EP3068865A1

EP3068865A1 - Microtitre plate with capillary membrane supply unit

Info

Publication number: EP3068865A1
Application number: EP14798794.5A
Authority: EP
Inventors: Florian BONN; Carsten MEIXNER; Haythem KORBI
Original assignee: 3M Innovative Properties Co
Current assignee: 3M Innovative Properties Co
Priority date: 2013-11-13
Filing date: 2014-11-12
Publication date: 2016-09-21
Also published as: CN106062171B; WO2015071278A1; CN106062171A; US20160289626A1; JP2016537000A

Abstract

An apparatus for growing and/or examining cells, comprising arrangement of at least one bowl-shaped culture dish having a base and a side wall, and an interior which is bounded by the base and side wall and has an opening at the top end, characterized in that – at least one sheetlike capillary membrane system composed of at least one capillary membrane is disposed in the interior of the culture dish, – wherein the at least one capillary membrane has a semipermeable wall, a lumen which is enclosed by the wall and has at least one open end and has a fluid connection via its open end to a supply line having a wall and a lumen, such that liquids, media, gases and/or other substances can be passed through the supply line and the capillary membrane system, – wherein the capillary membrane system is disposed in the region of the base of the respective culture dish and its areal extent is limited by the side wall of the culture dish and – wherein the at least one supply line leads out of the interior through the opening.

Description

Microtiter plate with capillary membrane supply unit

Description:

The invention relates to a device for cultivating and examining cells, comprising an arrangement of a plurality of cup-shaped culture dishes insulated from each other, each having a bottom and a side wall and an inner space bounded by bottom and side wall, which has an opening at the top.

For the investigation and cultivation of adherent, suspension and

Hybridoma cells are often used cell culture plates, for example, as so-called microtiter plates with e.g. 1, 4, 6, 24 or 96 cup-shaped

Cell culture dishes and, for example, under the names 6, 24, 96 Well plates are available. Such cell culture plates allow e.g. a rapid screening of drugs on cell cultures, such as to assess the effect of cytostatics on cancer or tumor cells of a cancer patient.

The performance of such cell experiments in the laboratory often requires a large number of parallel experiments, which are usually carried out in such microtiter plates. In particular, the intervalwise feeding or removal of media from the depressions (wells) of the titer plate is extremely labor-intensive in the cultivation of the cells. Furthermore, the supply of cells, for example, with nutrient medium, often too irregular. The concentration of the ingredients (nutrients, messengers, extracellular substances) is therefore strong Subject to fluctuations. As a result, the cell development can be impaired.

EP-A-1 159 444 discloses individual membrane modules suitable for testing a variety of drugs on cells. These

Membrane modules include a housing having an interior bounded by a lid, a bottom and a sidewall. In the interior, at least one system of first capillary membranes and a system of second capillary membranes are arranged, which are arranged in the interior to planar layers. The capillary membranes pass through at least one of their ends through the side wall of the interior and are separated by systems in bundles combined at this at least one end each embedded in a potting compound. DE-A-10 2006 031 871 describes a Petri dish for breeding and

Examination of cells. In the interior of the Petri dish is a

Hollow-fiber membrane system with a multiplicity of hollow-fiber membranes

arranged through which liquids or gases are passed. The

Hollow fiber membranes are bundled at their ends and connected to a lead or drain. Above the hollow fiber membrane system, several, e.g. six circular culture spaces are arranged, which lie along the running direction of the hollow-fiber membranes one behind the other, so that the hollow-fiber membranes by several

Cultural areas run one behind the other and supply or dispose of several cultural areas.

In DE-A-102 21 565 microtiter plates for culturing, for example, cells are described in which flat membranes are arranged in the bottom of the cup-shaped depressions or culture dishes, on the basis of a arranged under the culture dishes common feeding eg nutrient media in the culture dishes and thus the cells located in these culture dishes can be supplied.

