Modular Bioprocessing Systems

Abstract

The present disclosure relates to a modular bioprocessing system having multiple bioprocessing modules, each of which independently accepts a biological handling vessel and performs one or more unit operations on the biological handling vessel and / or its contents, and a robot that moves the biological handling vessel between each of the multiple bioprocessing modules.

Description

[Technical Field]

[0001] The present invention relates to a modular bioprocessing system and method for processing materials, such as biological materials. [Background technology]

[0002] The large-scale manufacturing process of biopharmaceuticals is costly because each unit operation requires significant human labor. In particular, cell and / or gene therapy manufacturing processes involve multiple unit operations performed in various systems that do not synergize with each other, thus increasing process complexity and costs for therapeutic drug manufacturers. As a result, access to therapeutic drugs is limited for the majority of patients. Therefore, affordable cell-based research and / or therapeutic drug manufacturing systems are becoming increasingly important for patients.

[0003] More recently, there has been a shift toward automated cell-based research and / or therapeutics manufacturing systems. In some instances, automated systems have been provided in which entire modules and devices are moved between various locations in the system for appropriate processing. However, such systems have numerous drawbacks. For example, such systems require complex and mechanically robust robotic mechanisms to enable the transfer of such heavy devices between locations, which are often expensive. Additionally, such systems have difficulty incorporating new and existing processing technologies, which are sometimes required by end users. This is because new modules require the entire module to be fabricated, rather than simply incorporating commercially available devices directly into the system. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2021 / 123760 Summary of the Invention [Problem to be solved by the invention]

[0005] It is therefore an object of the present invention to provide a scalable, automated, cost-effective bioprocessing system, particularly one capable of producing biological therapeutics such as cell and / or gene therapy products.

[0006] Yet a further object of the present invention is to provide a scalable automated bioprocessing system that can be automated cost-effectively and / or made compatible with new or existing commercially available technologies. [Means for solving the problem]

[0007] According to one aspect of the present invention, a modular bioprocessing system is provided comprising a plurality of bioprocessing modules, each bioprocessing module independently configured to receive at least one biological handling vessel and perform one or more unit operations on the biological handling vessel and / or contents of the biological handling vessel, and a robot configured and arranged to transfer the biological handling vessel or each biological handling vessel between each of the plurality of bioprocessing modules.

[0008] That is, there are several, i.e., two or more, bioprocess modules, each capable of accepting one or more biological handling vessels. Each bioprocess module may have a portion, such as a holder, gripper, mounting plate, drawer, stand, etc., for accepting one or more biological handling vessels. Alternatively or additionally, each bioprocess module may have a portion, such as an actuator, plunger, gripper, sensor, etc., that allows one or more unit operations to be performed on the biological handling vessel itself, on the contents within the biological handling vessel, or on both the biological handling vessel itself and the contents within the biological handling vessel. In particular, each bioprocess module may include an actuator configured to actuate a connector, such as a needle-based connector, coupled to the biological handling vessel. Alternatively or additionally, the actuator may be configured to actuate the biological handling vessel to dispense the contents of the biological handling vessel. In particular, the actuator can be configured to apply a force, such as a compressive force, on at least a portion of the biological handling container, where the at least a portion of the biological handling container is flexible and / or compressible. The actuator configured to actuate the connector and / or the biological handling container can be formed as a single actuator or as separate actuators.

[0009] That is, a robot is provided for transferring one or more biological handling vessels between each of the bioprocess modules. The robot may include a robotic arm, gripper, etc., that allows the robot to accept or collect a biological handling vessel from one bioprocess module. The robot may also be mounted on rails, wheels, etc. to enable movement between the bioprocess modules. The robot may also include an actuator configured to actuate a portion of the biological handling vessel. The actuator may be configured to actuate a connector, such as a needle-based connector, coupled to the biological handling vessel. Alternatively, or in addition, the actuator may be configured to actuate the biological handling vessel to dispense the contents of the biological handling vessel. In particular, the actuator may be configured to apply a force, such as a compressive force, on at least a portion of the biological handling vessel, where the at least a portion of the biological handling vessel is flexible and / or compressible. The actuator configured to actuate the connector and / or the biological handling vessel may be formed as a single actuator or as separate actuators.

[0010] As used herein, the term "bioprocessing system" is intended to refer to a system capable of performing one or more operations in the manufacture of a biopharmaceutical, such as a cellular drug. The term "biopharmaceutical manufacturing system" may be used interchangeably. Such operations include, but are not limited to, analyzing, preparing, processing, storing, modifying, manipulating, culturing, mixing, diluting, harvesting, etc., of any suitable materials used in the manufacture of a biopharmaceutical, such as a cellular drug. Materials may include media for cells, which may or may not contain cells, growth factors, viruses, bead-based reagents, final drug products, such as final biopharmaceutical products, etc. The cellular drug may be a CAR-T drug.

[0011] As used herein, the term "biological processing module" is intended to refer to a module capable of performing one or more specific operations in the manufacture of biopharmaceuticals, such as cellular medicines. In some examples, each biological processing module is fixed or immobile. That is, the biological processing module is not moved by a robot or other alternative means, and cannot be moved by a robot or other alternative means. That is, each biological processing module is fixed, and a robot is movable relative to each biological processing module. Each biological processing module may include apparatus that enables one or more specific operations to be performed. The apparatus enables one or more specific operations to be performed, and may remain fixed or immobile within each biological processing module of the apparatus. That is, the apparatus is not moved by a robot or other alternative means, and cannot be moved by a robot or other alternative means.

[0012] As used herein, the term "biological handling vessel" is intended to refer to a vessel suitable for handling biological materials or materials used in the production of biopharmaceuticals. In some examples, the biological handling vessel may be a bioreactor, a consumable, an auxiliary vessel, a sampling vessel, a vacutainer, or the like. In some examples, the biological handling vessel may include an interface coupling element, such as an interface coupling plate, to enable fluid communication with the biological handling vessel. In certain examples, the biological handling vessel includes at least a portion that is flexible and / or compressible, or the entire biological handling vessel is compressible and / or flexible. In some examples, the biological handling vessel may be coupled to a connector, such as a needle-based connector. The needle-based connector may be a needle-based connector such as that described in U.S. Patent No. 5,629,994.

[0013] Advantageously, the bioprocessing systems described herein can produce biopharmaceuticals with minimal human intervention. Even more advantageously, the bioprocessing systems described herein can produce biopharmaceuticals in a semi-automated or fully automated manner. Even more advantageously, materials can be provided to the associated bioprocessing module in a timely manner, i.e., the associated biological handling vessel is transferred to the associated bioprocessing module only when deemed necessary by the user or the system. Furthermore, by moving the biological handling vessel and not the biological processing module itself, the bioprocessing systems described herein are better suited to incorporating new and existing commercially available technologies as required by the end user.

[0014] Optionally, the modular bioprocessing system comprises a biological handling vessel. In such a case, a modular bioprocessing system is provided comprising: a biological handling vessel; a plurality of bioprocessing modules, each bioprocessing module independently configured to receive the biological handling vessel and perform one or more unit operations on the biological handling vessel and / or contents within the biological handling vessel; and a robot configured to move the biological handling vessel between each of the plurality of bioprocessing modules.

