A CELL CULTURE CHAMBER DEVICE FOR CELL AND TISSUE GROWTH
20230212491 · 2023-07-06
Inventors
- Krzysztof Wrzesinski (Blommenslyst, DK)
- Hans Henrik Jochumsen (Blommenslyst, DK)
- Stephen John Fey (Blommenslyst, DK)
Cpc classification
C12M29/04
CHEMISTRY; METALLURGY
C12M21/08
CHEMISTRY; METALLURGY
International classification
Abstract
A cell culture chamber device for growing cell cultures and tissues. The device includes: an enclosure containing a cell culture media, the enclosure being defined partly by a first end, a second end, and a connecting wall. The first end or a part or window thereof is substantially transparent, and the second end and/or the connecting wall, or a respective part or window thereof, is/are substantially transparent/translucent. The first end is configured to be optically aligned, at least for some period of time or periodically, with the second end and/or with the connecting wall so that light or another illumination or visualisation signal, transmitted through or by the second end and/or through or by the connecting wall into the enclosure is transmitted through the cell culture media and out through the first end to outside the enclosure, and e.g. to outside the cell culture chamber device.
Claims
1. A cell culture chamber device (100) for the growing of cell cultures and tissues, the cell culture chamber device (100) comprising an enclosure (110) configured to contain a cell culture media, and a first end (111), a second end (112), and at least one connecting wall (114) connecting the first and the second ends (111, 112), where the first end (111), the second end (112), and the at least one connecting wall (114) at least in part defines the enclosure (110), wherein the first end (111), or a part or window (113) thereof, is substantially transparent and the second end (112) and/or at least one of the at least one connecting wall (114), or a respective part or window (113) thereof, is/are substantially transparent or is/are substantially translucent, where the first end or the part or window thereof (111, 113) is configured to be optically or otherwise aligned, at least for some period of time or periodically, with the second end or the part or window thereof (112, 113) and/or with the at least one of the at least one connecting wall or the part or window thereof (114, 113) so that light (703) or another illumination or visualisation signal, transmitted through or by the second end or the part or window thereof (112, 113) and/or through or by the at least one of the at least one connecting wall or the part or window thereof (114, 113) into the enclosure (110), is transmitted or propagates through at least a part of the cell culture media and out through the first end or the part or window thereof (111, 113) to outside the enclosure (110), and e.g. to outside the cell culture chamber device (100).
2. The cell culture chamber device (100) according to claim 1, wherein the cell culture chamber device (100) is configured for rotation about a predetermined rotational axis (200) and/or for a use in or as part of a bioreactor.
3. The cell culture chamber device (100) according to any one of claims 1-2, wherein the first end or the part or window thereof (111, 113) and the second end or the part or window thereof (112, 113) are opposite each other in a predetermined direction, e.g. along a central axis (200) of the enclosure (110) and/or the cell culture chamber device (100) where the central axis (200) extends between the first end or the part or window thereof (111, 113) and the second end or the part or window thereof (112, 113).
4. The cell culture chamber device (100) according to any one of claims 1-3, wherein a material or a group of materials of one or more predetermined parts, e.g. all parts, of the enclosure (110) and/or of the cell culture chamber device (100) is or are opaque to UVC light where the one or more predetermined parts are configured so no or substantially no UVC light can reach inside the enclosure (110).
5. The cell culture chamber device (100) according to any one of claims 1-4, wherein the cell culture chamber device (100) further comprises a circumferential gas exchanger (130, 140, 151, 310) arranged circumferentially about or along at least a part of the enclosure (110) or about a central and/or lengthwise axis (200) of the cell culture chamber device (100), and e.g. or preferably about a predetermined rotational axis (200), and comprising a cavity (310) comprising a volume (310) connecting a gas exchange interface (120) of the enclosure (110) with ambient air or gas of the cell culture chamber device (100).
6. The cell culture chamber device (100) according to claim 5, wherein the gas exchange interface (120) is or comprises a circumferential gas permeable membrane (120), e.g. a semipermeable membrane, configured to exchange gases, such as oxygen and carbon dioxide, with an inside and/or content of the enclosure (110) where the circumferential gas permeable membrane (120) is arranged circumferentially along a circumferential part of the enclosure (110).
7. The cell culture chamber device (100) according to claim 6, wherein the circumferential gas permeable membrane (120) constitutes at least a part of at least one of the at least one connecting wall (114) of the enclosure (110).
8. The cell culture chamber device (100) according to any one of claims 5-7, wherein the gas exchange interface (120) or the circumferential gas permeable membrane (120) is supported by at least one support structure (130), e.g. a grid like support structure (130), comprising a number of openings configured to connect the gas exchange interface (120) or the circumferential gas permeable membrane (120) with air or gas of the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310)
9. The cell culture chamber device (100) according to any one of claims 5-8, wherein the circumferential gas exchanger (130, 140, 151, 310) is connected with the ambient air or gas of the cell culture chamber device (100) via at least one gas or air inlet and/or outlet (140).
10. The cell culture chamber device (100) according to claim 9, wherein at least one of the at least one gas or air inlet and/or outlet (140) is a double vent or port (140) configured to, e.g. or preferably simultaneously, draw in ambient air or gas into the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310) and expel air or gas out of the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310) in response to the cell culture chamber device (100) being rotated thereby creating an air flow (310).
