Disposable cartridge for use with a platform in a flexible system for handling and / or manipulating fluids
Through the flexible system of disposable boxes and platforms, the problem of over-fixed design of fluid treatment systems in the prior art is solved, and flexible culture of different types of cells and efficient execution of fluid treatment processes is achieved.
Patent Information
- Application Number
- CN201980038323.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2018-04-19
- Filing Date
- 2019-04-17
- Publication Date
- 2025-03-25
- Estimated Expiration
- 2039-04-17
AI Technical Summary
In the prior art, the system design for fluid treatment processes such as cell culture is too fixed, and it is difficult to adapt to the culture needs of different types of cells, and the system is complex and has a high connection error rate.
A flexible system of disposable boxes and platforms is used to connect the biological reaction chamber, conduit network and flow control device in the disposable boxes to realize the circulation and control of the fluid, supporting the flexible execution of different fluid processing processes.
It realizes flexibility and efficiency of the fluid treatment process, reduces the complexity and cost of system design and manufacturing, and improves the ease of use and reliability of the system.
Smart Images

Figure CN112437808B_ABST
Abstract
Description
Technical Field
[0001] Purpose of the Invention
[0002] The present invention includes devices and / or apparatus for manipulating and processing fluids. The present invention relates to integrating these devices and / or apparatuses in systems for manipulating and / or processing any type of fluid. Specifically, the present invention relates to disposable boxes and platforms that cooperate with each other in a flexible system for manipulating fluids, and a flexible system for manipulating fluids. More specifically, the present invention is intended for use in culturing cells. Background Art
[0003] A kind of specific system or equipment is designed for the process of each fluid treatment and / or operation now, so that the process can be carried out.More specifically, there are different bioreactors or systems that are intended to be used for the process of cultivating or growing cells now, and each of the bioreactors or systems is specific as a whole for the type of culture process and cells to be cultivated.In other words, there is not enough flexible system to allow the cultivation of different types of cells, and there is not system for other processes of handling and / or operating fluids.The process for handling and / or operating fluids can be understood as cell culture process, chemical engineering process, drug production, etc.
[0004] To date, each culture system or bioreactor has been designed to solve the problems associated with culturing a specific type of cell, taking into account that each cell type is cultured in a different way and under different physical and / or chemical conditions. Nevertheless, this practice has the following disadvantages: for each process to be performed, the equipment or system must be designed completely from scratch.
[0005] In each cell culture system or bioreactor, a large number of valves are usually used in the whole system, which are connected to a plurality of channels or pipelines included in the system. These bioreactors have the following disadvantages: in order to be able to operate the whole equipment or system, in addition to the need to connect each of these valves to the system so that they are controlled by a computer, each pipeline or channel must be placed in its corresponding position and between each valve. Therefore, the known culture system also has the disadvantages of being too artificial and complicated, and the disadvantages of being able to cause errors when making numerous connections between the components integrated in the cell culture system. Furthermore, these same disadvantages can be extrapolated to other processes for handling and / or operating fluids.
[0006] A flexible system has been developed that allows the treatment and / or manipulation of any fluid to solve these technical problems. In other words, a platform that cooperates with a disposable box (which acts as a disposable box) has been developed so that only suitable consumable elements are required for each process of treating and / or manipulating a fluid, and a single platform is always used for each process. Thus, a flexible system is provided that allows any process to be performed, in particular the cultivation of any type of cell under any physical and / or chemical conditions. Summary of the invention
[0007] The present invention proposes a solution to the aforementioned problems by means of a disposable cartridge for cooperating with a platform according to claim 1, a platform for cooperating with a disposable cartridge according to claim 11 and a flexible system for manipulating fluids according to claim 15. The dependent claims define preferred embodiments of the invention.
[0008] A first inventive aspect provides a disposable cartridge for cooperating with a platform in a system for culturing cells, characterized in that the disposable cartridge comprises:
[0009] at least one bioreactor chamber, the bioreactor chamber being suitable for storing and / or processing a fluid therein,
[0010] a network of conduits configured to circulate a fluid therein and for fluid communication with the interior of at least one bioreactor chamber, and
[0011] a flow control device for controlling the flow of a fluid circulating through the conduit network, the flow control device for controlling the flow of the fluid being configured to be connected to the actuating device of the platform through a first multi-connector,
[0012] The fluid to be circulated in the conduit network and the fluid to be stored and / or processed in the bioreactor chamber is culture medium or fluid medium or cells or any combination thereof.
[0013] Throughout the document, a "disposable box" is to be understood as a fixed element or device formed by a series of components, which in particular include one or more chambers, a conduit for fluid circulation, and a flow control device for controlling the flow of the fluid circulating through the conduit. In addition, the disposable box is understood to be a disposable element, i.e. an element that can be disposed of and replaced with another element once it has been used and / or the fluid treatment process has ended.
[0014] The disposable box that can be replaced with a new disposable box that cooperates with the same platform advantageously provides flexibility to the system for processing and / or operating fluids. In other words, there is no need to design and manufacture the entire system for a specific fluid processing process, but instead, different consumable elements that cooperate with the platform for different processes for operating and processing fluids are used.
[0015] The disposable cartridge comprises a chamber, which is understood to be a container or reservoir in which fluids can be stored in order to process and / or manipulate them by means of different processes for processing and / or manipulating fluids. More specifically, a chamber can be understood to be a bioreaction chamber or chamber in which a chemical reaction is carried out or a biological process is carried out.