[0015] Optionally, at least one of the plurality of bioprocess modules is a bioreactor module configured to maintain conditions suitable for cell culture, i.e., the bioreactor module is configured to receive a biological handling vessel, such as a bioreactor, and enable a cell culture process to be carried out within the biological handling vessel at conditions suitable for maintaining such a cell culture. Optionally, the bioreactor module houses a bioreactor therein.

[0016] Optionally, the bioreactor module comprises a first dock configured to receive a first biological handling container and a second dock configured to receive a second biological handling container, in particular, the first biological handling container may be a bioreactor and the second biological handling container may be an auxiliary container, with or without a connector coupled to the second biological handling container.

[0017] Optionally, the bioreactor module includes an incubator configured to substantially maintain an internal atmosphere and / or temperature. In some examples, the internal atmosphere may include a carbon dioxide content of about 5% to about 10%, preferably about 5%. In some examples, the temperature may be about 37°C.

[0018] Optionally, at least one of the plurality of bioprocess modules is a biological analysis module. That is, the biological analysis module is configured to receive a biological handling container and perform one or more analyses on the biological handling container itself and / or its contents. The analyses may be performed on the biological handling container to verify its sterility, integrity, or other mechanical properties. Alternatively, or additionally, the analyses may be performed directly on the contents of the biological handling container, in which case a sample of the contents is taken from the biological handling container, or may be performed indirectly, in which case the contents remain within the biological handling container.

[0019] Optionally, the biological analysis module comprises at least one of a pH meter, a cell counter, a cell seeding density meter, a flow cytometer, a polymerase chain reaction device, a sterility analyzer, a media analyzer, a metabolite analyzer, a cell imaging device, and a microscope.

[0020] Optionally, at least one of the plurality of bioprocess modules is a preparation module. That is, the preparation module is configured to receive a biological handling vessel and prepare the contents for distribution to the biological handling vessel. Optionally, the preparation module includes a dispensing device configured to dispense a fluid into the biological handling vessel. The fluid may include a liquid, a gas, a slurry, a suspension, a gel, and other fluid-like materials. Optionally, the preparation module includes a plurality of reservoirs, each reservoir containing a fluid, a mixing device for optionally mixing the fluids, and a dispensing device for dispensing the fluid or mixed fluid into the biological handling vessel.

[0021] Optionally, the preparation module is configured to prepare and / or process at least one of cell culture media, growth factors, viral vectors, non-viral vectors, and bead-based reagents.

[0022] Optionally, the preparation module is configured to dispense at least one of cell culture media, growth factors, viral vectors, non-viral vectors, and bead-based reagents into the biological handling container.

[0023] Optionally, at least one of the plurality of bioprocess modules is a cell selection module. In particular, the cell selection module can be a magnetically activated cell selection module. In particular, the cell selection module can include a selectively, i.e., positively or negatively, magnetizable device configured to select cells from a sample. Any such selectively magnetizable device is suitable for such a module.

[0024] Optionally, at least one of the plurality of bioprocess modules is a centrifuge module, i.e., the centrifuge module may include a centrifuge configured to receive a biological handling vessel for centrifuging the contents of the biological handling vessel.

[0025] Optionally, at least one of the plurality of bioprocess modules is a washing module. That is, the washing module may include an apparatus configured to receive a biological handling vessel and wash its contents (such as cell culture medium). In particular, the washing module may include a centrifuge, a counterflow centrifugal elutriation (CCE) device, a filtration device, etc.

[0026] Optionally, at least one of the plurality of bioprocess modules is an electroporation module, i.e., the electroporation module may include an electroporation device configured to apply an electric field to the contents of the biological handling device.

[0027] Optionally, at least one of the plurality of bioprocess modules is a cell harvesting module. That is, the cell harvesting module may include a device for harvesting cells, i.e., removing cells from the remainder of the contents within the biological handling vessel. The device may include a cell harvesting device and a container, such as a flexible bag, for receiving the harvested cells.

[0028] Optionally, at least one of the multiple bioprocess modules is a compounding module. That is, the compounding module may include a device for compounding harvested cells from a biological handling container into a final formulation for administration to a patient. The device may include a container, such as a flexible bag, configured to receive (or contain) the harvested cells, and one or more additional containers, each configured to receive (or contain) buffers, pharmaceutically acceptable excipients or media, and similar reagents to enable administration of the final cell therapy pharmaceutical formulation to a patient. The device may also include means for enabling mixing and / or dispensing of the harvested cells and buffers, pharmaceutically acceptable excipients or media, and other similar substances to provide the final formulation in the final formulation container. The final formulation container may be a flexible bag, such as an intravenous (IV) bag.

[0029] Optionally, at least one of the plurality of bioprocess modules is a storage module. That is, the storage module may include a storage device such as an incubator, cabinet, refrigerator, or freezer. The storage module may be configured to maintain a temperature of about 4°C. In such an example, the storage module may be a culture medium storage module, i.e., configured to maintain a biological handling container having culture medium therein at a temperature of about 4°C. The storage module may be configured to maintain a temperature of about -20°C. In such an example, the storage module may be a growth factor storage module or a DNA storage module, i.e., configured to maintain a biological handling container having growth factors and / or DNA therein at a temperature of about -20°C. The storage module may be configured to maintain a temperature of about -80°C. In such an example, the storage module may be a virus storage module, i.e., configured to maintain a biological handling container having viruses therein at a temperature of about -80°C. In some examples, the storage module may include various compartments, each configured to maintain a different temperature as noted above. In some examples, the storage module can be configured to freeze or thaw the contents of a biological handling container.

[0030] Optionally, at least one of the plurality of bioprocess modules comprises a device for reading designated features on the biological handling vessel, i.e., a device such as a scanner may be provided for detecting and reading features located on the biological handling vessel.

[0031] Optionally, the designation feature is one or more of an RFID tag, an NFC tag, a barcode, or a QR code.

[0032] Optionally, the modular bioprocessing system further comprises a microprocessor configured to receive a signal from at least one of the plurality of bioprocessing modules and, in response to receiving the signal from the at least one of the plurality of bioprocessing modules, generate and send a signal to the robot to cause the robot to move the biological handling container from the first bioprocessing module to the second bioprocessing module.

[0033] Optionally, each bioprocess module is formed as a compartment, in some instances having a substantially cubic volume.

[0034] Optionally, the bioprocessing system comprises a first side and a second side, each compartment formed on the first side and a maintenance portion formed on the second side, the maintenance portion comprising at least one of a fluid connector, a fluid reservoir, an electrical connector, a gas connector, a gas supply, a computer, a network adapter, and a control panel.

[0035] Optionally, the interior of each compartment is isolated from the interior of another compartment. Optionally, the interior environments of each compartment are isolated from each other.

[0036] Optionally, each compartment is integrally formed within the wall.

[0037] Optionally, the bioprocess modules are arranged in an array of rows, or columns, or a combination of rows and columns.

[0038] According to another aspect of the present invention, there is provided a mobile facility comprising a modular bioprocessing system as described herein. Optionally, the mobile facility is provided as a trailer having wheels.