11. The cell culture chamber device (100) according to any one of claims 5-10, wherein the cell culture chamber device (100) further comprises a circumferential humidifier (301) arranged circumferentially about at least a part of the enclosure (110) or about a central and/or lengthwise axis (200) of the cell culture chamber device (100), e.g. or preferably about a predetermined rotational axis (200), and comprises or is connected to one or more liquid or moisturising reservoirs or elements (301) configured to humidify or moisturise air or gas in at least a part of the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310) or of the air flow (310).
12. The cell culture chamber device (100) according to claim 11, wherein the one or more liquid or moisturising reservoirs or elements (301) is/are configured to humidify or moisturise air or gas in vicinity of or being adjacent to at least a part of the gas exchange interface (120) or the circumferential gas permeable membrane (120), the part being outside the enclosure (110).
13. The cell culture chamber device (100) according to claim 11 or 12, wherein at least one of the one or more liquid or moisturising reservoirs or elements (301) comprises a liquid being either a sterile aqueous solution or an aqueous solution containing one or more additives configured to maintain sterility and/or other compounds extending shelf life and/or providing a predetermined function or utility.
14. The cell culture chamber device (100) according to any one of claims 11-13, wherein at least one of the one or more liquid or moisturising reservoirs or elements (301) comprises a water or solute-containing material such as a gel, sponge, or a particulate material (e.g. water- or aqua beads).
15. The cell culture chamber device (100) according to any one of claims 11-14, wherein a material or a group of materials of the one or more liquid or moisturising reservoirs or elements (301) and/or one or more predetermined parts of the cell culture chamber device (100) is configured to allow transmission of UVC light to decontaminate a content of the one or more liquid or moisturising reservoirs or elements (301).
16. The cell culture chamber device (100) according to any one of claims 1-15, wherein the cell culture chamber device (100) comprises a first or central housing (101) and a cover (102) where the first or central housing (101) comprises the second end (112) and the cover (102) comprises the first end (111), and wherein the first or central housing (101) is configured to receive, e.g. releasably, the cover (102), where a cavity between the first or central housing (101) and the cover (102) is defined when the cover (102) is received by the first or central housing (101), and where the resulting cavity defines at least a part of the enclosure (110).
17. The cell culture chamber device (100) according to claim 16 as dependent on any one of claims 7-15, wherein the cavity between the first or central housing (101) and the cover (102) comprises the circumferential gas permeable membrane (120) constituting at least a part of the at least one the connecting wall (114) of the enclosure (110) thereby connecting the first end (111) of the cover (102) with the second end (112) of the first or central housing (101).
18. The cell culture chamber device (100) according to claim 16 or 17, wherein the cell culture chamber device (100) further comprises a main housing (105) configured to receive the first or central housing (101) and the cover (102), e.g. where the main housing (105) comprises an opening (185) aligning with the second end (112) of the first or central housing (101) when the first or central housing (101) is received by or in the main housing (105) where the size of the opening (185) is substantially of the same size as the second end (112).
19. The cell culture chamber device (100) according to claim 18, wherein the main housing (105) and the first or central housing (101), when received by the main housing (105) defines the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310), and wherein the first or central housing (101) comprises the double vent or port (140) arranged to be substantially perpendicular to the predetermined rotational axis (200).
20. The cell culture chamber device (100) according to claim 17-19 as dependent on claim 8, wherein the first or central housing (101) comprises the at least one support structure (130).
21. The cell culture chamber device (100) according to any one of claims 1-20, wherein the second end or the part or window thereof (112, 113) is substantially transparent and wherein the cell culture chamber device (100) further comprises or is connected to a light diffusor (175) configured to receive light and to provide substantially uniform light (703) to the second end or the part or window thereof (112, 113) thereby providing substantially uniform illumination of the cell culture media when contained in the enclosure (110).
22. The cell culture chamber device (100) according to any one of claims 1-21, wherein a respective cross section, substantially perpendicular to a central axis (200) extending between the first and the second end (111, 112), of the first end (111) and/or the second end (112) is/are substantially circular.
23. The cell culture chamber device (100) according to any one of claims 1-22, wherein the enclosure (110) and/or the cell culture chamber device (100) further comprises one or more fiducial and/or identification markers (155, 180).
24. The cell culture chamber device (100) according to any one of claims 1-23, wherein the second end (112) and/or at least one of the at least one connecting wall (114) comprises one or more integrated light sources (701).
25. The cell culture chamber device (100) according to any one of claims 1-24, wherein the second end (112) and/or at least one of the at least one connecting wall (114) is/are or comprises a fluorescent light emitting element (701).
26. The cell culture chamber device (100) according to any one of claims 1-25, wherein the cell culture chamber device (100) comprises a closable and/or sealable first port (103) connected to an inside of the enclosure (110) and a closable and/or sealable second port (104) connected to the inside of the enclosure (110), e.g. where the first port (103) and the second port (104) are arranged on or to separate sides of the cell culture chamber device (100).
27. A cell culture chamber system (400) for the growing of cell cultures and tissues, the cell culture chamber system (400) comprising a cell culture chamber device (100) according to any one of claims 1-26.