[0016] The disposable cartridge further comprises a conduit network formed by a plurality of conduits and / or tubes which may be in fluid communication with each other and / or with the interior of the chamber.
[0017] The flow control device for controlling the flow of fluid is configured to be operated by the actuating device included in the platform. When the disposable box cooperates with the platform, the fluid flow control device is connected with the actuating device through the first multiple connector included in the disposable box. "Connection" will be understood as the action of making two or more parts communicated. In other words, the fluid flow control device is configured to be communicated with the actuating device of the platform.
[0018] The disposable box is configured to cooperate with the platform in the flexible system for operating fluid. In other words, when the disposable box cooperates with the platform, the different parts of the disposable box are connected or communicated with the platform or its parts. In addition, in order to make the disposable box start to cooperate with the platform or vice versa, the disposable box must be connected or communicated with the platform, such as by the connection and / or coupling between the first multi-connector of the consumable element (disposable box) and the second multi-connector of the platform, for example, for connecting the flow control device of the consumable element with the actuating device of the platform.
[0019] In a specific embodiment, the disposable box further comprises a fixing device configured to fix the disposable box to the platform. Advantageously, it can be fixed and / or coupled to and / or connected to the platform of the system for operating and / or processing fluid. In other words, due to the fixing device, the disposable box can be fixed to the platform.
[0020] In a specific embodiment, the flow control device for controlling the flow of fluid is configured to be connected in a fluid-connected manner with an actuating device by a first multi-connector. In other words, when the disposable box cooperates with the platform, the flow control device for controlling the flow of fluid is operated by the actuating device included in the platform by means of a fluid connection through the first multi-connector. In other words, there is a fluid connection between the flow control device for controlling the flow of fluid and the platform (especially the actuating device), which means that they are in fluid communication with each other.
[0021] Advantageously, the presence of a first multiconnector in the disposable box and a second multiconnector in the platform, as well as the coupling and / or connection existing between the two, facilitate the fluid connection of the pipe or connector, through which the fluid (compressed air or nitrogen) of the disposable box circulates, respectively, thanks to the actuation device of the platform providing compressed air or nitrogen.
[0022] In a more specific embodiment, the fluid communication between the flow control device for controlling the flow of the fluid and the actuation device of the platform is compressed air or nitrogen. In other words, the actuation device operates the fluid flow control device of the disposable box by means of compressed air or nitrogen.
[0023] In another specific embodiment, the flow control device for controlling the flow of fluid is configured to be connected in an electrically connected manner with the actuating device through the first multi-connector. In other words, when the disposable box cooperates with the platform, the flow control device is operated by the actuating device included in the platform by means of the electrical connection through the first multi-connector. In other words, there is electrical connection between the flow control device for controlling the flow of fluid and the platform (especially the actuating device), which means that they are electrically connected to each other.
[0024] The presence of a first multiconnector in the disposable cartridge and a second multiconnector in the platform, and the coupling and / or connection therebetween, advantageously facilitate electrical connection of the disposable cartridge or tubing to the actuation device of the platform, thereby providing electrical communication.
[0025] In a more specific example, culture medium and initial cells are initially contained within at least one chamber to obtain a desired cell culture.
[0026] In a specific embodiment, the disposable box includes a plurality of containers, the plurality of containers are connected to the conduit network, the plurality of containers are suitable for storing fluids therein, and the plurality of containers are configured to be in fluid communication with each other and / or with the interior fluid of at least one bioreactor chamber.
[0027] Each of the multiple containers included in the disposable cassette is understood to be a storage container or chamber, each storage container or chamber having a different purpose depending on its application (i.e., depending on the fluid treatment process involved). Advantageously, the disposable cassette gives the user overall freedom to design a fluid treatment process and to perform the fluid treatment process with a single piece of equipment (i.e., with a single system for handling and / or processing fluids).
[0028] In a more specific embodiment, the disposable cartridge includes a residue container connected to the conduit network, the residue container being configured to contain fluid residue from at least one chamber therein. In another specific embodiment, the disposable cartridge includes a reservoir, the reservoir being configured to store a fluid or a final product, the reservoir being in fluid communication with the interior of the at least one chamber via the conduit network.
[0029] The residue container advantageously allows the storage of fluids circulating through the conduit network and fluids from the interior of the chamber or even other fluids from other containers included in the interior of the disposable box (such as cleaning fluids from a cleaning container). The residue container is in fluid communication with the interior of at least one chamber through the conduit network. In addition, the residue container is suitable for storing therein remaining fluids or fluids that are negligible or uninteresting to the user during the process of handling or operating the fluid.
[0030] In the specific example of cell culture, remaining culture medium or culture medium residue from the chamber is transferred to a residue container.
[0031] A reservoir is understood to be a final container in which a fluid or final product is stored (i.e., the resulting fluid, final product, or part thereof of interest after processing and / or manipulating one or more initial fluids initially inside a chamber), or is introduced into a chamber for a process of processing and / or manipulating at least one fluid. Advantageously, a fluid or a combination of several fluids can be obtained directly from a reservoir as a final product without having to perform additional steps to obtain the desired final product. In a specific example of cell culture, the desired final product or fluid will be understood to be the cultured cells or final cells and / or culture medium, and the desired final product or fluid will be contained in a reservoir.
[0032] In a specific embodiment, at least one bioreactor chamber is configured to receive at least one first initial product from the first preparation chamber via the conduit network. For the specific example of cell culture, the first initial product can be understood as initial cells or initial cells and culture medium.
