Sparger Apparatus for a Bioprocessing System and Method of Manufacturing the Sparger Apparatus - Patent application

Abstract

The sparger apparatus includes a sparge tube having opposite distal ends, an inlet opening, and a plurality of sparge holes along a longitudinal extent of the sparge tube between the opposite distal ends, and a central hub coupled to the sparge tube at a location intermediate the opposite distal ends of the sparge tube, the central hub having a fluid passageway in fluid communication with the sparge tube through the inlet opening.

Description

[Technical field]

[0001] FIELD OF THE DISCLOSURE

[0002] Embodiments of the present invention relate generally to bioprocessing systems and methods, and more particularly to a sparger apparatus for single-use biological reaction systems. [Background technology]

[0002] A variety of vessels, devices, components, and unit operations are known for carrying out biochemical and / or biological processes and / or manipulating the liquids and other products of such processes. To avoid the time, expense, and difficulty associated with sterilizing vessels used in biopharmaceutical manufacturing processes, single-use or disposable bioreaction bags and single-use mixing bags are used as such vessels. By way of example, biological materials (e.g., animal and plant cells), including, for example, mammalian, plant, or insect cells, and microbial cultures, can be processed using disposable or single-use mixing vessels and bioreactors.

[0003] Increasingly, single-use or disposable containers are being used in the biopharmaceutical industry. Such containers can be flexible or collapsible plastic bags supported by an outer rigid structure such as a stainless steel shell or vessel. The use of sterilized disposable bags eliminates the time-consuming step of vessel cleaning and reduces the chance of contamination. The bag is positioned within the rigid vessel and filled with the desired fluid for mixing. A stirring assembly located within the bag is used to mix the fluid. Existing stirrers are either top-driven (having a shaft that extends downward into the bag and on which one or more impellers are mounted) or bottom-driven (having an impeller located at the bottom of the bag that is driven by a magnetic drive system or motor located outside the bag and / or vessel). Most magnetic stirring systems include a rotating magnetic drive head on the outside of the bag and a rotating magnetic stirrer (also referred to in this context as an "impeller") within the bag. The movement of the magnetic drive head allows for torque transmission, thereby allowing the magnetic stirrer to rotate, causing the stirrer to mix the liquid within the vessel.

[0004] Depending on the fluid being processed, the bioreactor system may include several fluid lines and different sensors, probes, and ports that are coupled to the bag for monitoring, analysis, sampling, and liquid transfer. For example, a sampling port is typically located at the bottom of the disposable bag and vessel, and a sampling line can be connected to the bag for sampling and draining from the bag. Existing bioreactor systems also typically utilize a sparger to introduce a controlled amount of a particular gas or combination of gases into the bioreactor. The sparger outputs small bubbles into the liquid to agitate the gas and / or to diffuse the gas into the liquid or for carbon dioxide separation. The delivery of gas through the sparger helps mix the materials and maintain a homogenous environment throughout the interior of the bag, which may be essential for cell growth in the bioreactor. Ideally, the sparger and the agitator are in close proximity to ensure optimal distribution of the gas throughout the vessel.

[0005] One common type of sparger is generally T-shaped and connectable to a gas supply line extending at the bottom of the bioreactor vessel. The sparger extends upward into the interior of the vessel / single-use bag to deliver gas to the culture in the interior volume. This type of sparger is typically manufactured from three component parts: a vertical hub with a central passageway, and two opposing tube sections with multiple longitudinally spaced holes that form arms of a T that extend horizontally outward from the vertical hub. The central passageway of the hub is in fluid communication with the opposing tube sections to deliver gas to the tube sections, which are threaded through the holes along the longitudinal extent of the tube sections to the culture. Such spargers are typically manufactured by intersecting a vertical bar with a horizontal bar to form a T shape, and then molding around the bar to form the hub. The bar sections are then removed, leaving the T-shaped passageway in the hub. The opposing tube portion is then coupled to the hub in fluid communication with the T-shaped passageway.

