall 7 surrounds the cavity 11 essentially in the shape of a hollow truncated cone. Preferably, the side wall 7 is formed as a hollow truncated cone over its entire axial extent. The cavity 11 is then formed, in particular, as a truncated cone or in the shape of a truncated cone.

[0101] The side wall 7, in particular the inner side 8 of the side wall 7, preferably forms an angle to the insert axis 10, wherein the angle is in particular at least 0.5 °, preferably at least 3 °, and / or less than 10 °, preferably less than 8 °.

[0102] The cavity 11 then preferably narrows from the opening delimited by the opening edge 12 towards the bottom opening delimited by the bottom edge 13, in particular conically at an angle of at least 0.5° and / or less than 10° relative to the insert axis 10. However, it is also possible for the cavity 11 to taper conically only in sections along the insert axis 10 in the direction of the opening delimited by the bottom edge 13.

[0103] In both of the above-mentioned cases, the cavity 11 has a uniform or constant taper along the insert axis 10.

[0104] The unmounted or unattached membrane 14 can be disc-shaped or cylindrical. In particular, the membrane 14 can have a larger diameter than the fastening element 18. Alternatively or additionally, it is possible for the membrane 14 to be preformed, as shown in Fig. 9 and Fig. 10. The membrane 14 can, in particular, be cup-shaped.

[0105] As Fig. 9 and Fig. 10 further show, the fastening element 18 preferably has an outer side. The outer side has, in particular, an outer radial contour that is complementary to at least one section of the side wall 7. In particular, the radial contour of the fastening element 18 is complementary to at least one section of the inner side 8 of the side wall 7. The membrane 14 is preferably dimensioned such that, in the assembled state of the cell culture insert 6 shown in Fig. 9, the outer side, in particular the radial contour, of the fastening element 18 is at least partially covered by the membrane 14.

[0106] The side wall 7 preferably forms a stop surface 22A against which the membrane 14, in particular the edge portion 14A, rests in the fastened state. As shown in Fig. 10, the membrane 14 or the edge portion 14A rests, in particular with the underside 21, against the stop surface 22A. The fastening element 18 preferably rests with an outer side, in particular its radial contour, against the top side 20 of the membrane 14 and clamps the membrane 14 against the stop surface 22A. The membrane 14 and the fastening element 18 are thus fixed in the cell culture insert 6.

[0107] The membrane 14 shown in Fig. 9 and 10 is, in the attached state, preferably arranged at least substantially at the level of the bottom edge 13 delimiting the end face of the cavity 11. The term "height" is to be understood here preferably as a plane that extends at least substantially perpendicular to the insert axis 10. The term "substantially" is to be understood here, with reference to the height, as meaning that there can be a dimensional deviation in the axial direction of up to 1.5 mm, preferably up to 1.2 mm, more preferably up to 1 mm between the bottom edge 13 and the membrane 14 forming the bottom of the cell culture insert 6.

[0108] In this way, the membrane 14 can form a plane with the bottom edge 13 delimiting the side wall 7 in the axial direction, taking into account the above-mentioned deviation in the axial direction, and can delimit the cell culture insert 6 at the front.

[0109] The radial contour of the fastening element 18 can have grooves to improve the force-fitting and / or form-fitting fastening of the fastening element 18 and / or membrane 14 to the inner side 8 of the side wall 7. Alternatively or additionally, it is possible for the inner side 8 to have at least one recess 23 on the stop surface 22A and for the fastening element 18 to have at least one complementary projection 24 on an outer side, as already explained with reference to Fig. 6 and Fig. 7. In the fastened state, the projection 24 can engage in the recess to create a form-fitting engagement between the fastening element 18 and the side wall 7.

[0110] For assembly purposes, the fastening element 18 can be inserted or pushed into the opening in the side wall 7 defined by the opening edge 12, as already explained above. The fastening element 18 can be inserted or pushed in together with the membrane 14.

