Incubator for receiving a plurality of cell culture chamber devices

Abstract

The invention relates to an incubator (200, 200') configured to receive a predetermined number of at least one or more cell culture chamber devices (100), each cell culture chamber device (100) comprising an enclosure (110) configured to contain a cell culture medium, the incubator (200, 200') comprising: a housing (210) comprising a culture chamber (201) configured to contain at least a respective portion of the cell culture chamber device (100) when the cell culture chamber device (100) is received by the incubator (200, 200'); and at least one revealing and / or detecting device (220) integrated with the incubator (200, 200') and configured to reveal and / or detect an illumination or visualization signal (703) after the illumination or visualization signal has passed through, reflected off or propagated through at least a portion of the enclosure (110) of at least one of the predetermined number of cell culture chamber devices (100) when the predetermined number of cell culture chamber devices (100) is received by the incubator (200, 200').

Description

Technical Field

[0001] The present invention generally relates to a culture vessel configured to receive a predetermined number of cell culture chamber devices (also referred to herein as bioreactors), wherein each cell culture chamber device includes an enclosure (also referred to herein as a cell chamber) configured to contain cell culture medium (typically comprising cells). Furthermore, the present invention relates to a culture vessel system comprising a first culture vessel and at least a second culture vessel. Background Technology

[0002] When cells and tissues are grown using more conventional cell culture chamber setups, typically with largely flat cell support surfaces, primary cells and biopsy tissues tend to dedifferentiate and lose their normal structural organization and in vivo function. One example is cell migration from tissue blocks to flat support surfaces (the so-called "melting ice cream effect"). Dedifferentiated cells often express biochemical characteristics different from those normally expressed by corresponding cells in a intact organism. Furthermore, some cells often lose their specialized functions compared to their counterparts in an intact organism.

[0003] An improvement in this regard is that certain cell culture chamber devices or bioreactors used for the growth of cell cultures (whether for single or multiple cell types, or tissues) typically, or even preferably, operate under omnidirectional normal gravity conditions, i.e., conditions initiated by a gyroscope, because this allows for the preservation of the differentiation state of many cell types in the culture. Furthermore, it promotes the restoration (or redifferentiation) of in vivo-like structures and functions in many different cell lines. This is important because cell lines are used for the majority of cell culture work currently being conducted.

[0004] This omnidirectional normal gravitational condition can be induced by continuous rotation of the compartment containing the cell culture, thereby preventing cell adhesion to the compartment walls (strictly speaking, rotation increases gravity (centripetal acceleration) by an infinitesimal amount). Appropriate rotation promotes cell adhesion within a fluid environment while minimizing shear forces acting on the culture. If desired, shear forces can be introduced for specific cell / tissue types by varying the rotation speed of the bioreactor. This causes cells to aggregate into colonies commonly named spheroids or organoids (collectively referred to as spheroids in this disclosure). Tissue sheets are also included under the genus term "spheroids" because they are subject to similar effects.

[0005] As the spheroids grow, they become larger, thus requiring, for some applications, the rotation rate of the bioreactor to be adjusted to maintain optimal conditions, where the spheroids remain in a essentially “fixed track” relative to the bioreactor, as this promotes improved spheroid homogeneity. For other applications, the spheroids should not or need to be kept in a fixed track, but are allowed to exhibit different behaviors, such as being allowed to tumble or be located on or near the bottom of the cell culture chamber, or be held against the walls of the cell culture chamber by centripetal acceleration, and so on. However, in any case, it is highly beneficial to be able to clearly examine the spheroids in the bioreactor in several situations, for example, to see if speed adjustments should be made, and to what extent. Improved spheroid homogeneity leads to more standardized metabolic performance, which in turn enables more reliable in vitro predictive toxicology assessments of drug candidates from cell cultures before proceeding to expensive clinical trials or similar trials, i.e., it leads to more reliable “screening” before initiating animal or clinical trials.

[0006] At least for some culturers, several cell culture chambers or bioreactors are used within the culturer. These chambers or bioreactors contain, for example, cells of different types and / or sizes / states, and are typically located within the same closable open space or cavity. Even with internal lighting, the use of such a culturer reduces the individual visibility of the contents of each cell culture chamber or bioreactor, often prompting the user to repeatedly open and close the culturer over time, and, for example, remove the cell culture chambers or bioreactors for closer manual inspection. Repeatedly opening and closing the culturer can at least increase the risk of contamination and at least temporarily disrupt the controlled internal environment of the culturer. More specifically, opening and closing the culturer disturbs the internal environment (e.g., temperature, humidity, CO2, etc.). Even when the door is not open and closed, there is a tendency for hot air to rise, i.e., the atmosphere at the top is hotter than the atmosphere at the bottom. Therefore, if high atmospheric uniformity is preferred or required for high performance and high reproducibility, some form of recirculation to mix the internal atmosphere is advantageous. However, this increases the risk of contamination, for example, as spores or bacteria located at the bottom of the culture chamber will rotate and come into contact with the contained cell culture chamber apparatus and / or its culture chamber / enclosure. Therefore, it would be beneficial to provide a culture vessel that helps reduce the need to open and close the vessel, and furthermore, reducing the risk of contamination would also be advantageous.

[0007] In addition, it is generally desirable to be able to purify the culture vessel, more specifically, the space or cavity used to contain the cell culture chamber device or bioreactor, and to at least reduce the risk of contamination as effectively as possible.

[0008] Therefore, it would be advantageous to provide a culture vessel that at least partially addresses one or more of the aforementioned disadvantages. In particular, it would be advantageous to provide a culture vessel that reduces the risk of contamination of the culture vessel space or cavities. It would also be advantageous to provide a culture vessel that reduces the need to open and close the culture vessel. A further or additional advantage would be a culture vessel that enhances the observation of any contained cell culture chamber apparatus, especially the observation of the contents of any contained cell culture chamber apparatus (within their respective enclosures). Summary of the Invention

[0009] One objective is to provide a culture device that at least partially addresses one or more of the aforementioned disadvantages. Another objective is to provide a culture device that reduces the risk of contamination of the culture device space or cavity, and / or provides enhanced observation of the contents of any contained cell culture chamber device or their respective surrounding portions (i.e., the cell culture medium contained therein).

[0010] According to the first aspect, one or more of these objectives are achieved, at least in part, by a culture vessel configured to receive a predetermined number of at least one or more cell culture chamber devices (also equivalently referred to herein as bioreactors). The predetermined number of cell culture chamber devices may be, for example, 1, 2, 3, 4, 5, 6 or more. Each (or at least some of them) cell culture chamber device includes an enclosure (also equivalently referred to herein as a cell chamber) configured to contain cell culture medium (typically, at least in use, containing cells). The culture vessel also includes

[0011] - A housing comprising a culture chamber configured to include at least a corresponding portion of the cell culture chamber apparatus when received by a culture vessel, and

[0012] - At least one registration and / or detection device, integrated with the culturer, and configured to, when a predetermined number of cell culture chamber devices are received by the culturer, display and / or detect the lighting or visualization signal after the lighting or visualization signal has passed through, reflected or propagated through at least a portion of the enclosure of at least one of the predetermined number of cell culture chamber devices.

[0013] This facilitates monitoring (and / or other display and / or detection), where monitoring can be local or even remote, as further disclosed herein. The illumination or visualization signal can be, for example, a visible light signal, and the display and / or detection device can be, for example, a camera configured to provide video feed or video capture of the contents of the enclosure of any included cell culture chamber apparatus, such as periodic still images. Alternatively, the illumination or visualization signal can be a different signal, such as those disclosed herein.

[0014] Observing and monitoring the contents of the enclosed compartment in this way significantly reduces the need for repeatedly opening and closing the incubator, which in turn significantly reduces the risk of contamination of the incubator. Furthermore, opening or accessing the incubator disrupts the controlled environment within (e.g., regarding temperature, humidity, and / or CO2). In some known types of incubators, it has been shown, for example, that after opening the door to the incubator for only about 30 seconds, it takes approximately 6 minutes to re-establish appropriate temperature and CO2 levels.

[0015] Furthermore, compared to manually observing the culture chamber through a glass panel or similar object (even if there is lighting in the culture chamber), display and / or detection devices can easily provide enhanced observation (e.g., magnification / zoom, IR, etc.). Typically, the user will have to access the culture chamber for inspection, or even stop the culturer and remove the cell culture chamber device for closer inspection, which can be harmful to the contents of the cell culture chamber device (e.g., because it has not been rotated for a period of time and may be shaken or disturbed even with careful handling).

[0016] Traditionally, when a culture chamber is opened or accessed, for example for inspection, cell culture chamber devices and their surrounding areas are exposed to light, which can be harmful to certain types of cells and spheroids. As described below, a culture vessel may include one or more light sources for illuminating the culture chamber. When the contents of the culture chamber (the contents of the cell culture chamber device) are inspected or recorded using a display and / or detection device (e.g., a camera), the light source can be selectively turned on and then off afterwards, reducing the time of light exposure. Furthermore, users can inspect, record, etc., the contents of the multi-cell culture chamber device more quickly, further reducing the degree of light exposure.

[0017] In some embodiments, the culture chamber is configured to completely contain the cell culture chamber apparatus (when the cell culture chamber apparatus is received by a culture vessel). Alternatively, the culture chamber is configured to contain only a portion of the cell culture chamber apparatus, particularly at least a portion, or all, of the respective enclosure. In some embodiments, the cell culture chamber apparatus may be, for example, a perfusion bioreactor (capable of self-sustaining for an extended period, e.g., up to about 14 days or longer), including respective fresh and used culture medium reservoirs, drive elements, etc., and it is advantageous to have certain components or parts, such as the fresh and used culture medium reservoirs, drive elements, etc., located outside the culture chamber, thereby reducing the risk of contamination and making cleaning easier. See, for example, the applicant's co-pending PCT patent application PCT / EP2020 / 068632, for examples of perfusion cell culture chamber apparatuses or bioreactors.

[0018] In some embodiments, the incubator further includes at least one rotation drive unit, each rotation drive unit (or at least some thereof)

[0019] - Configured, for example or preferably releasably to receive at least one of the cell culture chamber devices, and

[0020] - The received cell culture chamber device is configured to rotate about (at least) a predetermined axis of rotation (e.g., or preferably a horizontal axis) of the cell culture chamber device received by the rotary drive unit.

[0021] The rotary drive units are configured to rotate one (or more) of the received cell culture chamber apparatus about one, two, or three substantially perpendicular axes. A culture vessel rotating about two or three such axes is sometimes referred to as a so-called random positioning machine. In some embodiments, the predetermined axis of rotation is a predetermined central axis of the received cell culture chamber apparatus. Alternatively, the predetermined axis of rotation is a predetermined central axis of the enclosure of the received cell culture chamber apparatus. In some embodiments, the central axis of the received cell culture chamber apparatus may be the same as or coincide with the central axis of the enclosure of the received cell culture chamber apparatus, i.e., if the enclosure is centrally located within the cell culture chamber apparatus (this is not always necessary).

[0022] In some embodiments, the rotary drive unit is a rotator drive unit.

[0023] In at least some (preferred) embodiments, the at least one display and / or detection device is arranged horizontally / vertically aligned with the at least one cell culture chamber device, for example, aligned in a direction along a predetermined axis of rotation or an axis substantially parallel thereto.

[0024] The at least one display and / or detection device may, in principle (in some embodiments), be located outside the culture vessel rather than integrated with it, wherein the culture vessel includes a plurality of transparent windows, etc., aligned with the cell culture chamber device (when received by the culture vessel), thereby allowing the display and / or detection device to display and / or detect the contents of any received cell culture chamber device when it is properly arranged.

[0025] In some embodiments, the incubator includes an openable and closable door or lid (or other access element), and the incubation chamber includes at least one incubation chamber wall that, together with the door or lid (or other element), at least partially defines the incubation chamber when the door or lid (or other element) is closed. In some embodiments, the at least one incubation chamber wall and the door or lid (or other access element) completely define the incubation chamber when the door or lid (or other access element) is closed. In some embodiments, the incubation chamber includes only a single incubation chamber wall. In some further embodiments, the (single) incubation chamber wall is preferably generally "bowl"-shaped or "plate"-shaped or generally hemispherical or semi-elliptical, for example, having a cylindrical portion (with a circular cross-section substantially perpendicular to a first or longitudinal direction (e.g., the horizontal direction), so that the incubation chamber has no sharp corners or edges, thereby facilitating easy and efficient cleaning of the incubation chamber, which is important for maintaining the incubation chamber in a state of at least purification (if not complete sterility). It should be noted that incubators including the “circular” culture chamber (having a circular cross-section substantially perpendicular to the first direction or longitudinal direction (e.g., the horizontal direction) as described above) can be provided without any display and / or detection device and can be used independently of any display and / or detection device.

[0026] In some embodiments, the incubator also includes one or more locking, latching, or fastening elements for the door or lid, such as those providing so-called push-to-open and push-to-close locking functions, allowing the user to open and close the incubator without hands, thereby reducing the risk of incubator contamination. Alternatively, these elements are of another type, such as touchless, remotely operated, etc.

[0027] In some further embodiments, the first side or inner side of the door or cover (or other receiving element) (i.e., the side facing the culture chamber when the door, cover, etc. are closed) includes at least one display and / or detection device, wherein the at least one display and / or detection device is oriented such that the enclosure of at least one received cell culture chamber device is within the display and / or detection field of view of at least one of the at least one display and / or detection device, i.e., the enclosure of any received cell culture chamber device is located within the field of view of at least one display and / or detection device.

[0028] In some embodiments (embodiments having multiple display and / or detection devices), the display and / or detection devices are arranged equidistantly in a substantially circular pattern in the door, lid, or similar part of the culture vessel.

[0029] In some embodiments, the culturer includes a predetermined number of display and / or detection devices, i.e., one display and / or detection device for each cell culture chamber device that can be received by the culturer, or in other words, a one-to-one relationship. In some further embodiments, each display and / or detection device is arranged such that the central axis of the display and / or detection field of view of the respective display and / or detection device is at least substantially aligned with the central axis of the corresponding enclosing portion of the received cell culture chamber device. In this way, one display and / or detection device is dedicated to displaying and / or detecting the illumination or visualization signal of a particular cell culture chamber device, which will generally enhance the quality of the corresponding illumination or visualization signal and / or also enhance the display and / or detection (e.g., observation) of the particular culture chamber device, particularly the contents of any contained cell culture chamber device. Furthermore, it will ensure (or at least greatly facilitate) the proper alignment of the display and / or detection device and the cell culture chamber device (in the X, Y, and Z dimensions), which is particularly important where the distance between them is generally short in such an arrangement. Alternatively, a single display and / or detection device can be dedicated to displaying and / or detecting illumination or visualization signals from multiple specific cell culture chamber devices, thereby reducing the number of display and / or detection devices required.

[0030] In some embodiments, at least one display and / or detection device is an imaging or vision system or device, and the illumination or visualization signal is ultraviolet light, visible light, infrared light, and / or near-infrared light (and accordingly, at least one display and / or detection device is configured to display or detect ultraviolet light, visible light, infrared light, and / or near-infrared light).

[0031] In some further embodiments, the culture vessel also includes one or more light sources (or illumination sources) configured to illuminate at least a corresponding portion of the cell culture chamber apparatus, such as illuminating at least a portion of a corresponding enclosure of any received cell culture chamber apparatus. In other further embodiments, the one or more light sources (or illumination sources) are configured to respectively illuminate at least a first end or a portion or window of the enclosure of one or more cell culture chamber apparatuses received by the culture vessel. In some further embodiments, the one or more light sources are arranged in a door or cover, and are arranged to face the one or more cell culture chamber apparatuses when they are received by the culture vessel. Thus, (primarily) frontal illumination of the enclosure is provided, wherein "frontal illumination" is considered to be illumination from the opening of the culture chamber toward the cell culture chamber apparatus (when received).

[0032] In some embodiments, at least one corresponding drive unit (e.g., one, some, or all) of at least one rotary drive unit includes one or more light sources or illumination sources configured to illuminate at least a corresponding portion of the cell culture chamber apparatus, such as illuminating at least a portion of a corresponding enclosure of any received cell culture chamber apparatus. In other further embodiments, one or more light sources or illumination sources are configured to respectively illuminate at least a second end or a portion thereof or a window of the enclosure of one or more cell culture chamber apparatuses received by the corresponding drive unit.

[0033] In some alternative embodiments, at least one corresponding drive unit (e.g., one, some, or all) of at least one rotary drive unit includes a hollow rotary shaft that includes a light guide or other lamp or illumination element configured to illuminate at least a corresponding portion of the cell culture chamber device or its surrounding portion when the cell culture chamber device is received by the drive unit.

[0034] Therefore, (primary) "back" illumination is provided for the surrounding area, wherein "back" illumination is considered to originate opposite to the opening of the culture chamber and toward the cell culture chamber apparatus (when received).

[0035] In some embodiments, at least one drive unit (or at least a drive unit providing back illumination) includes a cavity disposed near the received cell culture chamber apparatus, wherein the cavity includes one or more light sources or illumination sources. This provides a very compact drive unit with back illumination.

[0036] In some embodiments, one or more light sources or illumination sources are arranged off-center from the central axis or rotation axis of the enclosure or cell culture chamber apparatus, which can provide simple / easier access to the enclosure and therefore its contents.

[0037] Embodiments of the incubator may include a mixture of front-illuminated and back-illuminated lamps or illumination sources to improve the quality of any acquired detection and / or display signals. Alternatively, embodiments may include only one or more back-illuminated lamps or illumination sources, or only one or more front-illuminated lamps or illumination sources.

[0038] The light source can be, for example, an LED light source, a laser light source, an LED emitting laser light source, or any other suitable light source.

[0039] Alternatively, other lighting or visual signal sources(s) are used as alternative light sources, configured to emit another type of lighting or visual signal, for example, through a second end or a portion thereof or a window, into the corresponding enclosure, wherein the at least one display and / or detection device is configured to capture at least a portion of the other type of lighting or visual signal transmitted to the outside of the enclosure through the first end or a portion thereof or a window. Such other type of display and / or detection device may, for example, be configured to display sound or sound waves (e.g., ultrasound), or electromagnetic radiation other than light (e.g., X-rays).