[0006] Due to the three-piece configuration of the sparger and the molding method used to manufacture the hub, the gas delivery holes along opposing tube sections may not be equally spaced from the hub. That is, a hole in one tube section may be located closer to the hub than a corresponding hole in the opposing tube section due to the way each tube section is seated in the hub. This can result in backflow near the hub, which can result in trapped cell debris inside the tube section. The sparger can also be prone to cell / media accumulation at the distal end of the tube section due to dead space in the tube section beyond the last gas delivery hole. Additionally, because the vertical section of the hub is not particularly rigid, the sparger can move around inside the bag and contact the impeller, bag, and / or sensor, which is undesirable. Summary of the Invention [Problem to be solved by the invention]

[0007] In view of the above, there is a need for an improved sparger apparatus that significantly reduces the likelihood of cell accumulation in the sparger, is less prone to bias, and can be produced from a variety of materials. In connection with such a sparger apparatus, there is a need for a manufacturing method that achieves more repeatable hole positioning and is simpler and less expensive than existing methods. [Means for solving the problem]

[0008] In an embodiment, a sparger apparatus is provided that includes a sparger tube having opposite distal ends, an inlet opening, and a plurality of sparge holes along a longitudinal extent of the sparger tube between the opposite distal ends, and a central hub coupled to the sparger tube at a location intermediate the opposite distal ends of the sparger tube, the central hub having a fluid passageway in fluid communication with the sparger tube through the inlet opening.

[0009] In another embodiment, a method of manufacturing a sparger apparatus is provided that includes providing a tube having opposed distal ends and an inlet opening in a sidewall of the tube between the opposed distal ends, inserting a pin into the inlet opening, overmolding around the pin and the tube to form a central hub, and removing the pin to form a feed passage in the central hub, the feed passage in fluid communication with an interior of the tube through the inlet opening.

[0010] In yet another embodiment, a bioprocessing system is provided comprising a vessel, a flexible bioprocessing bag positionable within the vessel, and a sparger apparatus coupled to a fluid port in the flexible bioprocessing bag, the sparger apparatus comprising a sparge tube having opposite distal ends, an inlet opening, and a plurality of sparge holes along a longitudinal extent of the sparge tube between the opposite distal ends, and a central hub coupled to the sparge tube at a location intermediate the opposite distal ends of the sparge tube, the central hub having a fluid passageway in fluid communication with the sparge tube through the inlet opening.

[0011] In yet another embodiment, a sparger assembly is provided that includes at least one sparge tube having a distal end and a plurality of sparge holes along a longitudinal extent of the sparge tube, a hub coupled to the sparge tube, the hub having a fluid passage in fluid communication with a central passage of the sparge tube for providing gas to the sparge tube, and a cap at the distal end of the sparge tube, the cap having a through hole in fluid communication with the central passage of the sparge tube.

[0012] The invention will be more readily understood from reading the following description of non-limiting embodiments, with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a front elevation view of a bioreaction system according to an embodiment of the present invention. [Diagram 2] FIG. 2 is a simplified cross-sectional side elevation view of the biological reaction system of FIG. 1. [Diagram 3] FIG. 2 is a simplified top plan view of the biological reaction system of FIG. 1. [Figure 4] FIG. 2 is a top plan view of a sparger apparatus for use with the biological reaction system of FIG. 1 in accordance with an embodiment of the present invention. [Diagram 5] 5 is a cross-sectional view of the sparger apparatus of FIG. 4 taken along line BB of FIG. 4. [Figure 6] FIG. 6 is an enlarged detail view of area C of FIG. 5. [Figure 7] FIG. 5 is an enlarged side elevational view of the sparger assembly of FIG. 4. [Figure 8] FIG. 5 is an exemplary cross-sectional view of a mold assembly used to manufacture the sparger apparatus of FIG. [Figure 9] 5 is an enlarged, partial cross-sectional view of the distal end of the sparger assembly of FIG. 4, showing a cap of the sparger assembly according to an embodiment of the present invention. [Figure 10] 5 is an enlarged cross-sectional view of a portion of the distal end of the sparger assembly of FIG. 4, showing a sparger assembly cap according to another embodiment of the present invention. [Figure 11] FIG. 5 is an enlarged, partial cross-sectional view of the distal end of the sparger apparatus of FIG. 4 in accordance with another embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Reference will now be made in detail to the exemplary embodiments of the present invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like parts.