[0111] The fastening element 18 can be inserted or inserted along the insertion axis 10 into the cavity 11 formed by the side wall 7 until the membrane 14 is pressed between the radial contour of the fastening element 18 and the inner side 8 of the side wall 7, in particular the stop surface 22A. In the fastened state, the fastening element 18 can additionally bear, in particular with its radial contour, against a stop surface 22A of the side wall 7.

[0112] For disassembly, the fastening element 18 can be pressed or pushed along the insert axis 10 out of the cavity 11 through the opening of the side wall 7 delimited by the opening edge 12.

[0113] It has been shown that the membrane 14 is permanently wrapped around the fastening element 18 when moistened with nutrient fluid, so that a unit consisting of membrane 14 and fastening element 18 is created. The membrane 14 can thus be removed from the cell culture insert 6 together with the fastening element 18 in a particularly simple manner. The unit consisting of membrane 14 and fastening element 18 can be easily handled manually and / or with the aid of a tool, for example tweezers or the like. The upper side 20 of the membrane 14 populated with cells can then be examined optically using a microscope, in particular a reflected light microscope. It is then not necessary to cut out the membrane 14 or parts of the membrane 14 from the cell culture insert 6, which could destroy cells.

[0114] According to the prior art, the determination of whether the membrane 14 is sufficiently populated with cells can be carried out by means of an electrical resistance measurement. Due to the simple and non-destructive removal of the membrane 14 from the cell culture insert 6, it is possible to determine optically, for example, using a microscope, whether the membrane 14 is sufficiently populated with cells or with a sufficient number of cells.

[0115] Fig. 10 shows a longitudinal section of a cell culture insert 6 according to a further embodiment. The side wall 7 of the cell culture insert 6 shown in Fig. 10 preferably has a stop 19 for clamping the membrane 14. The stop 19 is preferably designed as a clamping projection 30 on the inner side 8 of the side wall 7. In particular, the clamping projection 30 extends radially inward from the side wall 7. In particular, the clamping projection 30 is arranged in the region of the bottom edge 13 of the side wall 7 and / or merges into the bottom edge 13.

[0116] The clamping projection 30 has, in particular, a stop surface 22B against which the membrane 14 rests in the fastened state. The stop surface 22B preferably extends transversely to the radial direction and / or to the axial direction. The stop surface 22B on the clamping projection 30 is advantageously shaped circumferentially such that the clamping projection 30 is conical in longitudinal section, as shown in Fig. 10. In particular, the stop surface 22B forms an angle to the insert axis 10, wherein the angle is at least 10°, preferably at least 15°, and / or less than 45°, preferably less than 35°.

[0117] As shown in Fig. 9, the membrane 14, in the fastened state, preferably rests with its underside 21 against the stop surface 22B arranged transversely to the radial and / or axial direction on the clamping projection 30. The fastening element 18 rests with an outer side against the membrane 14, in particular the upper side 20, and clamps the membrane 14 against the stop surface 22B.

[0118] As Fig. 9 further shows, the fastening element 18 preferably has an outer side that has an outer radial contour and is shaped complementarily to the clamping projection 30. In the fastened state, the fastening element 18 can also bear with its outer side against the inner side 8 of the side wall 7, in particular against the stop surface 22A formed by the side wall 7. The stop surface 22A formed by the side wall 7 and the stop surface 22B formed by the clamping projection 30 are preferably arranged at an angle to one another. The two stop surfaces 22A, 22B preferably form an angle of at least 110° and / or less than 178°.

[0119] The radial contour may have grooves to improve the force-fitting and / or form-fitting fastening of the fastening element 18 and / or membrane 14 to the inner side 8 of the side wall 7 and / or to the clamping projection 30.

[0120] Alternatively or additionally, it is possible for the stop 19 to have at least one recess 23 on the stop surface 22B and for the fastening element 18 to have at least one complementary projection 24 on an outer side, in particular its radial contour, as explained with reference to Fig. 6 and Fig. 7. In the fastened state, the projection 24 can engage in the recess to create a positive engagement. As already mentioned, the fastening element 18 can be pushed or inserted into the opening in the side wall 7 delimited by the opening edge 12 for assembly purposes. To facilitate simple assembly, the cavity 11 can narrow, in particular conically at an angle of 0.5° to 10°, starting from the opening delimited by the opening edge 12 towards the bottom opening delimited by the bottom edge 13.In this way, a reliable at least force-locking fastening between the side wall 7 and the fastening element 18 can be ensured.