[0040] In the illustrated embodiment, the four light sources 701 are offset from the central axis or rotation axis of the surrounding portion or cell culture chamber apparatus (see, for example...). Figure 5 (260 in the middle), which can provide easy access to the contents of the surrounding section.

[0041] The light source 701 can be, for example, an LED light source or any other suitable light source.

[0042] In some embodiments, the driving unit includes multiple light sources, which may be of the same type or, alternatively, of different types (emitting different wavelengths).

[0043] In some further embodiments, the driving unit includes at least two different types of multiple light sources, wherein the at least two different types can be selected from ultraviolet light, visible light, near-infrared light, and infrared light.

[0044] In some embodiments, the driving unit includes a light diffuser disposed in the light propagation path from one or more light sources to or toward the enclosing portion of the received cell culture chamber apparatus. In some further embodiments, the light diffuser is disposed in the propagation path adjacent to or at least close to the received cell culture chamber apparatus (e.g., adjacent to or close to a second end of the enclosing portion). The light diffuser may, for example, be disposed within a cavity of the driving unit. The light diffuser will provide more uniform illumination to the enclosing portion, thus improving the quality of the back illumination, thereby improving the quality of the detection and / or display signal of the display and / or detection device.

[0045] In some embodiments, the corresponding motor component of at least one rotary drive unit is located outside the culture chamber and inside the culture vessel housing. This facilitates the removal of the typical heat-generating components of the drive unit from the culture chamber, making the ambient temperature of the culture chamber easier to control and maintain, and also reduces the risk of unexpected temperature increases / "surges" in the culture chamber, which could be harmful to the contents of the cell culture vessel located within the culture chamber. Another significant advantage is that keeping the culture chamber clean is thus made easier, which is crucial for avoiding undesirable contamination of the received cell culture vessel by viruses, various types of microorganisms, etc. Furthermore, the culture vessel typically consumes less energy because there is no need to actively remove the generated heat from the culture chamber. Heat generated within the housing can, for example, be passively removed.

[0046] It should be noted that a culturer with a drive unit having corresponding motor portions located outside the culture chamber and inside the culturer housing can be configured without any display and / or detection devices and can be used independently of any display and / or detection devices.

[0047] In some embodiments, the incubator further includes a fan or ventilation unit (e.g., or preferably, a rotary fan or ventilation unit) disposed within the incubation chamber and configured to induce airflow within the incubation chamber in response to a control signal. The presence of the fan or ventilation unit within the incubation chamber (or a fan or ventilation unit disposed elsewhere in the housing but still generating airflow within the incubation chamber) promotes a uniform environment within the incubation chamber, which is generally beneficial for providing uniform humidity, uniform temperature, and other key parameters that may need to be controlled when using the incubator. Furthermore, the fan or ventilation unit also helps to quickly re-establish a uniform environment after doors, lids, etc., have been opened and closed.

[0048] In some embodiments, the fan or ventilation unit is typically centrally positioned within the culture chamber (located at or towards the bottom or end wall of the culture chamber), which further enhances the efficiency of the fan or ventilation unit, particularly when combined with culture chambers of the shapes described above and elsewhere (bowl-shaped, hemispherical, etc.). For some embodiments, such as where the cell culture chamber apparatus is arranged in a substantially circular pattern within the culture chamber, central space is readily available for such a central fan or ventilation unit, thus enabling a compact design.

[0049] In some further embodiments, the central fan or ventilation unit is located "behind" the cell culture chamber apparatus (when received), i.e., between the bottom or end wall of the cell culture chamber apparatus and the culture chamber.

[0050] The incubator may include two or more (e.g., smaller) fans or ventilation units, instead of a single fan or ventilation unit, for example, arranged in another way.

[0051] It should be noted that a culture vessel with such a fan or ventilation unit can be configured without any display and / or detection device and can be used independently of any display and / or detection device, wherein the fan or ventilation unit is arranged in the culture vessel and configured to generate an airflow within the culture vessel in response to a control signal (and embodiments thereof).

[0052] In some embodiments, the incubator also includes an arrangement for directly exposing the culture chamber to UVC light to purify the culture chamber, such as one or more UVC light sources. It should be noted that this differs from (and is generally more effective for purification) arrangements that ventilate or otherwise divert air from the culture chamber to the area exposed to UVC light and through that area. Such conventional UVC irradiation areas are typically located elsewhere within the incubator housing and generally require forced ventilation via ducts or the like, resulting in significantly less air exposure.

[0053] By positioning the UVC light inside the culture chamber, the interior of the culture chamber is directly exposed with UVC light. This is particularly effective for culture chambers with a generally cylindrical cross-section (which is substantially perpendicular to the first or longitudinal direction, which is usually horizontal) and without sharp corners or edges (as is typically the case with a square culture chamber), such as culture chambers designed in shapes as described above and elsewhere (bowl-shaped, hemispherical, etc.).

[0054] UVC light should be emitted in the culture chamber only when the cell culture chamber apparatus is not present, or only when the cell culture chamber apparatus has a UVC light shielding enclosure for containing cell cultures is present.

[0055] In some embodiments, the UVC lamp is a rotating UVC lamp configured to rotate within the culture chamber about a predetermined axis (e.g., about a first or longitudinal direction or an axis parallel to it, which would typically be horizontal) to sweep across the interior of the culture chamber and enhance the effect of the UVC light (especially when combined with culture chambers designed in the shape of such as described above and elsewhere (bowl-shaped, hemispherical, etc.)).

[0056] In some further embodiments, the UVC lamp is asymmetrical, that is, it emits UVC light in (at least) two different, for example, opposite directions, which works particularly well when combined with rotation.

[0057] The UVC light source can be positioned, for example, roughly centered in the culture chamber (located at or towards the bottom or end wall of the culture chamber).

[0058] In some embodiments, a rotating UVC light source or the like is integrated with a rotating fan or ventilation unit, providing a very compact and efficient design. Furthermore, the UVC lamp thus rotates together with the fan or ventilation unit, effectively sweeping across the culture chamber. Preferably, activation of the UVC lamp can be accomplished independently of activation of the fan or ventilation unit; that is, the fan or ventilation unit should be able to rotate (and thus rotate the integrated UVC lamp) without emitting UVC light.

[0059] In some other embodiments, the incubator includes (e.g., a rotating) UVC arrangement / UVC lamp and has no fan or ventilation unit (rotating or otherwise). In some further embodiments, the incubator includes a fan or ventilation unit (rotating or otherwise) and has no UVC arrangement / UVC lamp.

[0060] In some embodiments, at least a portion of the inner surface of the culture chamber (e.g., at least a portion of at least one culture chamber wall and / or the first or inner side or surface of a door, cover, etc.) comprises a UVC reflective material or coating, which typically enhances the effect of UVC light.

[0061] Furthermore, this swept UVC illumination within the culture chamber will distribute the light fairly evenly, and if the culture chamber includes UVC reflective materials or coatings, the UVC light will reach the un-directly irradiated areas of the culture chamber more effectively. Both of these factors ensure that the UVC irradiation dose is kept as low as possible while still achieving the required level of purification.

[0062] It should be noted that a culture vessel (and its embodiments) having a UVC arrangement located inside the culture chamber and configured to directly expose the interior of the culture chamber with UVC light can be configured without any display and / or detection device and can be used independently of any display and / or detection device.

[0063] In some embodiments, the incubator further includes at least one heating element configured to controllably heat the interior of the culture chamber in response to a control signal. In some further embodiments, the heating element includes a back or main portion substantially conforming to the planar shape of, for example, the culture chamber wall, forming a “back” or “end” wall of the culture chamber, and includes a plurality of heating “arms,” “wings,” or “tongues” extending to one or more sides of the culture chamber wall, thereby effectively increasing the area of ​​the culture chamber wall that can be directly exposed to heating, and consequently increasing the possible heating rate and uniformity inside the culture chamber. The heating element can be any suitable heating element, preferably a relatively flat or thin element, such as a heating foil, grid, etc. In some embodiments, the heating element is a self-adhesive heating element. Alternatively, it can be fastened to the culture chamber wall in another suitable manner. In at least some embodiments, the heating element is located on the exterior of the culture chamber wall, i.e., on a surface opposite to the interior surface of the culture chamber.

[0064] Heating elements, together with fans or ventilation units (e.g., as disclosed herein), create airflow within the culture chamber, resulting in a highly uniform heat distribution within the chamber, which is crucial for effective and rapid temperature control.

[0065] In some embodiments, the incubator also includes

[0066] -One or more processing units,

[0067] - Electronic memory and / or electronic storage devices, and

[0068] - One or more signal transmitter and receiver communication elements configured to communicate with a network.

[0069] The one or more processing units are configured to communicate with at least one external computing device via a network, such as a user interface device, a client and / or server computer or device, a network-connected storage device, and / or one or more additional incubators.

[0070] In some embodiments, the video and / or images and / or other detection and / or display signals captured or obtained by the display and / or detection device may be transmitted by the incubator to an external computing device, for example for presentation (e.g., remote observation or remote online observation), storage and / or further digital processing.

[0071] The user interface device can be configured, for example, to monitor online signals obtained by the display and / or detection devices of the culturer.

[0072] In some embodiments, the incubator is also configured to receive user input control data via a network obtained from a user interface device and / or another external computing device (e.g., a client, server, host, etc.), and to change or adjust its operation in response to at least a portion of the received user input control data.

[0073] In some further embodiments, a culturer (e.g., a master device unit) is configured to receive other user input control data and transmit at least a portion of it to another culturer (e.g., a slave device unit), wherein the other culturer is configured to change or adjust its operation in response to at least a portion of the other user input control data received.

[0074] For example, combining Figure 16 This article discloses additional embodiments of such a culture device.

[0075] In some embodiments, the culture apparatus includes at least one cell culture chamber device for cell culture and tissue growth, wherein the cell culture chamber device includes an enclosure configured to contain a cell culture medium, typically aqueous. The cell culture chamber device also includes a first end, a second end, and at least one connecting wall (e.g., a circumferential wall) connecting the first end and the second end. The first end, the second end, and at least one connecting wall at least partially define the enclosure. The enclosure may also be referred to, for example, as a cell culture enclosure, a cell chamber, etc. The first end may also be referred to, for example, as a first end segment or a first portion of the enclosure, and the second end may also be referred to, for example, as a second end segment or a second portion of the enclosure. The first end may also be referred to, for example, as an observation end or portion, or as a primary observation end or portion. The first end, or a portion thereof or a window thereof, is substantially transparent. At least one of the second end and / or at least one connecting wall, or a corresponding portion thereof or a window thereof, is substantially transparent or substantially translucent. The first end or a portion thereof or window is configured to be optically or otherwise (e.g., or i.e., relative to other electromagnetic radiation or mechanical waves such as sound or acoustic waves) aligned (at least for a period of time or periodically) with the second end or a portion thereof or window and / or with at least one of the at least one connecting wall or a portion thereof or window, such that light or other illumination or visualization signals transmitted through or from the second end or a portion thereof or window to the enclosure, and / or transmitted through or from at least one of the at least one connecting wall or a portion thereof or window to the enclosure, are transmitted or propagated through at least a portion of the cell culture medium, and transmitted through the first end or a portion thereof or window to the outside of the enclosure, for example, to the outside of the cell culture chamber apparatus. It should be noted that (for the relevant embodiments), the first end (or a portion thereof or window) does not need to be optically aligned or otherwise aligned with the second end (or a portion thereof or window) by crossing each other or directly crossing, even though this provides a very advantageous way to provide alignment. For example, suitable optical or other electromagnetic radiation-based, sound / sound wave-based, etc. systems or one or more suitable devices or components (e.g., reflectors, mirrors, sound or light guides, etc.) can be used to align the corresponding end (or component / window) at least for a period of time. In the broadest sense, it is important that light or other illumination or visualization signals pass through a portion or most of the cell culture medium within the enclosure and are then emitted to the outside of the enclosure in a manner as unobstructed as possible or necessary (other than being affected by the contents of the cell culture medium), thereby allowing the exposure and / or characterization of some or all of the contents of the enclosure. In some embodiments, the first end (or at least a portion thereof or window) is substantially planar, as this provides an undistorted optical image or projection. However, the end (or portion thereof or window) may be curved at least to some extent.The second end and / or connecting wall (or its corresponding portion or window) may be curved, but in some embodiments, the second end and / or connecting wall (or its corresponding portion or window) is substantially planar.

[0076] In this way, a cell culture chamber apparatus is provided having an unobstructed (except for the influence of the contents of the cell culture medium) path for the propagation of light or other illumination or visualization signals, said path propagating through at least a portion of any cell culture medium contained within the enclosure. It also enables backlighting or the emission of other illumination or visualization signals from the "rear," i.e., light or other illumination or visualization signals irradiated through the second end and / or connecting walls (e.g., toward the second end), thereby greatly enhancing visual inspection (manual or automatic) from the other / opposite side (i.e., via the first end). This is particularly useful for, for example, inspecting several cell culture chamber apparatuses arranged in the like, such as a culture vessel. If the second end is transparent, visual or other inspections (e.g., sound or electromagnetic radiation other than light), manual inspections (in the case of light), and / or automatic inspections (using suitable sensors in the case of light or other electromagnetic radiation or sound or acoustic waves) can also be achieved from both ends of the enclosure, i.e., both sides. In some embodiments, all parts of the cell culture chamber apparatus are transparent.

[0077] Furthermore, this cell culture chamber device is particularly useful for use in conjunction with a culture vessel according to the first aspect and as disclosed herein, because the transparent first end (and being transparent) allows for improved detection and / or exposure of its contents by means of one or more exposure and / or detection devices as disclosed herein. As described above, the culture vessel according to the first aspect and as disclosed herein is configured to receive one or more such cell culture chamber devices.

[0078] In at least some embodiments, the light is natural light or artificial light or a combination thereof, typically or preferably visible light having a wavelength of about 400 to about 700 nanometers or at least a subrange thereof. Alternatively, the light may be, for example, infrared or near-infrared light having wavelengths of about 700 nanometers to about 1 millimeter or about 900 nanometers to about 2500 nanometers, respectively. As another alternative, the illumination or visualization signal is electromagnetic radiation of light with a wavelength different from visible light or, for example, infrared or X-ray signals. As a further alternative, the illumination or visualization signal is sound or acoustic wave signal, such as ultrasound. (Substantially) transparent and (substantially) translucent means that the end or wall (or its corresponding portion or window) is sufficiently (substantially) transparent and / or sufficiently (substantially) translucent with respect to the type of light or other illumination or visualization signal intended for use in the cell culture enclosure / cell culture chamber apparatus.

[0079] In some embodiments, the cell culture chamber apparatus (and surrounding portion) is configured (or at least adapted) for rotation about (at least one) predetermined axis of rotation, as is well known. In some further embodiments, the cell culture chamber apparatus (and surrounding portion) is configured for rotation of the rotary element, or for rotation that at least partially counteracts or complements the effects of gravity on the contents of the cell culture chamber apparatus or, more specifically, the contents of the surrounding portion. The cell culture chamber apparatus may, for example, include one or more attachment or connection elements for releasable attachment or connection to the drive unit, preferably but not necessarily.

[0080] In some embodiments, the first end or a portion thereof or window and the second end or a portion thereof or window are opposite to each other in a predetermined direction, for example along the center and / or longitudinal axis of the enclosure and / or cell culture chamber device, wherein the axis extends between the first end or a portion thereof or window and the second end or a portion thereof or window. In some further embodiments (where the cell culture chamber device is configured for rotation as described elsewhere), the central axis may also be an axis around which the cell culture chamber device rotates or at least is capable of rotating around it.

[0081] In at least some embodiments, the surrounding portion is located symmetrically within the cell culture chamber apparatus with respect to the axis of rotation / central axis.

[0082] In some embodiments, the material or group of materials of one or more predetermined portions (e.g., all portions) of the enclosure and / or cell culture chamber apparatus is opaque to UVC light (i.e., light with wavelengths ranging from about 100 to about 280 nanometers), wherein said one or more predetermined portions are configured such that no or substantially no UVC light can reach the interior of the enclosure. In this way, the entire cell culture chamber apparatus can be exposed to UVC light (utilizing the well-known sterilizing and disinfecting properties of UVC light) without adversely affecting the contents inside the enclosure of the cell culture chamber apparatus. In some further embodiments, the UVC opaque material or group of materials is or includes well-known UVC opaque plastics. See examples such as https: / / www.gsoptics.com / transmission-curves / and UVC absorbing plastics, particularly UVC opaque plastics such as polycarbonate, polystyrene, poly(methyl methacrylate) (PMMA - commonly known as acrylic resin or plexiglass), polyester (e.g., OKP4), or polyetherimide (e.g., Ultem) or UVC absorbing additives https: / / polymer-additives.specialchem.com / product-categories / additives-light-stabilizers-uv-absorbers (see https: / / polymer-additives.specialchem.com / product-categories / additives-light-stabilizers-uv-absorbers), including but not limited to. ADK STAB or

[0083] In some embodiments, the cell culture chamber apparatus further includes a circumferential gas exchanger.

[0084] - Circumferentially arranged around the enclosure or along at least a portion of the enclosure or around the central axis or longitudinal axis of the cell culture chamber apparatus (as disclosed herein, typically the central axis or longitudinal axis of the cell culture chamber apparatus and the central axis or longitudinal axis of the enclosure will coincide or at least be substantially parallel), and, for example or preferably, around a predetermined axis of rotation (if the cell culture chamber apparatus is configured to rotate), and

[0085] - Includes a cavity, the cavity comprising (or defining) a volume that connects the gas exchange interface of the surrounding portion to the ambient air or gas of the cell culture chamber apparatus.

[0086] A gas exchanger that is circumferential (and other related elements specified herein as circumferential, such as a circumferential humidifier) ​​means that the gas exchanger is arranged radially around at least a portion of the enclosure. For an enclosure having a circular cross-section substantially perpendicular to the central and / or longitudinal axis and a circumferential / radial surrounding gas exchanger, the cross-sections of both the circular cross-section and the gas exchanger (substantially perpendicular to the central and / or longitudinal axis) will create an inner circle (which is the surrounded portion of the enclosure) and an outer surrounding ring (which is the gas exchanger). See, for example, Figure 10, for an example according to the illustrated embodiment. In this way, the gas exchanger is arranged longitudinally offset from the center (but generally still around the central and / or axis of rotation) and away from the central and / or longitudinal axis (generally extending between the first and second ends and substantially parallel to the axis of rotation), i.e., the gas exchanger is not "stacked" longitudinally next to the enclosure or any other component, but is positioned radially around or around the outside of the enclosure. Since the gas exchanger no longer blocks light or illumination or visualization signals from one or more light or illumination or visualization signal sources located at or near the second end, this enables more efficient backlighting or other illumination or visualization via another type of illumination or visualization signal. Furthermore, the gas exchanger will block light or illumination or visualization signals from one or more light or illumination or visualization signal sources located at or near at least one connecting wall (e.g., towards the second end) to at least a lesser extent.