It is an object of the present invention to provide a device for cultivating and examining cells having a multiplicity of cup-shaped culture dishes which can be supplied independently of one another in a controlled manner, for example with a nutrient solution. At the same time easy handling and flexible use of the device should be possible. The object is achieved by a device for cultivating and examining cells, which has an arrangement of at least one cup-shaped

Culture dish comprising a bottom and a side wall and an inner space bounded by the bottom and side wall, which has an opening at the top, wherein the device is characterized in that

in the interior of the at least one culture dish, at least one planar-shaped capillary armature system of at least one capillary membrane is arranged,

wherein the at least one capillary membrane has a semipermeable wall, a lumen enclosed by the wall and at least one open end,

wherein the at least one capillary membrane is in fluid communication with at least one open end having at least one supply line with a wall and a lumen so that liquids, media, gases and / or other substances can be conducted through the supply line and the at least one capillary armature system,

- And wherein the at least one Kapillarmembransystem in the field of

Bottom of the at least one culture dish is arranged and is limited in its planar extent by the side wall of the at least one culture dish and

- Wherein the at least one supply line via the opening of the

Interior leads. By means of the present device, a separate supply of cell cultures present in the culture dishes isolated from one another is possible, without there being any mutual interference of the cell cultures. In this case, the individual cell cultures, for example, different media can be supplied without causing a mixing of the media.

Preferably, the cup-shaped culture dishes are common in microtiter plates, here 2-hole, 4-hole, 6-hole, 12-hole, 24-hole plates, etc. (2, 4, 6, 12, 24 well plates) common are. Therefore, in a preferred embodiment, the device comprises at least two culture dishes, which are isolated from each other and have no connection to one another and which are provided separately with at least one Kapillarmembransystem. In a further preferred embodiment, the device comprises at least six culture dishes, which are insulated from each other and have no connection to one another and which are provided separately with at least one Kapillarmembransystem. The bottom of the at least one cup-shaped culture dish preferably has an area in the range of 2 to 30 cm ² and particularly preferably an area in the range of 2 to 15 cm ² . The interior of the at least one cup-shaped culture dish is open at its top and bounded by the bottom and the side wall. The

Sidewall itself preferably has no openings and is closed. The bottom and inner wall are preferably fluid-impermeable, i. tight against the passage of gases and / or liquids. The interior can

have different cross-sectional geometries. Preferably, the

Interior a circular, oval, rectangular or square

Cross-section.

The at least one culture dish is preferably provided with a lid which covers the opening of the interior of the culture dish, in which case the at least one supply line passes through the lid. For several Culture dishes, the lid may also be a common for all culture dishes of the device cover through which the individual culture dishes associated supply lines in the range of

Pass through openings. It has proven to be advantageous if in the cover over the openings of the at least one culture dish connecting pieces are attached, with which the supply lines are connected and through which they pass through the lid and lead out of the interior. Preferably, the connecting pieces are glued into the lid, wherein respect. Of gluing can be made of common adhesive.

The at least one planar-shaped Kapillarmembransystem is understood to mean an arrangement of at least one Kapillarmembran extending flat in the region of the bottom of the culture dish or in its vicinity. In this case, the at least one planar-shaped

Kapillarmembransystem touch the side wall, the at least one sheet-shaped Kapillarmembransystem or this forming at least one Kapillarmembran does not pass through the side wall or the floor. The at least one capillary membrane opens inside the interior into a supply line, which leads out of the invention via the opening of the interior of the at least one culture dish.

The dimensions of the at least one planar design

Kapillarmembransystems arise from its outer dimensions in the planar extension. The at least one sheet-shaped

Kapillarmembransystem can extend over the entire cross section of the interior to the side wall of the cup-shaped culture dish maximum. Preferably, the at least one planar-shaped Kapillarmembransystem extends over 30 to 90% and more preferably over 50 to 80% of the surface of the bottom of the at least one culture dish or

Cell culture dish. In a likewise preferred embodiment, the at least one planar-shaped Kapillarmembransystem of the Interior removable or attached attached executed. There is no material connection with the floor or side wall of the interior.