[0121] In the preferred embodiment shown in Fig. 11 and Fig. 12, the fastening element 18 is provided with at least one removal element 25 for manual removal and / or removal by means of a tool. The removal element 25 can simplify the removal of the fastening element 18 for the user through improved force application or by forming a lever arm. The removal element 25 can extend in the radial and / or axial direction.

[0122] Furthermore, it is particularly advantageous if the fastening element 18 has at least one externally accessible recess 26 for removal by means of a tool. The tool can at least partially engage in the recess 26 and simplify the removal of the fastening element 18 for the user by improving force application or by forming a lever arm. In the preferred embodiment shown in Fig. 11 and Fig. 12, the removal element has the recess 26.

[0123] Fig. 12 shows, by way of example, that the fastening element 18 has at least one projection 27 (four in Fig. 12) projecting radially inward from an inner side of the fastening element 18, with an externally accessible, substantially axially aligned recess 26 for removal by means of a tool. Alternatively or additionally, it is possible for the projection 27 to be spaced from an edge of the inner side of the fastening element 18, as shown in detail in Fig. 13.

[0124] Alternatively, it is also possible to remove the fastening element 18 using a so-called key-lock principle, in which a locking, in particular a positive locking, between the fastening element 18 and the side wall 7 can be released by means of a tool, for example in the form of a key, such as a Torx or screw wrench or a screwdriver.

[0125] The fastening element 18 can be ferromagnetic for removal by means of a magnetic device. Using a permanent magnet or an electromagnet, it is then possible to exert a force on the fastening element 18 to remove it.

[0126] In the embodiment shown in the figures, the fastening element 18 is formed in one piece. However, it is also possible for the fastening element 18 to be constructed in multiple parts, preferably in two parts. It is then possible for the membrane 14 to be clamped between the parts of the fastening element 18.

[0127] It is particularly advantageous if the fastening element 18 is designed in several parts, preferably two parts, and the parts of the fastening element 18 can be fixed to one another. In this way, a pre-assembled functional unit consisting of the membrane 14 and the fastening element 18 can be obtained. "Pre-assembled" means in this case that the individual components are already fixed to one another as a unit. The term "functional unit" means that the pre-assembled unit has all the components required for the respective functionality. The term "functional unit" is therefore to be understood in this case as having all the components required for the force-fitting and / or form-fitting fastening of the membrane 14 to the side wall 7.The fastening element 18 can then be inserted together with the membrane 14 as a pre-assembled functional unit into the bottom opening of the side wall 7 and pressed against the stop 19 in a manner to be explained below.

[0128] It is also possible to construct the fastening element 18 in multiple parts along the circumferential direction. The parts of the fastening element 18 can then be inserted simultaneously or sequentially into the bottom opening of the side wall 7 and pressed against the stop 19 to secure the membrane 14 to the side wall 7 in a force-fitting or form-fitting manner.

[0129] Particularly with large diameters of the cell culture insert 6 and / or with particularly sensitive membranes 14, it is imperative for cell cultivation to prevent warping and / or damage to the membrane 14. In the embodiment shown in Fig. 12, the fastening element 18 is provided with a support device 28 arranged beneath the membrane 14. The support device 28 also stiffens the fastening element 18, whereby the membrane 14 can be clamped particularly evenly and the likelihood of warping of the membrane 14 can be reduced. Warping or sagging of the membrane 14 can be particularly effectively prevented if the membrane 14 rests with its underside 21 against the support device 28.