[0039] Optionally, the mobile facility comprises a clean room and a service room, the clean room and the service room being separated by a modular bioprocessing system, hi some examples, the clean room and the service room are separated by a wall, and the modular bioprocessing system is integrally formed within the wall.

[0040] According to yet another aspect of the present invention, there is provided a modular bioprocessing system comprising a plurality of bioprocessing modules having a first side and a second side, each bioprocessing module formed as a compartment on the first side, each bioprocessing module independently configured to receive at least one biological handling vessel and perform one or more unit operations on the biological handling vessel and / or contents within the biological handling vessel; and a maintenance portion formed on the second side and configured to provide one or more services to each bioprocessing module.

[0041] Optionally, the one or more services include at least one of a fluid connection, an electrical connection, a gas connection, and a network connection.

[0042] Optionally, the second side comprises a control panel configured to control one or more services provided to each bioprocess module.

[0043] It should be noted that any modular bioprocessing system embodiment described herein may be combined with any other modular bioprocessing system described herein.

[0044] It should be noted that the biological handling container may have any suitable form. For example, the biological handling container may include an upper portion, a lower portion disposed parallel to the upper portion, and a flexible wall element extending between the upper portion and the lower portion. The flexible wall element may be compressible to allow relative movement between the upper portion and the lower portion. The flexible wall element may have multiple folds, such as Z-folds. The biological handling container may be a flexible bag, a flexible bag held within a rigid support, or a rigid container. The biological handling container may be substantially gas-impermeable, substantially gas-permeable, or have a substantially gas-permeable portion (such as a gas-permeable flexible wall element and / or a gas-permeable lower portion). Each biological handling container is independent of the others; thus, one biological handling container may take the form of a compressible container and another biological handling container may take the form of a rigid container, or any other combination contemplated herein.

[0045] According to yet another aspect of the present invention, there is provided a method for processing biological material, comprising the steps of loading a biological handling vessel into a first bioprocessing module of a plurality of bioprocessing modules, performing a first unit operation on the biological handling vessel and / or contents of the biological handling vessel in the first bioprocessing module, removing the biological handling vessel from the first bioprocessing module via a robot, transferring the biological handling vessel to a second bioprocessing module of the plurality of bioprocessing modules via the robot, and performing a second unit operation on the biological handling vessel and / or contents of the biological handling vessel in the second bioprocessing module.

[0046] Optionally, the first unit operation and / or the second unit operation includes introducing the cell population into a biological handling container.

[0047] Optionally, the first unit operation and / or the second unit operation includes introducing at least one of a cell culture medium, a growth factor, a viral vector, a non-viral vector, or a bead-based reagent into the biological handling container.

[0048] Optionally, the first unit operation and / or the second unit operation includes at least one of culturing, genetically modifying, stimulating, growing, washing, separating, selecting, or harvesting cells contained within the biological handling container.

[0049] Optionally, the first unit operation and / or the second unit operation includes storing the biological handling container under predetermined conditions.

[0050] Optionally, the first unit operation and / or the second unit operation comprises analyzing, centrifuging, or electroporating the contents of the biological handling vessel.

[0051] Optionally, loading the biological handling container into a first bioprocess module of the plurality of bioprocess modules comprises loading the biological handling container into the first bioprocess module via a robot.

[0052] Any of the features or steps described herein with respect to one embodiment, aspect, or example of a bioprocessing system, bioprocessing module, biological handling vessel, robot, mobile equipment, or method for processing biological material described herein is equally applicable to any other embodiment, aspect, or example described herein. In particular, the bioprocessing systems described herein may have any combination of the bioprocessing modules described herein.

[0053] The present disclosure will now be described in more detail with reference to the figures. [Brief explanation of the drawings]

[0054] [Figure 1] FIG. 1 is a schematic diagram of components included in an exemplary modular bioprocessing system. [Figure 2A] FIG. 1 illustrates a mobile facility according to an exemplary modular bioprocessing system. [Figure 2B] FIG. 1 illustrates a curved bank of robots and bioprocess modules according to an exemplary modular bioprocess system. [Figure 2C] FIG. 1 illustrates a bank of robots and bioprocess modules on rails according to an exemplary modular bioprocessing system. [Figure 2D] FIG. 1 illustrates a robot on rails and a bank of bioprocess modules recessed into a wall included in an exemplary modular bioprocess system. [Figure 3] FIG. 1 illustrates a clean room with a robot and a bank of bioprocess modules arranged around the robot. [Figure 4] FIG. 1 shows a bioreactor module. [Figure 5A] FIG. 1 shows a first embodiment of a biological handling container. [Figure 5B] FIG. 10 shows a second embodiment of a biological handling container. [Figure 5C] FIG. 5C shows a cross section of the biological handling container of FIG. 5B. [Figure 5D] FIG. 10 shows a third embodiment of a biological handling container. [Figure 5E] FIG. 10 shows a fourth embodiment of a biological handling container. [Figure 5F] FIG. 10 shows a fifth embodiment of a biological handling container. [Figure 6] FIG. [Figure 7] FIG. 1 illustrates a partial section of a modular bioprocessing system. DETAILED DESCRIPTION OF THE INVENTION

[0055] Referring to FIG. 1, a modular bioprocessing system 100 is provided that includes a plurality of bioprocessing modules 102 and a robot 104. The bioprocessing modules 102 are arranged in an array of rows and columns recessed into a wall. The bioprocessing modules 102 may be selected from any suitable modules described herein, but for illustrative purposes, a biological analysis module 102a including a biological analysis device 106, such as a pH meter, microscope, or cell density meter; a bioreactor module 102b including an incubator unit 108 for housing a bioreactor (not shown) and including a dock 110; a server module 102c including a server 112; a cell processing module 102d including a spinning membrane filtration device 114; and a storage module 102e including a plurality of docks (not shown). Generally, each module 102 may have a means for receiving a biological handling vessel 200, such as the dock 110 described above. The dock 110 may be provided as a holding or receiving mechanism and may allow interfacing of the biological handling container 200 with one or more processing devices to perform unit operations on the container 200 and / or its contents.

[0056] The robot 104 includes a base 104a, an articulating arm 104b, and a gripper 104c. The gripper 104c can be actuated to allow it to grip or otherwise receive a biological handling container 200 during use. The robot 104, i.e., the base 104a, can be mounted on rails 104d to allow movement. Alternatively, the base 104a can include wheels. Movement along the rails 104d or on the wheels can be remotely controlled by a computer system.

[0057] The modular bioprocessing system 100 may be formed from a first side 150 and a second side 160. The first side 150 includes a frame with holes or apertures in which each bioprocess module 102 is disposed. The first side 150 may be considered the side from which the interior of each bioprocess module 102 can be accessed. The second side 160 is provided on the opposite side of the system 100 and may be considered the side from which maintenance of each bioprocess module 102 can be performed. In particular, the second side 160 may provide access to various services, such as gas connections 120, network connections 122, or electrical connections 124. Interface connections 155 are also provided between the first side 150 and the second side 160. The interface connections allow for service, i.e., gas, network, and electrical connections, from the second side 160 to each bioprocess module 102 on the first side 150. For example, gas connections 120a, network connections 120b, and electrical connections 120c may be provided through interface couplings 155. First side 150 may be provided in a clean room. Second side 160 may be provided in a service or maintenance room or corridor.