[0033] In a more specific embodiment, at least one bioreactor chamber is further configured to receive a second initial product from a second preparatory chamber by means of a conduit network, preferably through a first preparatory chamber. In other words, the second preparatory chamber can be directly fluidically connected to the interior of at least one chamber. However, the second preparatory chamber will preferably be fluidically connected to the first preparatory chamber, i.e., the second initial product is initially introduced into the interior of the first preparatory chamber and then transported to the interior of at least one chamber through the conduit network together with the first initial product. For the specific example of cell culture, the second initial product can be understood as a culture medium, i.e., a culture medium suitable for culturing cells.
[0034] In a particular embodiment, the disposable cartridge comprises at least one first preparation chamber suitable for storing at least one first initial product, wherein the first preparation chamber comprises a first inlet for introducing the first initial product therein.
[0035] At least one first fluid or initial product is initially contained in a first preparation chamber (ie, prior to a process for treating and / or manipulating the fluid) and then circulated or transported through the network of conduits to the interior of the chamber for subsequent treatment or manipulation.
[0036] In this specific embodiment, the first preparation chamber is located in the disposable cartridge. However, in another specific embodiment, the first preparation chamber is not part of the disposable cartridge and can be arranged in the platform or outside the system for processing and / or operating fluids.
[0037] In another more specific embodiment, the first preparatory chamber initially accommodates at least one first initial product, and at least one chamber accommodates a second initial product. In other words, when the first initial product from the first preparatory chamber is introduced into the interior of the chamber, it reacts with the second initial product, causing the processing or operation of the fluid (product). Nevertheless, the presence of the first preparatory chamber advantageously allows at least one initial product to be initially accommodated in a container, rather than being accommodated in at least one chamber in which fluid processing and / or operation will be performed, and therefore this prevents the processing of the fluid from starting or suddenly starting before the expectation.
[0038] In a more specific embodiment, the first preparatory chamber includes a second inlet for introducing a second initial product from the second preparatory chamber. In a more specific embodiment, the second preparatory chamber is located in a disposable box. In another specific embodiment, the second preparatory chamber is located in the platform. In the specific example of cell culture, it should be understood that before the cell culture process begins, that is, before the two initial products are introduced into the interior of the chamber and the processing and / or operation of the fluid begins, the culture medium contained in the second preparatory chamber can be introduced into the first preparatory chamber together with the initial cells or the initial cells with the medium.
[0039] In another specific embodiment, the disposable cartridge includes at least one sensor coupled to the conduit network, the at least one sensor configured to measure at least one fluid parameter.
[0040] At least one sensor included in the disposable cartridge is configured to be connected to a processing device of a control unit of the platform. Advantageously, the presence of one or more sensors allows the control of the processing of at least one fluid contained in the chamber and / or circulating through the conduit network. In the specific example of cell culture, these sensors allow the control of the state of cells and culture medium during the cell culture process implemented inside the bioreactor chamber.
[0041] In a specific embodiment, the disposable cartridge includes a cleaning container connected to the conduit network, the cleaning container being configured to release a cleaning fluid from an interior thereof along the conduit network.
[0042] In a specific embodiment, the disposable cartridge includes a regulating device configured to regulate at least one of the initial products before introducing it into the interior of at least one bioreactor chamber. The regulating device can regulate the pH of the fluid or the concentration of dissolved O2 in the fluid, or the ionic force of the fluid, etc. Advantageously, the initial fluid can be regulated by the regulating device before entering the interior of at least one chamber.
[0043] In a more specific embodiment, the regulating device is a heating device, which is configured to heat at least one of the initial products before being introduced into the interior of at least one bioreactor chamber. In other words, if one of the initial products is contained in the preparatory chamber at a specific temperature or these same initial products are themselves at a specific temperature, the specific temperature is preferably less than the initial required temperature, and the temperature of the initial product can be advantageously changed by these heating devices before it is introduced into the interior of at least one chamber. In a more specific embodiment, the heating device is a heater. For the specific example of cell culture, if the culture medium is subjected to a temperature lower than the required temperature, the culture medium can be heated by these heating devices. However, due to the introduction of the culture medium into the first preparatory chamber or directly into the interior of the bioreactor chamber, the culture medium of the cultured cells of interest must be heated before it contacts the initial cells.
[0044] In a specific embodiment, the flow control device for controlling the flow of the fluid is:
[0045] valve, or
[0046] Pump, or
[0047] A combination of the above.
[0048] In a more specific embodiment, the valve is a pipe pinch valve and / or a solenoid valve. Advantageously, the use of this type of valve does not interfere with the pipe or conduit.
[0049] In another more specific embodiment, these pumps are peristaltic micropumps. Peristaltic micropumps are configured to drive or circulate fluid through a conduit, and they can also act as conventional pumps or valves. In addition, this type of micropump can be disposable.
[0050] In a specific embodiment, system includes a device for driving the fluid contained in at least one chamber to circulate through the conduit network. In a more specific embodiment, the device for driving the fluid circulation is a peristaltic pump or compressed air injection or a connected container or a combination thereof. The peristaltic pump for driving the fluid contained in the chamber is mainly formed by a motor and a head, and the motor is understood as an actuator, and the head has an inlet and an outlet connected to the conduit of the actual conduit network of the disposable box. Specifically, the pump motor is located in the platform, and the inlet and outlet of the pump head connected with the conduit network are a part of the disposable box itself. In a specific embodiment in which the disposable box is coupled to the platform, the head of the disposable box is connected and / or coupled to the motor arranged in the platform. In a more specific embodiment, at least one peristaltic pump, especially the pump motor, is configured to be fixed to the fixed structure of the platform by a fixing device.
