HOLDERS FOR BIOREACTOR SENSORS, BIOREACTORS HAVING SUCH HOLDERS, AND METHODS CULTURING BIOLOGICAL MATERIAL

Abstract

A bioreactor is provided that includes a container for receiving fluid media that contain biological material and a passage with a passage opening between an interior of the container and an exterior of the container. The bioreactor includes a holder configured to hold a sensor that extends at least partially in the passage opening of the passage. The holder has a sensor chamber and a fine-pored glass layer with a pore size of up to 0.2 m. The fine-pored glass layer bounds the sensor chamber at least partially, whereby, in particular, an exchange of fluids between the interior of the container for receiving fluid media that contain biological material and the interior of the sensor chamber is made possible.

Claims

1. A bioreactor for fluid media that contain biological material, comprising: a container having an interior configured to hold the fluid media and an exterior; a passage with a passage opening between the interior and the exterior; and a holder that extends at least partially in the passage opening, wherein the holder comprises a sensor chamber and a fine-pored glass layer with a pore size of up to 0.2 m, wherein the fine-pored glass layer at least partially bounds the sensor chamber to allow an exchange of fluid between the interior of the container and the sensor chamber.

2. The bioreactor of claim 1, further comprising a sensor in the sensor chamber.

3. The bioreactor of claim 1, wherein the container comprises a material selected from a group consisting of stainless steel, plastic, and sterilizable plastic.

4. The bioreactor of claim 1, wherein the holder extends inside the passage in a form-fitting manner.

5. The bioreactor of claim 1, wherein the container, passage, and holder are autoclavable while the holder is held at least partially in the passage opening.

6. A holder for the sterile holding of sensor, comprising: a sensor chamber having an interior and an exterior; and a fine-pored glass layer with a pore size of up to 0.2 m, the fine-pored glass layer bounding the sensor chamber at least partially to allow an exchange of fluids between the interior and the exterior.

7. The holder of claim 6, further comprising a second porous layer surrounding the fine-pored glass layer, wherein the second porous layer has a pore size of 200-700 m with a porosity of up to 85%.

8. The holder of claim 7, wherein the sensor chamber is a cylindrical sensor chamber and the fine-pored glass layer and the second porous layer extend in a longitudinal direction of the cylindrical sensor chamber.

9. The holder of claim 7, wherein the fine-pored glass layer comprises a first glass and the second porous layer comprises a second glass.

10. The holder of claim 9, wherein the first glass and second glass are the same or different.

11. The holder of claim 7, wherein the first layer and/or the second layer do not extend continuously in the longitudinal direction.

12. The holder of claim 11, wherein the first layer and/or the second layer are held on a tubular glass support.

13. The holder of claim 8, further comprising a piston in the cylindrical sensor chamber, the piston being displaceable in the longitudinal direction.

14. The holder of claim 13, wherein the piston further comprises a sensor holder.

15. The holder of claim 13, wherein the piston is displaceable between a first position associated with sterilization or autoclaving and a second position associated with the sensor recording.

16. The holder of claim 13, wherein the piston comprises a material selected from a group consisting of plastic, ethylene propylene diene monomer (EPDM) rubber, and ground glass.

17. A method for propagating or culturing biological material in a fluid media, comprising: providing a bioreactor having an interior configured to hold the fluid media and an exterior, the bioreactor having passage with a passage opening between the interior and the exterior and a holder that extends at least partially in the passage opening, the holder having a sensor chamber with a sensor and a fine-pored glass layer that partially bounds the sensor chamber to allow an exchange of fluid between the interior of the container and the sensor; introducing the fluid media having a biological material or a precursor of a biological material into the bioreactor; and using the sensor to record a physical, chemical, or biological variable of the fluid media and/or the biological material.

18. The method of claim 17, further comprising, prior to introducing the fluid media into the bioreactor, sterilizing the interior of the bioreactor, the sensor chamber, fine-pored glass layer, and sensor.

19. The method of claim 18, wherein the step of sterilizing comprises autoclaving.

20. The method of claim 18, further comprising moving the sensor in the sensor chamber from a first position during the sterilizing and a second position during the using the sensor to record.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0061] FIG. 1 a sectional view of multi-use bioreactor and a holder taken along line A-A in FIG. 4;

[0062] FIG. 2 a view from the top of the holder of FIG. 1;

[0063] FIG. 3 a view of the holder of FIG. 1 taken along line B-B in FIG. 2;

[0064] FIG. 4 a view of the holder of FIG. 1 taken along line C-C in FIG. 2;

[0065] FIG. 5a a sectional view of another multi-use bioreactor and holder taken along line A-A in FIG. 8;

[0066] FIG. 5b is a magnified view of the holder FIG. 5a;

[0067] FIG. 6 a view from the top of the holder of FIG. 5a;

[0068] FIG. 7 a view of the holder of FIG. 5a taken along line B-B in FIG. 6;