[0058] As shown in FIG. 1, the biological handling container 200 may include a container portion and a connector portion 400. The biological handling container 200, described in more detail below and illustrated in FIGS. 5A-5F, generally includes an upper portion and a lower portion that are compressible toward each other to allow dispensing. The connector portion 400 may be a needle-based connector, described below and illustrated in FIG. 6. The biological handling container 200 may be suitable for handling culture media, cellular material, viruses, etc. The biological handling container 200 may be a bioreactor or an auxiliary container for inputting materials into a bioreactor.

[0059] 1 , during use, the robot 104 uses the gripper 104c to retrieve a biological handling container 200 from a biological processing module 102 and transfer such container 200 to another, i.e., a different, biological processing module 102. In this manner, biological handling containers 200 can be automatically transferred between different modules 102, each module handling a distinct unit operation in a biopharmaceutical manufacturing process. For example, the robot 104 retrieves a container 200 containing culture medium therein from the storage module 102e, transfers the container 200 from the storage module 102e to the bioreactor module 102b, and places the container 200 in the dock 110 within the bioreactor module 102b for dispensing by an actuator within the bioreactor module 102b. The contents of the container 200, such as culture medium, cellular material, or virus, can be dispensed into a bioreactor received within the bioreactor module 102b. Upon completion of the operation, the robot 104 may return the used container 200 to the storage module 102e or remove it for disposal in a bin or waste module (not shown).

[0060] As will be appreciated by those skilled in the art, the robot 104 may be controlled automatically by a control system over a network, such as a wireless network, or alternatively, the robot 104 may be controlled by a user interface or human-machine interface provided on a mobile application, tablet, or screen.

[0061] The bioprocessing modules 102 may be any suitable module suitable for use in the manufacture of biopharmaceuticals, such as cell and / or gene therapy products, more specifically CAR-T products. Each bioprocessing module 102 may be independently selected from a bioreactor module configured as an incubator for housing a bioreactor therein, as described above; a biological analysis module including a pH meter, a cell counter, a cell seeding density meter, a flow cytometer, a polymerase chain reaction (PCR) device, a sterility analyzer, a media analyzer, a metabolite analyzer, a cell imaging device, or a microscope; a preparation module for conditioning materials and / or dispensing materials into biological handling vessels; a cell selection module including a magnetically activated cell selection device; a centrifugation module including a centrifugation device; an electroporation module including an electroporation device; a cell harvesting module including means for enabling the harvesting of cellular material from a vessel, such as a biological handling vessel, into a final form and / or package; or a storage module, or any other suitable module. The present disclosure is not intended to be limited in any way with respect to the modules and / or devices utilized.

[0062] Referring now to FIG. 2A, an example of a biological treatment system 100 is provided in a mobile facility 300 having wheels 302 so that a user can move the mobile facility 300 from one location to another. The mobile facility 300 includes multiple biological treatment modules 102 therein. Nevertheless, the mobile facility 300 can include the functionalities described with respect to FIG. 1, such as various services including gas connections, electrical connections, and network connections. In this manner, the bioprocess modules 102 can be provided with gas, power, and network connections during transport from a first location to a second location or on-site while not being transported. The mobile facility 300 can include a means for attachment to a vehicle, such as a mooring point, so that the mobile facility 300 can be transported over the road or within a larger facility, such as a warehouse. The mobile facility 300 can include space for a robot (not shown), so that the bioprocess modules 102 and the robot can be transported simultaneously within a single trailer.

[0063] Referring now to Figure 2B, an example of a biological processing system 100 is provided. In this example, the robot 104 is mounted on a platform 170 and can rotate about a vertical axis on a pedestal 172. The bioprocess modules 102 are arranged in an arc around the robot 104, allowing the robot 104 to perform operations on each bioprocess module 102. This configuration increases the number of bioprocess modules 102 that a single robot 104 can act on while being able to move around a single point (i.e., without rails). In Figure 2B, the biological processing system 100 includes stacked bioprocess modules 102, i.e., two bioprocess modules 102 stacked on top of each other, but three or more bioprocess modules 102 can be stacked on top of each other, and the robot 104 can translate and / or extend vertically or telescopically to reach higher bioprocess modules 102.

[0064] 2C, an example of a biological treatment system 100 is provided in which bioprocess modules 102 are linearly arranged in an array of rows and columns adjacent to a robot 104 on rails 104d as described with respect to FIGURE 1. In this particular example, the rails 104d may extend parallel to the array of biological treatment modules 102.

[0065] Referring now to FIG. 2D, an example of a biological treatment system 100 is provided in which the bioprocess module 102 is recessed into a wall 180. The wall 180 may be a clean room wall, limiting access to the interior of the bioprocess module 102 to a defined number of users, i.e., only those with clean room access, thereby minimizing exposure to potentially harmful materials such as viruses, fungi, or bacteria. In this configuration, the side of the wall 180 that allows access to the bioprocess module 102 is the first side of the overall system 100 (see FIG. 1), and the opposite side (not shown) is the second side of the overall system 100 (see FIG. 1). The first side allows a robot or designated human technician to access the interior of the bioprocess module 102. The second side includes various features that are more difficult to optimize for robotic control and / or that can be accessed by personnel who do not require, or are not trained or qualified to access the clean room side. For example, the second side is configured for maintenance operations and includes gas supplies, network adapters, and electrical connections. These features are likely to require human intervention for maintenance, repair, and the like, and preferably do not require human technicians to enter the cleanroom environment for such activities. The first and second sides are separated, e.g., fluidly separated, i.e., not in fluid communication, so that hazardous substances cannot pass between the first and second sides. In particular, a fluid-tight or gas-tight seal 182 is provided around each biological treatment module to ensure separation between the first and second sides. In this way, the cleanroom is primarily occupied by robots during normal operation, with minimal human intervention, and the second side can be accessed by human technicians without having to prepare to enter the cleanroom environment and / or potentially be exposed to hazardous substances.

[0066] 3 shows an example of a clean room 300 that includes a circular array of bioprocess modules 102 arranged to surround a robot 104. The bioprocess modules 102 are arranged in this manner to maximize the utilization of floor space within a first zone 302 of the clean room 300, and the robot 104 can access each bioprocess module 102 without the need for rails. The first zone 302 is generally defined by an enclosure wall 304 that separates the first zone 302 from a second zone 306. The enclosure wall 304 has openings through which each bioprocess module 102 is positioned during use and which can be accessed by the robot 104.

[0067] First zone 302 may be thermally controlled or maintained to ensure that the volume defined therein is maintained at a substantially constant temperature, for example, 37° C. Additionally or alternatively, first zone 302 may have a controlled atmosphere, whereby the gas content therein is controlled or maintained. For example, the carbon dioxide content of first zone 302 may be maintained at about 5% to about 10%.

[0068] Each bioprocess module 102 is positioned on a slidable access tray 308, allowing each to be slidably moved between a first position and a second position. In the first position, as shown in FIG. 3 , each module 102 is positioned such that an open end of each module 102, i.e., the end for access via the robot 104, is disposed within the first zone 302. The open end is sealed around the periphery to ensure a thermally and / or fluidly and / or gas-tightly sealed first zone 302, particularly from and relative to the second zone 306. In the second position (not shown), each module 102 is moved laterally away from the array of processing modules 102, thereby disposing each module 102 entirely within the second zone 306, thereby facilitating maintenance and / or servicing of each module 102.