[0051] In a specific embodiment, the disposable box includes a housing structure, at least one chamber, a portion of the conduit network, and a flow control device for controlling the flow of the fluid are contained in the housing structure, wherein the housing structure is configured to be fixed to a first structure of the platform by a fixing device, and the first structure can be understood as a convex structure. In a more specific embodiment, these fixing devices are a second structure, which can be understood as a concave structure, and the concave structure is configured to be fixed and / or coupled to the first structure (i.e., the convex structure of the platform).
[0052] Advantageously, the housing structure allows easy integration in the platform, thus simplifying the connection and / or integration of the disposable cartridge with the platform.
[0053] In another specific embodiment, the remnant container and the reservoir are located outside the housing structure and are configured to be housed in the second compartment of the platform, wherein the remnant container and the reservoir are both fluidically connected to the interior of the housing structure via an external conduit connected to the conduit network or the interior of the chamber and are adapted to be connected by means of a connector. In the specific case of cell culture, the connector is sterile.
[0054] The fact that both the reservoir and the residual container are located outside the housing structure advantageously allows, in processes where more than one final fluid or excess fluid residual is available, both the reservoir and the residual container to be replaced with a new container. Furthermore, in the specific embodiment of cell culture or in other processes where it is important not to contaminate the fluid circulating through the system from the outside, the fact that both the reservoir and the residual container can be replaced with a new container due to the sterile connectors results in such replacement or substitution of the containers without disturbing the disposable cartridge.
[0055] In another specific embodiment, the heating device is configured to be housed in the second compartment of the platform.
[0056] In another specific embodiment, the housing structure is configured to include a temperature therein that is higher than a temperature of the storage module of the fixture.
[0057] In a second invention aspect, the present invention provides a platform for cooperating with the disposable cartridge of any one of the embodiments of the first invention aspect in a system for culturing cells, characterized in that the platform comprises:
[0058] an actuating device adapted to act on the flow control device to control the flow of the fluid of the disposable cartridge,
[0059] a second multiconnector configured to connect the first multiconnector of the disposable cartridge and the actuation means, and
[0060] A control unit is configured to control the operation of the actuating device and the disposable box.
[0061] When the disposable box cooperates with the platform, the second multi-connector is coupled to or connected to the first multi-connector of the disposable box. Advantageously, these multi-connectors allow the connection of each of the flow control devices for controlling the flow of the fluid with the actuating device to be centralized through the multi-connector, thereby allowing a simple and fast connection between the disposable box and the platform due to the coupling of these multi-connectors.
[0062] The control unit is responsible for controlling the actuation means and the flow control means in order to control the flow of the fluid located in the disposable cartridge and operated by the actuation means.
[0063] In a specific embodiment, the platform comprises a first structure, which can be understood as a convex structure configured to fix the disposable box, preferably its housing structure, thereon.
[0064] In a specific embodiment, when the flow control device for controlling the flow of the fluid of the disposable box is configured to be connected in fluid communication with the actuation device through the first multi-connector, the actuation device is a gas distribution device, and they are configured to be in fluid communication with the disposable box through the first multi-connector and the second multi-connector. More specifically, the gas distribution device is a device for distributing compressed air or nitrogen or air enriched with CO2.
[0065] In a specific embodiment, when a flow control device for controlling the flow of fluid in a disposable box is configured to be electrically connected to an actuating device through a first multi-connector, the actuating device is a current distribution device, and they are configured to be electrically connected to the disposable box through the first multi-connector and the second multi-connector.
[0066] In a specific embodiment, the platform includes a storage module configured to be in fluid communication with the disposable cartridge and for maintaining a predetermined temperature therein. In a more specific embodiment, the storage module includes a second preparation chamber adapted to store a second initial product, the second preparation chamber configured to be in fluid communication with the disposable cartridge. In a specific example of cell culture, the culture medium can be stored in the second preparation chamber located in the storage module at a temperature lower than the internal temperature of the disposable cartridge.
[0067] In a specific embodiment, when the disposable cartridge includes a pump for driving the inflowing fluid, the platform further includes a pump motor configured to be connected or coupled to a pump head arranged in the disposable cartridge. In particular, the pump motor is operated by a control unit of the platform.
[0068] In a third aspect of the invention, the present invention provides a system for culturing cells, the system comprising:
[0069] The disposable cartridge according to any one of the embodiments of the first inventive aspect, and
[0070] A platform according to any one of the embodiments of the second inventive aspect.
[0071] From the perspective of flexibility, this system is advantageously interesting because it allows to perform different processes for processing and / or operating fluids by integrating disposable boxes with platforms. In other words, the disposable boxes required for the desired process only depend on the process to be performed, and the disposable boxes must be integrated in the platform or connected to the platform. In addition, in some fluid handling processes, the process itself changes, that is, it has such steps, and in order to implement these steps, it is necessary for the system to have special parts that have been originally included in the consumable elements and must be replaced, or they need to be combined with new parts to the consumable elements, or even be combined with the platform. In order to continue working in a particular process, in this way, it is enough to change the consumable elements and redesign its parts or platform parts.
[0072] The system is easy to install and use, which advantageously reduces connection failures between components, wherein it is necessary only to couple the disposable cartridge to the platform and begin the process for handling and / or manipulating the fluid.