28. The cell culture chamber system (400) according to claim 27, wherein the cell culture chamber system (400) comprises or is connected to an imaging, vision, or other registration or detection system or device (704) and wherein at least one light source or another illumination or visualisation signal source (701) is configured to emit light or the other illumination or visualisation signal (703) received through the second end or the part or window thereof (112, 113) into the enclosure (110), and wherein the imaging, vision, or other registration or detection system or device (704) is configured to capture at least a part of the light or the other illumination or visualisation signal transmitted through the first end or the part or window thereof (111, 113) to outside the enclosure (110).
29. A cell culture chamber device (100) for the growing of cell cultures and tissues, the cell culture chamber device (100) comprising an enclosure (110) configured to contain a cell culture media, a circumferential gas exchanger (130, 140, 151, 310) arranged circumferentially about or along at least a part of the enclosure (110) or about a central and/or lengthwise axis (200) of the cell culture chamber device (100), e.g. or preferably about a predetermined rotational axis (200) of the cell culture chamber device (100), wherein the circumferential gas exchanger (130, 140, 151, 310) comprises a cavity (310) comprising a volume (310) connecting a gas exchange interface (120) of the enclosure (110) with ambient air or gas of the cell culture chamber device (100).
30. The cell culture chamber device (100) according to claim 29, wherein the gas exchange interface (120) is a circumferential gas permeable membrane (120), e.g. a semipermeable membrane, configured to exchange gases, such as oxygen and carbon dioxide, with an inside and/or content of the enclosure (110) where the circumferential gas permeable membrane (120) is arranged circumferentially along a circumferential part of the enclosure (110).
31. The cell culture chamber device (100) according to claim 29, wherein the circumferential gas permeable membrane (120) is a connecting wall (114) connecting a first end (111) and a second end (112) wherein the first end (111), the second end (112), and the connecting wall (114) at least in part defines the enclosure (110).
32. The cell culture chamber device (100) according to claim 29, 30, or 31, wherein the gas exchange interface (120) or the circumferential gas permeable membrane (120) is supported by at least one support structure (130), e.g. a grid like support structure (130), comprising a number of openings configured to connect the gas exchange interface (120) or the circumferential gas permeable membrane (120) with air or gas of the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310).
33. The cell culture chamber device (100) according to any one of claims 29-32, wherein the circumferential gas exchanger (130, 140, 151, 310) is connected with the ambient air or gas of the cell culture chamber device (100) via at least one gas or air inlet and/or outlet (140).
34. The cell culture chamber device (100) according to claim 33, wherein the cell culture chamber device (100) is configured for rotation about a predetermined rotational axis (200) and wherein at least one of the at least one gas or air inlet and/or outlet (140) is a double vent or port (140) configured to, e.g. or preferably simultaneously, draw in ambient air or gas into the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310) and expel air or gas out of the cavity (310) of the circumferential gas exchanger (130, 140, 151, 310) in response to the cell culture chamber device (100) being rotated about the predetermined rotational axis (200) thereby creating an air flow (310).
35. A cell culture chamber device (100) for the growing of cell cultures and tissues, the cell culture chamber device (100) comprising an enclosure (110) configured to contain a cell culture media, a gas exchanger (130, 140, 151, 310), and a circumferential humidifier (301), wherein the circumferential humidifier (301) is arranged circumferentially about at least a part of the enclosure (110) or about a central and/or lengthwise axis (200) of the cell culture chamber device (100), e.g. or preferably about a predetermined rotational axis (200) of the cell culture chamber device (100), and comprises or is connected to one or more liquid or moisturising reservoirs or elements (301) configured to humidify or moisturise air or gas in at least a part of a cavity (310) of the gas exchanger (130, 140, 151, 310).
36. The cell culture chamber device (100) according to claim 35, wherein the one or more liquid or moisturising reservoirs or elements (301) is/are configured to humidify or moisturise air or gas in vicinity of or being adjacent to at least a part of a gas exchange interface (120) or a gas permeable membrane (120), the part being outside the enclosure (110).
37. The cell culture chamber device (100) according to claim 35 or 36, wherein at least one of the one or more liquid or moisturising reservoirs or elements (301) comprises a liquid being either a sterile aqueous solution or an aqueous solution containing one or more additives configured to maintain sterility and/or other compounds extending shelf life and/or providing a predetermined function or utility.
38. The cell culture chamber device (100) according to any one of claims 35-37, wherein at least one of the one or more liquid or moisturising reservoirs or elements (301) comprises a water or solute-containing material such as a gel, sponge, or a particulate material (e.g. water- or aqua beads).
39. A cell culture chamber device (100) for the growing of cell cultures and tissues, the cell culture chamber device (100) comprising an enclosure (110) configured to contain a cell culture media, a gas exchanger (130, 140, 151, 310), and a humidifier (301), wherein the humidifier (301) comprises or is connected to one or more solid moisturising elements (301) configured to humidify or moisturise air or gas in at least a part of a cavity of the gas exchanger (310), wherein at least one of the one or more solid moisturising elements (301) comprises a water or solute-containing material such as a gel, sponge, or a particulate material (e.g. water- or aqua beads, slush powder, or water gel powder).
40. A cell culture chamber device (100) for the growing of cell cultures and tissues, the cell culture chamber device (100) comprising an enclosure (110) configured to contain a cell culture media, wherein a material or a group of materials of one or more predetermined parts, e.g. all parts, of the enclosure (110) and/or of the cell culture chamber device (100) is or are opaque to UVC light and where the one or more predetermined parts are configured so no or substantially no UVC light can reach inside the enclosure (110).