[0069] The volume of the first zone 302 and the volume of each processing module 102 can be defined singly, i.e., without the need for a door on each bioprocess module 102. In this manner, a single thermal and / or atmospheric environment is provided without the need to individually control each module 102. In other examples, each bioprocess module 102 includes a door. Furthermore, in some examples, each cavity includes a door within which the bioprocess module 102 is located and seals the first zone 302 before moving the bioprocess module 102 to the second position. A user may access the first zone 302 through a door 310 in the wall 304 separating the first zone 302 and the second zone 306.

[0070] As an example of one such module for use in any of the systems described above, bioreactor module 102b, shown in FIG. 4, is provided. Bioreactor module 102b has an enclosure 1020 in the form of an incubator that encloses an internal volume. A dock 110 configured to hold a biological handling container 200 is provided within the internal volume. Dock 110 may be provided in a fixed, i.e., immobile, state, or may be movable. In some examples, dock 110 can rotate about a central axis so that it can be positioned near the opening of the enclosure at the front of the internal volume, a position that can be easily accessed by the robot described above. Additionally or alternatively, multiple docks can be arranged around this central axis, allowing several biological handling containers to be positioned within the internal volume. In such cases, the docks can be movable similar to a carousel. For example, upon receiving a signal that a particular biological handling container is required for a unit operation, the associated dock can be rotated or positioned to a position at the front of the internal volume. Similarly, when an empty dock is needed, it is rotated or positioned into a position at the front of the interior volume, thus simplifying robot movement since only one location within bioreactor module 102b needs to be accessed.

[0071] Additionally or alternatively, bioreactor module 102b includes a movable interface 1022. The movable interface 1022 may move along a longitudinal axis, i.e., up and down relative to enclosure 1020, and / or the movable interface 1022 may rotate about a central longitudinal axis. The movable interface 1022 may be provided attached to the bioreactor (not shown) and serve to allow interfacing of the internal lumen of the bioreactor with another component, such as a vessel. The movable interface 1022 includes an upper surface 1022a having ports 1022b. The ports 1022b are constructed to interface and form a sterile and fluid-tight or airtight seal with the biological handling vessel 200 via a connector (see FIG. 6), thereby allowing liquids, such as culture media, and gases to be provided to the biological handling vessel 200. Notably, the ports 1022b may each be provided as a resealable septum seal. Ports 1022b may include an additional sterile barrier, such as a sterile paper seal, configured to mate with a corresponding sterile barrier, such as a corresponding sterile paper seal, which is removed prior to interfacing biological handling container 200 with the respective port 1022b via a connector (see FIG. 6).

[0072] 5A, 5B, 5C, 5D, and 5E show various examples of biological handling vessels 200, 200', 200", 200'", and 200"" configured for use in the modular bioprocessing system 100. Each of the biological handling vessels 200, 200', 200", 200'", and 200"" includes an upper portion 202, a lower portion 204, and a flexible, compressible wall 206 disposed between the upper portion 202 and the lower portion 204. Each biological handling vessel 200, 200', 200", 200'", and 200"" includes a connector 400, specifically a needle-based connector, coupled to its distal end; the connectors 400 are described in more detail below. Generally, connector 400 can serve as both an inlet and an outlet for fluids, including liquids, gases, suspensions, slurries, gels, etc., between each biological handling container 200, 200', 200'', 200''', 200'''', and another container or component.

[0073] As shown in FIG. 5A, the lower portion 204 of the biological handling container 200 is coupled to and partially encloses the vial 208. The vial 208 includes an internal volume for holding a fluid. The fluid within the internal volume can be dispensed through the connector 400. The upper compressible wall 206 of the vial 208 is flexible and includes a plunger (not shown), which can reciprocate within the vial 208, thereby changing the volume of the vial 208 by applying a compressive force to the upper portion 202 and / or lower portion 204. The biological handling container 200 shown in FIG. 5A also includes a mounting collar 210. The mounting collar 210 includes features that allow the mounting collar 210 to be removably attached to a connector. One exemplary feature is external threads for connecting the mounting collar to the threaded portion of the connector 400. Additionally or alternatively, the mounting collar 210 can be pressed into the connector 400 and can include an O-ring or other elastomeric member to enhance retention. It will be appreciated that other connection mechanisms may be provided on the mounting collar 210 and connector 400 to provide the connection mechanism.

[0074] The biological handling container 200 shown in FIG. 5A may be constructed and arranged to store and / or dispense viruses, magnetically activated reagents, or magnetic beads.

[0075] As shown in Figures 5B and 5C, the lower portion 204 of the biological handling container 200' is coupled to and partially encloses the vial 208. The vial 208 includes an internal volume for holding a fluid, similar to the vial 208 described above with respect to Figure 5A. However, the vial 208 of Figure 5B does not include a plunger; instead, compressing the upper portion 202 relative to the lower portion 204 dispenses the contents of the vial 208 due to a compressed air drive mechanism (i.e., generating positive air pressure). Notably, a one-way valve 212 is provided between the lower portion 204 and the vial 208, allowing fluid, such as air, contained within the volume defined by the upper portion 202, lower portion 204, and compressible sidewall 206 to flow in one direction into the vial 208 and pass the fluid from the vial 208 through the hollow needle 11 of the connector 400. 5B also includes a feed tube 214, which can be used to add and remove fluid from vial 208 via stopcock 216. After use, feed tube 214 can be detached or sealed, for example, plugged or welded shut. Any portion of feed tube 214 that remains attached to biological handling container 200' can be clipped to vial 208. Biological handling container 200' also includes a funnel portion 206 that extends from vial 208 and tapers inward so that fluid is directed toward connector 400 during use.

[0076] The biological handling container 200' shown in Figures 5B and 5C may be constructed and arranged to store and / or dispense cell culture media or cell starting material.

[0077] As shown in FIG. 5D , biological handling container 200′″ does not include a vial, as compared to the examples of FIGS. 5A and 5B . Instead, the volume defined by upper portion 202, lower portion 204, and compressible sidewall 206 is arranged to hold a fluid for dispensing. In particular, upper portion 202, lower portion 204, and compressible sidewall 206 define a frusto-conical container. Lower portion 204 includes a threaded portion 218 for coupling biological handling container 200′″ to connector 400. During use, upper portion 202 is compressed against lower portion 204, causing fluid to be dispensed from within the volume defined therein.

[0078] The biological handling container 200'' shown in FIG. 5D may be constructed and arranged to store and / or dispense cell culture media or cell starting material.