[0073] In other words, the same platform can be used to control and execute any desired fluidic process. For example, different types of cells can be cultured without having to design an entire cell culture system or bioreactor for a specific cell culture process. Likewise, any type of cell desired can be cultured in any fluid dynamic configuration by simply changing the disposable cartridge coupled to the platform for use in conjunction therewith.
[0074] All features and / or steps of the methods described in this specification (including claims, description and drawings) may be combined in any combination, except those combinations of mutually exclusive features. BRIEF DESCRIPTION OF THE DRAWINGS
[0075] These and other characteristics and advantages of the present invention will be more clearly understood on the basis of the following detailed description of preferred embodiments given purely by way of illustrative and non-limiting examples with reference to the accompanying drawings.
[0076] Figure 1A A specific example of a flexible system according to the invention is schematically shown.
[0077] Figure 1B A specific example of a flexible system according to the invention is schematically shown.
[0078] Figure 2 A perspective view of a platform according to a specific example of the present invention is shown.
[0079] Figure 3A A perspective view showing a housing structure of a disposable cartridge according to a specific example of the present invention.
[0080] Figure 3BA rear view showing a housing structure of a disposable cartridge according to a specific example of the present invention.
[0081] Figure 4 A perspective view showing details of a flexible system according to a specific example of the invention.
[0082] Figure 5 A perspective view showing details of a flexible system according to another specific example of the present invention.
[0083] Figure 6 A specific example of a segment of a flexible system according to the invention is schematically shown.
[0084] Figure 7 A specific example of a segment of a flexible system according to the invention is schematically shown. DETAILED DESCRIPTION
[0085] Figure 1 to Figure 5 A specific example of the invention is shown, wherein the flexible system (1) is a system for culturing cells. In this specific example, the chamber (4) is a bioreactor chamber and the fluid is a culture medium, a culture medium with cells and / or a cleaning fluid.
[0086] Figure 1A to Figure 1B A system (1) for culturing cells is schematically shown, the system (1) comprising a platform (2) and a disposable cartridge (3) cooperating with each other.
[0087] Specifically, Figure 1A to Figure 1B The disposable box (3) shown in the figure has a bioreactor chamber (4) for culturing cells, the bioreactor chamber (4) is fluidically connected to a first preparation chamber (13), and an initial product (such as a culture medium and cells suspended therein) is stored in the first preparation chamber (13). In addition, the chamber (4) is fluidically connected to a first reservoir (11), for example, a desired final product (such as cells cultured in a culture medium) is stored in the first reservoir (11). Furthermore, the bioreactor chamber (4) is fluidically connected to a residue container (10), and the remaining residual fluid (such as remaining culture medium) from the bioreactor chamber (4) is stored in the residue container (10). Specifically, Figure 1B A cleaning container (12) is also shown, in which a cleaning fluid or phosphate buffered saline (PBS) is stored. In a specific example, the preparation chamber (13) has a first inlet (14) and a second inlet (15), and cells are introduced through the first inlet (14) and culture medium is introduced through the second inlet (15) (e.g., Figure 7 The second inlet (15) is in fluid communication with a second preparation chamber (16) arranged in a storage module (17) of the platform (2) (as shown). Figure 1BBefore the medium from the second preparation chamber (16) is introduced into the first preparation chamber (13), the medium will flow through the heating device (20), which heats the medium, that is, they change the temperature of the medium, so that the medium is introduced into the first preparation chamber (13) together with the initial cells. Figure 1A to Figure 1B In the system shown, the chamber (4) and the different containers or devices arranged in the system are fluidically connected to each other through a conduit network (5) formed by a plurality of pipes or conduits. Each of the flow control devices for controlling the flow of the fluid is connected to the first multi-connector (9a) through a pipe or conduit, and the compressed air from the actuator device (7) located in the platform (2) circulates through the pipe or conduit. These flow control devices for controlling the flow of the fluid are a combination of a valve (6) and a pump (30, 37). Specifically, in these examples, the valve (6) is a pinch valve, and the pump (30, 37) is a peristaltic pump and / or a micro pump (6) for driving the fluid (30). Specifically, the micro pump (37) is part of the disposable box and is fluidically connected to the first multi-connector (9a), and the peristaltic pump (30) for driving the fluid is formed by a pump motor (36) and a pump head (23), the pump motor (36) is located in the platform (2) (not shown in the figure), and the pump head (23) is located in the disposable box (3) (as shown in the figure). Figure 5 ) and coupled to a pump motor (36).
[0088] A first multiconnector (9a) arranged in the disposable box (3) is coupled to a second multiconnector (9b) arranged in the platform (2). In addition, the second multiconnector (9b) is connected to the actuating means (7) by means of a pipe or conduit, through which the flow control means delivered to the disposable box (3) is used to operate the compressed air circulation.
[0089] Figure 1A to Figure 1B The platform (2) shown in the figure also has a control unit (18), which controls the disposable cartridge (3), the actuation means (7) and the storage module (17).
[0090] In the specific example of cell culture, the storage module (17) has a temperature of 4°C therein, while the housing structure (21) containing the disposable cartridge (3) has a temperature of 37°C.
[0091] Specifically, Figure 1B The flexible system (1) shown in also has two sensors (26) located in the conduit network (5). These sensors (26) are configured to detect properties of interest of the fluid circulating through the conduit network (5).