[0015] As used herein, the terms "flexible" or "foldable" refer to structures or materials that are pliable or can bend without cracking, and can also refer to materials that are compressible or expandable. An example of a flexible structure is a bag formed from a polyethylene film. The terms "rigid" and "semi-rigid" are used interchangeably herein to describe structures that are "non-collapsible", i.e., structures that do not fold, collapse, or deform under normal forces to substantially shorten their elongated dimensions. Depending on the context, "semi-rigid" can also refer to structures that are more flexible than a "rigid" element, such as a bendable tube or conduit, but still do not collapse in the longitudinal direction under normal conditions and forces.

[0016] The term "vessel" is used herein and may refer to a flexible bag, flexible container, semi-rigid container, rigid container, or flexible or semi-rigid tubing, as the case may be. The term "vessel" as used herein is intended to cover bioreactor vessels having walls or portions of walls that are flexible or semi-rigid, single-use flexible bags, and other vessels or conduits commonly used in biological or biochemical processes, including, for example, cell culture / purification systems, mixing systems, media / buffer preparation systems, and filtration / purification systems. As used herein, the term "bag" refers to a flexible or semi-rigid vessel or vessel used, for example, as a bioreactor or mixer for the contents therein.

[0017] An embodiment of the present invention provides a biological reaction system and a sparger apparatus for the biological reaction system. In an embodiment, the sparger apparatus for the bioprocessing system is formed as a two-piece assembly and includes a sparge tube having opposite distal ends, an inlet opening, and a plurality of sparge holes along the longitudinal extent of the sparge tube between the opposite distal ends, and a central hub coupled to the sparge tube at approximately the midpoint of the sparge tube, the central hub having a fluid passage in fluid communication with the sparge tube through the inlet opening. The sparger apparatus is formed by inserting a core pin into the inlet opening in the sparge tube to form an interference fit, overmolding around the core pin and the sparge tube to form a central hub, and removing the core pin to provide a feed passage in fluid communication with the sparger tube through the inlet opening.

[0018] 1 and 2, a bioreactor system 10 according to an embodiment of the present invention is shown. The bioreactor system 10 includes a generally rigid bioreactor vessel or support structure 12 mounted on a base 14 having a plurality of legs 16. The vessel 12 may be formed, for example, from stainless steel, polymers, composites, glass, or other metals and may be cylindrical in shape, although other shapes may be utilized without departing from the broader aspects of the present invention. The vessel 12 may be provided with a lifting structure 18 that provides support for a single-use flexible bag 20 disposed within the vessel 12. The vessel 12 may be of any shape or size so long as it is capable of supporting the single-use flexible bioreactor bag 20. For example, according to one embodiment of the present invention, the vessel 12 is capable of receiving and supporting a 10-2000 L flexible or collapsible bioprocess bag assembly 20.

[0019] The vessel 12 may include one or more visual windows 22 that allow visualization of the fluid level in the flexible bag 20, and a window 24 positioned in a lower region of the vessel 12. The window 24 allows access to the interior of the vessel 12 for insertion and positioning of various sensors and probes (not shown) within the flexible bag 20, as well as for connecting one or more fluid lines to the flexible bag 20 for fluids, gases, etc., to be added to or withdrawn from the flexible bag 20. Sensors / probes and controls for monitoring and controlling critical process parameters include, for example, any one or more and combinations of temperature, pressure, pH, dissolved oxygen (DO), dissolved carbon dioxide (pCO2), mixing ratios, and gas flow rates.

[0020] With particular reference to FIG. 2, a schematic side elevation cross-sectional view of a bioreaction system 10 is shown. As shown therein, a single-use flexible bag 20 is placed within and held by the vessel 12. In an embodiment, the single-use flexible bag 20 is formed from a suitable flexible material, such as a homopolymer or copolymer. The flexible material may be USP Class VI approved, for example, silicone, polycarbonate, polyethylene, and polypropylene. Non-limiting examples of flexible materials include polymers such as polyethylene (e.g., linear low density polyethylene and very low density polyethylene), polypropylene, polyvinyl chloride, polyvinyl dichloride, polyvinylidene chloride, ethylene vinyl acetate, polycarbonate, polymethacrylate, polyvinyl alcohol, nylon, silicone rubber, other synthetic rubbers, and / or plastics. In an embodiment, the flexible material may be a laminate of several different materials, such as, for example, laminates of Fortem™, Bioclear™ 10, and Bioclear 11 available from GE Healthcare Life Science. A portion of the flexible container may comprise a substantially rigid material, such as a rigid polymer, e.g., high density polyethylene, metal, or glass. The flexible bag may be supplied pre-sterilized, such as using gamma irradiation.