[0069] FIG. 8 a view of the holder of FIG. 5a taken along line C-C in FIG. 6;

[0070] FIG. 9 a sectional view of another multi-use bioreactor and holder taken along line A-A in FIG. 12;

[0071] FIG. 10 a view from the top of the holder of FIG. 9;

[0072] FIG. 11 a view of the holder of FIG. 9 taken along line B-B in FIG. 10;

[0073] FIG. 12 a view of the holder of FIG. 9 taken along line C-C in FIG. 10;

[0074] FIG. 13 a sectional view of a third embodiment of a multi-use bioreactor and holder;

[0075] FIG. 14 a magnified view of the holder FIG. 13 taken at rectangle K of FIG. 13;

[0076] FIG. 15 a magnified view of another embodiment of the holder of FIG. 14; and

[0077] FIG. 16 a side view of a multi-use bioreactor with a holder of the present disclosure showing a container partially disassembled; and

DETAILED DESCRIPTION

[0078] FIG. 1 a cross-sectional view of a first preferred embodiment of a multi-use bioreactor 1 and a holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 for receiving fluid media 4 containing biological material 5, but which is illustrated only in part, wherein the sectional plane extends along the sectional plane AA illustrated in FIG. 4, in which a piston 130 of the holder 2 is shown in a position that is associated with a sensor-based recording.

[0079] FIG. 2 a view from the top of the first preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, as viewed obliquely from above, but from the inner side or wall 28 of the container 3 for receiving fluid media 4, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor is shown in a position that is associated with a sensor-based recording.

[0080] FIG. 3 a cross-sectional view, which illustrates the first preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 for receiving fluid media 4 containing biological material 5, but which is illustrated only in part, wherein the sectional plane extends along the sectional plane BB illustrated in FIG. 2, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor 8 is shown in a position that is associated with a sensor-based recording.

[0081] FIG. 4 a cross-sectional view of the first preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends along the sectional plane CC illustrated in FIG. 2, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor 8 is shown in a position that is associated with a sensor-based recording.

[0082] FIG. 5a a cross-sectional view of the first preferred embodiment of a multi-use bioreactor 1 and a holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends along the sectional plane AA illustrated in FIG. 4, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor 8 is shown in a position that is associated with a sterilization and/or an autoclaving.

[0083] FIG. 6 a view from the top of the first preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, as viewed obliquely from above, but from the inner side 28 of the container 3 for receiving fluid media 4, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor 8 is shown in a position that is associated with a sterilization and/or an autoclaving.

[0084] FIG. 7 a cross-sectional view of the first preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends along the sectional plane BB illustrated in FIG. 2, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor 8 is shown in a position that is associated with a sterilization and/or an autoclaving.

[0085] FIG. 8 a cross-sectional view of the first preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends along the sectional plane CC illustrated in FIG. 2, in which a piston 130 of the holder 2 for the sterile holding of at least one sensor 8 is shown in a position that is associated with a sterilization and/or an autoclaving.

[0086] FIG. 9 a cross-sectional view of a second preferred embodiment of a single-use bioreactor 1 and a holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends essentially as in FIG. 1 for the first embodiment, but without the piston 130 arranged in the sensor chamber 100 and without its piston rod.

[0087] FIG. 10 a view from the top of the second preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, but as viewed from the inner side 28 of the container 3 for receiving fluid media 4.

[0088] FIG. 11 a cross-sectional view of the second preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends vertically through the container 3 for receiving biological material 5 in front of the holder 2 and in front of the passage 6, but without the piston 130 arranged in the sensor chamber 100 and without its piston rod.

[0089] FIG. 12 a cross-sectional view of the second preferred embodiment of the holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 that is intended for receiving fluid media 4 containing biological material 5, but is illustrated only in part, wherein the sectional plane extends horizontally through the container 3 for receiving biological material 5 in front of the holder 3 and in front of the passage 6, but without the piston 130 arranged in the sensor chamber 100 and without its piston rod.

[0090] FIG. 13 a cross-sectional view of a third preferred embodiment of a multi-use bioreactor 1 and a holder 2 for the sterile holding of at least one sensor 8, which is arranged in a passage opening 7 of a container 3 for receiving fluid media 4 containing biological material 5, but which is illustrated only in part, wherein the sectional plane extends essentially as in FIG. 1 for the first embodiment.

[0091] FIG. 14 an excerpt of the rectangle K shown in FIG. 13 of a preferred embodiment in enlarged illustration, in which the piston 130 comprises an ethylene propylene diene monomer (EPDM) rubber.

[0092] FIG. 15 an illustration, corresponding to the excerpt of the rectangle K shown in FIG. 13, of another preferred embodiment in enlarged illustration, in which the piston 130 comprises glass or is composed of glass.