41. The cell culture chamber device (100) according to claim 40, wherein the cell culture chamber device (100) further comprises a gas exchanger (130, 140, 151, 310), and a humidifier (301) comprising or being connected to one or more liquid or moisturising reservoirs or elements (301) configured to humidify or moisturise air or gas in at least a part of a cavity of the circumferential gas exchanger (130, 140, 151, 310), wherein a material or a group of materials of the one or more liquid or moisturising reservoirs or elements (301) and/or one or more predetermined parts of the cell culture chamber device (100) allows transmission of UVC light to decontaminate a content of the one or more liquid or moisturising reservoirs or elements (301).
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION
[0117] Various aspects and embodiments of a cell culture chamber device and a cell culture chamber system, as disclosed herein, will now be described with reference to the figures.
[0118] The shown figures are schematic representations for which reason the configuration of the different structures as well as their relative dimensions are intended to serve illustrative purposes only.
[0119] Some of the different components are only disclosed in relation to a single embodiment of the invention, but is meant to be included in the other embodiments without further explanation.
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[0121] Illustrated is a cell culture chamber device 100 for the growing of cell cultures and tissues comprising an enclosure 110 configured to contain a cell culture media and comprising a first end 111 and a second end 112 where the first and the second ends 111, 112 at least in part defines the enclosure 110. In the shown embodiment, the first end and the second ends 111, 112 together with one or more (e.g. side or lengthwise) connecting walls, parts, segments, or the like 114 define the enclosure 110 and the cell culture chamber device 100 has—as an example—an overall substantially cylindrical shape with the first and the second ends 111, 112 respectively forming the circular bases of the cylinder (see also
[0122] Further illustrated is a central axis 200 extending between the first and second ends 111, 112. In at least some embodiments (and as illustrated), the cell culture chamber device 100 is configured for rotation about the central axis 200 e.g. as generally known. In at least some embodiments, the enclosure is symmetrically located in the cell culture chamber device 100 with respect to the axis of rotation/the central axis 200.
[0123] According to the first aspect, the first end 111 or a part or window (see e.g. 113 in
[0124] In some embodiments, the cell culture chamber device 100 comprises a gas exchange circuit, element, or system (not shown; see e.g. 130, 140, 151, 310, etc. in
[0125] In some embodiments, the cell culture chamber device 100 comprises a humidifier e.g. as disclosed herein. In at least some embodiments, the humidifier is configured to humidify the gas or air close to or in the vicinity of the gas exchanger and/or the gas or air that is provided to the enclosure 110. In at least some embodiments, the humidifier is preferably a circumferential humidifier (see e.g. 301 in
[0126] The presence of a humidifier system will eliminate or at least significantly reduce loss of liquid from the enclosure 110 and will greatly enhance the gas exchange between the enclosure 110 and the surrounding air or atmosphere for certain types of cell culture media. The difference is so significant that the cell culture chamber device 100 will normally be able to be used e.g. in an incubator without additional humidification. This typically also reduces the risk of infection in the incubator as its gaseous environment then does not need to be as humid/humidified.
[0127] Further illustrated is a first extent or length ‘L’ and a second extent or height or (in case of e.g. a cylindrically shaped cell culture chamber device) diameter ‘D’ of the cell culture chamber device (100). The extents defines, at least in part, a form-factor of the cell culture chamber device 100. In some embodiments (as illustrated), L is larger than D. However, in other embodiments (see e.g.
[0128] The cross sections (and/or the shapes) of the first end 111 and the second end 112 may be different from each other or be the same or similar.
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[0130] The cell culture chamber device 100 may comprise one or more conduits, inlets, or access ports (not shown; see e.g. 103, 104, 140, 160, 170, etc. in subsequent Figures) e.g. gas inlet/outlet for the humidifier, liquid inlet/outlet connected to the enclosure 110 to provide access to contained cell culture media e.g. for taking out a sample of the enclosure 110 or introducing cell culture media or another liquid into the enclosure 110.
[0131] In some embodiments, (at least one of) the ends 111, 112 is a removable cover or lid providing access to the enclosure 110 when removed.
[0132] In some embodiments, all or substantially all the material of the cell culture chamber device 100 is transparent (rather than only one or both ends 111, 112) (see e.g. also
[0133] In some embodiments one or more ports or inlet/outlets may be used to change growth media (nutrients), add (potentially biologically active) compounds, virus, bacteria, etc. and other to the content of the enclosure 110, remove spheroids from the enclosure 110, etc.
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[0135] Illustrated in
[0136] Shown in
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[0138] Illustrated (see both views) is a cell culture chamber device 100 as disclosed herein. The cell culture chamber device 100 comprises an enclosure 100 as disclosed herein defined by a first end 111, a second end 112, and at least one connecting wall 114 connecting the ends 111, 112. The enclosure 110 is e.g. comprised by a housing/a main housing 105 where the main housing 105 is cylindrical (as an example) and centrally (as an example) comprises the enclosure 110. In the shown and corresponding embodiments, the at least one connecting wall 114 is constituted by a (supported) circumferential gas permeable membrane 120 arranged along or as a circumferential part, i.e. the perimeter or part thereof, of the enclosure 110 and being configured for exchange of gases, e.g. oxygen and carbon dioxide. The circumferential gas permeable membrane 120 may e.g. be a semipermeable membrane.