[0087] Furthermore, the longitudinal extent of the cell culture chamber device is greatly reduced by having a circumferential gas exchanger, thereby reducing the longitudinal footprint / shape factor, which is beneficial for design considerations and shortens the path of light or other lighting or visualization signals.

[0088] It should be noted that providing such a circumferential gas exchanger is particularly effective for incubators according to the first aspect (because it is off-center, thus blocking light or other illumination or visualization signals to at least a lesser extent).

[0089] In some embodiments, the gas exchange interface is or includes a circumferential gas permeation membrane, such as a semipermeable membrane, which may be porous or non-porous, configured to exchange gases, such as oxygen and carbon dioxide, with the interior and / or contents of the enclosure, wherein the circumferential gas permeation membrane is arranged circumferentially along the circumferential portion of the enclosure.

[0090] In some embodiments, the circumferential gas permeation membrane constitutes at least a portion, or preferably all, of at least one of the connecting walls of the enclosure. Thus, the first and second ends, together with the gas permeation membrane, at least partially define the enclosure. It should be noted that the circumferential gas permeation membrane does not need to occupy the entire circumference.

[0091] In some embodiments, the gas exchange interface or circumferential gas permeation membrane is supported by at least one support structure, such as a grid-like support structure, which includes a plurality of openings configured to connect the gas exchange interface or circumferential gas permeation membrane to the volume of air or gas in the cavity of the circumferential gas exchanger.

[0092] In some embodiments, the circumferential gas exchanger is connected to the ambient air or gas of the cell culture chamber apparatus via at least one gas or air inlet and / or outlet.

[0093] In some embodiments, at least one of the at least one gas or air inlet and / or outlet is a dual vent or port configured, for example or preferably, in response to rotation of the cell culture chamber apparatus, to simultaneously draw in ambient air or gas into the cavity of a circumferential gas exchanger and to expel air or gas from the cavity of the circumferential gas exchanger, thereby generating an airflow. The dual vents or ports may, for example, be configured to operate according to the Coanda effect or principle. In at least some such embodiments, the mirror-but symmetrical vents or ports constituting the dual vents or ports enable the intake and exhaust of air or gas (with only reversed airflow) during both clockwise and counterclockwise rotation of the cell culture chamber apparatus, resulting in equal rates of gas exchange when rotating in either direction (at the same speed). In some further embodiments, the degree of air movement or flow can be adjusted by adjusting the corresponding size of the vents of the dual vents, for example by using a slider (e.g., adjustable between 0% and approximately 100% of the maximum airflow) or plugs of different sizes (e.g., plugs for 1 / 3, 2 / 3, 3 / 3 of the maximum airflow), or in another suitable manner.

[0094] In some embodiments, the cell culture chamber apparatus further includes a circumferential humidifier.

[0095] - Arranged circumferentially around at least a portion of the enclosure or around the center and / or longitudinal axis of the cell culture chamber apparatus, for example or preferably around a predetermined axis of rotation (if the cell culture chamber apparatus is configured to rotate), and

[0096] - Includes or is connected to one or more liquid or humidifying reservoirs or elements, said liquid or humidifying reservoirs or elements being configured to humidify or wet air or gas in at least a portion of the cavity or airflow of a circumferential gas exchanger.

[0097] It should be noted that this circumferential humidifier setting is particularly effective for incubators according to the first aspect (because it is off-center, thus blocking light or other illumination or visualization signals to at least less extent).

[0098] In some embodiments, one or more liquid or humidifying reservoirs or elements are configured to humidify or moisten air or gas near or adjacent to at least a portion of a gas exchange interface or circumferential gas permeation membrane, said portion being outside the enclosure.

[0099] In some embodiments, at least one of one or more liquid or humidifying reservoirs or elements comprises a liquid that is a sterile aqueous solution (or at least an initially sterile aqueous solution) or an aqueous solution containing one or more additives, said additives being other compounds configured to maintain sterility and / or extend shelf life and / or perform a predetermined function or purpose, such as colored dyes, to aid in visualizing the remaining water content of the surrounding contents. It should be noted that sterile aqueous solutions typically and eventually become non-sterile during use.

[0100] In some embodiments, at least one of one or more liquid or humidifying reservoirs or elements comprises water or a solute-containing material, such as a gel, sponge, or particulate material (e.g., water droplets or aqueous beads, slush powder, or hydrogel powder (also referred to as "snow"), etc.). Water droplets or aqueous beads are sometimes also referred to as water-crystallizing gels, hydrated hydrogels, or gel beads, and are any gel that absorbs and contains a relatively large amount of water. They are typically spherical and may be composed, for example, of a water-absorbing superabsorbent polymer (SAP, also referred to as slush powder in its dry form), such as polyacrylamide, for example sodium polyacrylate.

[0101] In some embodiments, the material or group of materials of one or more predetermined components of one or more liquid or humidifying reservoirs or elements and / or cell culture chamber devices is configured to allow UVC light transmission to purify the contents of one or more liquid or humidifying reservoirs or elements.

[0102] In some embodiments, the cell culture chamber apparatus includes a first or central housing (also referred to as a panel or the like in some embodiments) and a cover, wherein the first or central housing includes a second end, the cover includes a first end, and wherein the first or central housing is configured, for example, to releasably receive the cover, wherein a cavity is defined between the first or central housing and the cover when the cover is received by the first or central housing, and wherein the cavity (resulting in) the cavity (between the first or central housing and the cover) defines at least a portion of the enclosure. Thus, the enclosure is provided in a particularly advantageous manner (at least partially).

[0103] In some embodiments, the cavity between the first or central housing and the cover includes a circumferential gas permeable membrane that forms at least a portion of at least one connecting wall of the enclosure, thereby connecting the first end of the cover and the second end of the first or central housing.

[0104] In some embodiments, the cell culture chamber apparatus further includes a main housing configured to receive a first or central housing and a cover. In some further embodiments, the main housing includes an opening aligned with a second end of the first or central housing when the first or central housing is received by or within the main housing, wherein the size of the opening is substantially the same as the size of the second end. Therefore, the main housing (in the case of a given opening) does not obstruct the view of the second end. In some further embodiments, the main housing and the first or central housing comprise tightly fitted elements, thus eliminating the need for sealing materials such as adhesives, welds, compressible components (e.g., O-rings), etc.

[0105] In some embodiments, when received by the main housing, the main housing and the first or central housing define a cavity for a circumferential gas exchanger (if the circumferential gas exchanger is present), and the first or central housing includes dual vents or ports arranged substantially perpendicular to a predetermined axis of rotation, for example, on the front side or forward-facing side of the main housing.

[0106] In some embodiments, the first or central housing includes at least one (e.g., grid-like) support structure that includes a plurality of openings.

[0107] In some embodiments, the second end or a portion thereof or the window is substantially transparent (rather than substantially translucent), and the cell culture chamber apparatus further includes or is connected to a light diffuser (also referred to as a light diffuser), which is configured to receive light and provide substantially uniform light to the second end or a portion thereof or the window, thereby providing substantially uniform illumination of the cell culture medium when it is contained within the enclosure. The light diffuser is located in the light propagation path between the light sources (natural and / or artificial) and before the enclosure / second end or a portion thereof or the window. Such substantially uniform illumination of the cell culture medium readily enables (further) enhanced visual (manual or automatic) monitoring for visual evaluation of the contents of the enclosure.

[0108] In an alternative embodiment, where the second end or a portion thereof or window is substantially translucent (rather than substantially transparent), the translucent end or portion thereof or window will effectively serve as a light diffuser, thus eliminating the need for such an additional component. In another alternative embodiment, where the second end or a portion thereof or window is substantially translucent (rather than substantially transparent), the light diffuser still exists, thus effectively providing a dual diffuser (one through the translucent end or a portion thereof or window, and one through the light diffuser), which can produce even more uniform light distribution (at the expense of some, but typically not most, of the light energy).

[0109] In yet another alternative embodiment, the diffuser is not a light diffuser, but a diffuser relative to other types of lighting or visual signals, such as an acoustic diffuser or a diffuser for electromagnetic radiation other than light.

[0110] In some alternative embodiments, the cell culture chamber apparatus is configured for frontal illumination (or other frontal application of illumination or visualization signals) as an addition or alternative to backlighting or emitting other illumination or visualization signals from the rear. In some such further alternative embodiments, the diffuser (if present) may be replaced by a suitable reflector (e.g., a parabolic reflector).

[0111] In some alternative embodiments, the cell culture chamber apparatus is configured for side lighting (or other types of lighting or visualization signals applied from other sides) as an addition or alternative to back lighting or front lighting or other illumination or visualization signals emitted from the rear or "side".

[0112] In some embodiments, the respective cross-sections of the first end and / or the second end (each substantially perpendicular to the central axis extending between the first end and the second end) are substantially circular.

[0113] The overall shape of the cell culture chamber apparatus is preferably such that it is well adapted to rotate about at least one axis. That is, it should preferably avoid sharp corners (cross-sections perpendicular to the axis of rotation), as these may introduce unwanted / irregular / excessive shear forces, unwanted changes in the growth environment, etc., into the growing cells or tissues during rotation, which may be detrimental to, for example, the optimal and / or uniform formation of spheroids.

[0114] In some further embodiments, the overall shape of the cell culture chamber apparatus is (substantially) cylindrical, wherein the first and second ends respectively form circular bases of a cylinder.

[0115] This provides a simple and suitable shape, making it easy to manufacture a simple / simpler cell culture chamber device. Furthermore, this generally cylindrical shape is also well-suited for rotation about an axis, such as a (longitudinal) central axis extending between its first end (or a portion or window thereof) and second end (or a portion or window thereof).

[0116] In an alternative embodiment, the overall shape of the cell culture chamber device is (substantially) spherical.

[0117] Alternatively, the cross-sections of the first and / or second ends are not circular, but rather the cross-sections (or one of them) can be, for example, an n-order polygon, where n is equal to or greater than 3, preferably equal to or greater than at least 6 (i.e., hexagonal), for example equal to or greater than 8 (i.e., octagonal) or more. Preferably, n is an even number, as this promotes symmetry of the cell culture chamber apparatus about a central axis or axis of rotation extending between the ends (the central axis may coincide with the axis of rotation). As n increases, the cross-section approaches a circular shape.

[0118] The cross-section of the first end and / or the second end may also be elliptical.

[0119] Cell culture chamber apparatus may have a first extent (e.g., length) and at least a second extent (e.g., height, depth, or diameter) (see example). Figure 8 (The "L" and "D" in the original text). In some embodiments, the first extent / length (L) is smaller than the second extent / height, depth, or diameter (D), i.e., the circumferential extent is larger than the longitudinal extent (for generally cylindrical shapes and similar shapes). In some embodiments, the ratio between the first extent / L and the second extent / D is approximately 1:1 to approximately 1:10. In some further embodiments, this ratio is approximately 1:2 to approximately 1:5, and in other further embodiments, this ratio is approximately 1:3 to approximately 1:4. These embodiments respectively provide very (longitudinally) compact cell culture chambers. The circumferential design of the gas exchanger and / or humidifier greatly enables a higher ratio, thereby achieving a smaller (longitudinally) shape factor.

[0120] The cross-sections (and / or shapes) of the first and second ends may be different from each other.

[0121] In principle, cell culture chamber devices can have any suitable regular or irregular shape (while supporting rotation as described herein), but a relatively simple shape is preferred for manufacturing purposes.

[0122] In some embodiments, the enclosure and / or cell culture chamber apparatus further includes one or more reference and / or identification markers, such as identification markers, barcodes, reference points, etc. At least some of the reference and / or identification markers are preferably machine-readable. This can, for example, be advantageously used with at least one display and / or detection device as disclosed herein (see, for example...). Figure 1 , 2 It is used in conjunction with monitoring, for example, imaging or vision systems or devices (e.g., 220 in 5). The reference marker enables the determination of the orientation of a cell culture chamber apparatus (e.g., particularly the enclosure) used with at least one of the display and / or detection devices disclosed herein. Preferably, the identification marker is unique for the specific cell culture chamber apparatus containing it.

[0123] In some embodiments, the cell culture chamber apparatus further includes one or more alignment elements (e.g., positioning rods and slits or slots, etc.) for aligning different components of the cell culture chamber (e.g., aligning the cover with the first or central housing or main housing in a relevant embodiment).

[0124] In some further embodiments, the alignment element may also be used as a reference mark.

[0125] In some embodiments, at least one of the second end and / or at least one connecting wall includes one or more integrated light sources.

[0126] In some embodiments, at least one of the second end and / or at least one connecting wall is or includes a fluorescent emitting element.

[0127] In some embodiments, the cell culture chamber apparatus includes a closable and / or sealable first port connected to the interior of the enclosure and a closable and / or sealable second port connected to the interior of the enclosure. In some further embodiments, the first and second ports are arranged on or to separate sides of the cell culture chamber apparatus.

[0128] According to the second aspect, a culture system is provided, including...

[0129] - A first culture device, such as or preferably a culture device according to the first aspect and its embodiments.

[0130] - At least one second culturer, such as or preferably a culturer according to the first aspect and its embodiments, and

[0131] - User interface device and / or client and / or server computer or device and / or at least one other external computing device.

[0132] in,

[0133] - The first culture unit is configured as a master device unit, and the at least one second culture unit is configured as a slave device unit.

[0134] - The master device unit is configured to control communication and / or data exchange between the master device unit and all slave device units and user interface devices and / or client computers or devices.

[0135] - The user interface device and / or client computer or equipment are configured to acquire user input control data and transmit the user input control data to the master device unit, and

[0136] - The master device unit is configured to change or adjust operation in response to at least a portion of the received user input control data, and / or transmit at least a portion of the received user input control data to at least one slave device unit, which is configured to change or adjust operation in response to at least a portion of the received user input control data.

[0137] In some embodiments, one or more of the culturers include at least one display and / or detection device as disclosed herein, and are configured to display and / or detect the lighting or visualization signal after the lighting or visualization signal has passed through, reflected or propagated through at least a portion of the enclosure of at least one of the predetermined number of cell culture chamber devices when the predetermined number of cell culture chamber devices are received by the respective culturer.

[0138] The illumination or visualization signal may be, for example, a visible light signal, and the display and / or detection device may be, for example, a camera configured to provide video feed or video capture of the contents of the enclosure of any included cell culture chamber apparatus, such as periodic still images. Alternatively, the illumination or visualization signal may be a different signal, such as those disclosed herein.

[0139] The user interface device may be configured, for example, for online monitoring of any of the first and / or at least one second culture chamber. In some embodiments, the user interface device is configured to display, in the user interface, or on a screen, an online video feed or the latest single or series of images of one or more of each culture chamber obtained by the culture chamber via its respective camera (if including those disclosed herein). Additional data for each particular cell culture chamber device, such as current rotation speed, rotation direction, ID, etc., may also be obtained and transmitted to the user interface device, for example, displayed on the device along with the video or images of the corresponding cell culture chamber device. In addition to cell culture chamber device-specific data, data for each culture chamber may also be obtained and provided, such as one or more of the following for each culture chamber of the humidifier: current temperature, current pH, current humidity, current CO2, O2 and / or N2 levels, etc., as obtainable by multiple suitable sensors appropriately located in the humidifier. If one or more parameters are outside the acceptable range, above or below an acceptable value, etc. (e.g., if the measured current temperature exceeds a given temperature threshold or value, etc.), the humidifier may also send a warning or alarm, for example, to the user interface device (or another connected external computing device).

[0140] Online feeds or images can easily enable manual inspection of the condition of the contained spheres, such as their size and orbit, which may prompt the user to make changes, such as increasing the rotation speed, if, for example, the spheres have become larger and therefore heavier (suggesting an increase in rotation speed). The ID of a specific cell culture chamber apparatus can be automatically obtained, for example, by capturing images or videos of one or more benchmarks and / or identification markers or codes and performing appropriate image analysis or other digital processing. Similarly, the presence of air bubbles and / or the actual volume of cell culture medium contained in a specific enclosure of the cell culture chamber apparatus can also be obtained and presented by capturing images or videos of multiple suitable level or fill rate indicators.

[0141] In some embodiments, the culture unit and / or user interface device are also configured to perform data logging and / or documentation, for example, for at least some, if not all, of the cell culture chamber device, to collect and store data such as temperature, humidity levels, rotation speed, timeouts, and, for example, average values, as well as the duration and number of pauses (no rotation). This may be supplemented, for example, with video and / or still images. The data from the data logging or documentation may be stored, for example, in a cloud computing environment.

[0142] Additionally or alternatively, the above-described functionality may be provided for other types of lighting or visual signals, such as those disclosed herein, in addition to video and images.

[0143] This document discloses additional embodiments of such a culture system, such as in conjunction with the first aspect and / or Figure 16 .

[0144] According to a third aspect, a culture apparatus is provided, configured to receive a predetermined number of at least one or more cell culture chamber devices, each cell culture chamber device including a surrounding portion configured to contain cell culture medium, the culture apparatus comprising...

[0145] - A housing comprising a culture chamber configured to receive at least a corresponding portion of the cell culture chamber apparatus (100) when the cell culture chamber apparatus is received by a culture vessel, and

[0146] -UVC arrangement, configured to directly expose the interior of the culture chamber with UVC light.

[0147] Positioning the UVC light inside the culture chamber, thereby directly exposing the interior of the culture chamber with UVC light, works particularly well for culture chambers with a generally cylindrical cross-section (substantially perpendicular to the first or longitudinal direction, which is usually horizontal) without sharp corners or edges (as is typically the case with a square culture chamber), such as culture chambers designed in shapes as described above and elsewhere (bowl-shaped, hemispherical, etc.).

[0148] In some embodiments, the UVC arrangement includes one or more UVC lamps arranged inside the culture chamber.