Here, the sheet-shaped Kapillarmembransystem can consist of a single capillary membrane, which is arranged meandering. In this embodiment, at least one of the ends of the meandering capillary membrane is open and connected to the supply line. The

However, at least one Kapillarmembransystem can also several

Include meandering arranged capillary membranes, which open together with their ends in the supply line.

In particular, for use in culture dishes having a circular or oval cross-section of the interior, an embodiment may be advantageous in which the planar-shaped Kapillarmembransystem consists of at least one capillary membrane which is arranged spirally in the region of the bottom of the at least one culture dish. In this embodiment, preferably one of the ends of the at least one spirally arranged capillary membrane is open and connected to the supply line while the other end is closed. Likewise, the planar-shaped Kapillarmembransystem can be constructed of a plurality of arranged in concentric circles Kapillarmembranen whose ends in a

Embodiment open and are each embedded on opposite sides of the wall of a single supply line. In a preferred embodiment, the at least one planar-shaped Kapillarmembransystem comprises a plurality of mutually parallel arranged Kapillarmembranen and may preferably be composed of 2 to 100 mutually parallel arranged Kapillarmembranen. Particularly preferably, the number of capillary membranes arranged parallel to one another can be 5 to 50. The capillary membranes of the mutually parallel arranged capillary membranes are at its open ends so on its outer periphery fluid-tight in the supply line embedded that between the lumen of the

Supply line and the lumen of the capillary membranes is a fluid connection and through the supply line and the capillary membranes

Liquids, media, gases and / or other substances are durchleitbar.

Preferably, the at least one supply line is open at one end and connectable to a supply unit or a unit for disposal, while the other end of the at least one supply line is closed. The embedding can, for example, with a curable

Silicone material, carried out with a polyurethane or an epoxy resin.

For their better flexibility, curable silicone materials are preferably used. In the case that the capillary membranes are embedded in one supply line with only one of their ends, the other, opposite end of the capillary membranes is closed, for example by welding or gluing. In this case, the area-shaped

Kapillarmembransystem also be adapted to the example round contour of the interior of the cup-shaped culture dish, for example, by appropriately adjusted Abweißen welding the non-embedded ends of Kapillarmembranen in Kapillarmembransystemen with only one supply line, so that there is an arcuate contour at this edge of the sheet-shaped Kapillarmembransystems. The capillary membranes can also be embedded with their two ends on one side of the arrangement in a supply line, for which purpose the capillary membranes are U-shaped at their free end. In these cases, the capillary membranes are operated in dead-end mode.

In a further embodiment of the Kapillarmembransystems are

Capillary membranes at both ends open and embedded with one end in each case a supply line, the supply lines are then preferably located on opposite sides of the sheet-shaped Kapillarmembransystems. Also in this case the embedding is like that stated that the capillary membranes are embedded in a fluid-tight manner at their outer periphery and there is a fluid connection between the lumen of the respective supply line and the lumen of the capillary membranes. Such an embodiment with two supply lines allows a flow through the at least one Kapillarmembransystems in cross-flow mode.

The diameter of the at least one supply line depends primarily on the outer diameter of the capillary membranes embedded in it. Therefore, the at least one supply line preferably has one

Inner diameter in the range of 0.1 to 10 mm. It is also preferred if the wall thickness of the flexible silicone tube is in the range of 0.1 to 5 mm. In the case of using a supply line with non-circular

Cross section is set as the inner diameter of the equivalent diameter d = 4A / U of the inner cross section with A as the area of the inner cross section and U as its circumference. For example, the supply line can also have an oval, or approximately square or rectangular inner cross section. For the at least one supply line, e.g. one

Silicone hose proved to be suitable, through the wall of the

Pass capillary membrane ends and in which they are glued.