[0139] Humidification of the atmosphere close to or in the vicinity of the circumferential gas permeable membrane 120 will typically reduce or avoid cell culture media evaporation and may for certain cell culture media furthermore greatly facilitate the exchange of gases through the circumferential gas permeable membrane 120. Cells produce CO.sub.2 which in solution combines with water to form bicarbonate (which is acidic). Humidification of the atmosphere results in the outer surface of the circumferential gas permeable membrane 120 becoming humid and this facilitates the escape of CO.sub.2 from the culture media and in doing so slow the acidification process. This process occurs in types of cell culture that do not rely on CO.sub.2 to buffer the media (e.g. those that contain HEPES, a zwitterionic sulfonic acid buffering agent). The most widely used types of growth media rely on bicarbonate in the media and CO.sub.2 in the atmosphere to buffer the pH of the media. Here also humidification of the outer surface of the circumferential gas permeable membrane facilitates the ‘capture’ or ‘release’ of CO.sub.2 improving stabilisation of the pH of the medium. Humidification can be provided by the cell culture chamber device 100 being located in a humidified incubator or by a humidifier as described in the following.
[0140] The cell culture chamber device 100 comprises, as shown by the front view (to the right in the Figure), a gas exchange intake and outlet for a gas exchanger that may be any suitable intake, conduit, etc. Preferably, and as shown, the gas exchange intake and outlet is in the form of a double vent or similar 140 (see e.g. also 140 e.g. in
[0141] The gas exchange intake and outlet/the double vent 140 is in fluid connection with the membrane 120 thereby connecting the membrane 120 with outside or ambient air or gas of the cell culture chamber device 100. In at least some embodiments, the double vent 140 is configured to operate according to the Coanda effect or principle. In such embodiments, a wall or other suitable barrier 151 (indicated in the Figure by a straight dashed line) is located in-between the two respective vents of the double vent 140 separating and sealing them from each other at this location, i.e. in this particular example separating and sealing them in the shortest direction between them. However, the two vents of the double vent 140 are in fluid connection with each other via another path inside the housing 105 of the cell culture chamber device 100 and are also in fluid connection with at least parts of the gas exchange membrane 120 e.g. via one or more conduits, open spaces, cavities, etc. When the cell culture chamber device 100 is rotated anticlockwise, ambient air or gas is sucked into and out of the cell culture chamber device 100 via the double vent 140 as indicated by the arrows of the front view and cross-sectional side view of
[0142] In this way, an effective air flow 310 is readily provided being in contact with the membrane 120 and the ambient gas or air thereby e.g. expediently adding oxygen and removing carbon dioxide to/from the membrane 120 and thereby the content of the enclosure 110.
[0143] In some further embodiments, the degree of air movement or flow 310 can be regulated by regulating the respective sizes of openings of the vents of the double vent 140 for example with a slider or small or differently sized plugs or in another suitable manner.
[0144] In some further embodiments (and as shown), the cell culture chamber device 100 optionally further comprises a circumferential humidifier or humidification or moisturising element or system (herein equally referred to as humidifier) 301 configured to humidify or moisturise air or gas at least in the vicinity of the membrane 120 (at least parts thereof). A humidifier will greatly enhance a gas exchange between the content of the enclosure 110 and the ambient air or gas and will furthermore reduce or eliminate water or liquid loss from the enclosure 110 when containing a liquid or aqueous solution. The effect is so significant that the cell culture chamber device 100 will normally be able to be used in an incubator without additional humidification. This is advantageous since it typically will reduce a risk of infection in the incubator and also enables simplification of the incubator.
[0145] In some such embodiments, the circumferential humidifier 301 comprises (or is connected to) one or more liquid or moisturising reservoirs or elements. It is advantageous if the weight distribution of the circumferential humidifier 301 is at least somewhat uniformly distributed, at least to some extent, about a central axis or a rotational axis of the cell culture chamber device 100. It is also an advantage if such one or more liquid or moisturising reservoirs or elements has, or provides, a relatively large surface area for evaporation.
[0146] There are several expedient possibilities for humidifying or moisturising air or gas at least in the vicinity of the membrane 120 (at least parts thereof).
[0147] In some embodiments, the circumferential humidifier 301 comprises an element or reservoir containing (preferably sterile) liquid water or other moisturising liquid e.g. with one or more suitable filters, outlets, further (gas permeable and particularly semipermeable) membranes, etc. interfacing the water or liquid with the air flow 310 thereby humidifying or moisturising the air flow 310. The element or reservoir may e.g. be a single circumferential unit or alternatively be several separate and distinct units (e.g. evenly distributed about the central and/or rotational axis).
[0148] In alternative embodiments, the circumferential humidifier 301 comprises one or more of a water or solute-containing material such as a gel, sponge, a particulate material (e.g. water-beads, aqua-beads, etc.) that readily provides evaporation of water or liquid and efficiently influences the air flow 310. Such solid humidifying or moisturising elements may be supported or secured in the housing 105 e.g. by or to an (open) enclosure, a wall or other support structure (e.g. 145 in the following Figures).