[0149] In some embodiments, the UVC lamp is a rotating UVC lamp configured to rotate within the culture chamber about a predetermined axis (e.g., about a first or longitudinal direction or an axis parallel to it, which would typically be horizontal) to sweep across the interior of the culture chamber and enhance the effect of the UVC light (especially when combined with culture chambers designed in the shape of such as described above and elsewhere (bowl-shaped, hemispherical, etc.)).

[0150] In some further embodiments, the rotating UVC lamp is integrated with a rotating fan or ventilation unit.

[0151] In some embodiments, the UVC lamp is asymmetrical, that is, it emits UVC light in (at least) two different directions (e.g., opposite directions), which works particularly well with rotation.

[0152] In some embodiments, the UVC lamp is positioned approximately centrally within the culture chamber (e.g., located at or towards the bottom or end wall of the culture chamber).

[0153] In some embodiments, at least a portion of the inner surface of the culture chamber (e.g., at least a portion of at least one culture chamber wall and / or the first or inner side or surface of a door, cover, etc., if present) comprises a UVC reflective material or coating.

[0154] The aspects and embodiments of the UVC lamps in the third aspect are identical or correspond to, at least in some embodiments, the UVC lamps and their embodiments described herein in conjunction with the first aspect (having the same or corresponding advantages for the same reasons).

[0155] According to a fourth aspect, a culture vessel (200, 200') is provided, configured to receive a predetermined number of at least one or more cell culture chamber devices (100), each cell culture chamber device (100) including an enclosure (110) configured to contain cell culture medium, the culture vessel (200, 200') including a housing (210) comprising a culture chamber (201) configured to contain at least a corresponding portion of the cell culture chamber device (100) when the cell culture chamber device is received by the culture vessel (200, 200'), wherein the culture chamber (201) includes a circular cross-section substantially perpendicular to a first or longitudinal direction (e.g., a horizontal direction).

[0156] In some embodiments, the culture chamber (201) is preferably generally "bowl" or "plate" shaped or generally hemispherical or semi-elliptical, for example having a cylindrical section (with a circular cross-section), so that the culture chamber has no sharp corners or edges, thereby facilitating easy and efficient cleaning of the culture chamber.

[0157] The aspects and embodiments of the fourth aspect of the culture chamber are identical or correspond to, at least in some embodiments, the culture chambers and their embodiments described herein in conjunction with the first aspect (having the same or corresponding advantages for the same reasons).

[0158] According to a fifth aspect, a culture apparatus is provided, configured to receive a predetermined number of at least one or more cell culture chamber devices, each cell culture chamber device including a surrounding portion configured to contain cell culture medium, the culture apparatus comprising...

[0159] - A housing comprising a culture chamber configured to include at least a corresponding portion of the cell culture chamber apparatus when received by a culture vessel, and

[0160] - At least one rotary drive unit, each rotary drive unit

[0161] 〇 is configured, for example or preferably releasably receive at least one of the cell culture chamber devices, and

[0162] The cell culture chamber device received by the rotation drive unit is configured to rotate about a predetermined rotation axis of the received cell culture chamber device, such as a predetermined central axis of the received cell culture chamber device or the surrounding portion of the received cell culture chamber device.

[0163] The corresponding motor components of the at least one rotary drive unit are located outside the culture chamber and inside the shell.

[0164] This facilitates the removal of typical heat-generating components from the drive unit from the culture chamber, making the ambient temperature of the culture chamber easier to control and maintain. It also reduces the risk of unexpected temperature increases / "surges" within the culture chamber, which could be harmful to the contents of the cell culture apparatus located within it. Another significant advantage is that keeping the culture chamber clean is thus made easier, which is crucial for preventing unwanted contamination of the received cell culture apparatus by viruses, various types of microorganisms, etc. Furthermore, the culture vessel typically consumes less energy because there is no need to actively remove the generated heat from the culture chamber. Heat generated within the shell can, for example, be passively removed.

[0165] The aspects and embodiments of the rotary drive unit in the fifth aspect are, at least in some embodiments, the same or corresponding to the rotary drive unit and its embodiments described herein in conjunction with the first aspect (having the same or corresponding advantages for the same reasons).

[0166] According to a sixth aspect, a culture apparatus is provided, configured to receive a predetermined number of at least one or more cell culture chamber devices, each cell culture chamber device including an enclosure configured to contain cell culture medium, the culture apparatus comprising...

[0167] - A housing comprising a culture chamber configured to include at least a corresponding portion of the cell culture chamber apparatus when received by a culture vessel, and

[0168] - For example, a rotary fan or ventilation unit is arranged in the culture chamber and configured to induce airflow inside the culture chamber in response to a control signal.

[0169] The aspects and embodiments of the fan or ventilation unit in the sixth aspect are, at least in some embodiments, the same or corresponding to the fan or ventilation unit and its embodiments described herein in conjunction with the first aspect (having the same or corresponding advantages for the same reasons).

[0170] The cell culture chamber apparatus of the third, fourth, fifth and sixth aspects may correspond to the cell culture chamber apparatus and its embodiments as disclosed herein, according to the first aspect and / or.

[0171] Further details and embodiments are disclosed below.

[0172] definition

[0173] All headings and subheadings used herein are for convenience only and should not in any way constitute a limitation of the invention.

[0174] The term “cell culture” herein refers to the maintenance of the viability of any kind of cells, cell colonies, tissue-like structures, tissue biopsies, spheroids, organoids or similar samples obtained or initially cultured by any method known in the art.

[0175] The term “cell” as used in this article means primary, immortal, or stem cell (including pluripotent or induced pluripotent) or genetically modified cells derived from any type of living organism (whether archaea, prokaryotes, or eukaryotes), and also includes viruses or other entities that require living cells for replication.

[0176] The use of any and all examples or exemplary language provided herein is merely for the purpose of better illustrating the invention and not for limiting the scope of the invention, unless otherwise stated. No language in the specification should be construed as indicating that any unclaimed element is essential to the practice of the invention.

[0177] This invention includes all modifications and equivalents of the subject matter described in the appended claims as permitted by applicable law. Attached Figure Description

[0178] Figure 1 A perspective view schematically illustrating an exemplary embodiment of the culturer disclosed herein is shown;

[0179] Figure 2 schematically shown Figure 1 A perspective view of the culture vessel, with cuts and enlarged views;

[0180] Figure 3A and 3B A side view and a cross-sectional side view of an exemplary embodiment of the rotary drive unit of the cell culture chamber receiving apparatus are schematically shown, both of which are disclosed herein;

[0181] Figure 4A A cross-sectional side view schematically illustrates an exemplary embodiment of a rotary drive unit fixed in the culture chamber wall of a culturer as disclosed herein, according to some embodiments, wherein the rotary drive unit includes at least one lamp or illumination element;

[0182] Figure 4B A cross-sectional side view schematically illustrates another exemplary embodiment of a rotary drive unit fixed in the culture chamber wall of a culturer as disclosed herein, according to other embodiments, wherein the rotary drive unit includes at least one lamp or lighting element;

[0183] Figure 5 The cell culture chamber apparatus of the culturer disclosed herein is schematically shown, as well as lamps or other lighting or visualization signal sources and imaging, vision or other display or detection units;

[0184] Figures 6A-6C Different views of the culture chamber wall, rotating fan, and rotating UVC light source are schematically shown;

[0185] Figures 7A-7C The diagram illustrates different views of the culture chamber wall and heating element;

[0186] Figure 8 A side view schematically illustrates an exemplary embodiment of the cell culture chamber apparatus disclosed herein;

[0187] Figures 9A-9C They are shown schematically respectively. Figure 8 An end view of an exemplary embodiment of a cell culture chamber apparatus;

[0188] Figure 10 schematically shows a front view and a cross-sectional side view of an embodiment of a cell culture chamber apparatus according to some embodiments, and as disclosed herein, the cell culture chamber apparatus includes a circumferential gas exchanger and a circumferential humidifier;

[0189] Figure 11A-11EA front view, a first (“right”) side view, a first cross-sectional view (AA), a second cross-sectional view (CC), and a third cross-sectional view (BB) of an exemplary embodiment of the cell culture chamber apparatus disclosed herein are shown schematically, respectively.

[0190] Figure 12 schematically shown Figure 11A-11E An exploded perspective view of an exemplary embodiment of a cell culture chamber apparatus;

[0191] Figure 13 A perspective view of the main housing of the cell culture chamber apparatus disclosed herein is shown schematically;

[0192] Figure 14A and 14B Two perspective views of the central housing of the cell culture chamber apparatus disclosed herein are shown schematically;

[0193] Figure 15 A perspective view schematically illustrating the cover of the cell culture chamber apparatus disclosed herein; and

[0194] Figure 16 The communication between multiple incubators and user interface devices is illustrated schematically. Detailed Implementation

[0195] Various aspects and embodiments of culturers and culturer systems configured to receive one or more cell culture chamber devices will now be described with reference to the accompanying drawings, all of which are disclosed herein.

[0196] The accompanying drawings are schematic representations, and therefore the construction of different structures and their relative dimensions are for illustrative purposes only.

[0197] Some different components are disclosed only with respect to a single embodiment of the invention, but are meant to be included in other embodiments without further explanation.

[0198] Figure 1 A perspective view schematically illustrating an exemplary embodiment of the culturer disclosed herein is shown.

[0199] An embodiment of a culture vessel 200 is shown, configured to receive a predetermined number of cell culture chamber devices (also referred to herein as bioreactors) 100. For example, the illustrated embodiment is configured to receive six individual and independent cell culture chamber devices, but other embodiments may be configured to receive different numbers of cell culture chamber devices. Each cell culture chamber device 100 to be received includes an enclosure (also referred to herein as a cell chamber) (see example...). Figure 3B , 5(110 in 8, 10, 11, etc.), the surrounding portion is configured to contain cell culture medium. Depending on the purpose and / or embodiment of the culture vessel 200, the specific type, design, etc., of the cell culture chamber apparatus 100 may vary. Various embodiments of the culture vessel can be adapted to receive various embodiments of the cell culture chamber apparatus. However, advantageous embodiments of the cell culture chamber apparatus, for example, combine... Figure 8-15 The description and explanation are provided and disclosed herein. A single culture vessel 200 can, for example, be configured to receive cell culture chamber devices of different types or designs.

[0200] The illustrated culture vessel 200 includes a housing 210, such as a main housing, which includes (or at least partially defines) a culture chamber 201 configured such that the culture chamber 201 contains the cell culture chamber device 100 when it is received by the culture vessel 200, i.e., when the cell culture chamber device 100 is properly placed in the culture vessel 200 for use. The illustrated culture vessel 200 is configured to completely receive the cell culture chamber device 100 within the culture chamber 201; however, other embodiments of the culture vessel may be configured to receive only a portion of the cell culture chamber device 100 within the culture chamber 201 (thus, for example, another portion / remaining portion is arranged in another portion of the housing 201). The culture vessel 200 is configured to releasably receive the cell culture chamber device 100. Note that even if the culture vessel is configured to receive a predetermined number of cell culture chamber devices, here six, the culture vessel may also receive a smaller number of cell culture chamber devices and operate using only those.

[0201] The culture vessel 200 also includes a predetermined number (one or more) of rotation drive units (see, for example, 300 in Figures 3 and 4), which are configured to rotate about a corresponding predetermined axis of rotation of the respective cell culture chamber apparatus 100 (see, for example...). Figure 5 and Figure 8 (260) Rotate the corresponding received cell culture chamber device 100. The rotation drive unit can be configured to rotate each received cell culture chamber device 100 about one, two, or three corresponding axes. In some embodiments, the culture vessel 200 includes one rotation drive unit for each cell culture chamber device 100 that the culture vessel 200 can receive. In at least some embodiments, the rotation drive unit is a rotator drive unit. In some embodiments, backlighting of the surrounding portion of the received cell culture chamber device 100 is also provided by certain embodiments of the drive unit, which will be further explained in conjunction with Figures 4 and 5.

[0202] In some embodiments, the corresponding motor components of the rotary drive unit are located outside the culture chamber 201 and inside the housing 210 or elsewhere. This easily removes typical heat-generating components of the drive unit from the culture chamber 201, making the ambient temperature of the culture chamber 201 easier to control and maintain, and also reducing the risk of unexpected temperature increases / "surges" in the culture chamber 201, which could be harmful to the spherical structures of the cell culture chamber apparatus 100 located in the chamber 201. Furthermore, the absence of a motor / motor component within the culture chamber 201 makes it easier to keep the culture chamber 201 clean. Exemplary embodiments of the rotary drive unit are further shown and explained, for example, in conjunction with Figures 3 and 4, and are disclosed herein.

[0203] In the illustrated embodiment, the incubator 200 includes an openable and closable door, cover, etc. 211, thereby providing a user with access to the incubation chamber 201. The door, cover, etc. 211 (when closed) together with at least one (shown as a single) incubation chamber wall 202 of the incubation chamber 201 (at least partially) defines the incubation chamber 201.

[0204] In at least some embodiments (and as shown), the culture chamber 200 also includes one or more locking, latching, or fastening elements 213, 213' configured to reliably keep the door or cover 211 closed and further enable a tight seal of the culture chamber 201. In some further embodiments, elements 213, 213' are of the type that provide so-called push-to-open and push-to-close locking functionality, allowing the user to open and close the chamber without hands, thereby reducing the risk of contaminating the culture chamber 201. Alternatively, elements 213, 213' are of another type, such as touchless, remotely operated, etc.

[0205] The culture chamber 201 has a relatively large access opening, which makes it easy and convenient for users to remove and insert the corresponding cell culture chamber device 100.

[0206] The culture chamber wall 202 is preferably generally arc-shaped, that is, generally cylindrical in the predetermined first / longitudinal direction (e.g., Figure 2 As shown), there are no sharp corners or edges, which facilitates easy and efficient cleaning of the culture chamber 201, which is important for keeping the culture chamber 201 in a clean environment.

[0207] According to the first aspect, the culture vessel 200 further includes at least one display and / or detection device (see, for example...). Figure 2 and 5 220 in the example is configured to display and / or detect the illumination or visualization signal after it has passed through, reflected, or propagated through at least a portion of the respective enclosure of one or more of the received cell culture chamber apparatus 100 (see example 220). Figure 5(referring to 703 in the original text). In some embodiments, at least one displaying and / or detecting device is an imaging or vision system or device, such as a camera, configured to display and / or detect electromagnetic radiation, such as one or more of ultraviolet, visible, infrared, and near-infrared light. In some embodiments, the imaging or vision system or device is a more or less standard camera (e.g., a small one) configured to display (at least) visible light. Alternatively, at least one displaying and / or detecting device is configured to display and / or detect sound or sound waves (e.g., ultrasound) or electromagnetic radiation other than visible light (e.g., X-rays).

[0208] In at least some advantageous embodiments, at least one display and / or detection device is integrated with the culture vessel 200. In some further embodiments, as shown in the figure (see also...) Figure 2 In the culture chamber 200 (220), at least one display and / or detection device is integrated into the door or cover 211 of the culture chamber 200 and is arranged behind an appropriate number of windows or holes 223 facing the culture chamber 201.

[0209] Window 223 is superior to orifice in order to better seal culture chamber 201 and maintain its sterility.

[0210] In some embodiments, the culture vessel 200 includes only one or a few display and / or detection devices arranged such that, when located within the culture vessel 200, its field of view (FOV) readily captures the relevant portion of the cell culture chamber apparatus 100.

[0211] However, in other embodiments (as shown), for each cell culture chamber device 100 that can be received by the culturer 200, the culturer 200 includes a specific and separate display and / or detection device. In some further embodiments, each (or at least a plurality of) display and / or detection devices are arranged in a door or cover 211 such that they are aligned with a specific different cell culture chamber device 100 in a first or longitudinal direction, which will generally be a horizontal direction, i.e., the display and / or detection device is arranged one-to-one with the cell culture chamber device 100. In a particular embodiment, a specific display and / or detection device is aligned with a specific cell culture chamber device 100 such that the specific cell culture chamber device 100 (at least its relevant portion, typically at least a portion of its enclosure) is within the display or detection FOV of the specific display and / or detection device. In some embodiments, this may require arranging each display and / or detection device such that the central axis of the corresponding enclosure 110 of the received cell culture chamber device 100 (see, for example) Figure 5 and 8 260) is at least substantially aligned with the central axis of the display and / or detection field of view of the corresponding display and / or detection device.

[0212] In some embodiments (embodiments having multiple display and / or detection devices), the display and / or detection devices are arranged at equal intervals in the door or cover 211 of the incubator 200 in a generally circular pattern (e.g., as shown in the figure).

[0213] In some embodiments, the signal obtained by the display and / or detection device can be transmitted to other devices via a suitable network, such as in conjunction with... Figure 16 Further illustrated and explained, this allows, for example, online monitoring and data capture of the contents of each enclosing portion of the received cell culture chamber apparatus 100.

[0214] At least one display and / or detection device disclosed herein works particularly well with a cell culture chamber apparatus 100, each comprising an invisible (or at least detectable) enclosure, such as having a transparent end (at least partially transparent) (also referred to herein as a first end in some embodiments; see, for example, 111 elsewhere), which, if necessary, faces the appropriate display and / or detection device. For embodiments including backlighting or back illumination, at least one display and / or detection device disclosed herein also works particularly well with the cell culture chamber apparatus 100, which includes an enclosure having another end further / farthest from at least one display and / or detection device (generally opposite the aforementioned transparent end), which is transparent or at least translucent. Figure 4A and 4B Various embodiments are shown that easily provide backlighting or back illumination.

[0215] In some embodiments, the culture vessel 200 further includes one or more light sources 222 configured to illuminate at least a first end of a corresponding enclosing portion of the received cell culture chamber apparatus 100 (see, for example...). Figure 5 and 8 -111 in Figure 15) or a portion thereof or a window (see, for example, 113 in Figure 9). In some embodiments (as shown), one or more light sources 222 are arranged in a door or cover 211 facing the culture chamber 201 (and any cell culture chamber apparatus 100 received therefrom). In some further embodiments, the light source 222 is located behind a suitable window (also labeled 222) (preferably) or an opening (subpreferably) in the door or cover 211. In some embodiments, the number of light sources is the same as the number of cell culture chamber apparatus 100 that can be received, but can easily be different. The light sources may, for example, include one or more suitable LED lights.