[0021] The flexible bag 20 includes an impeller 28 attached to a magnetic hub 30 at the bottom center of the interior of the bag, and the impeller 28 rotates on an impeller plate (not shown) also positioned at the bottom of the interior of the bag 20. Together, the impeller 28 and hub 30 (and in some embodiments the impeller plate) form an impeller assembly. A magnetic drive 34 external to the vessel 12 provides the motive force to rotate the magnetic hub 30 and impeller 28 to mix the contents of the flexible bag 20. While FIG. 2 shows the use of a magnetically driven impeller, other types of impellers and drive systems are possible, including a top driven impeller.

[0022] As also shown in FIG. 2, the flexible bag 20 includes a sparger apparatus 100 that can be engaged with a port shown (not shown) in the bottom of the flexible bag 20, which receives a supply of gas from the gas supply line 36. The sparger apparatus 100 extends upward into the interior volume defined by the flexible bag 20 and is positioned adjacent the impeller 28. FIG. 2 is intended to show the general configuration and positioning of the sparger apparatus 100. In practice, the sparger apparatus 100 may have a horizontal extent that spans nearly the entire inner diameter of the bag 20 and / or vessel 12 (see, e.g., FIG. 3). It is also contemplated that the sparger apparatus 100 may be attached to a port anywhere in the bottom of the bag (not necessarily adjacent the periphery of the bottom of the bag 20) or even to a port in a sidewall of the bag 20.

[0023] 4-6, a sparger apparatus 100 is shown according to one embodiment of the present invention. As shown therein, the sparger apparatus 100 is generally T-shaped and includes a first tube (sparge tube 102) and a second tube (feed tube 104) connected to and oriented substantially perpendicular to the sparge tube 102. The sparge tube 102 has a central passageway 106 and a plurality of radial sparge holes 108 or openings along the length of the tube 102 and in fluid communication with the central passageway 106. In an embodiment, the sparge holes 108 are spaced equidistant from one another along the length of the tube 102, although in some embodiments the sparge holes 108 may be spaced irregularly along the tube 102. The sparge tube 102 also includes a central inlet opening 110 on the underside of the tube 102 at an intermediate location along the length of the tube 102. In an embodiment, the inlet opening 110 is located approximately 180 degrees from the distribution holes 108 in the top of the tube 102 .

[0024] As best shown in FIGS. 5 and 6, the supply tube 104 also includes a central supply passage 112 in fluid communication with the central passage 106 of the sparge tube 102 via an inlet opening 110 in the sparge tube 102. In one embodiment, the central passage 112 may have a large diameter portion 114, a small diameter portion 116, and a shoulder portion 118 forming a transition between the large diameter portion 114 and the small diameter portion 116. As shown in FIG. 6, the supply tube 104 defines a central hub having a generally T-shaped sleeve 120 that surrounds the sparge tube 102 and serves to couple the sparge tube 102 to the supply tube 104. In an embodiment, the small diameter portion 116 of the central passage 112 of the supply tube 104 and the central passage of the sparge tube 102 may have an inner diameter of between about 0 inches and about 0.25 inches. In an embodiment, the sparge holes may have a diameter of between about 0 inches and about 0.25 inches. In other embodiments, the dispersion holes may have a diameter between about 0 inches and about 0.125 inches, or between about 0 inches and about 0.0625 inches. In embodiments, the supply tube 104 may have a generally consistent outer diameter of about 0.25 inches to about 0.5 inches.

[0025] Although the sparge tube 102 has been described above as being generally rectilinear in shape, it is contemplated that the sparge tube 102 may have most any shape so long as it is a unitary component. Specifically, the sparge tube 102 may be generally circular or arcuate in shape so as to extend adjacent the inner periphery of the flexible bag 20 around the impeller.