[0149] In case of water-beads or a gel, these may be secured, adhered, pasted, etc. to an inner wall (as mentioned e.g. or preferably uniformly about the central and/or rotational axis) of the main housing/housing 105, whereby support structures are not necessary.
[0150] For embodiments not comprising a water or liquid reservoir (e.g. water-beads, gel, etc. as mentioned above) it is possible to locate such directly in a conduit, cavity, open space, etc., comprising the air flow 310, thereby greatly increasing the humidifying or moisturising effect of the air flow 310 and enabling reduction of overall space/foot-print of the cell culture chamber device 100.
[0151] It is noted, that for embodiments without a humidifier (e.g. for use in a humidified incubator or other), the shown cell culture chamber device 100 will not comprise the illustrated circumferential humidifier 301 and may have a reduced size as a result.
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[0153] Illustrated is a cell culture chamber system 400 for the growing of cell cultures and tissues comprising a cell culture chamber device 100 as disclosed herein. The cell culture chamber 100 comprises a first end 111, a second end 112, at least one connecting (e.g. circumferential) wall, part, segment, or the like 114 connecting the first and the second ends 111, 112 and together defining an enclosure 110 of the cell culture chamber device 100 as disclosed herein. The cell culture chamber device 100 may e.g. be substantially cylindrical, e.g. as illustrated in
[0154] In at least some embodiments and as shown, the cell culture chamber system 400 comprises (or is connected to) an imaging or vision system or device 704, such as a camera or the like, and at least one light source 701 configured to emit light 702 passing into, through, and out again of the enclosure 110 (and thereby its content), where the imaging or vision system or device 704 is configured to capture at least a part of light transmitted through and out of the enclosure 110 e.g. as an image or a video. The cell culture chamber system 400 may comprise (or be connected) to a plurality of imaging or vision systems or devices and/or a plurality of light sources. The light source(s) 701 may e.g. be LED light source(s).
[0155] The light source(s) 701 emit(s), at least in some embodiments, natural or artificial light or a combination thereof, typically or preferably visible light having a wavelength of about 400 to about 700 nanometres or at least a sub-range thereof. Alternatively, the light source(s) 701 could e.g. be infrared or near-infrared light respectively having a wavelength of about 700 nanometres to about 1 millimetre or about 900 nanometres to about 2500 nanometres. The light source(s) 701 may e.g. be LED light source(s).
[0156] In some embodiments and as shown, the light source 701 is located on the side of the enclosure 100 being closest to the second end 112, e.g. on or substantially on the axis 200 where the imaging or vision system or device 704 is located generally opposite to the light source 701, i.e. on the side of the enclosure 100 being closest to the first end 111. The imaging or vision system or device 704 may be located on the axis but does not necessarily need to be, as long as the exiting light is in its field of view. In further embodiments, the first end 111 is transparent and the second end 112 is transparent or translucent. A light diffusor 175 (see e.g. 175 in
[0157] In alternative embodiments, the connecting wall(s), etc. 114 is transparent or translucent instead of (or in addition to) the second end 112 where the light source 701 then may be arranged adjacent or at least sufficiently close to the transparent or translucent connecting wall 114 to enable sufficient light to propagate through and out of the enclosure 110. This will not be as optimal as having the light source 701 arranged opposite the first end 111 with the enclosure 110 arranged in-between (and a transparent or translucent second end 112), but may for some uses or designs be sufficient.
[0158] In some further alternative embodiments, the light source is integrated into the second end 112 (for embodiments with a transparent/translucent second end) or integrated into the connecting wall(s) 114 (for embodiments with transparent/translucent connecting wall(s) 114).
[0159] In some additionally alternative embodiments, the second end 112 or the connecting wall(s) 114 is/are or comprises a fluorescent element, e.g. a fluorescent end 112 or a fluorescent connecting wall 114.
[0160] The fluorescent element may e.g. be an IR or a NIR induced fluorescent element or any other suitable fluorescent light source or element.
[0161] The light source(s) 701 of one or more connecting wall(s) 114 may emit light directed at or towards the first end 111.
[0162]
[0163] As mentioned, the second end 112 and/or the connecting wall(s) 114 may comprise a transparent or transparent/translucent window (see e.g. 113 in
[0164] In some embodiments, the light source(s) 701 may be arranged inside the enclosure 110 e.g. adjacent to the transparent/translucent second end 112 (for relevant embodiments) or adjacent to the transparent/translucent connecting wall(s) 114 (for relevant embodiments).
[0165] In some alternative embodiments, at least some of the illustrated light source(s) 701 is/are replaced by one or more other illumination or visualisation signal sources 701, e.g. one or more acoustic transducers configured to emit acoustic waves, e.g. ultrasound, or one or more emitters configured to emit electromagnetic radiation other than light, e.g. infrared or x-rays. Furthermore, the imaging or vision system or device 704 is replaced by another registration or detection system or device configured to register the other illumination or visualisation signal. The other registration or detection system or device 704 may e.g. be configured for registration of sound or acoustic waves (e.g. ultrasound) or for registration of electromagnetic radiation different than light (e.g. infrared, x-rays).