[0130] It is possible for at least three support elements 16a to be attached to an underside of the fastening element 18 for setting up the cell culture insert 6 in a way that prevents it from tipping over and for removing the fastening element 18, as shown in Fig. 14. The support elements 16a are thus designed as a multifunctional part that, on the one hand, enables the cell culture insert 6 to be set up in a way that prevents it from tipping over and, on the other hand, serves to remove the fastening element 18. The support elements 16a are thus designed as removal elements 25. As can be seen from Fig. 11, it is possible for the cell culture insert 6 to be placed on a base together on the support elements 16a and the feet 16. In this way, tipping over of the cell culture insert 6 can be effectively prevented. When using a fastening element 18 with support elements 16a, it is also possible to use a cell culture insert 6 without feet 16.It is then nevertheless possible, via the support elements 16a, to place the cell culture insert 6 on a base with a small, uniform distance between the membrane 14 and the base in a manner that prevents it from tipping over.

[0131] To describe the production of the connection between the side wall 7 and the membrane 14, reference is made to Fig. 4. The membrane 14 is first placed on the stop surface 22, which extends essentially radially and runs circumferentially. The fastening element 18 is then inserted into the bottom opening of the side wall 7 in an assembly movement, in particular in the axial direction, and pressed against the stop 19, in particular in the axial direction. A pressure stamp of a tool (not shown), in particular a tool of a machine tool, can be used for this purpose. In addition to being easy to carry out, mechanical pressing has the advantage that force values ​​can be specified in a particularly simple manner in order to achieve optimal pressing between the side wall 7 and the fastening element 18.

[0132] The fastening element 18 is pressed against the stop 19 with a contact force of 30 N to 1000 N. For example, if the outer side of the fastening element 18 has an oversize of 0.05 mm compared to the stop surface 22 which runs essentially in the radial direction and in the circumferential direction, the fastening element 18 can be pressed against the stop 19 with a contact force of 30 N to 300 N, preferably of 40 N to 250 N, more preferably of 50 N to 200 N. If the outer side of the fastening element 18 is 0.1 mm larger than the stop surface 22 which runs substantially radially and circumferentially, the fastening element 18 can be pressed against the stop 19 with a contact force of 300 N to 1000 N, preferably 400 N to 850 N, preferably 500 N to 700 N.If the fastening element 18 has support elements 16a, the pressure stamp may have corresponding recesses for receiving the support elements 16a. It is then possible that the force generated by the stamp on the fastening element 18 does not act on the support elements 16a.

[0133] It is also possible that the force generated by the pressure stamp also or exclusively acts on the support elements 16a.

[0134] In a further and in this respect preferred embodiment, it is also possible to introduce the membrane 14 together with the fastening element 18 into the bottom opening of the side wall 7 until the membrane 14 bears against the stop surface 22 extending substantially in the radial direction and encircling in the circumferential direction and / or the fastening element 18 is pressed against the stop 19.

[0135] The insertion of the fastening element 18 into the opening of the side wall 7 delimited by the bottom edge 13 can be facilitated if the transition from the inner side 8 of the side wall 7 to the bottom edge 13 of the side wall 7 is formed by a chamfer 29. In this way, the mechanical stress between the bottom edge 13 of the side wall 7 and the end face of the fastening element 18 facing the cell culture chamber 15 in the assembled state can be reduced. Alternatively or additionally, the transition from the end face of the fastening element 18 facing the cell culture chamber 15 and the outer side of the fastening element 18 can be formed by a chamfer 29. The chamfer angle is between 35° and 55°, preferably substantially 45°, as shown in Fig. 4.

[0136] The cell culture insert 6 can be delivered fully assembled. Due to the modular design, it is also possible to deliver individual components of the cell culture insert 6, such as the fastening element 18, the membrane 14, and / or the side wall 7, individually or in any number and / or in combination with other components of the cell culture insert 6. In this case, the membrane 14 is preferably formed as a stamped part, which enables particularly simple, in particular mechanical, production of the membrane 14 using a stamping process.

[0137] In an alternative and, in this respect, preferred embodiment, the fastening element 18 is connected to the side wall 7 in a form-fitting and / or material-fitting manner. The fastening element 18 can be inserted into the bottom opening of the side wall 7 and fixed in a form-fitting manner relative to the side wall 7 and / or on the side wall 7, in particular in the axial and / or radial direction. For example, the fastening element 18 can have at least one form-fitting element, in particular a protruding one, and the side wall 7 can have a form-fitting counter-element, in particular a protruding one, that can be brought into engagement with the form-fitting element.