[0216] In some embodiments, the cell culture chamber apparatus 100 is positioned (and thus, in at least some embodiments, the windows 223) at equal intervals in a substantially circular pattern. Alternatively, other arrangements may be used. If present, one or more light sources or their windows 222 may be positioned, for example, in a circular pattern between the windows 223.

[0217] In some embodiments, the first or inner surface 212 of the door or cover 211 is or includes a surface of glass, ceramic, or other similar easily cleanable material, thereby helping to maintain a sterile environment within the incubator 200, i.e., within the culture chamber 201. As described above, the first or inner surface or surface 212 of the door or cover 211 may include one or more windows 223 for display and / or detection devices, and / or may include one or more windows 222 for any additional light source. Window 223 may be, for example, substantially transparent, while window 222 may be, for example, substantially transparent or, for example, substantially translucent, for example, to diffuse the light from the light source.

[0218] In some embodiments, the culture vessel 200 further includes a fan or ventilation unit 230 disposed within the culture chamber 201 and configured to induce airflow within the culture chamber 201 in response to a control signal. In some embodiments (as shown), the fan or ventilation unit 230 is a rotary fan or ventilation unit 230. The presence of the fan or ventilation unit 230 in the culture chamber 201 (or the fan or ventilation unit disposed elsewhere in the housing 210 but still inducing airflow within the culture chamber 201) promotes a uniform environment within the culture chamber 201, which is generally beneficial for providing uniform humidity, uniform temperature, and other key control parameters that may be relevant to the use of the culture vessel 200. In some embodiments (as shown), the fan or ventilation unit 230 is located substantially centrally within the culture chamber 201, which also improves the efficiency of the fan or ventilation unit 230, particularly when combined with a circular culture chamber 201. For embodiments of the cell culture chamber apparatus 100 arranged in a substantially circular pattern within the culture chamber 201, it is easy to provide a central space for such a central fan or ventilation unit 230, thereby enabling a compact design. In some embodiments (as shown), the central fan or ventilation unit 230 is also located "behind" the cell culture chamber apparatus 100, i.e., between the bottom or wall 202 of the cell culture chamber apparatus 100 and the culture chamber 201 (see also Figure 6). It should be understood that a single central fan or ventilation unit 230 may be replaced by two or more, for example, smaller fans or ventilation units.

[0219] In some embodiments, the culture vessel 200 further includes means for exposing the culture chamber 201 to UVC light for purification. Using such means (at least if UVC is intended to be activated while any cell culture chamber apparatus 100 is still present in the culture chamber 201), it is generally necessary that the cell culture chamber apparatus 100, or at least their enclosures, include a UVC-opaque material or be shielded against UVC light to prevent the contents within the enclosures from being exposed to UVC light. In some embodiments, the arrangement is a UVC light source. Alternatively (it is not required that the cell culture chamber apparatus 100 and / or their (for cell culture) enclosures be UVC-shielded), the UVC lamp is activated only when there are no cell culture chamber apparatus 100s in the culture chamber 201, for example, as part of a UVC purification procedure or mode.

[0220] In some embodiments (as shown), a UVC light source or the like (see, for example, 232 in FIG. 6) is integrated with a rotating fan or ventilation unit 230, thereby providing a very compact and efficient design. Furthermore, the UVC lamp thus rotates together with the fan or ventilation unit 230, sweeping across the culture chamber 201 and enhancing the effect of the UVC light. In some embodiments, the UVC lamp is asymmetrical, i.e., emitting UVC light in (at least) two different, for example, opposite directions, which is particularly effective when combined with rotation. An embodiment of the integrated rotating fan or ventilation device and the asymmetrical UVC light source is illustrated and further explained with reference to FIG. 6.

[0221] Note that some embodiments include only a UVC arrangement, such as a rotating UVC lamp, but without a rotating fan or ventilation unit 230, or without a fan or ventilation unit 230 at all, or the fan or ventilation unit is in another design and / or location.

[0222] In some embodiments (embodiments with UVC purification), at least a portion of the inner surface of the culture chamber 201 (e.g., at least a portion of the culture chamber wall 202 and / or the first or inner side or surface 212 of the door or cover 211) includes a UVC reflective material or coating, thereby increasing the effect of UVC light.

[0223] In some embodiments, the housing 210 is stackable, in which case one culture vessel 200 disclosed herein can be reliably and stably stacked on top of another culture vessel disclosed herein. In some further embodiments, the housing 210 includes a foot, ridge, or similar element 205 located below or on a first side of the housing 210, and one or more cavities, openings, slits, etc. 206 (which mate with the foot, ridge, etc. 205) located on the top or second side of the housing 210. In this way, several culture vessels 200 can be compactly arranged while allowing the culture function of a cell culture chamber apparatus 100 to support a greater number of cells than a single culture vessel 200 can support. In some embodiments, the housing (and including a door or cover 211 when closed) is generally box-shaped. Therefore, multiple culture vessels 200 can be constructed / stacked in an array or the like.

[0224] Figure 2 schematically shown Figure 1 A perspective view of the culture vessel, with cuts and magnified views.

[0225] It shows Figure 1 The incubator 200, with its enlarged cutouts showing more clearly the display and / or detection device 220, here in the form of a camera unit fastened and electrically connected to another circuit in the PCB or embedded in the door or cover 211. Figure 2 An optional light source 222 is also shown for frontal illumination of at least one cell culture chamber apparatus 100, and more specifically, for the respective surrounding portions of at least one cell culture chamber apparatus 100 located in the culture chamber 201 of the culture vessel 200 (see, for example...). Figure 3B , 5 Frontal illumination of 110 (e.g., 8, 10, 11, etc.). As described above, in the specifically illustrated embodiment, the door or cover 211 includes a camera unit 220 for each cell culture chamber device 100, which can be received by the illustrated culture vessel 200, wherein when the door or cover 211 is closed, the camera unit 220 is aligned with the specific cell culture chamber device 100.

[0226] Figure 3A and 3B Side view and cross-sectional side view of an exemplary embodiment of the rotary drive unit of the cell culture chamber receiving device are schematically shown, both of which are disclosed herein.

[0227] exist Figure 3A and 3B An embodiment of a rotary drive unit 300 is shown, together with an embodiment of a cell culture chamber apparatus 100 received by the rotary drive unit 300 (hereinafter referred to herein as the drive unit), both of which are disclosed herein.

[0228] The culture device disclosed herein (see, for example) Figure 1 and Figure 2 At least some embodiments of (200) include a plurality of such drive units 300, with one drive unit 300 for each cell culture chamber device 100 to which the culture vessel is designed to receive.

[0229] In the embodiment specifically shown, the drive unit 300 includes an engagement member or portion 304 configured to releasably attach the cell culture chamber device 100 to the drive unit 300 via a corresponding releasable fastening element (e.g., snap-fit, friction fit, or similar element).

[0230] The fastening element may be suitable only for a specific type of cell culture chamber device 100, or alternatively suitable for multiple different types of cell culture chamber devices 100. The drive unit may also be able to attach to a series of different adapters, which in turn attach to different types of cell culture chamber devices 100.

[0231] The illustrated drive unit 300 is adapted to only a single cell culture chamber device 100, but in alternative embodiments, the drive unit 300 may be adapted to, for example, two (i.e., dual drive units), three or other numbers of cell culture chamber devices 100.

[0232] In at least some embodiments, the drive unit 300 is configured for rotation of the rotary device, or for rotation that at least partially counteracts or complements the effects of gravity on the contents of the cell culture chamber apparatus, or more specifically on the contents of the enclosure of the attached cell culture chamber apparatus 100. In at least some embodiments, the drive unit 300 is capable of rotating clockwise and counterclockwise.

[0233] The specific embodiment shown includes a motor component comprising a motor 301 with a rotating connecting shaft or similar 305, which in turn is connected to a coupling member or portion 304. A smaller / narrower section 302, i.e., having a reduced diameter, is also shown, which will be fitted into the culture chamber wall, etc. (see, for example...) Figure 1 In the openings (see, for example, 240 in Figure 7) of 202 in 4, 6 and 7, thus forming the “rear” or “end” wall of the culture chamber (see, for example) Figure 1 (e.g., 201 in 4, etc.). This allows the motor / motor component 301 to be positioned outside the culture chamber (and typically inside another part of the culture vessel housing), thereby removing the variable heat source from the culture chamber.

[0234] In alternative embodiments, another type of drive (different from rotary motors and shafts or the like) may be used, such as a magnetic rotary drive or another type.

[0235] from Figure 3B As can be seen, the drive unit 300 includes a hollow conical or horn-shaped portion that defines a cavity 303 and connects a smaller area 302 to a connecting member or portion 304.

[0236] Figure 4A A cross-sectional side view schematically illustrates an exemplary embodiment of a rotary drive unit secured in the culture chamber wall of a culturer as disclosed herein, according to some embodiments, wherein the rotary drive unit includes at least one lamp or illumination element.

[0237] A drive unit 300 is shown, which more or less corresponds to the drive unit in FIG. 3, and as otherwise disclosed herein, the drive unit 300 includes a motor 301 that rotates a connecting shaft or similar 305, which is in turn fastened to a coupling member or portion 304, thereby rotating the coupling member or portion 304 (together with the attached cell culture chamber apparatus). Further shown is a portion of a culture chamber wall 202 defining a culture chamber 201 (e.g., together with a door or lid or otherwise). The culture chamber wall 202 includes an opening (see, for example, 240 in FIG. 7) that receives (in the assembled state of the drive unit 300) a portion of the drive unit 300 (e.g., a smaller / narrower section, see, for example, 302 in FIG. 3).

[0238] Therefore, the drive unit 300 has a connecting part or portion 304 in the culture chamber 201, and its motor part / motor 301 is outside the culture chamber 201. The drive unit 300 can be assembled, for example, with parts from different sides of the opening.

[0239] As described above, the drive unit includes a cavity 303. According to some embodiments and as shown, the drive unit 300 also includes at least one light source 701 (or alternatively, other light or illumination elements) such that light is emitted within the cavity 303 of the drive unit 300, for example or preferably in a direction toward the enclosure or cell culture chamber apparatus. Thus, “backlighting” illumination is provided to “backlight” the received cell culture chamber apparatus (see, for example, 100 elsewhere), or more specifically, to “backlight” the enclosure of the received cell culture chamber apparatus (see, for example, 110 elsewhere). In some embodiments, at least one light source 701 is configured to illuminate at least a second end of the enclosure of the cell culture chamber apparatus received by the drive unit 300 in a substantially uniform manner (see, for example, 110 elsewhere). Figure 5 and 8 -15 in 112) or a portion thereof or window (see, for example, 113 in Figure 9).

[0240] Backlighting, or more generally back illumination, serves as a supplement to or alternative to front lighting, enabling better capture (display and / or detection) of the contents of the enclosed portion by means of a display and / or detection device (see, for example, 220 elsewhere), which is in the form of a camera unit (when light is provided). This will combine Figure 5 Further explanation.

[0241] In some embodiments, the driving unit 300 includes a predetermined number of light sources 701. In the illustrated embodiment, the driving unit 300 includes four light sources 701 (of which only two are visible in the cross-sectional view). In alternative embodiments, the number of light sources 701 may be, for example, one, two, three, or other numbers.

[0242] In the illustrated embodiment, the four light sources 701 are offset from the central axis or rotation axis of the surrounding portion or cell culture chamber apparatus (see, for example...). Figure 5 (260 in the middle), which can provide easy access to the contents of the surrounding section.

[0243] The light source 701 can be, for example, an LED light source or any other suitable light source.

[0244] If the driving unit 300 includes multiple light sources, they can be, for example, different types of light sources, such as light sources emitting different wavelengths. As an example, if the driving unit includes four LED light sources 701, then one can, for example, emit UV light, another can emit visible light, a third can emit near-IR light, and a fourth can emit IR light. The driving unit 300 may also include more than one light source of the same type (e.g., two light sources of one type, one light source of another type, etc.).

[0245] In some embodiments, the driving unit 300 may optionally include a light diffuser 175, which may optionally be arranged in the light propagation path from the light source 701 to the surrounding portion 110 or toward the light 702 of the surrounding portion 110, and in particular, for the illustrated embodiment, the light diffuser 175 may be arranged before or near the second end 112.

[0246] In some embodiments (as shown), the driving unit 300 further includes an optional light diffuser 175 (see also, for example...). Figure 4B and Figure 5A light diffuser 175 is arranged in the light propagation path between the light source 701 and the enclosure of the received cell culture chamber apparatus. As shown, the light diffuser 175 may be located, for example, in the cavity 303, adjacent to or at least close to the received cell culture chamber apparatus (e.g., adjacent to or close to the second end of the enclosure). The light diffuser 175 will provide more uniform illumination toward the enclosure and thus can improve the quality of backlighting, thereby improving the quality of the detection and / or display signal of the display and / or detection device.

[0247] Diffuser 175 is also advantageous when there are several different types of light sources.

[0248] according to Figure 4A The back-lighting arrangement provides a very compact and advantageous way to provide back-lighting for the surrounding section / cell culture chamber device in the culture vessel.

[0249] Alternatively, another (one or more) lighting or visualization signal source is used instead of the light source, the signal source being configured to emit another type of lighting or visualization signal, for example, entering the corresponding enclosure through a second end or a portion thereof or a window, wherein at least one display and / or detection device is configured to capture at least a portion of the other type of lighting or visualization signal transmitted to the outside of the enclosure through the first end or a portion thereof or a window. This other type of display and / or detection device may, for example, be configured to display sound or sound waves (e.g., ultrasound) or electromagnetic radiation different from light (e.g., X-rays). In such an alternative embodiment, the diffuser 175 (if present) is not an optical diffuser, but a diffuser relative to another type of lighting or visualization signal, such as an acoustic diffuser or a diffuser for electromagnetic radiation different from light.

[0250] Figure 4B A cross-sectional side view is schematically shown of another exemplary embodiment of a rotary drive unit fastened to the culture chamber wall of a culturer as disclosed herein, according to other embodiments, wherein the rotary drive unit includes at least one lamp or illumination element.

[0251] The drive unit 300 is shown, which more or less corresponds to Figure 4A The driving unit, and as otherwise disclosed herein, but in which backlighting is provided in a different manner. Figure 4B In one embodiment, the rotation axis 305 of the drive unit 300 includes, for example, a centrally located (in the first / longitudinal direction) through-conduit, channel, etc. 306 that receives a light guide, light bar, or other lamp or lighting element 307 terminating in the cavity 303, thereby achieving back illumination.

[0252] Figure 5The illustration schematically depicts a cell culture chamber apparatus as disclosed herein, along with lamps or other lighting or visualization signal sources and imaging, vision, or other display or detection units.

[0253] The illustration shows a cell culture chamber apparatus 100 for cell culture and tissue growth, as disclosed herein (see, for example, 200 elsewhere). The cell culture chamber 100 includes a first end 111, a second end 112, at least one connecting (e.g., circumferential) wall connecting the first end 111 and the second end 112, portions, segments, etc., 114, which together define an enclosure 110 of the cell culture chamber apparatus 100 disclosed herein. The cell culture chamber apparatus 100 may be, for example, substantially cylindrical, such as... Figure 1 Figures 10-15-3, 8, and 9-15 show a central or rotational axis 260, which may coincide with the central axis of the surrounding portion 110 and / or the cell culture chamber apparatus 100. The cell culture chamber apparatus 100 may also include a circumferential gas exchanger comprising a circumferential gas permeation membrane (not shown; see, for example, 140, 151, 310, and 120 in Figures 10-15). The cell culture chamber apparatus 100 may also additionally include, for example, a circumferential humidifier (not shown; see, for example, 301 in Figure 10).

[0254] In at least some embodiments, as shown, the culture vessel includes (or is connected to) an imaging or vision system or device 220, such as a camera, and at least one light source 701 configured to emit light 702 that penetrates, passes through, and exits the enclosure 110 (and thus penetrates, passes through, and exits the contents of the enclosure 110), wherein the imaging or vision system or device 220 (see also, for example,...) Figure 2 The incubator is configured to capture at least a portion of the light passing through and exiting the enclosure 110, such as an image or video. The incubator may include (or be connected to) multiple imaging or vision systems or devices and / or multiple light sources. Light source 701 may be, for example, an LED light source or any other suitable light source.

[0255] In at least some embodiments, the light source 701 emits natural light or artificial light, or a combination thereof, typically or preferably, visible light having wavelengths of about 400 to about 700 nanometers or at least a subrange thereof. Alternatively, the light source 701 may be, for example, outside the visible portion of the electromagnetic spectrum, such as infrared or near-infrared light having wavelengths of about 700 nanometers to about 1 millimeter or about 900 nanometers to about 2500 nanometers, or ultraviolet light having wavelengths of about 300 nanometers to about 300 nanometers. The light source 701 may be, for example, an LED light source.

[0256] In some embodiments, as shown, the light source 701 is located on the side of the enclosure 100 closest to the second end 112, for example, on or substantially on axis 260, wherein the imaging or vision system or device 220 is generally opposite the light source 701, i.e., on the side of the enclosure 100 closest to the first end 111. The light source 701 may, for example, be a combination of... Figure 4A and 4B As shown and explained. The imaging or vision system or device 220 may be located on this axis, but is not required to be, as long as the emitted light is within its field of view. In a further embodiment, the first end 111 is transparent, and the second end 112 is transparent or translucent. The light diffuser 175 may optionally be arranged in the light propagation path of the light 702 from the light source 701 to or toward the enclosure 110, and particularly for the illustrated embodiment, is arranged before or near the second end 112. If the second end 112 is translucent and / or the light diffuser 175 is present, more uniform illumination 703 will propagate through the enclosure and outside the enclosure to be automatically displayed or observed by the imaging or vision system or device 220 and / or manually displayed or observed by the user.

[0257] The light source 701 readily provides back illumination to the contents of the enclosure 110. In at least some embodiments, the light source 701 may be disposed within the drive unit (see 300 elsewhere), for example, as shown and explained in conjunction with FIG4. Instead of back illumination, or in addition to back illumination, the culture vessel may also include front illumination as disclosed herein (see, for example...). Figure 1 and 2 (See section 222). Back lighting disclosed herein typically enhances contrast, for example, to better see and / or count entire cellular structures, while front lighting disclosed herein typically increases the level of perceptible or visible detail, for example, allowing for better seeing or display of details of cellular structures.