Preferably, the at least one common supply line is a flexible silicone tube. The embedding or sticking in the wall of the supply line can by means of conventional glue such. by means of hardenable

Silicone materials, polyurethane resins or epoxy resins. In an advantageous embodiment, the Kapillarmembransystem can be formed in the form of a Kapillarmembranmatte in which a plurality of capillary membranes by means of mutually spaced and mutually parallel

Connecting elements are interconnected and held by the connecting elements to each other at a distance. In this case, the connecting elements can extend transversely to the mutually parallel arranged capillary membranes or at a different angle. The fasteners may be to act adhesive tape or, for example, to strand-shaped elements of a silicone material. In a preferred embodiment, the

Capillary membranes by means of yarn-shaped connecting elements connected to a mat. The connecting elements are particularly preferably textile multifilament yarns. Have proven particularly useful as textile

Multifilament yarns multifilament polyester yarns, polypropylene yarns or

Polytetrafluorethylengarne.

In a preferred embodiment, the capillary membrane mat may be a knitted mat in which the capillary membranes and the capillary membranes

Connecting threads are forfeited together and in which the capillary membranes extend transversely to the direction of extension of the Kapillarmembranmatte and the length of the Kapillarmembranen is determined by the width of the mat. In a further preferred embodiment, the capillary membrane mat may be a woven mat in which the capillary membranes and the connecting threads are interwoven and in which the capillary membranes in

Extension direction or direction of the Kapillarmembranmatte run and the textile threads across it. Kapillarmembranwirkmatten and -webmatten and ways of their preparation are described for example in DE 38 39 567, DE 43 08 850 and in EP 0 442 147. Such mat-shaped Kapillarmembransysteme allow for a good handling and

Introduction of the area-shaped Kapillarmembransysteme in the interiors of the culture dishes. In addition, results in such

Arrangements a very uniform distribution, e.g. of nutrient media on the cell culture in the respective culture dish or a uniform

Disposal of breakdown products from cell culture.

For a uniform supply of cells located in the interior of the at least one cell culture dish, it is advantageous, in particular in the case of culture dishes having a rectangular or square cross-section of the interior, when the capillary membranes are in contact with each other through the mat-shaped structure a uniform distance. Preferably, the distance between the capillary membranes in the mat is 1 to 10 times that of

Outside diameter of the capillary membranes, wherein the distance from the longitudinal axes of the capillary membranes is measured. Particularly preferred is a distance which is 1, 05 to 3 times the outer diameter of the

Capillary membranes is. It is also advantageous if the

Connecting elements are at a defined distance from each other, which should preferably be in the range of 1 to 20 mm, with a distance in the range of 3 to 7 mm is preferred.

In a spiral configuration of the at least one capillary armature system or in an arrangement of the capillary membranes in the capillary armature system in concentric circles, it is also advantageous in view of a uniform supply of the cells if the distances between the capillary membranes are uniform, i. if the spiral turns or the concentrically arranged capillary membranes in

Kapillarmembransystem be kept at the same distance from each other. This can also be achieved by suitable connecting elements, e.g. by

Connecting threads, adhesive strips or strand-like elements made of silicone material. Suitable materials for the capillary membranes are in principle all known in the art organic polymers in question, which are suitable for the formation of Kapillarmembranen, said polymers have a good

Biocompatibility. In addition, it is also required that the membrane polymer allow sterilization of the device, for example, by steam sterilization, γ-ray sterilization or ethylene oxide sterilization. The organic polymers may be natural polymers or polymers prepared by synthetic routes. natural

Polymers are especially those based on cellulosic polymers, which includes polymers which have been subjected to so-called polymer-analogous reactions. Examples of cellulose-based polymers are those of regenerated cellulose, cellulose acetate or modified cellulose such as Cellulose esters, cellulose ethers, benzyl group-modified cellulose

(Benzyl cellulose) or diethylaminoethyl modified cellulose or

Mixtures of these cellulosic polymers. Furthermore, it is also possible to use polymers based on chitin or chitosan.