[0079] As shown in FIG. 5E, biological handling container 200'''' is substantially the same as the biological handling container described in FIG. 5D. In this example, biological handling container 200'''' includes a first foldable sidewall 206a and a second foldable sidewall 206b. First sidewall 206a and second sidewall 206b each have a frustoconical shape. First sidewall 206a and second sidewall 206b each have a first end 220a, 220b and a second end 222a, 222b, where first end 220a, 220b is larger than second end 222a, 222b. First foldable sidewall 206a and second foldable sidewall 206b are joined end-to-end, thereby defining a single interior volume or lumen, and are folded in the same direction. In the illustrated example, second ends 222a, 222b (i.e., smaller ends) are joined to one another. First end 220a of first foldable sidewall 206a comprises lower portion 204 and is attached to connector 400 via threaded portion 224. First end 220b of second foldable sidewall 206b comprises upper portion 202. Thus, first foldable sidewall 206a tapers inward from lower portion 204 to narrower body 226, and then second foldable sidewall 206b flares outward to upper portion 202. Lower portion 204 also includes threaded portion 218 to enable coupling to connector 400.

[0080] The biological handling container 200''''' shown in Figure 5E may be constructed and arranged to store and / or dispense cell culture media or cell starting material.

[0081] As shown in FIG. 5F, biological handling container 250 may not include a connector, as compared to the previous example. In this example, biological handling container 250 includes upper portion 202, lower portion 204, and flexible, compressible sidewalls 206. As shown, and as noted in other examples, the flexible, compressible sidewalls have several annular rigid portions 252 arranged laterally and parallel to both upper portion 202 and lower portion 204. The annular rigid portions are alternated with deformable regions 254 to allow compression. Biological handling container also includes port 256 in upper portion 202, although this may be a threaded portion of upper portion 202 in other examples.

[0082] The biological handling vessel 250 shown in Figure 5F can be a bioreactor.

[0083] Biological handling containers 200, 200', 200'', 200''', 200'''', 250 may include an on-board network adapter and may also include on-board control and analytical devices such as batteries, sensors, heaters, pH meters, thermometers, etc., allowing their contents to be constantly monitored. The network adapter can transmit signals indicating the status of the on-board control and analytical devices, including medium temperature, pH, battery charge level, etc.

[0084] As an optional feature, it should be noted that each of the biological handling containers 200, 200', 200'', 200''', 200'''' in Figures 5A, 5B, 5C, 5D, and 5E has an engagement feature 230, which is adapted to an actuator, which may be part of the robot 104 or part of the biological processing module, to engage and dispense the contents of the biological handling container 200, 200', 200'', 200''', 200'''' by compressing the upper part 202 against the lower part 204.

[0085] The biological handling containers 200, 200', 200", 200'", 200"", 250 described above may also include designation features, which may be RFID tags, NFC tags, barcodes, or QR codes, or any combination thereof. The robot 104, preferably the robot's gripper 104c, has a complementary reader, such as a scanner, that is used to detect which biological handling container 200, 200', 200", 200'", 200"", 250 is being collected by the robot 104. In this manner, if a biological handling container 200, 200', 200", 200'", 200"", 200"", 250 is removed from its known location by, for example, a technician and relocated to a different dock than the location previously stored on the network, the reader can ascertain which biological handling container 200, 200', 200", 200'", 200"", 200"", 250 was collected from the set of biological handling containers 200, 200', 200", 200'", 200"", 250. Using a microprocessor and associated memory, each dock 110 can be designated with identification information and a known location, and the memory can be updated with information to verify the presence or absence of a biological handling container 200, 200', 200", 200'", 200"", 200"", 250 when it is docked. The robot can scan the designation feature each time it interacts with a biological handling container 200, 200', 200'', 200''', 200'''', 200'''', 250 to ensure that the correct biological handling container 200, 200', 200'', 200''', 200'''', 250 is collected each time. If the robot is performing an operation to collect a biological handling container 200, 200', 200'', 200''', 200'''', 200'''', 250 and detects that the biological handling container 200, 200', 200'', 200''', 200'''', 250 is missing or incorrectly designated, a signal indicating an error can be provided to a technician via the network adapter.

[0086] The biological handling vessel 200, 200', 200'', 200''', 200'''' of Figures 5A-5E includes a connector 400 that is complementary to the dock 110 and / or the movable interface 1022 of the bioreactor module 102b (see Figure 4). The connector 400 may include one or more docking features, which additionally include connection elements for receiving gas from the gas source 120, connection elements for electrical connection with the electrical connector 124, and connection elements for connection with a network terminal. In this way, when docked, the biological handling vessel 200, 200', 200'', 200''', 200'''', i.e., its connector 400, can transmit signals indicating the status of media, cells, temperature, battery charge, etc. If power, additional gas, or fluid is needed, a signal can be sent to the network adapter 122 via the on-board network adapter. Connector 400 is a needle-based connector and has a hollow needle 11 positioned to pierce a septum seal of the connector (as described below with respect to Figure 6) and to pierce a septum seal disposed either at the distal end (Figures 5A, 5B, 5C) or at the bottom 204 (Figures 5D, 5E) of the vial.

[0087] 6 shows a cross-sectional view of a connector 400, which in use is used to connect a biological handling container 200 to another component, such as the interface 1022 of a bioreactor module 102b (see FIG. 4). The connector 400 comprises a housing having an upper housing portion 12a and a lower housing portion 12b. The housing extends along a longitudinal axis between a distal end and a proximal end. The upper housing portion 12a may be axially movable or slidable relative to the lower housing portion 12b, as described further below.

[0088] The housing includes a threaded portion 17 at its distal end for connecting to a corresponding threaded portion of a vial. The threaded portion 17 is formed on the upper housing portion 12a. As will be apparent to those skilled in the art, the housing may not include the threaded portion 17, but instead may include another suitable connection mechanism for connecting to a portion of a vial.

[0089] The connector 400 also includes a connector portion at the proximal end of the connector for connecting to the bioreactor module 102b of the movable interface 1022. The connector portion may be a groove 14 configured to receive one or more protrusions extending from the movable interface 1022. Alternatively, the connector 400 may include a threaded portion or other connector portion for connecting to the movable interface.

[0090] The connector 400 includes a first septum seal 18 disposed at the distal end of the housing and a second septum seal 10 disposed at the proximal end of the housing. The first septum seal 18 includes a substantially planar, i.e., flat, pierceable, surface facing outward at the distal end. The second septum seal 10 includes a generally annular portion extending outward at the proximal end and sealing against the substantially planar, i.e., flat, pierceable, surface facing outward at the proximal end. The housing further includes a hollow needle 11 biasably mounted within the housing. The hollow needle 11 is generally coaxially aligned with the longitudinal axis. The hollow needle 11 includes a first end 24 facing the first septum seal 18 and a second end 22 facing the second septum seal 10. The first end 24 is configured to be able to pierce the first septum seal 18 in use, and the second end 22 is configured to be able to pierce the second septum seal 10 in use. The first septum seal 18, the second septum seal 10, or both the first septum seal 18 and the second septum seal 10 may optionally include a removable sterile paper seal 16.

[0091] The hollow needle 11 is mounted within the housing through a collar 28, which is spring-biased by a first helical spring 20a and a second helical spring 20b. In other embodiments, the hollow needle 11 may be mounted in another suitable manner; for example, the hollow needle 11 may be fixedly mounted, i.e., the hollow needle 11 is stationary and the housing may move around the hollow needle 11. The first spring 20a acts between the distal end of the housing and the collar 28. The second spring 20b acts between the proximal end of the housing and the collar 28. In this manner, the first spring 20a imparts a first biasing force to the hollow needle 11 via the collar 28 in a direction toward the proximal end of the housing, and the second spring 20b imparts a second biasing force to the hollow needle 11 via the collar 28 in a direction toward the distal end of the housing.