[0138] It is then additionally or alternatively possible to create a material-fit, in particular essentially punctiform, connection between the form-fitting element and the form-fitting counter-element for secure fixation of the fastening element 18 to the side wall 7. It is particularly advantageous if the membrane 14 does not come into contact with any adhesive that may be used. Due to the essentially punctiform form-fitting connection, only a small amount of adhesive is required. It is then also possible to use adhesives that are only toxic to the cell culture and / or the nutrient fluid in larger quantities. The adhesive used is preferably not soluble in the nutrient fluid in order to rule out any negative influence on the nutrient fluid, the cell cultures and / or the membrane. The punctiform connection can also be created by thermally bonding the form-fitting element to the form-fitting counter-element.

[0139] To detach the fastening element 18 from the side wall 7, it is necessary to break the positive connection. This is particularly easy and requires little force due to the essentially point-based material bond and the associated small connection surface. Detachment can also be achieved by separating or cutting off the materially bonded positive-locking elements and counter-positive-locking elements. The fastening element 18 can then be removed, particularly together with the membrane 14.

[0140] All aspects of the invention described above can be used both individually and in combination with one another.

[0141] List of reference symbols: Well plate 17 Support arm of 6 Well of 1 18 Fastening element of 6 Side of 1 19 Stop of 7 Wall of 2 20 Top of 14 Edge of 2 21 Bottom of 14 Cell culture insert 22 Stop surface of 19 Side wall of 6 22A Stop surface of 7 Inside of 7 22B Stop surface of 30 Outside of 7 23 Recess of 22 Insert axis 24 Projection of 18 Cavity of 6 24a Projection of 18 Opening edge of 7 25 Removal element of 18 Bottom edge of 7 26 Recess of 27 Membrane of 6 27 Projection of 18 A Edge section of 14 28 Support device of 18 Cell culture chamber of 6 29 Chamfer of 7 or 18 Stand feet of 6 30 Clamping projection of 7a Support element of 18

Claims

Patent claims: 1 . Cell culture insert for cultivating cells, comprising a side wall (7) which encloses a cavity (11) and has an inner side (8) delimiting the cavity (11) and an outer side (9), preferably wherein the side wall (7) forms a hollow cylinder and / or surrounds the cavity (11) essentially in the shape of a hollow cylinder, a base designed as a membrane (14) and a fastening element (18), wherein the membrane (14) is fastened to the inner side (8) of the side wall (7) by means of the fastening element (18) in a force-fitting and / or form-fitting manner.

2. Cell culture insert according to claim 1, wherein the membrane (14) is arranged in the cavity (11) and / or is designed as a cylinder or cylindrical or disc-shaped and / or has a radially outer edge portion (14A) which is arranged between the inner side (8) of the side wall (7) and an outer side of the fastening element (18) and / or - is arranged at least substantially at the level of a bottom edge (13) delimiting the cavity (11) at the end face and / or is formed from at least one organic material, preferably collagen, or is formed from at least one material which cannot be bonded to the side wall (2).

3. Cell culture insert according to claim 1 or 2, wherein the fastening element (18) - is arranged at least partially in the cavity (11) and / or projects outwards beyond the side wall (7) and / or is pressed against the inner side (8) of the side wall (7) and / or has a pressing force acting radially outwards on the side wall (7) and / or forms a press fit with the side wall (7) and / or is formed in one piece and / or is designed as a hollow cylinder, preferably with a rectangular or conical longitudinal section, and / or has an outer diameter which is larger than the diameter of the membrane (14), and / or has an inner diameter which is smaller than the diameter of the membrane (14) and / or polypropylene, polyethylene, polystyrene and / or polylactic acid or consists of polypropylene, polyethylene, polystyrene and / or polylactic acid and / or has a roughened surface on an outer side.