[0026] As such, as indicated above, the sparger apparatus 100 has a two piece construction, a single sparger tube 102 having a central inlet opening 110, and a supply tube 104 in fluid communication with the sparger tube 102 via the central inlet opening 110. It is contemplated that the sparger tube 102 and the supply tube may be manufactured from a variety of materials, such as, for example, polypropylene. In an embodiment, the supply tube 104 is manufactured with a wall thickness and / or material such that it is substantially rigid and robust. In an embodiment, the supply tube 104 may be formed by overmolding around the sparger tube 102, as described hereinafter.

[0027] Specifically, with reference to Figure 8, the sparger apparatus 100 may be manufactured by first forming the sparger tube 102 with a central inlet opening 110 and sparge holes 108 at predetermined spaced locations from the midpoint of the tube 102. For example, this may be done using a variety of molding processes, although the invention is not so limited in this respect. Specifically, it is contemplated that the sparger tube 102 may be manufactured utilizing a variety of techniques, such as, for example, molding or additive manufacturing techniques.

[0028] The sparge tube 102 is positioned in a mold 140 having a molded area 142 that corresponds in shape / configuration to the shape / configuration of the central hub to be formed as it is formed. As shown in FIG. 8, the mold 140 has a core pin 150 that is inserted into the inlet opening 110 in the sparge tube 102 when the sparge tube is positioned in the mold 140. The core pin 150 has a diameter equal to or slightly larger than the diameter of the inlet opening 110 in the sparge tube 102. In an embodiment, the core pin 150 may have a diameter from about 0 to about 0.01 inches larger, more specifically from about 0 to about 0.004 inches larger, and even more specifically from about 0.002 to about 0.004 inches larger than the diameter of the inlet opening 110 so as to form an interference fit with the sparge tube 102 when inserted into the inlet opening 110. In an embodiment, the core pin 150 can have a diameter slightly (e.g., 0.01 inches) smaller than the diameter of the inlet opening, which would still prevent the flow of injected material due to normal clearance spaces. The core pin 150 also has a tapered tip 152 that facilitates insertion of the core pin 150 into the inlet opening 110. As shown in FIG. 8 , the core pin 150 can have a large diameter portion 154, a small diameter portion 156, and a shoulder portion 158 that forms a transition between the large diameter portion 154 and the small diameter portion 156.

[0029] After the sparge tube 102 is received in the core pin 150 and positioned in the mold 140, material is passed around the core pin 150 and the sparge tube 102 into the mold forming area 142 to form a central hub (i.e., the sleeve 120 and the supply tube 104). The sparge device 100 is then removed from the mold 140. Removal of the core pin 150 forms the central passage 112 of the supply tube 104. As will be appreciated, receiving the core pin 150 in the inlet opening 110 of the sparge tube 102 ensures that the holes on opposite sides of the sparge tube 102 are equally spaced from the middle position of the sparge tube 102. Also, the core pin 150 forms an interference fit with the sparge tube 102 when inserted into the opening 110, preventing material from seeping into the sparge tube 102 through the opening 110, which could create a restriction in the passage 106 (leading to a pressure drop during use).

[0030] Once the sparging device is removed from the mold (or in some embodiments, removed prior to overmolding the central hub), the opposite distal end of the sparging tube 102 may be plugged or capped. FIG. 9 illustrates a cap 200 for the sparging tube 102 according to one embodiment of the present invention. As shown in this figure, the cap 200 includes a body portion 202 having a cylindrical recess 204 that generally corresponds in diameter to the outer diameter of the sparging tube 102, which allows the cap 200 to create an interference / press fit with the sparging tube 102. The cap 200 also includes a central through hole or bore 206 that is generally aligned with the longitudinal axis of the sparging tube 102 when the cap is received on the distal end of the sparging tube 102. As shown in FIG. 9, the cap 200 may be rounded in shape and / or have chamfered corners to minimize or prevent damage to or scratching of system components (bag membrane, impeller, sensor, etc.). In an embodiment, the through holes 206 have a diameter that is substantially the same as the diameter of the sparge holes 108. The through holes 206 in the cap 200 allow the sparge gas to exit axially through the cap 200 at the distal end of the sparge tube 102. This effectively eliminates dead space at the end of the sparge tube 102 beyond the last sparge hole 108.