[0258] In an alternative embodiment, the connecting wall 114 is transparent or translucent, rather than the second end 112 (or other than the second end 112), wherein the light source 701 can then be arranged near or at least sufficiently close to the transparent or translucent connecting wall 114 to allow enough light to propagate through and out of the enclosure 110. This is not as optimal as arranging the light source 701 opposite the first end 111 and the enclosure 110 between them (and having the transparent or translucent second end 112), but may be sufficient for some uses or designs.

[0259] In some further alternative embodiments, the light source is integrated into the second end 112 (for embodiments with a transparent / semi-transparent second end) or into the connecting wall 114 (for embodiments with a transparent / semi-transparent connecting wall 114).

[0260] In some alternative embodiments, the second end 112 or connecting wall 114 is a fluorescent element or includes a fluorescent element, such as the fluorescent end 112 or the fluorescent connecting wall 114.

[0261] The fluorescent element can be, for example, an IR or NIR-sensing fluorescent element or any other suitable fluorescent light source or element.

[0262] One or more light sources 701 of the connecting wall 114 can emit light that is directed or toward the first end 111.

[0263] As described above, the second end 112 and / or connecting wall 114 may include a transparent or transparent / semi-transparent window (see, for example, 113 in Figure 9 and elsewhere).

[0264] In some embodiments, the light source 701 may be arranged inside the enclosure 110, for example, adjacent to the transparent / semi-transparent second end 112 (for relevant embodiments) or adjacent to the transparent / semi-transparent connecting wall 114 (for relevant embodiments).

[0265] In some alternative embodiments, at least some of the illustrated light sources 701 are replaced by one or more other illumination or visualization signal sources 701, such as one or more acoustic transducers configured to emit sound 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 220 is replaced by other display or detection systems or devices configured to display other illumination or visualization signals. These other display or detection systems or devices 220 may, for example, be configured to display sound or sound waves (e.g., ultrasound) or electromagnetic radiation other than light (e.g., infrared, X-rays).

[0266] In an alternative embodiment, diffuser 175 is not an optical diffuser, but a diffuser 175 relative to another type of lighting or visual signal, such as an acoustic diffuser or a diffuser for electromagnetic radiation other than light.

[0267] In some other alternative embodiments, the diffuser 175 (as disclosed herein) is replaced by a suitable reflector, such as a parabolic reflector, for example, an embodiment for front lighting (or front application of another type of lighting or visualization signal), as an addition or replacement to backlighting or back emission of another lighting or visualization signal.

[0268] Figures 6A-6C Different views of the culture chamber wall, rotating fan, and rotating UVC light source are schematically shown.

[0269] Some embodiments are shown that integrate a UVC light source or similar 232 and a fan or ventilation unit 230, wherein 230, 232 are both configured to rotate (as a unit). The integrated UVC light source 232 and fan or ventilation unit 230 are shown as centrally arranged on the culture chamber wall 202 that defines the culture chamber (see 201 elsewhere, for example).

[0270] Figure 6A A front view of the culture chamber wall 202 is shown. Figure 6B A perspective view of the culture chamber wall 202 is shown, while Figure 6C It shows the corresponding Figure 6A The front view shows a plurality of cell culture chamber devices 100, which, as disclosed herein, receive multiple cell culture chamber devices, six of which are shown as an example.

[0271] The illustrated rotating fan or ventilation unit 230 includes multiple (three in this example) blades, propellers, etc. 231, which are configured to generate airflow in the culture chamber when rotated.

[0272] The shape of blades, propellers, etc. 231 can vary depending on the embodiment or implementation, and Figure 1 and 2 Different shapes of blades, etc. (which are curved rather than straight) are shown (and an integrated UVC light source is also shown). Any number and any suitable shape of blades, propellers, etc. can be used 231.

[0273] In the illustrated embodiment, the UVC light source 232 is centrally positioned within the fan or ventilation unit 230 and protrudes from it to a certain extent (e.g., in the first / longitudinal direction). For example, the illustrated UVC light source 232 is asymmetrical and emits UVC light in (at least) two different directions (here, opposite directions), which is particularly effective in terms of rotation. Therefore, the UVC light source 232 will effectively "sweep" the interior of the culture chamber, thereby purifying it (as mentioned above, the cell culture enclosure of the received cell culture chamber apparatus 100 is required to shield the UVC light, or the UVC light is activated only when there is no cell culture chamber apparatus in the culture chamber). Furthermore, this UVC illumination will also be distributed fairly uniformly within the culture chamber, and if the culture chamber includes a UVC reflective material or coating, the UVC light will reach the un-directly irradiated areas of the culture chamber more effectively.

[0274] Note that some embodiments of the incubator disclosed herein may include only a UVC arrangement, such as a rotating UVC lamp 232, but without a rotating fan or ventilation unit 230, may not include a fan or ventilation unit 230 at all, or may include a fan or ventilation unit in another design and / or location. Embodiments may also include only a fan or ventilation unit 230, without the UVC arrangement / UVC lamp 232.

[0275] Figures 7A-7C Different views of the culture chamber wall and heating element are shown schematically.

[0276] The perspective view (in A), the first side view (in B), and the view from the perspective view (in A), are shown respectively. Figure 7A Another perspective view (in C) taken from a different angle shows an embodiment of a culture chamber wall 202 (which at least partially defines the culture chamber) as disclosed herein, comprising a plurality of openings 240 equidistantly arranged in a substantially circular pattern, six openings 240 here as an example, and an additional, for example, a seventh single opening 240 arranged at the center of the circular pattern. The openings 240 in the circular pattern are used to receive corresponding drive units (see, for example, 300 elsewhere), for example, in combination. Figure 4A and 4B As shown and explained, the central opening 241 is used to receive a UVC light source (see 232 elsewhere, for example) and / or a fan or ventilation unit (see 230 elsewhere), which is integrated and rotated, for example, as explained in conjunction with FIG6.

[0277] Heating element 235 for controllably heating the interior of a culture chamber is also shown. Heating element 235 can take many suitable shapes and forms. In the illustrated and corresponding embodiments, heating element 235 includes a rear or main portion substantially matching the planar shape of, for example, the culture chamber wall 202, forming the “rear” or “end” wall of the culture chamber, and a plurality of “arms,” “wings,” or “tongues” extending to one or more sides of the culture chamber wall 202, thereby effectively increasing the area of ​​the culture chamber wall 202 that can be directly exposed to heating, and consequently increasing the possible heating rate and uniformity inside the culture chamber. Note that the shape of the main portion, such as the arms, can differ from the generally square shape shown.

[0278] The culture apparatus disclosed herein may include a temperature sensor configured to display (enable monitoring) the temperature within the culture chamber, thereby enabling temperature control.

[0279] The heating element 235 can be any suitable heating element, preferably a relatively flat or thin element, such as well-known heating foil, grids, etc. The heating element can be, for example, self-adhesive or otherwise secured to the culture chamber wall 202. The illustrated heating element 235 is located on the outside of the culture chamber wall 202, i.e., on the surface opposite to the surface inside the culture chamber.

[0280] It should be noted that the arms of the heating element 235, etc., are not shown in their final state in the drawings; that is, they are not shown as tightly wrapped around the culture chamber wall 202.

[0281] The heating element 235, together with a fan or ventilation unit (see, for example, 230 in Figure 6), induces airflow in the culture chamber, enabling a very uniform heat distribution within the culture chamber, which is crucial for effective temperature control.

[0282] Figure 8 A side view schematically illustrates an exemplary embodiment of the cell culture chamber apparatus disclosed herein.

[0283] A cell culture chamber apparatus 100 for cell culture and tissue growth is shown, comprising an enclosure 110 configured to contain cell culture medium, and including a first end 111 and a second end 112, wherein the first end 111 and the second end 112 at least partially define the enclosure 110. In the illustrated embodiment, the first end and the second end 111, 112 together define the enclosure 110 with one or more (e.g., lateral or longitudinal) connecting walls, components, segments, etc. 114, and the cell culture chamber apparatus 100 has, for example, a generally substantially cylindrical shape, wherein the first end and the second end 111, 112 each form a circular base of a cylinder (see also...). Figure 9A , 9B (e.g., 11, 11, etc.). In the case where the overall shape is substantially cylindrical, there is only a single (circumferential) wall, component, segment, etc., which connects the first and second ends 111, 112. In some embodiments, at least one or more, but for example all, components of the connecting wall, etc., of the surrounding portion 110 are formed by a circumferential gas permeable membrane (see, for example, 120 in Figures 10, 11A, and 12). It should also be noted that the surrounding portion 110 does not need to, and typically does not, fill the entire extent of the cell culture chamber apparatus 100 (see, for example, the following figures). In such embodiments, the housing and / or multiple housing components (e.g., see 105, 101, and 102 below) may include the surrounding portion 110 (thus including the ends 111, 112 and one or more walls connecting the ends 111, 112).

[0284] A central axis 260 extending between the first and second ends 111, 112 is also shown. In at least some embodiments (as shown), the cell culture chamber apparatus 100 is configured to rotate about the central axis 260, as is well known, for example. In at least some embodiments, the surrounding portion is symmetrically located in the cell culture chamber apparatus 100 with respect to the axis of rotation / central axis 260.

[0285] According to the first aspect, the first end 111 or a portion thereof or window (see example) Figure 8 and 9C 113) is substantially transparent, and the second end 112 or a portion thereof or a window (see example) Figure 8 and 9C 113) is substantially transparent or substantially translucent. Furthermore, the first end 111, or a portion thereof or a window thereof, is configured to be optically aligned or otherwise aligned with the second end 112, or a portion thereof or a window thereof, as disclosed herein. Thus, light or other illumination or visual signals (see, for example, 113) received through the second end 112 (or a portion thereof or a window thereof) and / or through at least one sidewall 114 (or a portion thereof or a window thereof) entering the enclosure 110. Figure 5 (703) The cell culture medium is transferred through the cell culture medium and through the first end 111 or a portion thereof or a window to the outside of the surrounding portion 110, for example, the outside of the cell culture chamber device 100.

[0286] In some embodiments, the cell culture chamber apparatus 100 includes a gas exchange loop, element, or system (not shown; see, for example, 130, 140, 151, 310, etc. in Figures 10, 11, and 12; referred to herein as equivalently simply as a gas exchanger), configured, for example, as disclosed herein, to exchange gases (e.g., or primarily oxygen and carbon dioxide) into and out of the enclosure 110 (e.g., most commonly oxygen, but sometimes carbon dioxide). In at least some preferred embodiments, the gas exchange loop or system is a circumferential gas exchange loop, element, or system (see, for example, 130, 140, 151, 310, etc. elsewhere) that includes a gas permeation membrane (see, for example, 120 in Figure 10 and elsewhere). Alternatively, gas exchange can be achieved through the sidewalls 114 of the enclosure 110, for example, if the material of the longitudinal sidewalls 114 is polydimethylsiloxane (PDMS) (which can be made transparent) or the like, or through special filters installed in one or more end / walls 111, 112, 114. The cell culture chamber apparatus 100 may include one or more special filters and / or gas inlets / outlets to allow gas transfer or exchange with the enclosure 110. As another alternative, the cell culture chamber apparatus 100 may be functionally connected to a gas exchange loop or system outside the cell culture chamber apparatus 100.

[0287] In some embodiments, the cell culture chamber device 100 includes a humidifier, such as those disclosed herein. In at least some embodiments, the humidifier is configured to humidify gas or air near or adjacent to a gas exchanger and / or gas or air supplied to the enclosure 110. In at least some embodiments, the humidifier is preferably a circumferential humidifier as disclosed herein (see, for example, 301 in FIG. 10). Alternatively, the cell culture chamber device 100 is functionally connected to a humidifier external to the cell culture chamber device 100. As yet another alternative, the cell culture chamber device 100 is intended for use in a culture vessel or similar device that provides a well-known controlled humidification environment, in which case the cell culture chamber device 100 does not require a humidifier.

[0288] The presence of a humidifier system will eliminate or at least significantly reduce liquid loss from the enclosure 110, and for certain types of cell culture media, will greatly enhance gas exchange between the enclosure 110 and the surrounding air or atmosphere. The difference is so significant that the cell culture chamber apparatus 100 can often be used, for example, in a culture vessel without additional humidification. This also typically reduces the risk of infection in the culture vessel, as its gaseous environment does not need to be so humid / humid.

[0289] A first extent or length 'L' and a second extent or height or (in the case of a cylindrical cell culture chamber device) diameter 'D' of the cell culture chamber device (100) are also shown. These extents at least partially define the shape factor of the cell culture chamber device 100. In some embodiments (as shown), L is greater than D. However, in other embodiments (see, for example...) Figure 1 , 2 (3, 5, 10, and 12-15), where L is less than D, meaning the circumferential range is greater than the longitudinal range. In some embodiments, the ratio between L and D is approximately 1:1 to approximately 1:10, for example, approximately 1:2 to approximately 1:5. In further embodiments, the ratio is approximately 1:3 to approximately 1:4.

[0290] The cross-sections (and / or shapes) of the first end 111 and the second end 112 may be different from each other, or they may be the same or similar.

[0291] Figures 9A to 9C Cross-sections of different shapes of the first and / or second ends 111, 112 according to different exemplary embodiments are shown.

[0292] The cell culture chamber apparatus 100 may include one or more pipes, inlets or access ports (not shown; see, for example, 103, 104, 140, 160, 170, etc. in the following figures), such as a gas inlet / outlet of a humidifier, a liquid inlet / outlet connected to the enclosure 110 to provide access to the contained cell culture medium, for example, to remove a sample from the enclosure 110 or to introduce cell culture medium or another liquid into the enclosure 110.

[0293] In some embodiments, at least one of the ends 111, 112 is a removable cover or cap that provides access to the enclosure 110 when removed.

[0294] In some embodiments, all or substantially all materials of the cell culture chamber apparatus 100 are transparent (instead of only one or two ends 111, 112) (see, for example) Figure 8-1 0). In some further embodiments, all or substantially all materials of the cell culture chamber apparatus 100 are transparent (including the first end 111) (see also, for example...). Figure 13-15 Except for the second end 112, which is semi-transparent.

[0295] In some embodiments, one or more ports or inlets / outlets may be used to change the growth medium (nutrients), add (potentially bioactive) compounds, viruses, bacteria, etc. to the contents of the enclosure 110, remove spheroids from the enclosure 110, etc.

[0296] Figures 9A-9C They are shown schematically respectively. Figure 8 An end view of an exemplary embodiment of the cell culture chamber apparatus.

[0297] Figure 9A and 9B End views or cross-sectional views of one (or both) of ends 111 and 112 are shown respectively. It can be seen that... Figure 9A The shape is circular (e.g., for a cylindrical cell culture chamber apparatus), and as an example, in Figure 9B The middle part is octagonal. As mentioned above, the shape of the ends (and the shape of the cell culture chamber apparatus) can be any suitable shape, such as the shape disclosed herein.

[0298] Figure 9C An end view or cross-sectional view of one (or both) of ends 111 and 112 is shown. This corresponds to Figure 9A Except for the end portion, which includes window 113. In such an embodiment, it is the window that is transparent (or semi-transparent), rather than the entire end portion 111, 112. The size and position of window 113 can be any suitable size and position, but preferably should easily allow for visual or other types of inspection and control of the contents of the enclosure 110.

[0299] Figure 10 schematically shows a front view (shown on the right side of the figure) and a cross-sectional side view (shown on the left side of the figure) of an embodiment of a cell culture chamber apparatus according to some embodiments, and includes a circumferential gas exchanger and a circumferential humidifier as disclosed herein.

[0300] The illustration (see two views) shows a cell culture chamber apparatus 100 as disclosed herein. The cell culture chamber apparatus 100 includes an enclosure 110 as disclosed herein, defined by a first end 111, a second end 112, and a connecting wall 114 connecting the ends 111, 112. The enclosure 110 is formed, for example, by a housing / main housing 105, wherein the main housing 105 is cylindrical (by way of example) and includes the enclosure 110 at its center (by way of example). In the illustrated and corresponding embodiments, at least one connecting wall 114 is formed by a (supported) circumferential gas permeable membrane 120 arranged along or as a circumferential portion (i.e., its periphery or portion) of the enclosure 110 and configured for the exchange of gases (e.g., oxygen and carbon dioxide). The circumferential gas permeable membrane 120 may be, for example, a semi-permeable membrane.

[0301] Humidification of the atmosphere near or adjacent to the circumferential gas permeation membrane 120 generally reduces or prevents evaporation of the cell culture medium and, for some cell cultures, can also greatly promote gas exchange through the circumferential gas permeation membrane 120. Cells produce CO2, which combines with water in solution to form bicarbonate (which is acidic). Atmospheric humidification causes the outer surface of the circumferential gas permeation membrane 120 to become wet, which promotes the escape of CO2 from the culture medium and slows down the acidification process in doing so. This process occurs in cell culture types that do not rely on CO2 to buffer the culture medium (e.g., those containing HEPES, a zwitterionic sulfonic acid buffer). The most widely used growth media rely on bicarbonate in the medium and CO2 in the atmosphere to buffer the pH of the medium. Here, humidification of the outer surface of the circumferential gas permeation membrane also promotes the “capture” or “release” of CO2, thereby improving the stability of the pH of the culture medium. Humidification can be provided by the cell culture chamber device 100 located in the humidified culture vessel or by a humidifier as described below.

[0302] As shown in the front view (right side of the figure), the cell culture chamber apparatus 100 includes a gas exchange inlet and outlet for a gas exchanger, which can be any suitable inlet, conduit, etc. Preferably, as shown, the gas exchange inlet and outlet are in the form of a dual vent or similar 140 (see, for example, 140 in Figures 11, 12, and 14A), which connects the circumferential gas exchanger to external or ambient air or gas of the cell culture chamber apparatus 100. In the illustrated embodiment, as an example, the dual vents 140 are located on the front side or forward-facing side (see also the following figures) or similar of the housing or main housing 105. In this particular (and corresponding embodiment) gas exchanger, the gas exchanger includes a gas permeable membrane 120 configured to exchange gases, such as oxygen and carbon dioxide, with the contents (e.g., cell culture medium) of the enclosure 110 / enclosure. Specifically, oxygen can be supplied to the enclosure 110, and carbon dioxide can be removed from the enclosure 110. In the illustrated and corresponding embodiments, the membrane 120 constitutes at least one connecting wall 114 of the surrounding portion 110 or one or more of its components.