As synthetically produced polymers, i. as synthetic

Polymers may be used those which consist of polyolefins, polyamides, polyacrylonitrile, polycarbonates, polyesters or sulfone polymers, as well as modifications, blends, mixtures or copolymers of these polymers obtained therefrom. Preferably, those are used which are based on sulfone polymers, in particular polysulfone or polyethersulfone. These polymers may be further polymers such as e.g. Polyethylene oxide, polyhydroxyether,

Polyethylene glycol, polyvinyl alcohol or polycaprolactone be admixed as additives. The capillary membranes may additionally have a coating with an additive. Preferably contain such

Capillary membranes, a hydrophilizing agent, e.g. Polyvinylpyrrolidone or hydrophilic modifications of these polymers.

As has already been carried out for embodiments of the device which have a lid for covering the opening of the interior of the at least one culture dish, it is advantageous if the supply lines are connected to connecting pieces, through which they pass through the lid

pass through and be led out of the interior. About such

Connector can be a simple connection with e.g. a storage container for a nutrient solution or with a vacuum unit, by means of which e.g. an extraction of dissolved degradation products from the cell culture dishes can be done. Preferably, the connecting pieces are Luer-Lock

Connections that allow a simple and clean connection. In an advantageous embodiment, the interior of the

Cell culture dishes leading out supply lines each with a Connecting piece in the form of a Y-connector connected with its free ends, for example with a system for supplying fluids and a system for disposal of the at least one Kapillarmembransystems

is connectable, i. a single supply line can thus be connected by means of the Y-connector via a first part of line with a liquid feed and a second part of line with a vacuum unit. The connection can also be made via Luer-Lock connections. through

controllable shut-off valves can intermittently over predetermined time intervals either a supply of liquid or a suction of

Degradation products take place from the interior.

The device according to the invention is characterized by a high degree

Flexibility. Thus, for example, in devices with a plurality of bowl-shaped culture dishes, different cell cultures can be grown in the individual bowl-shaped culture dishes of the apparatus without any mutual influence on the cell cultures, since the culture dishes are isolated from one another. In addition, arranged in the interiors, sheet-shaped Kapillarmembransysteme can be independently coupled via their supply lines with different supply or disposal units, so that, for example, a supply of settled in the culture dishes cell cultures can be done with different nutrient media. Likewise, for example, a different supply of the different cell cultures with regard to nutrient solution concentrations or time intervals of the supply can take place. Furthermore, it is also possible that different Kapillarmembransystem be arranged in the culture dishes of the device, which differ for example in their function or in terms of the characteristics of the capillary membranes used therein. Another advantage of the device according to the invention is also that individual Kapillarmembransysteme the device can be replaced, for example, if it comes to a too strong growth of Kapillarmembranen on the outside. In the device according to the invention is also in the application a

Operation possible, in which in the interior of the at least one culture dish cells for cell cultures, e.g. be presented as a cell suspension and then colonize the soil. Subsequently, the supply system is then placed in the form of the sheet-shaped Kapillarmembransystems.

The device according to the invention can also have at least one further capillary arm system in individual or in all of its culture dishes, which performs further tasks for the cultivation of the cells. Thus, at least one of the culture dishes of the device in addition to a Kapillarmembransystem for

Supply of nutrient solution contain another Kapillarmembransystem with membranes for oxygenation, via which a supply of cell culture in the interior of the respective culture dish can be made with oxygen. Likewise, at least one further Kapillarmembransystem may be included, via which a disposal of decomposition substances can be made, so that supply and disposal can be done via different Kapillarmembransysteme. It is also possible that, for example, two different

Capillary arm systems in one another into a mat e.g. be woven or knitted together via connecting yarns to form a knitted mat. In these cases, the supply lines assigned to the respective capillary armature system are then expediently located on different sides of the capillary membrane mat thus formed.