4. Cell culture insert according to one of the preceding claims, wherein the side wall (7) forms a hollow truncated cone and / or surrounds the cavity (11) substantially in the shape of a hollow truncated cone, wherein the fastening element (18) is formed on an outer side complementary to the side wall (7) delimiting the cavity (11), in particular the inner side (8) of the side wall (7), and wherein the fastening element (18) holds the membrane (14) or is pressed against the inner side (8), preferably wherein the inner side (8) of the side wall (7) has at least one stop surface (22A) and wherein the membrane (14) bears against the stop surface (22A).

5. Cell culture insert according to one of the preceding claims, wherein a preferably circumferential stop (19) for fastening the membrane (14) is formed on the inner side (8) of the side wall (7), the fastening element (18) is pressed onto the stop (19) and the fastening element (18) holds the membrane (14) or presses it against the stop (19).

6. Cell culture insert according to claim 5, wherein the membrane (14) has a top side (20) and a bottom side (21) and wherein the membrane (14) is preferably rests exclusively with a section of its upper side (20) or exclusively with a section of its lower side (21) on the stop (19).

7. Cell culture insert according to claim 5 or 6, wherein the stop (19) is formed by a recess on the inner side (8) of the side wall (7) and has two stop surfaces (22) arranged at an angle, in particular at right angles, to one another, preferably circumferentially, preferably wherein one stop surface (22) extends at least substantially in the radial direction and in the circumferential direction and the other stop surface (22) extends at least substantially in the axial direction and in the circumferential direction.

8. Cell culture insert according to claim 7, wherein the membrane (14) rests against one stop surface (22) and is spaced from the other stop surface (22).

9. Cell culture insert according to claim 7 or 8, wherein the stop (19) has at least one recess (23) on the stop surface (22) running essentially in the axial direction and in the circumferential direction and the fastening element (18) has at least one complementary projection (24) on an outer side, and wherein the recess (23) and the projection (24) engage or form a positive connection in the fastened state, and / or at least one recess (23) on the stop surface (22) running essentially in the radial direction and in the circumferential direction and the fastening element (18) has at least one projection (24a) on an end face, and wherein the projection (24a) engages at least partially in the recess (23) and braces the membrane (14) in the axial direction.

10. Cell culture insert according to claim 6, wherein the stop (19) is formed by a clamping projection (30) on the inner side (8) of the side wall (7) and has a circumferential stop surface (22), wherein the membrane is against the stop surface (22), preferably wherein the stop surface (22) extends transversely to the radial direction and / or to the axial direction.

11. Cell culture insert according to claim 10, wherein the stop (19) has at least one recess (23) on the stop surface (22) and the fastening element (18) has at least one complementary projection (24) on an outer side, and wherein the recess (23) and the projection (24) are in engagement in the fastened state or form a positive connection, and / or - at least one section of the fastening element (18) bears against the inner side (8) of the side wall (7).

12. Cell culture insert according to one of the preceding claims, wherein the fastening element (18) and / or the stop (19) and / or the clamping projection (30) and / or the side wall (7) has / have grooves or a sealing lip.

13. Cell culture insert according to one of the preceding claims, wherein the fastening element (18) and the membrane (14) are detachable from the side wall (7), preferably wherein the fastening element (18) has at least one removal element (25) for manual removal and / or for removal by means of a tool, and / or the fastening element (18) has at least one recess (26) accessible from the outside for removal by means of a tool, and / or the fastening element (18) has at least one projection (27) projecting radially inward from an inner side of the fastening element (18) with an externally accessible recess (26) for removal by means of a tool, in particular wherein the projection (27) is spaced from an edge of the inner side of the fastening element (18), or the fastening element (18) is ferromagnetic for removal by means of a magnetic device.

14. Cell culture insert according to one of the preceding claims, wherein the fastening element (18) is designed in several parts, preferably two parts, and the membrane (14) is clamped between parts of the fastening element (18).

15. Cell culture insert according to one of the preceding claims, wherein the Fastening element (18) has a support device (28) which is arranged below the membrane (14).

16. Cell culture insert according to one of the preceding claims, wherein at least three support elements (16a) are attached to an underside (21) of the fastening element (18) for setting up the cell culture insert (6) in a tilt-proof manner and for removing the fastening element (18).

Images