[0092] Figure 2A perspective view of a platform (2) of a system (1) for cell culture is shown, the system (1) not having any component of a disposable cassette (3). As can be seen in the figure, the platform (2) comprises a storage module (17) arranged at one end of the platform (2), which storage module (17) is understood as a refrigerator, because it stores therein, for example, culture medium, cleaning fluid or other fluid at a specific temperature, which is preferably lower than the temperature of the disposable cassette (3) or the structure or compartment to which the disposable cassette (3) is fixed to the platform (2).
[0093] The platform (2) also has a first compartment (28) at its other end, the first compartment (28) being configured to accommodate the disposable box (3) therein. Furthermore, the platform (2) includes a second compartment (24) in a lower portion relative to the first compartment (28), the second compartment (24) being suitable for accommodating a first reservoir (11), a residue container (10) and a heating device (20). The first compartment (28) of the platform (2) includes a convex structure (22), and the shell structure (21) of the disposable box (3) is fixed to the convex structure (22) by its concave structure (8) (fixing device). In addition, the first compartment (28) of the platform (2) includes a fixing structure (19), and the motor (36) (not shown) of the peristaltic pump (30) is positioned in the fixing structure (19), and the head (23) of the peristaltic pump (30) of the disposable box (3) is coupled or fixed to the motor (36) (as in Figure 5 The first compartment (28) also includes an actuating device (7) (not shown in the figure), which is in fluid communication with the flow control device of the disposable box (3) through a first multi-connector (9a) (not shown in the figure) and a second multi-connector (9b). In this particular example, the platform (2) has two second multi-connectors (9b).
[0094] The first compartment (28) of the platform (2) has a first door (29) closing the first compartment (28). In turn, the second compartment (24) has a second door (31) closing the second compartment (24). Thus, each compartment (24, 28) can be accessed independently of the other, so that it is advantageously possible to extract, for example, the final product from the reservoir (11) or the residue stored in the residue container (10) without having to disturb the first compartment (28). In particular, the first door (29) of the first compartment (28) has a first window (32), which advantageously allows the interior of the compartment to be seen during the cell culture process.
[0095] Likewise, the platform (2) has a control unit (18) arranged between the storage module (17) and the first compartment (28). The control unit (18) comprises a display device (33) on which information about the cell culture is displayed in addition to information related to the storage module (17) and the first compartment (28).
[0096] In a specific example, the platform comprises a storage module 17, a control unit 18 and a plurality of first compartments 28 and second compartments 24. Thus, different cell culture processes can be carried out simultaneously, all of which are controlled by the control unit 18.
[0097] FIG. 3A to FIG. 3B The housing structure (21) of the disposable cartridge (3) is shown, wherein the chamber (4) and other components (not shown in the drawings) are accommodated in the housing structure. Figure 3A A perspective view of a housing structure (21) is shown, in which it can be observed in more detail that the structure comprises a series of holes (34) through which different connections and / or communications of the disposable box (3) with the platform (2) and with the actual components integrated in the disposable box (3) are realized. The housing structure (21) comprises a first part, in which the holes (34) are arranged, and a second part, which is understood to be a cover of the housing structure (21). This cover or second part of the housing structure has a second window (35) through which the interior of the housing structure (21) and the elements integrated therein can be seen. In addition, this second part or cover of the housing structure (21) has a closing device, by which the second part is closed and / or assembled with the first part, so that the housing structure (21) appears as a closed structure or compartment. Figure 3B A rear view of the shell structure (21), in particular a rear view of the first part of the structure, is shown, wherein a concave structure (8) (fixing device) can be seen, which is configured to be coupled and / or fixed to a convex structure (22) of the platform (2).
[0098] Figures 4 to 5A perspective view of a compartment (24, 28) of a platform (2) and a disposable box (3) fixed to the platform (2) is shown. In both figures, the housing structure (21) can be seen coupled to the platform in the first compartment (28) of the platform (2). In addition to the two heads (23) of the peristaltic pump (30) coupled to the pump motor (36) in the fixed structure (19) of the platform (2), two second multiple connectors (9b) can be seen arranged one by one in the first compartment (28). These figures also show the second compartment (24), in which the first reservoir (11), the residue container (10) and the heating device (20) are located. Furthermore, the second compartment (24) has through grooves (27) through which pipes and / or conduits as part of the conduit network (5) pass, and the pipes and / or conduits connect the second preparation chamber (16) arranged in the storage module (17) (not shown) to the disposable box (3) fluid through the heating device (20). In addition, as Figure 4 and Figure 5 As shown, two sterile connectors (25) are coupled to the first compartment (28), the two sterile connectors (25) being part of the disposable cassette (3) and being adapted to maintain fluid communication along the conduit network (5) in the system (1).
[0099] Figure 5 Shown with Figure 4 The same perspective and the different connections and / or communications between the components integrated in the compartments 24, 28. Figure 5 In the figure, two heads (23) of the peristaltic pump (30) of the disposable cassette (3) can be seen, which are coupled to the fixed structure (19) of the platform (2), in which the pump motor is located. These pump heads 23 are in fluid communication with the interior of the housing structure 21 by means of the duct network 5 passing through these holes 34. It can be seen in particular how each pump head 23 has a duct inlet and a duct outlet of the duct network 5 of the disposable cassette 3. Figure 5 Also shown are two first multi-connectors (9a) each coupled to a second multi-connector (9b), and how these multi-connectors are in fluid communication with the interior of the housing structure (21) via a series of pipes and / or ducts through which the compressed air from the actuating device (7) circulates. In this specific example, for example, the actuating device (7) is a compressed air distribution device, such as a compressed air distribution rack or the like.