[0303] The gas exchange inlet and outlet / dual vent 140 are fluidly connected to the membrane 120, thereby connecting the membrane 120 to external or ambient air or gas of the cell culture chamber apparatus 100. In at least some embodiments, the dual vent 140 is configured to operate according to the Coanda effect or principle. In such embodiments, a wall or other suitable barrier 151 (indicated by straight dashed lines in the figure) is located between the two corresponding vents of the dual vent 140, thereby separating and sealing them from each other at that location, i.e., in this particular example, separating and sealing them in the shortest direction between them. However, the two vents of the dual vent 140 are fluidly connected to each other via another path within the housing 105 of the cell culture chamber apparatus 100, and are also fluidly connected to at least a portion of the gas exchange membrane 120, for example, via one or more pipes, open spaces, cavities, etc. As the cell culture chamber apparatus 100 rotates counterclockwise, ambient air or gas is drawn in and exhausted from the cell culture chamber apparatus 100 via the dual vent 140, as indicated by the arrows in the front view and cross-sectional side view of Figure 10. As can be seen, during counterclockwise rotation, air or gas is more specifically drawn into the cell culture chamber apparatus 100 through the left (in the front view) vent 140, as indicated by the arrows from black to gray, and discharged from the cell culture chamber apparatus 100 through the right (in the front view) vent 140, as indicated by the arrows from gray to black, thus creating an internal airflow 310, the direction of which is indicated by the light gray dashed circular arrow. This is for the counterclockwise rotation case. If the cell culture chamber apparatus 100 rotates clockwise, the direction of the airflow 310 within the housing 105 will be reversed due to symmetry, i.e., the light gray dashed circular arrow will be clockwise, and air or gas will be drawn in through the right vent 140 and discharged through the left vent 140.

[0304] In this way, an effective airflow 310 is easily provided to contact the membrane 120 and the ambient gas or air, thereby conveniently adding oxygen to the contents of the membrane 120 and the surrounding portion 110 and removing carbon dioxide from the contents of the membrane 120 and the surrounding portion 110.

[0305] In some further embodiments, the degree of air movement or flow 310 can be adjusted by adjusting the respective size of the openings of the vents of the dual vents 140, for example by using sliders or small or different sized plugs or in another suitable manner.

[0306] In some further embodiments (as shown), the cell culture chamber apparatus 100 optionally further includes a circumferential humidifier or humidifying or wetting element or system (referred to herein as a humidifier) ​​301, configured to humidify or moisten air or gas at least in the vicinity of the membrane 120 (at least a portion thereof). The humidifier will significantly enhance gas exchange between the contents of the enclosure 110 and the ambient air or gas, and will also reduce or eliminate water or liquid loss in the enclosure 110 when the enclosure 110 contains liquids or aqueous solutions. The effects are so significant that the cell culture chamber apparatus 100 can typically be used in a culture vessel without additional humidification. This is advantageous because it generally reduces the risk of infection in the culture vessel and also allows for simplification of the culture vessel.

[0307] In some such embodiments, the circumferential humidifier 301 includes (or is connected to) one or more liquid or humidification reservoirs or elements. It is advantageous if the weight distribution of the circumferential humidifier 301 is at least partially uniform around the central axis or rotation axis of the cell culture chamber apparatus 100. It is also advantageous if such one or more liquid or humidification reservoirs or elements have or provide a relatively large evaporation surface area.

[0308] There are several advantageous possibilities for humidifying or moistening air or gas, at least in the vicinity of membrane 120 (at least a portion thereof).

[0309] In some embodiments, the circumferential humidifier 301 includes an element or reservoir containing (preferably sterile) liquid water or other humidifying liquid, such as having one or more suitable filters, outlets, additional (gas-permeable and particularly semi-permeable) membranes, etc., to contact the water or liquid with the airflow 310, thereby humidifying or wetting the airflow 310. The element or reservoir may be, for example, a single circumferential unit, or alternatively, several separate and discrete units (e.g., uniformly distributed around a central and / or rotational axis).

[0310] In an alternative embodiment, the circumferential humidifier 301 comprises one or more water- or solute-containing materials, such as gels, sponges, or particulate materials (e.g., water droplets, water-based beads, etc.), which readily provide evaporation of water or liquid and effectively influence the airflow 310. This solid humidifying or wetting element may be supported or secured within the housing 105, for example, through or secured to an (open) enclosure, wall, or other support structure (e.g., 145 in the figure below).

[0311] In the presence of water droplets or gel, these can be fastened, adhered, glued, etc., to the inner wall of the main housing / housing 105 (as mentioned, for example, or preferably uniformly around the central and / or rotational axis), thus the support structure is not necessary.

[0312] For embodiments that do not include water or liquid reservoirs (such as water-containing droplets or gels as described above), they can be directly positioned in pipes, cavities, open spaces, etc., including airflow 310, thereby greatly increasing the humidification or wetting effect of airflow 310 and enabling a reduction in the total space / footprint of cell culture chamber device 100.

[0313] It should be noted that for embodiments without a humidifier (e.g., a culture vessel for humidification, etc.), the cell culture chamber apparatus 100 shown will not include the circumferential humidifier 301 shown, and thus may have a reduced size.

[0314] Figure 11A-11E A front view, a first (“right”) side view, a first cross-sectional view (AA), a second cross-sectional view (CC), and a third cross-sectional view (BB) of an exemplary embodiment of the cell culture chamber apparatus disclosed herein are shown schematically.

[0315] Figure 11A The image shown is a front view of an exemplary preferred embodiment of the cell culture chamber apparatus disclosed herein. The front of the cell culture chamber apparatus 100, including a transparent first end 111, is shown. In this particular (and corresponding embodiment), the base plate, bottom, or wall of the cover 102 (see, for example...) Figure 11C -E, 12, and 15, 102) constitutes the first end 111 (or a portion thereof or window 113) of the cell culture chamber apparatus 100. The base plate or bottom of the cover 102, together with the first or central housing 101, forms an enclosure as disclosed herein (see, for example...). Figure 11C-11E And 110 in other places), which will become more apparent from some of the accompanying figures below. In some embodiments (such as Figure 11C , 11D As shown in 11E, 12, etc., the first or central housing 101 includes a central cavity for (e.g., or preferably releasably) receiving at least a portion of the cover 102, and more specifically (in the illustrated and corresponding embodiments) for receiving the base plate or bottom of the cover 102. The first or central housing 101 and the cover 102 may, for example, include respective releasable fastening elements (e.g., snap-fit, bayonet, friction fit, etc.) to releasably fasten them together. Alternatively, they may be non-releasably fixed to each other, or, for example, integrally formed.

[0316] As an example, Figure 11A-11E The cell culture chamber device 100 is shaped as a generally cylindrical shape with a circular first end.

[0317] In this particular (and corresponding) embodiment, the central housing 101 also includes a gas exchange circuit, element, or system in the form of a circumferential gas exchange system including a circumferential gas permeation membrane (not shown; see, for example, 301 and 120 in Figures 10, 11D, and 12). As described above, the base plate or bottom of the cover 102 constitutes a first end 111 (or a portion thereof or window 113) of the cell culture chamber apparatus 100.

[0318] In this particular (and corresponding) embodiment, the central housing 101 also includes a circumferential humidifier (not shown) as disclosed herein and explained, for example, in conjunction with FIG10. Some alternative embodiments of the cell culture chamber apparatus 100 do not include any humidifier, such as a culture vessel for humidification, etc.

[0319] The central housing 101 may optionally include gas exchange inlets and outlets for gas exchangers as disclosed herein (see, for example, 130, 140, 151, 310, etc. in Figures 10-15), in the form of dual vents 140 located at the front of the central housing 101. The dual vents 140 have been described in more detail, for example, in conjunction with Figure 10.

[0320] Three cross-sections are also shown, labeled AA (e.g. Figure 11C As shown), BB (as shown) Figure 11E (as shown) and CC (as shown) Figure 11D (As shown).

[0321] In some embodiments (as shown), the cell culture chamber apparatus 100 further includes a closable and / or sealable (first) port 103 that provides a user with access to the interior of the enclosure, for example, for removing samples from the enclosure (e.g., removing spheroids), emptying or filling the enclosure, etc. In the illustrated embodiment, the closable and / or sealable port 103 includes a conduit (from the interior of the enclosure to the exterior of the cell culture chamber apparatus 100) and, for example, a simple plug or the like 160. The port 103 may advantageously be located at the top of the cell culture chamber apparatus 100, as this can prevent or reduce the formation of air bubbles, for example, by allowing overflow.

[0322] In some embodiments (as shown), the cell culture chamber apparatus 100 further includes one or more reference and / or identification markers, here identification code 155 and reference marker 180. Identification code 155 is preferably unique for a particular cell culture chamber apparatus 100. Reference marker 180 enables the determination of the orientation of the cell culture chamber apparatus 100. Reference and / or identification markers 155, 180 are preferably machine-readable, for example by a suitable imaging or vision unit or system, such as at least one display and / or detection device disclosed herein (see, for example, 220 elsewhere). In some embodiments, the cell culture chamber apparatus further includes one or more alignment elements (e.g., positioning rods and slits or slots, etc.) for aligning different components of the cell culture chamber (thereby ensuring or facilitating that one component can only be received by another component in the correct orientation) (e.g., properly aligning cover 102 with the first or central housing 101). Reference marker 180 may be such an alignment element (see also, for example, 220 elsewhere). Figure 14A (131 in the middle).

[0323] Therefore, a very compact (longitudinal) cell culture chamber apparatus 100 is provided, particularly because of the circumferential gas exchange system and (if present) circumferential humidifier. The gas exchange system and (if present) humidifier are circumferential, which also ensures that they do not obstruct the view of the contents surrounding the cell culture chamber apparatus 100 for any display and / or detection device.

[0324] Optionally, the transparent cover 102 includes a plurality of liquid level or fill rate indicators 190, which readily indicate the actual volume of cell culture medium contained within the enclosure.

[0325] In some embodiments, as shown, the cell culture chamber apparatus 100 also includes one or more (two in this case) feet, standing elements, etc. 501, thereby enabling the cell culture chamber apparatus 100 to stand upright and preventing it from rolling. This allows for easier or more reliable use of ports, inlets, etc. (e.g., see port 170 below).

[0326] Figure 11B As shown Figure 11A The cell culture chamber apparatus 100 viewed from the side and from right to left (according to...) Figure 11A A side view (of the orientation). The cell culture chamber apparatus 100 shown includes a main housing 105 that receives (e.g., permanently or in a fixed manner) a central housing 101, which in turn receives (e.g., releasably) a cover 102. A (second) port 104 (or more precisely, its plug or valve 170) is also shown, which is in fluid communication with the enclosure and provides (additional) access to the enclosure.

[0327] First range / length (in) Figure 11B (in the left and right directions) and the second range / height or diameter (in Figure 11B The ratio between the top and bottom directions is approximately 1 to approximately 3-4, for example, approximately 1 to approximately 3.5, but may be different for other embodiments, such as those disclosed herein.

[0328] Figure 11C It shows the result of Figure 11A The first cross-sectional view given by AA shows an enclosure 110 defined by a transparent first end 111 (which is the base plate or bottom of the cover 102, and a transparent or translucent second end 112 which is the base plate or bottom of the central housing 101) and the sidewalls of the cavity of the central housing 101. A main housing 105 that receives the central housing 101 and the cover 102 in a very compact manner is also shown.

[0329] As described above, the second port 104 (in addition to the first port 103) provides access to the enclosure. As explained in conjunction with, for example, Figure 3, the dual vents 140 connect the external or ambient air or gas of the cell culture chamber apparatus 100 to the circumferential gas exchange system (see, for example, 130, 140, 151, 310, etc. elsewhere).

[0330] As can be seen, the closable and / or sealable first port 103 and its conduit connect the interior of the enclosure 110 to the exterior of the cell culture chamber apparatus 100. The port wall is part of the cover 102, allowing easy access to the contents of the enclosure 110. Similarly, access to the interior of the enclosure 110 is provided via the second port 104 (with a plug 170). The wall with the plug 170 is part of the central housing 101. It should be noted that the first port 103 and the second port 104 are arranged on different sides of the cell culture chamber apparatus 100, thereby enabling easy access to the enclosure from several different sides of the cell culture chamber apparatus 100.

[0331] Gas exchange inlets and outlets in the form of dual vents 140, as already explained, are also shown.

[0332] Figure 11C The view is from left to right (according to) Figure 11A (The orientation of the view) is the center vertical sectional view.

[0333] Figure 11D It shows the result of Figure 11A The second cross-sectional view given by CC, viewed from right to left.

[0334] The enclosure 110, the first transparent end 111, the transparent or semi-transparent second transparent end 112, the central housing 101, the cover 102, the closable and / or sealable ports 103 and 104, and the main housing 105 are shown again.

[0335] Also shown is a gas permeation membrane 120 of the circumferential gas exchange system and a portion of the grid structure 130 of the circumferential humidifier (see, for example...). Figure 14A and 14B (130 in the middle).

[0336] Also shown are optional wall structure elements or the like 145 according to some embodiments of the circumferential humidifier for retaining and / or supporting water, liquid or wetting elements (in combination with...) Figure 13 (Further explanation).

[0337] In some embodiments, the cell culture chamber apparatus 100 may optionally further include one or more markers 115 (see also...). Figure 14A The 115 in the diagram—as an example here—is in the form of multiple concentric circles 115, which can provide the user with some fixed markings to refer to in order to see the slight movement of the contained spheres. The markings 115 (as an example) are arranged on the "outer side" of the second end 112.

[0338] Figure 11D The view is a vertical sectional view off-center to the left, and is viewed from right to left (according to...). Figure 11A (in terms of orientation).

[0339] Figure 11E It shows the result of Figure 11A The third cross-sectional view given by BB.

[0340] The illustration shows an enclosure 110, a first transparent end 111, a transparent or translucent second end 112, a cover 102, a closable and / or sealable port 103, and two optional wall structure elements or the like 145 for retaining and / or supporting water, liquid, or wetting elements, according to some embodiments.

[0341] Figure 11E The view is a horizontal center section view viewed from top to bottom (in accordance with...) Figure 11A (in terms of orientation).

[0342] It should be noted that if both ends 111 and 112 are transparent, the cell culture chamber apparatus 100 makes it easy to automatically and / or manually inspect the contents of the enclosure 110 from both sides (as shown in the first end 111 and the second end 112).

[0343] exist Figure 11A-11E In the illustrated embodiment (and corresponding embodiments), the second end 112 is preferably translucent rather than transparent, because this provides better (more uniform) illumination to the contents of the enclosure 110, while avoiding the need for a light diffuser.

[0344] Figure 12 schematically shown Figure 11A-11E An exploded perspective view of an exemplary embodiment of the cell culture chamber apparatus.

[0345] The diagram is shown in exploded view. Figure 11A-11E Components.

[0346] Figure 12 The grid-like structure 130 of the circumferential humidifier and the gas permeation membrane 120 are shown more clearly. In the assembled state of the cell culture chamber apparatus 100, the gas permeation membrane 120 is located near the interior of the grid-like structure 130, with its first end 111 facing (and optically aligned) with its second end 112, and the second end 112 aligned with the opening 185 of the main housing 105. If the second end 112 is transparent, the contents of the enclosure can also be easily inspected from this side. Another port 150 aligned with the first port 104 in the assembled state is also shown.

[0347] If the second end 112 is transparent, light can be provided from this side through the opening 185 of the main housing 105 (“backside” lighting), thereby enhancing inspection (manual or automatic) from the other / opposite side (via the first end 111).

[0348] If the second end 112 is translucent, appropriate (backside) lighting can provide more uniform illumination to the contents of the enclosure, thereby further enhancing inspection (manual or automatic) from the other / opposite side (via the first end 111).

[0349] If the second end 112 is transparent (or translucent), a light diffuser, preferably close to or adjacent to the second end 112, can be used to provide uniform illumination (or even more uniform illumination). This embodiment is exemplified in... Figure 5 As shown in the image.

[0350] In some embodiments, the main housing 105, the central housing 101 (and thus the second end 112), and the cover 102 (and thus the first end 111) may be made of the same (transparent) material (see also...). Figure 13-15 ).

[0351] The embodiment of the cell culture chamber apparatus 100 shown in Figures 11 and 12 provides a very compact (particularly in the longitudinal direction) fully equipped and fully functional cell culture chamber apparatus 100 or bioreactor, wherein the gas exchanger (and humidifier, if included) is arranged away from the central axis and / or the axis of rotation. Furthermore, the cell culture chamber apparatus 100 has a petri dish-like design, thereby making operation easy and familiar.

[0352] Figure 13 A perspective view of the main housing 105 of the cell culture chamber apparatus disclosed herein is shown schematically.

[0353] A main housing 105 is shown according to some embodiments, for example, combined with Figure 11A-11E The embodiments of 1 and 2 illustrate certain features and aspects more clearly.

[0354] The main housing 105 includes a cavity or open space and a first port 104 providing access to the enclosure (port 104 is aligned with another port in the assembled state of the cell culture chamber apparatus; see, for example) Figure 14B 150), wherein port 104 is fluidly connected to the surrounding portion 110.

[0355] The main housing 105 also includes a central opening 185, which, in the assembled state of the cell culture chamber apparatus, is connected to the second end (see example...). Figure 11A-11E Align or receive the second end with 112 (and other locations). As described above, the main housing 105 is configured to compactly receive the central housing (see, for example...). Figure 14A and 14B (101 in the middle).

[0356] In the specifically illustrated embodiment, the main housing 105 also includes a plurality of (four here as an example) wall structural elements or similar 145, each for holding and / or supporting water, liquid, or wetting elements, for embodiments that also include a humidifier (see further below). In alternative embodiments, the wall structural elements or similar 145 may be omitted. The wall structural elements or similar 145 may be more or less uniformly distributed in the cavities or open spaces of the main housing 105 around the central axis / axis of rotation of the cell culture chamber apparatus to more evenly distribute the weight of the water, liquid, or wetting elements. The wall structural elements or similar 145 may also provide structural integrity and / or support for the received central housing.

[0357] In some embodiments, as shown, each (or some) wall structure element or the like 145 includes a cut or channel 141 that forces gas or air into the immediate vicinity of the gas permeation membrane (see, for example, 120 in Figures 10, 11A and 12).