[0166]
[0167] Illustrated in
[0168] The cell culture chamber device 100 of
[0169] In this particular (and corresponding embodiments), the central housing 101 additionally comprises a gas exchange circuit, element, or system in the form of a circumferential gas exchange system comprising a circumferential gas permeable membrane (not shown; see e.g. 301 and 120 in
[0170] In this particular (and corresponding embodiments), the central housing 101 furthermore comprises a circumferential humidifier (not shown) as disclosed herein and e.g. as explained in connection with
[0171] The central housing 101 optionally comprises a gas exchange intake and outlet for a gas exchanger as disclosed herein (see e.g. 130, 140, 151, 310, etc. in
[0172] The double vent 140 has been described in more detail e.g. in connection with
[0173] Further indicated are three cross-sections designated AA (shown in
[0174] In some embodiments (and as shown), the cell culture chamber device 100 further comprises a closable and/or sealable (first) port 103 providing access for a user to the inside of the enclosure e.g. for taking out a sample from the enclosure (e.g. removing spheroids), emptying or filling the enclosure, etc. In the shown embodiment, the closable and/or sealable port 103 comprises a conduit (from the inside of the enclosure to outside the cell culture chamber device 100) and e.g. a simple plug or similar 160. The port 103 may advantageously be located on the top of the cell culture chamber device 100 as this may avoid or reduce bubble formation, e.g. by allowing for overflow.
[0175] In some embodiments (and as shown), the cell culture chamber device 100 further comprises one or more fiducial and/or identification markers, here an identification code 155 and a fiducial marker 180. The identification code 155 is preferably unique to the particular cell culture chamber device 100. The fiducial marker 180 enables determination of the orientation of the cell culture chamber device 100. The fiducial and/or identification markers 155, 180 is/are preferably machine readable, e.g. by a suitable imaging or vision unit or system. In some embodiments, the cell culture chamber device further comprises one or more aligning elements (e.g. location bar and slit or slot, etc.) for aligning different parts (ensuring or facilitating that a part may only be received with a proper orientation by another part) of the cell culture chamber (e.g. appropriately aligning the cover 102 with the first or central housing 101). The fiducial marker 180 may e.g. be such an aligning element (see e.g. also 131 in
[0176] Accordingly, a very compact (lengthwise) cell culture chamber device 100 is provided, in particular because of the circumferential gas exchange system and (if present) the circumferential humidifier.
[0177] Optionally, the transparent cover 102 comprises a number of level or fill-rate indicators 190 readily indicating an actual volume of cell culture media contained in the enclosure.
[0178] In some embodiments and as shown, the cell culture chamber device 100 further comprises one or more (here two) feet, standing elements or the like 501 enabling the cell culture chamber device 100 to stand and prevent it from rolling. This may make use of ports, inlets, etc. easier or more reliable (see e.g. port 170 in the following).
[0179] Illustrated in
[0180] The ratio between a first extent/length (in the left right direction of
[0181] Illustrated in
[0182] As mentioned, the second port 104 provides access (in addition to the first port 103) to the enclosure. As explained in connection with e.g.
[0183] As can be seen, the closable and/or sealable first port 103 and its conduit connects the inside of the enclosure 110 to outside the cell culture chamber device 100. The port walls are a part of the cover 102, allowing for easy access to the content of the enclosure 110. In a similar manner, access to the inside of the enclosure 110 is afforded via the second port 104 (with plug 170). The plug walls of 104/170 are a part of the central housing 101. It is noted, that the first port 103 and the second part 104 are arranged at different sides of the cell culture chamber device 100 enabling easy access to the enclosure from several different sides of the cell culture chamber device 100.
[0184] Further illustrated is the gas exchange intake and outlet in the form of a double vent 140 as already explained.
[0185] The view of
[0186] Illustrated in
[0187] Again, the enclosure 110, the first transparent end 111, the transparent or translucent second 112, the central housing 101, the cover 102, the closable and/or sealable ports 103 and 104, and the main housing 105 are illustrated.
[0188] Further shown, is the gas permeable membrane 120 of the circumferential gas exchange system and a (part of a) grid like structure 130 of the circumferential humidifier (see e.g. 130 in
[0189] Also illustrated is an optional wall structure element or similar 145 for holding and/or supporting a water, liquid, or moisturizing element (explained further in connection with
[0190] In some embodiments, the cell culture chamber device 100 optionally further comprises one or more markings 115 (see also 115 in
[0191] The view of
[0192] Illustrated in
[0193] Illustrated is the enclosure 110, the first transparent end 111, the transparent or translucent second 112, the cover 102, the closable and/or sealable port 103, and two optional wall structure elements or similar 145 for holding and/or supporting a water, liquid, or moisturizing element according to some embodiments.
[0194] The view of
[0195] It is noted, that the cell culture chamber device 100 readily enables inspection, automatic and/or manual, of the content of the enclosure 110 from two sides (as given by the first and the second ends 111, 112) if both ends 111, 112 are transparent.
[0196] In the embodiment illustrated in
[0197]
[0198] Illustrated are the elements of
[0199]
[0200] If the second end 112 is transparent, it is possible to provide lighting (‘back’-lighting) from this side through the opening 185 of the main housing 105 thereby enhancing inspection (manual or automatic) from the other/opposite side (via the first end 111).
[0201] If the second end 112 is translucent, suitable (back-)lighting may provide a more uniform illumination of the content of the enclosure further enhancing inspection (manual or automatic) from the other/opposite side (via the first end 111).