[0100] Figure 5It is also shown how the residue container (10) and the reservoir (11) are in fluid communication with the interior of the housing structure (21) independently of each other by means of a network of conduits (5) passing through holes (34). These conduits (5) that communicate the containers (10, 11) with the interior of the housing structure must be sterile, so there is a sterile connector (25) connected to each conduit (5) to keep the communication sterile.
[0101] same, Figure 5 It shows how the heating device 20 is connected by means of a through hole 34 ( Figure 3A The conduit network 5 (shown in FIG. 1 ) is connected to the internal fluid of the shell structure 21.
[0102] Figure 6 and Figure 7 The schematic diagram shows a first preparation chamber (13) having a first inlet (14) and a second inlet (15), into which the initial cells are introduced through the first inlet (14) and into which the culture medium is introduced through the second inlet (15). In addition, it shows how the first preparation chamber (13) is connected to the chamber (4) via a conduit network (5), in particular via a pipe / conduit, on which a pinch valve (6) is located for regulating the passage of cells suspended in the culture medium to the interior of the chamber (4).
[0103] Figure 7 It is also shown how the second inlet (15) is connected to a second preparation chamber (16) located in a storage module (17) arranged in the platform (2), the second preparation chamber (16) storing culture medium therein under specific temperature conditions. The connection between the second inlet (15) and the second preparation chamber (16) is implemented by a conduit network (5), in particular by a pipe / conduit, on which a pinch valve (6) is positioned for regulating the passage of culture medium to the second inlet (15).
[0104] In a preferred illustrative embodiment as “Embodiment 1”, a disposable cartridge (3) for cooperating with a platform (2) in a flexible system (1) for handling and / or manipulating fluids, characterized in that the disposable cartridge (3) comprises:
[0105] at least one bioreactor chamber (4) suitable for storing and / or processing fluids therein,
[0106] a network of conduits (5) configured to circulate a fluid therein and for communicating with the interior fluid of the at least one bioreactor chamber (4), and
[0107] A flow control device for controlling the flow of a fluid circulating through the conduit network (5), the flow control device for controlling the flow of the fluid being configured to be connected to an actuating device (7) of the platform (2) via a first multi-connector (9a).
[0108] "Example 2", according to the disposable box (3) described in "Example" 1, is characterized in that the flow control device for controlling the flow of the fluid is configured to be connected to the actuator device (7) of the platform (2) in a fluid-connected manner through the first multi-connector (9a).
[0109] "Example 3", according to the disposable box (3) described in "Example" 1, is characterized in that the flow control device for controlling the flow of the fluid is configured to be electrically connected to the actuator device (7) of the platform (2) through the first composite connector (9a).
[0110] "Example 4", according to the disposable box (3) described in any one of the aforementioned "Examples", it is characterized in that the disposable box (3) includes a plurality of containers, the containers are connected to the conduit network (5), the containers are suitable for storing fluids therein, and the containers are configured to be fluidically connected to each other and / or to the internal fluid of the at least one biological reaction chamber (4).
[0111] "Example 5", according to any one of the disposable boxes (3) described in the above "Examples", characterized in that the at least one bioreactor chamber (4) is configured to receive at least the first initial product from the first preparation chamber (13) through the conduit network (5).
[0112] "Example 6", according to the disposable box (3) described in "Example" 5, it is characterized in that the at least one bioreactor chamber (4) is configured to receive the second initial product from the second preparation chamber (16) with the aid of the conduit network (5), preferably through the first preparation chamber (13).
[0113] "Example 7", according to any one of "Example" 5 or "Example" 6, the disposable box (3) is characterized in that the disposable box (3) includes at least a first preparation chamber (13), and the at least first preparation chamber (13) is suitable for storing at least a first initial product, wherein the first preparation chamber (13) includes a first inlet (14) for introducing the first initial product therein.
[0114] "Example 8", a disposable box (3) according to "Example" 6 and "Example" 7, is characterized in that the first preparatory chamber (13) includes a second inlet (15), and the second inlet (15) is used to introduce a second initial product from the second preparatory chamber (16).
[0115] "Example 9", according to any one of "Examples" 7 to 8, the disposable box (3) is characterized in that the disposable box includes an adjustment device (20), and the adjustment device (20) is configured so that at least one of the initial products is adjusted before being introduced into the interior of the at least one biological reaction chamber (4).
[0116] "Example 10", according to any one of the disposable boxes (3) described in the aforementioned "Examples", characterized in that the disposable box (3) includes a device for driving the fluid contained in the at least one biological reaction chamber (4) to circulate through the conduit network (5).
[0117] "Embodiment 11", a platform (2) for cooperating with a disposable cartridge (3) according to any one of "Embodiments" 1 to 10 in a flexible system (1) for processing and / or manipulating fluids, in particular for cell culture, characterized in that the platform (2) comprises:
[0118] an actuating device (7) adapted to act on the flow control device to control the flow of the fluid in the disposable cartridge (3),
[0119] a second multiconnector (9b) configured to connect the first multiconnector (9a) of the disposable cassette (3) and the actuating means (7), and
[0120] A control unit (18) configured to control the operation of the actuation means (7) and the disposable cartridge (3).
[0121] "Example 12", according to the platform (2) described in "Example 11", it is characterized in that when the disposable box (3) is according to "Example 2", the actuating device (7) is a gas distribution device, and the actuating device (7) is configured to be fluidically connected to the disposable box (3) through the first multi-connector (9a) and the second multi-connector (9b).