[0092] The connector 400 further includes an actuation mechanism for causing the hollow needle 11 to pierce the septum seals 10, 18. The hollow needle 11 pierces the first septum seal 18 and the second septum seal 10, thereby forming a fluid pathway between the distal and proximal ends of the connector 400 and thus, in use, forming a fluid connection between the vials 208, 208′ of the biological handling container and the bioreactor module 102b.

[0093] 6, the actuation mechanism includes an outer sleeve 13 positioned to collapse the upper housing portion 12a relative to the lower housing portion 12b. The outer sleeve 13 is rotatable relative to the housing about a central longitudinal axis of the housing. For example, one of the outer sleeve 13 and the housing may include a spiral groove, and the other of the outer sleeve 13 and the housing may include a protrusion that engages the groove, thereby rotating the outer sleeve 13 as the upper housing portion 12a collapses relative to the lower housing portion 12b.

[0094] It should be noted that while an actuation mechanism including an outer sleeve and a spring biasing the needle and / or housing is illustrated, other actuation mechanisms are similarly contemplated. The illustrated connector 400 is provided merely as an example of a means for providing a connection between components of the system.

[0095] Referring now to FIG. 7, a modular bioprocessing system 500 and its compartments for five different bioprocessing modules are shown. Each bioprocessing module is dedicated to a different purpose and includes specific components. For example, the top left module may be the analytical module 102a, housing an analytical device. One possible analytical device may be an automated cell counter, which captures images indicative of cell density within the biological handling vessel 200, thereby enabling growth rate to be determined by taking periodic measurements. Alternatively, or additionally, the analytical module may include a pH meter, a cell counter, a cell seeding densitometer, a flow cytometer, a polymerase chain reaction device, a sterility analyzer, a media analyzer, a metabolite analyzer, or a cell imaging device.

[0096] The top center bioprocess module can be the bioreactor module 102b shown in FIG. 4 and described above.

[0097] The lower left module may be the server module 102c and includes a server 112. The server 112 provides computing services, including digital memory, robotic control, and network functionality, including Internet access. The server can process signals indicating the status and location of the dock 110 and biological handling vessel 200, as well as the temperature within the modular bioprocessing system 100, remaining stocks of gas, empty biological handling vessels, media and various supplies needed for media, consumables, and the like. These signals can be processed to generate alerts, such as a low gas supply alert, a low temperature alert, or a door open alert. Those skilled in the art will appreciate that there are various other alerts that the server may need to generate. The server may also generate error messages, for example, if a biological handling vessel is misplaced or dropped, or if a particular component, such as a heater, requires maintenance.

[0098] The lower, center module 102d is a preparation module that includes a dock 110 and at least one preparation device 114. The preparation device may be a device for preparing the medium to be added to the biological handling vessel 200, 200′ by heating, mixing, and decanting the medium. Alternatively, or additionally, the preparation device may be a spinning membrane filtration device, a centrifuge, a water bath, a flow cytometer, or a water purification system. Those skilled in the art will recognize that there are a variety of other preparation devices that can be used in this module, and that this is not an exhaustive list.

[0099] Each module can have a different size appropriate for the module's function, but preferably there is a standard 1x1 size, with larger modules sized to allow for a 1x2, 2x2, 3x1, or 4x4 planar packing of modules relative to the standard size. In a non-limiting example, the right-most module is a 1x2 sized storage module 102e. The storage module 102e can include several docks 110 for biological handling vessels 200, 200', 200'', 200''', 200'''', 250. The biological handling vessels 200, 200', 200'', 200''', 200'''', 250 can be held in the storage module 102e while the biological material grows inside the biological handling vessel. Periodic operations can be performed on the biological handling vessels 200, 200', 200'', 200''', 200'''', 200'''', 250 to grow the biological material at an expected rate. Alternatively, or additionally, the biological handling container 200, 200', 200", 200'", 200"", 250 may provide a signal to the server 112 indicating that an action needs to be performed, such as analysis by an analytical device or preparation of biological material for long-term storage or delivery. Alternatively, the storage module may be refrigerated to maintain a temperature of about 4°C, or -20°C, or -80°C when storing cell culture media and other components for future use.

[0100] For convenience only, and not limitation, certain terminology is used in the following description. The words "right," "left," "lower," "upper," "front," "rear," "upper," "lower," "below," "above," and "belower" designate directions in the drawings to which reference is made and to which reference is made when the components being described are assembled and installed (e.g., on site). The words "inner," "inward," and "outer," "outward" refer, respectively, to directions toward and away from a designated centerline or geometric center (e.g., central axis) of the element being described, with the particular meaning being readily apparent from the context of the description.

[0101] Furthermore, as used herein, terms such as "clean room," "cell culture laboratory," "sterile environment," etc. are intended to refer to a room where external contaminants may have a detrimental effect on cell cultures and where the interface layer is preferably located, while the maintenance layer should be accessed from outside the clean room (etc.).

[0102] Furthermore, as used herein, the terms "connected," "attached," "coupled," and "mounted" are intended to include a direct connection between two members with no other intervening members, as well as an indirect connection between members where one or more other intervening members are present. The terms include the words specifically mentioned above, derivatives thereof, and words of similar import.

[0103] Furthermore, unless otherwise specified, the use of ordinal numbers such as "first," "second," "third," etc., merely indicates that different instances of similar objects are being referred to and is not intended to imply that the objects so described must be in a given sequence, either in time or space, or in ranking or in any other manner.

[0104] In the description and claims of this specification, "comprises" and "includes" and variations thereof are to be construed to mean "including, but not limited to," other moieties, additives, components, integers, or steps, and are not intended to (and do not) exclude other moieties, additives, components, integers, or steps. Throughout the description and claims of this specification, the singular encompasses the plural unless the context requires otherwise. In particular, the specification should be understood where the indefinite article is used, as contemplating the plural as well as the singular, unless the context requires otherwise.