[0358] The contained air or gas and the grid-like structure of the central shell (see, for example) Figure 14A and 14BIt is connected to 130 and 101 in other locations, and ultimately to a gas permeation membrane (see, for example, 120 in Figures 10, 11A, and 12). The grid structure provides support for the membrane while still allowing gas or air to contact the membrane for gas exchange. The membrane can be fastened to the grid structure, for example, by welding, press fitting, or gluing. As described above, the gas permeation membrane is configured to exchange gases, such as oxygen and carbon dioxide, with the contents of the surrounding area.

[0359] This easily provides a circumferential gas exchanger that does not obstruct any view between the first and second ends of the partially defining enclosure.

[0360] The functions of the circumferential gas exchange system and the circumferential humidifier are further explained with reference to Figure 10.

[0361] Figure 14A and 14B Two perspective views of the central housing of the cell culture chamber apparatus disclosed herein are shown schematically.

[0362] exist Figure 14A and 14B The first or central housing 101 of transparent material is shown, and the grid-like structure 130 is shown more clearly as disclosed herein. Also shown are a second end 112, one or more reference and / or identification marks 155, one or more markers 115 in the form of multiple concentric circles 115, a gas exchange inlet and outlet in the form of dual vents or similar 140, another port 150, and alignment elements 131.

[0363] Figure 15 A perspective view of the cover of a cell culture chamber apparatus as disclosed herein is shown schematically.

[0364] Figure 15 The image shows a transparent material cover 102. Also shown are an end 111, a closable and / or sealable port (first) 103, and multiple level or fill rate indicators 190.

[0365] In an alternative embodiment, diffuser 175 is not an optical diffuser, but a diffuser 175 relative to another type of lighting or visual signal, such as an acoustic diffuser or a diffuser for electromagnetic radiation other than light.

[0366] In some other alternative embodiments, the diffuser 175 (as disclosed herein) is replaced by a suitable reflector (e.g., a parabolic reflector), for example for front illumination embodiments (or front application of another type of illumination or visualization signal), as a supplement or alternative to back illumination or back emission of another illumination or visualization signal.

[0367] Figure 16 The communication between multiple incubators and user interface devices is illustrated schematically.

[0368] A culture vessel 200 according to some embodiments as disclosed herein is schematically illustrated. The culture vessel 200 includes at least one display and / or detection device 220, which is integrated, for example or preferably, with the culture vessel 200 as disclosed herein.

[0369] The at least one display and / or detection device 220 may be, for example, an imaging or vision system or device, and may include, for example, one or more cameras configured to acquire still images and / or videos of the enclosing contents as disclosed herein.

[0370] The illustrated incubator 200 also includes: one or more processing units 802 connected to electronic memory and / or electronic storage devices 803 via one or more communication and / or data buses 801; one or more signal transmitter and receiver communication elements 804 (e.g., one or more selected from the group consisting of communication elements such as cellular, Bluetooth, WiFi, etc.) for communicating via computer networks, the Internet, and / or the like 809; one or more optional (e.g., graphical and / or physical) user interface elements 807, such as including optional displays; and one or more display and / or detection devices / cameras 220.

[0371] In some embodiments, the culture vessel 200 includes a plurality of cameras 220, the number of which is equal to the number of cell culture chamber devices to which the culture vessel 200 is configured to receive (see, for example, 100 elsewhere), wherein each camera 220 is configured to capture video and images of a particular cell culture chamber device or, more specifically, the enclosure of such device (see, for example, 110 elsewhere). Thus, video feeds or multiple images, such as along with additional information about each respective cell culture chamber device / enclosure, can be provided, enabling online monitoring of it.

[0372] In some embodiments, as shown, the culture vessel 200 is configured to communicate with at least one external computing device via a network 809, such as with one or more additional culture vessels 200', which may or may not be located in the same physical location as the culture vessel 200. In at least some embodiments, one or more additional culture vessels 200' (or at least one or more of them) correspond to the culture vessel 200.

[0373] Captured videos and / or images can be stored locally and / or elsewhere, such as in a cloud storage device connected to network 809.

[0374] In some embodiments, the user interface device 250 is connected to the incubator 200 at least at certain times via network 809 and / or another network (e.g., a local area network). The user interface device 250 may be, for example, a suitably programmed computing device, such as a PC, laptop, computer, server, client, smartphone, tablet, etc.

[0375] User interface device 250 may be configured, for example, for online monitoring of culture vessel 200. In some embodiments, user interface device 250 is configured to display online video feeds or the latest single or series of images of each culture vessel obtained by culture vessel 200 via its camera 220 on a user interface on an on-screen display. Additional data, such as the current rotation speed, direction of rotation, ID, etc., for each particular cell culture chamber device, may also be acquired and transmitted to user interface device 250, for example, displayed on the device along with the video or images of the corresponding cell culture chamber device. In addition to cell culture chamber device-specific data, data of culture vessel 200 may also be acquired and provided, such as one or more of the current temperature, current pH, current humidity, current CO2, O2 and / or N2 levels of the culture chamber of humidifier 200 (see 201 elsewhere, for example), as may be acquired by multiple suitable sensors appropriately located in humidifier 200. If one or more parameters exceed the acceptable range, are higher or lower than the acceptable value, etc. (e.g., if the measured current temperature exceeds a given temperature threshold or value, etc.), the humidifier 200 may also send an alarm or warning to the user interface device 250.

[0376] Online feeds or images can easily allow for manual inspection of the state of the included spheres, such as their size, their orbits, etc., which may prompt the user to make changes, such as increasing the rotation speed, if, for example, the spheres have now become larger and therefore heavier (suggesting an increase in rotation speed).

[0377] The ID of a specific cell culture chamber apparatus can be automatically obtained, for example, by capturing images or videos of one or more benchmarks and / or identification markers or codes (see, for example, 155, 180 elsewhere) and performing appropriate image analysis. In a similar manner, the presence of air bubbles and / or the actual volume of the cell culture medium contained in a specific enclosure of the cell culture chamber apparatus 100 can also be obtained and presented by capturing images or videos of multiple suitable level or fill rate indicators (see, for example, 190 elsewhere).

[0378] In some embodiments, the user interface device 250 is also configured to perform data logging and / or documentation, such as collecting and storing data, such as temperature, humidity levels, rotation speeds, timeouts, and, for example, average values, durations, and number of pauses (without rotation) of at least some, such as all, cell culture chamber devices.

[0379] This can be supplemented, for example, with video and / or still images. Data from data logs or documentation can be stored, for example, in a cloud computing environment.

[0380] User interface device 250 is configured, at least in some embodiments, to acquire (and present) data from a plurality of incubators 200, 200'.

[0381] In addition to acquiring data and information, the user interface device 250 may include input elements for its user interface to obtain selections and other inputs from the user. This could be, for example, a new rotational speed setting for one or more specific cell culture chamber devices 100. It could also be start and stop commands for the cell culture chamber device at an individual level.

[0382] Also shown connected to network 809 is an optional client computer or device 255. This may have the same functionality (or a superset or subset thereof) as described for user interface device 250. Users can log in, for example, on 250 or 255 to receive information and data, and, if supported, provide commands, make changes, etc. Client 255 may also be used in place of the user interface device. Client computer or device 250 may be, for example, a suitably programmed computing device, such as a PC, laptop, computer, server, client, smartphone, tablet, etc. As an alternative to or addition to client computer or device 255 and / or one or more additional incubators 200', one or more processing units 802 of incubator 200 are configured to communicate via network 809 with at least one other external computing device, such as a server computer or device, a network-connected storage device, etc.

[0383] Any external computing device of the type that the incubator 200 can communicate with can be, for example, a cloud computing (and / or storage) device.

[0384] In some embodiments, one of a group of incubators 200, 200' is configured as a "master device," while the others are configured as corresponding "slave devices" for organizational communication, information exchange, etc., with respect to user interface device 250 (and / or client 255), wherein the master device communicates with user interface device 250 (and / or client 255) and distributes data to the slave device units. Furthermore, the master device also collects information from the slave device units and passes it to user interface device 250 (and / or client 255). Alternatively, a different communication setup than master / slave may be used, such as a peer-to-peer setup, a one-to-many setup, etc.

[0385] In some alternative embodiments, at least one display and / or detection device 220 is not an imaging or vision system or apparatus configured to obtain still images and / or videos of the contents surrounding the part as disclosed herein. In such alternative embodiments, at least one display and / or detection device 220 may be configured, for example, to display sound or sound waves (e.g., ultrasound) or to display electromagnetic radiation (e.g., infrared, X-rays) different from the light disclosed herein.

[0386] Some preferred embodiments have been shown above, but it should be emphasized that the invention is not limited to these embodiments, but can be implemented in other ways within the scope defined by the appended claims.

[0387] It should be emphasized that, when used in this specification, the term "comprising / including" is used to specify the presence of the stated feature, element, step, or component, but does not exclude the presence or addition of one or more other features, elements, steps, components, or combinations thereof.

[0388] In a claim listing several features, some or all of these features may be implemented by the same element, component, or article. The fact that certain measures are described in mutually different dependent claims or different embodiments does not mean that combinations of these measures cannot be used advantageously.

[0389] In the claims, any reference numerals placed in parentheses should not be construed as limiting the claims. The word "comprising" does not exclude the presence of elements or steps other than those listed in the claims. The words "a" or "an" preceding an element do not exclude the presence of a plurality of such elements.

[0390] The fact that certain measures are referenced in mutually different dependent claims does not mean that a combination of these measures cannot be used advantageously.

[0391] It will be apparent to those skilled in the art that various embodiments and / or elements of the disclosed invention may be combined without departing from the scope of the invention as defined by the claims.

Claims

1. A culture vessel (200, 200') configured to receive a predetermined number of plurality of cell culture chamber devices (100), each cell culture chamber device (100) including an enclosure (110) configured to contain cell culture medium, the culture vessel (200, 200') comprising - A housing (210) including a culture chamber (201) configured to contain at least a corresponding portion of the cell culture chamber device (100) when received by the culture vessel (200, 200'), and - At least one display and / or detection device (220), said at least one display and / or detection device being integrated with said culture vessel (200, 200') and configured to display and / or detect said illumination or visualization signal (703) when said predetermined number of cell culture chamber devices (100) are received by said culture vessel (200, 200'), after said illumination or visualization signal has passed through, reflected or propagated through at least a portion of the enclosure (110) of said predetermined number of cell culture chamber devices (100). At least one rotary drive unit (300), each rotary drive unit (300) - Configured to releasably receive at least one of the cell culture chamber devices (100), and - The received cell culture chamber device (100) is configured to rotate about a predetermined rotation axis (260) of the cell culture chamber device (100) received by the rotation drive unit (300).

2. The incubator (200, 200') according to claim 1, wherein, The predetermined rotation axis (260) includes the predetermined central axis (260) of the received cell culture chamber device (100) or the surrounding portion (110) of the received cell culture chamber device (100).

3. The incubator (200, 200') according to claim 1 or 2, wherein, The culture vessel (200, 200') includes an openable and closable door or cover (211), and the culture chamber (201) includes at least one culture chamber wall (202), the at least one culture chamber wall (202) and the door or cover (211) at least partially defining the culture chamber (201) when closed, and wherein a first side or inner side (212) of the door or cover (211) includes the at least one display and / or detection device (220), wherein the at least one display and / or detection device (220) is oriented such that the enclosure (110) of at least one received cell culture chamber device (100) is within the display and / or detection field of view of at least one of the at least one display and / or detection device (220).

4. The incubator (200, 200') according to claim 3, wherein, The culture vessel (200, 200') includes the predetermined number of display and / or detection devices (220), wherein each display and / or detection device (220) is arranged such that the central axis of the display and / or detection field of view of the corresponding display and / or detection device (220) is aligned at least substantially with the central axis (260) of the corresponding enclosure (110) of the received cell culture chamber device (100).

5. The incubator (200, 200') according to claim 1, wherein, The at least one display and / or detection device (220) is an imaging or vision system or device (220), and the illumination or visualization signal (703) is ultraviolet light, visible light, infrared light and / or near-infrared light.

6. The incubator (200, 200') according to claim 5, wherein, The culture vessel (200, 200') also includes one or more light sources (222, 701) configured to illuminate at least a first end (111) or a portion of the first end or a window (113) of the enclosure (110) of one or more cell culture chamber devices (100) received by the culture vessel (200, 200').

7. The incubator (200, 200') according to claim 6. in, The one or more light sources (222) are arranged in the door or cover (211) and face one or more received cell culture chamber devices (100).

8. The incubator (200, 200') according to claim 1, wherein, At least one corresponding drive unit (300) of the at least one rotation drive unit (300) includes one or more light sources or illumination sources (701) configured to illuminate at least a second end (112) or a portion or window (113) of the enclosure (110) of the cell culture chamber device (100) received by the corresponding drive unit (300).

9. The incubator (200, 200') according to claim 1, wherein, At least one corresponding drive unit (300) of the at least one rotary drive unit (300) includes a hollow rotary shaft (305) including a light guide or other lamp or illumination element (307, 701) configured to illuminate at least a second end (112) or a portion or window (113) of the enclosure (110) of the cell culture chamber device (100) received by the corresponding drive unit (300).

10. The incubator (200, 200') according to claim 1, wherein, The corresponding motor component of the at least one rotary drive unit (300) is located outside the culture chamber (201) and inside the housing (210).

11. The incubator (200, 200') according to claim 1, wherein, The incubator (200, 200') further includes a fan or ventilation unit (230) disposed in the culture chamber (201) and configured to cause airflow inside the culture chamber (201) in response to a control signal, wherein the fan or ventilation unit (230) further includes a UVC lamp (232) configured to emit UVC light inside the culture chamber (201).

12. The incubator (200, 200') according to claim 11, wherein, The fan or ventilation unit (230) is rotating.

13. The incubator (200, 200') according to claim 11, wherein, At least a portion of the inner surface (202) of the culture chamber (201) includes a UVC reflective material or coating.

14. The incubator (200, 200') according to claim 13, wherein at least a portion of the at least one culture chamber wall (202) and / or the first or inner side (212) of the door or cover (211) comprises a UVC reflective material or coating.

15. The incubator (200) according to claim 1, wherein, The incubator (200) also includes - One or more processing units (802). - Electronic memory and / or electronic storage device (803), and - One or more signal transmitter and receiver communication elements (804) are configured to communicate with a network (809). The one or more processing units (802) are configured to communicate with at least one external computing device via the network (809).

16. The incubator (200, 200') according to claim 15. The external computing device includes a user interface device (250), a client and / or server computer or device (255), a network-connected storage device (255), and / or one or more additional incubators (200').

17. The incubator (200, 200') according to claim 1, wherein, The culture vessel (200, 200') includes a cell culture chamber device (100) for cell culture and tissue growth, the cell culture chamber device (100) including - The surrounding portion (110) is configured to contain cell culture medium, and - A first end (111), a second end (112), and at least one connecting wall (114) connecting the first end (111) and the second end (112), wherein the first end (111), the second end (112), and the at least one connecting wall (114) at least partially define the surrounding portion (110). Wherein, the first end (111) or a portion of the first end or window (113) is substantially transparent, and the second end (112) and / or at least one of the at least one connecting wall (114) or a portion of the respective window (113) is substantially transparent or substantially translucent, wherein the first end (111) or the portion of the first end or window (113) is configured to, at least for a period of time or periodically, interact with the second end (112) or the portion of the second end or window (113), and / or with at least one of the at least one connecting wall (114) or the respective window (113). At least one portion or window (113) of at least one of the connecting walls is optically aligned or otherwise aligned such that light (703) or other illumination or visualization signals transmitted through or from the second end (112) or its portion or window (113) into the enclosure (110), and / or transmitted through or from the connecting wall (114) or its portion or window (113) into the enclosure (110), are transmitted or propagated through at least a portion of the cell culture medium and reach outwards to the outside of the enclosure (110) through the first end (111) or its portion or window (113).

18. The incubator (200, 200') according to claim 17. The first end (111) or a portion or window (113) of the first end is configured to be optically aligned or otherwise aligned with the second end (112) or a portion or window (113) of the second end, and / or with at least one of the at least one connecting wall (114) or a portion or window (113) of at least one of the at least one connecting wall, such that light (703) or other illumination or visualization signals transmitted through or from the second end (112) or a portion or window (113) into the enclosure (110), and / or transmitted through or from the connecting wall (114) or a portion or window (113) into the enclosure (110), are transmitted or propagated through at least a portion of the cell culture medium and reach outward through the first end (111) or a portion or window (113) to the outside of the cell culture chamber apparatus (100).

19. The incubator (200, 200') according to claim 1, wherein, The incubator also includes a circumferential humidifier. - Arranged circumferentially around at least a portion of the enclosure or around the center and / or longitudinal axis of the cell culture chamber apparatus, and - Includes or is connected to one or more liquid or humidifying reservoirs or elements, said liquid or humidifying reservoirs or elements being configured to humidify or wet air or gas in at least a portion of the cavity or airflow of a circumferential gas exchanger.

20. The incubator (200, 200') according to claim 1, wherein the predetermined rotation axis (260) is a horizontal axis.

21. The incubator (200, 200') according to claim 1, wherein the incubator (200, 200') includes one or more light sources (701) configured to illuminate at least a second end (112) or a portion or window (113) of the enclosure (110) of the cell culture chamber device (100) received by the respective drive unit (300).

22. A culture system comprising - The first incubator (200) is an incubator (200, 200') according to any one of claims 1 to 21. - At least one second culture vessel (200') is a culture vessel (200, 200') according to any one of claims 1 to 21, and - User interface device (250) and / or client computer or device (255). in, - The first incubator (200) is configured as a master device unit, and the at least one second incubator (200') is configured as a slave device unit. - The master device unit is configured to control communication and / or data exchange between the master device unit and all slave device units and the user interface device (250) and / or the client computer or device (255). - The user interface device (250) and / or the client computer or device (255) are configured to obtain user input control data and transmit the user input control data to the master device unit, and - The master device unit is configured to change or adjust operation in response to at least a portion of the received user input control data, and / or transmit at least a portion of the received user input control data to at least one slave device unit, the at least one slave device unit being configured to change or adjust operation in response to at least a portion of the received user input control data.

Images