The invention will be explained in more detail with reference to the following figures, wherein the figures do not limit the scope of the invention:

1 shows a cross section through a single cup-shaped culture dish according to the invention. FIG. 2: in the direction of view from above, a cross section of that shown in FIG

Culture dish along the line A - A in Fig. 1.

Fig. 3: in the direction of view from above a cross section of a cup-shaped

Culture dish with a round inner cross-section.

Fig. 4: in the direction of view from above a cross section of a cup-shaped

Culture dish with a round inner cross section and a single, arranged in the region of the bottom of the culture dish and spiraling to a

capillary membrane system formed Kapillarmembran.

Fig. 5: in the direction of view from above a cross section through a device with four juxtaposed cup-shaped culture dishes with each

rectangular cross section, in each of which a sheet-like

Capillary arm system is arranged with a rectangular contour.

In Fig. 1, a cup-shaped culture dish 1 is shown in a device 100 in cross section, as it is suitable according to the invention for the cultivation and examination of cells. The cup-shaped culture dish 1 has an interior space 2 with a square cross section, which is delimited by a side wall 3 and a bottom 4. The upward opening of the interior is completed in the present case by a cover 5. In the region of the bottom, a planar capillary armature system of a plurality of mutually parallel capillary membranes 6 is arranged, with four capillary membranes being shown in cross section in FIG. 1 by way of example. The

Capillary membranes each have a semipermeable wall 7 and a lumen 8 enclosed by the wall. With her in viewing direction

At the rear end, the capillary membranes are embedded in a supply line 9 such that between the supply line 9 and the lumens of the Capillary membranes 6 is a fluid connection, so that through the

Supply line and the at least one Kapillarmembransystem

Liquids, media, gases and / or other substances are durchleitbar. The

Supply line leads with its vertical branch 10 through an opening in the lid 5 from the interior 2 of the culture dish 1 and can with a

Supply unit e.g. in the form of a pump or storage container or with a unit for disposal e.g. be connected in the form of a vacuum pump. FIG. 2 shows a cross section of the bowl-shaped culture dish 1 shown in FIG. 1 along the section A-A. The arranged in the interior 2 with square cross section in this example planar Kapillarmembransystem has a rectangular contour and is parallel to each other

arranged capillary 6 is formed. The capillary membranes 6 are embedded at their one end in a strand-shaped hot melt adhesive material 1 1, whereby the capillary membranes are closed at this end and at the same time held stable to each other at a distance.

With their other end, the capillary membranes are embedded in the supply line 9, which leads out via its upwardly leading branch 10 from the interior 2 of the cup-shaped culture dish 1, as shown in Fig. 1.

FIG. 3 shows an enlarged scale corresponding to FIG

Cross section of a cup-shaped culture dish 1 with a round inner cross-section. The sheet-like Kapillarmembransystem arranged in the interior has for this example on a contour adapted to the contour of the interior contour and is also formed of a plurality of mutually parallel arranged Kapillarmembranen. The capillary membranes 6 are adapted in their length to the contour of the inner cross section, so that formed on the formed by the free ends 12 of the capillary 6 edge of the sheet-like

Kapillarmembransystems results in an arcuate contour. The Capillary membranes 6 are closed at their free end 12, for example by welding or immersion in a hotmelt adhesive. In this example, the sheet-like Kapillarmembransystem is formed into a mat in which the Kapillarmembranen 6 are connected by yarn-shaped connecting elements 13 with each other and at the same time held stable to each other at a distance.

At its second end, the capillary membranes 6 are embedded in the supply line 9, which are perpendicular to their upward leading branch 10

View level out of the interior 2 of the cup-shaped culture dish 1 leads out.

In Figure 4 is also a cup-shaped culture dish 1 with round

Internal cross section shown. In this cup-shaped culture dish 1, a single capillary membrane 6 is wound spirally in the region of the bottom and thus formed into a flat capillary membrane system. In this embodiment, one of the ends of the spirally arranged capillary membrane 6 is open and connected to the supply line 10, which leads out of the culture dish still up. The other, free end 12 of the capillary 6 is closed. The individual turns of the spiral formed by the capillary membrane are connected by connecting elements 14a, b e.g. held in the form of adhesive strips or strand-like elements of silicone material to each other at a distance and stabilized against each other.