[0093] FIG. 16 a side view of a multi-use bioreactor 1 with a holder 2 for the sterile holding of at least one sensor 8, in which the container 3 for receiving fluid media 4 that contain biological material 5 is shown partially exploded.

[0094] FIG. 5b is an excerpt from the illustration of FIG. 5a, which encompasses its top right area and is rotated in such a way that the line of symmetry S extends perpendicular to the horizontal.

[0095] A bioreactor 1 comprising a container 3 for receiving fluid media 4 that contain biological material 5 is provided. The reactor has a passage 6 with a passage opening 7 between the interior 28 of the container 3 for receiving fluid media 4 that contain biological material 5 and the exterior of the container 3 for receiving fluid media 4 that contain biological material 5. The reactor 1 has a holder 2 for the sterile holding of at least one sensor 8 extends at least partially in the passage opening 6 of the passage 6. The holder 2 for the sterile holding of at least one sensor 8 comprises a sensor chamber 100 and a fine-pored glass layer 110 with a pore size of up to 0.2 m, wherein the fine-pored glass layer 110 with a pore size of up to 0.2 m at least partially bounds the sensor chamber 100, whereby, in particular, an exchange of fluids between the interior 28 of the container 3 for receiving fluid media 4 that contain biological material 5 and the interior of the sensor chamber 100 is made possible.

[0096] The bioreactor 1 is further characterized in that the container 3 comprises stainless steel or is composed of stainless steel or comprises a plastic, in particular a sterilizable plastic, or is composed of a plastic, in particular, a sterilizable plastic.

[0097] The bioreactor 1 is further characterized in that the holder 2 extends inside the passage 6 in a form-fitting manner to the passage 6.

[0098] The bioreactor 1 is further characterized in that the bioreactor 1, together with the holder 2 can be autoclaved, in particular, can be autoclaved while it is held at least partially in the passage opening 7 of the passage 6.

[0099] A holder 2 for the sterile holding of at least one sensor 8 is provided that includes a sensor chamber 100 and a fine-pored glass layer 110 with a pore size of up to 0.2 m, which bounds the sensor chamber 100 at least partially, whereby, in particular, an exchange of fluids between the interior 28 of the sensor chamber 100 and the exterior of the sensor chamber is made possible.

[0100] The holder 2 has the fine-pored glass layer 110 with a pore size of up to 0.2 m surrounded by a second porous layer 120, which has a pore size of 200-700 m with a porosity of up to 85%.

[0101] The holder 2 has the sensor chamber 100 with an essentially cylindrical shape and the first layer 110 and the second layer 120 extend in the longitudinal direction of the cylindrical sensor chamber 100 and, in particular, they extend distally to terminate at the front side 28.

[0102] The holder 2 has the first layer 110 is composed of a first glass or comprises a first glass and in which the second layer 120 is composed of a second glass or comprises a second glass.

[0103] The holder 2 has the first layer 110 is composed of a first glass or comprises a first glass and in which also the second layer 120 is composed of the first glass or comprises the first glass.

[0104] The holder 2 has the first layer 110 and the second layer 120 extend along the sensor chamber 100 in the longitudinal direction.

[0105] The holder 2 has the first layer 110 and the second layer 120 that do not extend continuously in the longitudinal direction, defining the sensor chamber 100, and are held on an essentially tubular support, in particular, are held on an essentially tubular support comprising a glass or composed of glass.

[0106] The holder 2 has a piston 130 that is displaceable in the longitudinal direction, in particular with a piston carrier or a piston rod, by means of which the piston is displaceable in the longitudinal direction.

[0107] The holder 2 has the piston 130 with a sensor holder. The holder 2 in which the piston 130 with sensor holder is displaceable between a first position, which is associated with a sterilization or an autoclaving, and a second position, which is associated with the sensor recording.

[0108] The holder 2 has the piston 130 has a place holder for at least one sensor 8.

[0109] The holder 2 has the piston 130 with a fasteningthat includes mount 15, friction element 16, preferably O-ring, cylindrical recess 17, ring-shaped compression element 18, lateral shoulder 20 that extends in the radial direction, top flange 21, cap nut 22, thread 24, counter thread 25, snap ring 26, and sealing element 27, in particular O-Ring, for the sensor.

[0110] The holder 2 has the piston 130 that includes a plastic and, in particular, comprises an ethylene propylene diene monomer (EPDM) rubber or a ground glass piston, preferably with an O-ring arranged thereon.

TABLE-US-00001 LIST OF REFERENCE NUMBERS 1 bioreactor 2 holder 3 container 4 fluid medium/media 5 biological material 6 port or passage 7 passage opening 8 sensor 14 passage opening 15 mount 16 friction element 17 cylindrical recess 18 compression element 20 lateral shoulder 21 top flange 22 cap nut 24 thread 25 counter thread 26 snap ring 27 sealing element 28 inner wall or side 100 sensor chamber 110 first porous layer 120 second porous layer 130 piston