[0105] It should be understood that any feature, integer, property, compound, chemical moiety, or group described in connection with a particular aspect, embodiment, or example of the invention is applicable to any other aspect, embodiment, or example described herein to the extent that it is compatible with any other aspect, embodiment, or example described herein. All features disclosed herein (including any accompanying claims, abstract, and drawings) and / or all steps of any method or process so disclosed may be combined in any combination, except combinations in which at least some of such features and / or steps are mutually exclusive. The invention is not limited to the details of the above embodiments. The invention extends to any novel feature, or any novel combination of features, or any novel step, or any novel combination of steps of any method or process so disclosed, disclosed herein (including any accompanying claims, abstract, and drawings). [Explanation of symbols]

[0106] 10 Second diaphragm seal 11 Hollow Needle 12a Upper housing part 12b Lower housing part 13 Outer sleeve 16 Sterile paper seals 17 Threaded part 18 First diaphragm seal 20a First spiral spring 20b Second spiral spring 22 second end 24 first end 28 colors 100 Modular Bioprocess System, Biological Treatment System 102 Bioprocess module, biological treatment module 102a Biological Analysis Module 102b Bioreactor Module 102c Server Module 102d Cell Processing Module 102e Storage Module 104 Robot 104a bass 104b Articulated Arm 104c Grip 104d rail 106 Biological analytical devices 108 Incubator Unit 110 Dock 112 servers 114 Spinning membrane filtration device, preparation device 120 Gas Connection 120a gas connection 120b network connection 120c electrical connection 122 Network connection, network adapter 124 Electrical connections, electrical connectors 150 First Side 155 Interface connection part 160 Second Side 170 Platform 172 Pedestal 180 Wall 182 stickers 200, 200', 200'', 200'''', 200'', 250 Biological Handling Containers 202 Upper 204 Lower part, vial 206 Wall, funnel part 206a first side wall 206b Second side wall 208 vials 208' vial 210 Mounting collar 212 One-way valve 214 Feed Tube 216 Stopper 218 Threaded Part 220a, 220b first end 222a, 222b second end 224 Threaded part 226 Torso 230 Engagement function part 252 Rigid part 254 Deformable Parts 256 ports 300 Mobile equipment, clean rooms 302 Wheels, First Zone 304 Siege Wall 306 Second Zone 308 Access Tray 310 Doors 400 Connector part 500 Modular Bioprocess System 1020 Enclosure 1022 Movable Interface 1022a Top side 1022b port

Claims

1. a plurality of bioprocess modules, each independently configured to receive at least one biological handling vessel and to perform one or more unit operations on the biological handling vessel and / or contents within the biological handling vessel; a robot configured to move the or each biological handling vessel between each of the plurality of bioprocess modules; A modular bioprocessing system comprising:

2. 10. The modular bioprocessing system of claim 1, wherein each bioprocessing module is stationary.

3. 3. The modular bioprocessing system of claim 1, wherein at least one of the plurality of bioprocessing modules is a bioreactor module configured to maintain conditions suitable for cell culture, and optionally the bioreactor module comprises an incubator configured to substantially maintain an internal atmosphere and / or temperature, and optionally the bioreactor module comprises a first dock configured to receive a first biological handling vessel and a second dock configured to receive a second biological handling vessel, and further optionally the first and second biological handling vessels are received in the respective first and second docks, and further optionally the first biological handling vessel is a bioreactor and the second biological handling vessel is an auxiliary vessel.

4. 4. The modular bioprocessing system of claim 1, wherein at least one of the plurality of bioprocess modules is a biological analysis module, and optionally the biological analysis module comprises at least one of a pH meter, a cell counter, a cell seeding densitometer, a flow cytometer, a polymerase chain reaction device, a sterility analyzer, a media analyzer, a metabolite analyzer, a cell imaging device, and a microscope.

5. 5. The modular bioprocessing system of claim 1, wherein at least one of the plurality of bioprocessing modules is a preparation module, optionally configured to prepare and / or process at least one of cell culture media, growth factors, viral vectors, non-viral vectors, and bead-based reagents.

6. 6. The modular bioprocessing system of claim 5, wherein the preparation module is configured to dispense at least one of cell culture media, growth factors, viral vectors, non-viral vectors, and bead-based reagents into the biological handling vessel.

7. 7. The modular bioprocessing system of claim 1, wherein one or more of the plurality of bioprocess modules each further comprises a biological handling vessel.

8. 8. The modular bioprocessing system of claim 7, wherein the biological handling vessel is one of a bioreactor, a consumable, an auxiliary vessel, a sampling vessel, or a vacutainer.

9. 9. The modular bioprocessing system of claim 7 or 8, wherein the biological handling vessel comprises a flexible wall element, optionally the flexible wall element being compressible or alternatively the flexible wall element comprising a plurality of folds.

10. 10. The modular bioprocessing system of claim 1, wherein at least one of the plurality of bioprocessing modules is selected from a cell selection module, such as a magnetically activated cell selection module, a centrifugation module, a washing module, an electroporation module, a cell harvesting module, a formulation module, and a storage module.

11. 11. The modular bioprocessing system of claim 1, wherein at least one of the plurality of bioprocess modules comprises a device for reading a designated feature on the biological handling vessel, and optionally the designated feature is one or more of an RFID tag, an NFC tag, a barcode, or a QR code.

12. Further comprising a microprocessor, the microprocessor comprising: receiving a signal from at least one of the plurality of bioprocess modules; 12. The modular bioprocessing system of claim 1, wherein the modular bioprocessing system is configured to generate and send a signal to the robot in response to receiving the signal from at least one of the plurality of bioprocess modules, to cause the robot to move the biological handling vessel from a first bioprocess module to a second bioprocess module.

13. 13. The modular bioprocessing system according to claim 1, wherein each bioprocessing module is formed as a compartment.

14. 14. The modular bioprocessing system of claim 13, wherein the modular bioprocessing system comprises a first side and a second side, each compartment formed on the first side and a maintenance portion formed on the second side, the maintenance portion comprising at least one of a fluid connector, a fluid reservoir, an electrical connector, a gas connector, a gas supply, a computer, a network adapter, and a control panel.

15. 15. The modular bioprocessing system of claim 13 or 14, wherein the interior of each compartment is isolated from the interior of another compartment.

16. 16. The modular bioprocessing system of any one of claims 13 to 15, wherein each compartment is integrally formed within a wall.

17. 17. The modular bioprocessing system of any one of claims 1 to 16, wherein the bioprocess modules are arranged in an array of rows and / or columns.

18. 18. A mobile facility comprising a modular bioprocessing system according to any one of claims 1 to 17.

19. 1. A method for treating biological material, comprising: loading a biological handling container into a first bioprocess module of the plurality of bioprocess modules; performing a first unit operation on the biological handling vessel and / or contents of the biological handling vessel in the first bioprocess module; removing the biological handling vessel from the first bioprocess module via a robot; transferring the biological handling container via the robot to a second bioprocess module of the plurality of bioprocess modules; performing a second unit operation on the biological handling vessel and / or contents of the biological handling vessel in the second bioprocess module; A method comprising:

20. 20. The method of claim 19, wherein the first unit operation and / or the second unit operation comprises introducing a population of cells into the biological handling container.

21. 21. The method of claim 19 or 20, wherein the first unit operation and / or the second unit operation comprises introducing at least one of cell culture media, growth factors, viral vectors, non-viral vectors, and bead-based reagents into the biological handling vessel.

22. 22. The method of any one of claims 19 to 21, wherein the first unit operation and / or the second unit operation comprises at least one of culturing, genetically modifying, stimulating, growing, washing, separating, selecting, or harvesting cells contained within the biological handling container.

23. 23. The method of any one of claims 19 to 22, wherein the first unit operation and / or the second unit operation comprises storing the biological handling container under predetermined conditions.

24. 24. The method of any one of claims 19 to 23, wherein the first unit operation and / or the second unit operation comprises analyzing, centrifuging, or electroporating the contents of the biological handling container.

25. 25. The method of any one of claims 19 to 24, wherein the step of loading a biological handling vessel into a first bioprocess module of a plurality of bioprocess modules comprises loading the biological handling vessel into the first bioprocess module via the robot.

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