Figure 5 shows a schematic representation of a device 100 with four juxtaposed cup-shaped culture dishes 1 ad, each having a rectangular cross-section. The cup-shaped culture dishes 1 ad are isolated from each other and are not related to each other. In each of these culture dishes 1 ad, a separate sheet-like Kapillarmembransystem is arranged in the interior 2a-d analogous to the culture dish shown in Figure 2 with a rectangular contour, each of a plurality of mutually parallel Kapillarmembranen 6a-d is formed. The capillary membranes 6a-d of respective Kapillarmembransysteme are embedded at its free end in strand-like hot melt adhesive material 1 1 ad, whereby they are closed at this end and at the same time held stable to each other at a distance. With their other end, the capillary membranes 6a-d are each one

Supply line 9a-d embedded. The supply lines 9a-d are led out separately from one another via their upwardly directed branches 10a-d from the culture dishes 1 a-d via their respective openings on the upper side.

Claims

Microtiter plate with capillary membrane supply unit

1 . Device for cultivating and / or examining cells, comprising an arrangement of at least one cup-shaped culture dish having a bottom and a side wall and an interior bounded by bottom and side wall, which has an opening at the top, characterized in that

- In the interior of the at least one culture dish at least one

planar Kapillarmembransystem is arranged from at least one capillary membrane,

- wherein the at least one capillary membrane is a semipermeable wall, a wall enclosed by the lumen and at least one open

Has end,

- wherein the at least one capillary membrane with its at least one open end with at least one supply line in fluid communication with a wall and a lumen, so that through the

Supply line and the at least one Kapillarmembransystem

Liquids, media, gases and / or other substances are durchleitbar,

- wherein the at least one Kapillarmembransystem in the field of

- Wherein the at least one supply line leads through the opening from the interior.

2. Apparatus according to claim 1, characterized in that the at least one culture dish is provided with a lid which covers the opening of its interior, and that the at least one supply line of the at least one culture dish passes through the lid.

3. Apparatus according to claim 1 or 2, characterized in that the at least one sheet-like Kapillarmembransystem comprises a plurality of mutually parallel capillary membranes, which by means of a plurality of mutually spaced and mutually parallel

Connecting elements are connected together to form a mat and held by the connecting elements to each other at a distance.

4. The device according to claim 3, characterized in that the distance between the capillary membranes to each other in the mat is 1, 0 to 10 times the outer diameter of the capillary membranes, wherein the distance from the longitudinal axes of the capillary membranes is measured.

5. Device according to one or more of claims 1 to 4, characterized

in that the capillary membranes of the at least one

Kapillarmembransystem is connected to two supply lines, wherein the capillary membranes are embedded with their opposite ends in each case a common supply line.

6. Device according to one or more of claims 1 to 5, characterized

characterized in that the at least one common supply line is a flexible silicone tube.

7. Device according to one or more of claims 1 to 6, characterized

characterized in that the outgoing from the interiors of the cell culture dishes supply lines each with a Y-connector connected with its free ends with a system for

Supply of fluids and a system for disposal is connectable.

8. The device according to one or more of claims 1 to 7, characterized in that the bottom of the at least one culture dish has an area in the range of 2 to 30 cm ² .

9. Device according to one or more of claims 1 to 8, characterized in that the surface of the at least one planar-shaped Kapillarmembransystem is 30 to 90% of the area of the bottom of the at least one culture dish.

10. The device according to one or more of claims 1 to 9, characterized in that it comprises at least two culture dishes, which are insulated from each other and have no connection to each other and separated from each other with at least one

Capillary arm system are provided.

1 1 device according to claim 10, characterized in that they

includes at least six culture dishes.