[0202] If the second end 112 is transparent (or translucent), uniform lighting (or even further uniform lighting) might be provided using a light diffusor placed between the light source(s) and the second end 112, preferably close to or adjacent to the second end 112. Such an embodiment, is e.g. shown in
[0203] In some embodiments, the material of the main housing 105, the central housing 101 (and thereby the second end 112), the cover 102 (and thereby the first end 111) may e.g. be the same (transparent) material (see e.g. also
[0204] The embodiments of a cell culture chamber device 100 as illustrated in
[0205]
[0206] The embodiment of a cell culture chamber device 100 of
[0207] In alternative embodiments, the light diffusor 175 could be contained inside the enclosure near the second end 112.
[0208]
[0209]
[0210] Illustrated is a main housing 105 according to some embodiments and e.g. as shown in connection with the embodiments of
[0211] The main housing 105 comprises a cavity or open space and a first port 104 providing access to the enclosure (the port 104 to align in an assembled state of the cell culture chamber device with a further port; see e.g. 150 in
[0212] The main housing 105 furthermore comprises a central opening 185 to be aligned with or receiving the second end (see e.g. 112 in
[0213] In the particular shown embodiment, the main housing 105 furthermore comprises a number (here four as an example) of wall structure elements or similar 145 each for holding and/or supporting a water, liquid, or moisturizing element for embodiments also comprising a humidifier (please see further in the following). In alternative embodiments, the wall structure elements or similar 145 may be omitted. The wall structure elements or similar 145 may be distributed more or less evenly in the cavity or open space of the main housing 105 about a central axis/a rotational axis of the cell culture chamber device to distribute weigh of the water, liquid, or moisturizing elements more evenly. The wall structure elements or similar 145 may also provide structural integrity and/or support the received central housing.
[0214] In some embodiments and as shown, each (or some) wall structure element(s) or similar 145 comprises a cut-out or passage 141 forcing gas or air flow into close(r) proximity to a gas permeable membrane (see e.g. 120 in
[0215] Contained air or gas is in connection with a grid-like structure of the central housing (see e.g. 130 and 101 in
[0216] This readily provides a circumferential gas exchanger not blocking any line of sight between the first end and the second end in part defining the enclosure.
[0217] The function of the circumferential gas exchange system and the circumferential humidifier is further explained further in connection with
[0218]
[0219] Illustrated in
[0220]
[0221] Illustrated in
[0222]
[0223] Illustrated is a circular optical diffusor 175. The optical diffusor 175 may be of any suitable translucent material where the refractive index is not uniform for the light of relevant wavelengths.
[0224] It is noted, that even though the shown optical diffusor 175 is substantially circular it could have other suitable shapes, e.g. square, rectangular, etc. The optical diffusor 175 may e.g. fit a window or part of a second end (see 112, 113 elsewhere), be curved to fit a connecting wall (see e.g. 114 elsewhere), etc.
[0225] In alternative embodiments, the diffusor 175 is not an optical diffusor but a diffusor 175 with respect to another type of illumination or visualisation signal, e.g. an acoustic diffusor or a diffusor for electromagnetic radiation different than light.
[0226] In some other alternative embodiments, the diffusor 175 (as disclosed herein) is replaced by a suitable reflector, e.g. a parabolic reflector, e.g. for use with front-lighting embodiments (or front-application of another type of illumination or visualisation signal) either in addition to or as an alternative to back-lighting or back-emission of another illumination or visualisation signal.
[0227]
[0228] Illustrated is an enclosure as disclosed herein having a first end 111 and a second 112 connected by at least one connecting wall 114. Illustrated are three exemplary positions of where a light source 701 may be positioned depending on whether the second end 112 and/or the at least one connecting wall 114 is transparent or translucent. In some embodiments, several light sources 701 may be used. As mentioned, one or more light sources may e.g. located outside the second end 112 or the at least one connecting wall 114 or alternatively be integrated into such or also be arranged inside the enclosure. As a further alternative, one or more of the light sources 701 may be or comprises a fluorescent light emitting element.
[0229] In some alternative embodiments, the illustrated light source(s) 701 is/are replaced by one or more other illumination or visualisation signal sources 701, e.g. one or more acoustic transducers configured to emit acoustic waves, e.g. ultrasound, or one or more emitters configured to emit electromagnetic radiation other than light, e.g. infrared or x-rays.
[0230] Some preferred embodiments have been shown in the foregoing, but it should be stressed that the invention is not limited to these, but may be embodied in other ways within the subject matter defined in the following claims.
[0231] It should be emphasized that the term “comprises/comprising” when used in this specification is taken to specify the presence of stated features, elements, steps or components but does not preclude the presence or addition of one or more other features, elements, steps, components or groups thereof.
[0232] In the claims enumerating several features, some or all of these features may be embodied by one and the same element, component or item. The mere fact that certain measures are recited in mutually different dependent claims or described in different embodiments does not indicate that a combination of these measures cannot be used to advantage.
[0233] In the claims, any reference signs placed between parentheses shall not be constructed as limiting the claim. The word “comprising” does not exclude the presence of elements or steps other than those listed in a claim. The word “a” or “an” preceding an element does not exclude the presence of a plurality of such elements.
[0234] The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to an advantage.
[0235] It will be apparent to a person skilled in the art that the various embodiments of the invention as disclosed and/or elements thereof can be combined without departing from the scope of the invention as defined in the claims.