[0122] "Example 13", according to the platform (2) described in "Example 11", is characterized in that when the disposable box (3) is according to "Example 3", the actuating device (7) is a current distribution device, and the actuating device (7) is configured to be electrically connected to the disposable box (3) through the first multi-connector (9a) and the second multi-connector (9b).
[0123] "Example 14", according to the platform (2) described in any one of "Examples" 11 to 13, it is characterized in that the platform includes a storage module (17), which is configured to be fluidically connected to the disposable box (3) and to maintain a preset temperature therein.
[0124] "Example 15", a flexible system (1) for processing and / or manipulating a fluid, preferably for cell culture, comprising:
[0125] A disposable box (3) according to any one of Embodiments 1 to 10, and
[0126] A platform (2) according to any one of Embodiments 11 to 14.
Claims
1. A disposable cartridge (3) configured to cooperate with a platform (2) in a system (1) for culturing cells, characterized in that The disposable box (3) comprises: at least one bioreactor chamber (4) suitable for storing and / or processing fluids therein, a conduit network (5) configured to circulate a fluid therein and to communicate with the interior fluid of the at least one bioreactor chamber (4), flow control means for controlling the flow of a fluid circulating through the conduit network (5), the flow control means for controlling the flow of the fluid being configured to be operated by an actuation means (7) included in the platform (2), and a first multiconnector (9a) configured to be connected to a second multiconnector (9b) of the platform, wherein The fluid to be circulated in the conduit network (5) and the fluid to be stored and / or processed in the bioreactor chamber (4) are culture medium or fluid medium or cells or any combination thereof; When the disposable box (3) cooperates with the platform (2): The connection between the first multiconnector (9a) of the disposable cartridge (3) and the second multiconnector (9b) of the platform (2) is configured to connect the flow control device with the actuation device (7) of the platform (2) in fluid or electrical communication; and The flow control device is connected to the first multi-connector (9a) through a plurality of tubes or pipes or connectors, and the fluid or current from the actuating device (7) of the platform (2) circulates through the plurality of tubes or pipes or connectors.
2. The disposable box (3) according to claim 1, characterized in that: The disposable box (3) comprises a plurality of containers connected to the conduit network (5), the containers being suitable for storing fluid therein and being configured to be in fluid communication with each other and / or with the interior fluid of the at least one bioreactor chamber (4).
3. A disposable cartridge (3) according to any one of the preceding claims, characterized in that The at least one bioreactor chamber (4) is configured to receive at least a first initial product from the first preparation chamber (13) via the conduit network (5).
4. The disposable box (3) according to claim 3, characterized in that: The at least one bioreactor chamber (4) is configured to receive the second initial product from the second preparatory chamber (16) via the first preparatory chamber (13) by means of the conduit network (5).
5. The disposable box (3) according to claim 4, characterized in that: The disposable cartridge (3) comprises at least one first preparation chamber (13) suitable for storing at least a first initial product, wherein the first preparation chamber (13) comprises a first inlet (14) for introducing the first initial product therein.
6. The disposable box (3) according to claim 5, characterized in that: The first preparatory chamber (13) comprises a second inlet (15) for introducing a second initial product from the second preparatory chamber (16).
7. The disposable box (3) according to claim 6, characterized in that: The disposable cartridge comprises conditioning means (20) configured such that at least one of the first initial product and the second initial product is conditioned before being introduced into the interior of the at least one bioreactor chamber (4).
8. A disposable cartridge (3) according to claim 1 or 2, characterised in that The disposable cartridge comprises means for driving the fluid contained in the at least one bioreactor chamber (4) to circulate through the conduit network (5).
9. A platform (2) configured to cooperate with a disposable cartridge (3) according to any one of claims 1 to 8 in a system (1) for culturing cells, characterized in that: The platform (2) comprises: an actuating device (7) adapted to act on the flow control device to control the flow of the fluid in the disposable cartridge (3), a second multiconnector (9b) configured to connect the first multiconnector (9a) of the disposable box (3) and the actuating device (7), so that when the disposable box (3) cooperates with the platform (2), the connection between the first multiconnector (9a) of the disposable box (3) and the second multiconnector (9b) of the platform (2) is configured to connect the flow control device for controlling the flow of fluid with the actuating device (7) in a fluid-connected or electrically connected manner; and A control unit (18) configured to control the operation of the actuation means (7) and the disposable cartridge (3).
10. The platform (2) according to claim 9, characterized in that The actuation device (7) is a gas distribution device and is configured to be in fluid communication with the disposable cassette (3) through the first multiconnector (9a) and the second multiconnector (9b).
11. The platform (2) according to claim 9, characterized in that The actuating device (7) is a current distribution device, and the actuating device (7) is configured to be in electrical communication with the disposable cartridge (3) through the first multiconnector (9a) and the second multiconnector (9b).
12. The platform (2) according to any one of claims 9 to 11, characterized in that The platform includes a storage module (17) configured to be in fluid communication with the disposable cartridge (3) and to maintain a predetermined temperature therein.
13. A system (1) for culturing cells, comprising: A disposable cartridge (3) according to any one of claims 1 to 8, and A platform (2) according to any one of claims 9 to 12.
Citation Information
Patent Citations
Integration of fluids and reagents into self-contained cartridges containing particle and membrane sensor elements
US20060257941A1
Biochemical cartridge, and biochemical cartridge and cartridge holder set
US20150361387A1
Apparatus and method for maintaining and growing biological cells
WO1996040858A1