[0031] 10 illustrates a cap 300 according to another embodiment of the present invention. As shown in this figure, the cap 300 is generally similar in shape and configuration to the cap 200 of FIG. 9, and includes a body portion 302 having a cylindrical recess 304 whose diameter generally corresponds to the outer diameter of the sparge tube 102, which allows the cap 300 to create an interference / press fit with the sparge tube 102. The cap 300 also includes a through hole 306. The through hole 306 is shaped to allow sparge gas to exit the cap in a direction generally perpendicular to the longitudinal axis of the sparge tube 102 (i.e., generally parallel to the direction in which the sparge gas exits through the sparge holes 108). For example, as shown in FIG. 10, the through hole comprises a first leg that is generally aligned with the longitudinal axis of the sparging tube 102 when the cap 300 is received on the distal end of the sparging tube 102, and a second leg that forms a substantially 90 degree angle with the first leg. As shown in FIG. 10, the cap 300 may be rounded in shape and / or have chamfered corners to minimize or prevent damage to or scratching of system components (bag membrane, impeller, sensor, etc.). In an embodiment, the through hole 306 has a diameter that is substantially the same as the diameter of the sparging holes 108. As with the cap 200, the through hole 306 in the cap 300 effectively eliminates dead space at the end of the sparging tube 102 beyond the last sparging hole 108.

[0032] It is contemplated that the caps 200, 300 of Figures 9 and 10 may be coupled to the distal end of the distribution tube 102 by a variety of means, including, but not limited to, press fit, adhesive, welding, and the like.

[0033] 11, in embodiments where a cap is not utilized, the sparge tube 102 may be manufactured with a tapered distal end 400. Specifically, the distal end of the sparge tube 102 may be formed into a pointed tip, with an axial opening 402 at the distal end that generally corresponds in diameter to the diameter of the sparge holes 108. Similar to the caps 200, 300 and their openings, the opening 402 allows the sparge gas to exit at the end of the sparge tube 102 and prevents dead space at the end of the sparge tube 102 beyond the last sparge hole 108.

[0034] As alluded to above, the sparger apparatus 100 is intended to be connected to a fluid port at the bottom of the flexible bag 20 of a bioreactor / bioprocessing system. The fluid port, and therefore the sparger apparatus 100, is connected to a supply of fluid (i.e., sparge gas) for use during the sparging operation of the bioreactor system. As indicated above, the sparger apparatus 100 is robust and substantially rigid due to the two-piece construction of the apparatus and the configuration of the central hub and supply tube 104. As a result, the sparger apparatus 100 is much less likely to move within the bag, thereby minimizing the possibility of the sparger apparatus 100 contacting the impeller, sensor, bag membrane, etc. Also, the provision of a hole or opening at the distal end of the sparger apparatus 100 (via a cap or narrowed distal end) eliminates dead space beyond the distal-most sparge hole in the sparge tube 102.

[0035] The structure of, and manufacturing process for, the sparger apparatus 100 also facilitates accurate and repeatable sparge hole location. Specifically, the core pin 150, when received in the central inlet opening 110 in the sparger tube 102, accurately positions the feed passage 112 of the feed tube 104 equidistant from the sparge holes 108 to either side of the feed passage 112 and the inlet opening 110. Furthermore, by utilizing a single (i.e., one-piece) sparge tube 102, assembly and alignment of the sparge tube 102 (and its sparge holes 108) relative to the feed tube 104 is simplified. As a result of this accurate sparge hole positioning, the possibility of backflow, which can result in trapped cellular debris inside the sparge tube, is minimized. The use of the core pin 150 as detailed above also provides reliable hole sealing, preventing seepage of mold material into the sparge tube 102, which can create restrictions that result in pressure drop during sparging.

[0036] The sparger apparatus 100 of the present invention, and the manufacturing method for the sparger apparatus 100, significantly reduces the likelihood of cell accumulation in the sparger and is less prone to bias. The manufacturing method described herein achieves more repeatable hole positioning, as detailed above, and is simpler and less expensive than existing methods. The sparger apparatus of the present invention disclosed above can be used to inject gas into a liquid for a variety of purposes, including, for example, to control the amount of dissolved gas (e.g., oxygen, nitrogen, carbon dioxide) in the liquid and / or for carbon dioxide separation.

[0037] In an embodiment, a sparger apparatus is provided. The sparger apparatus includes a sparge tube having opposite distal ends, an inlet opening, and a plurality of sparge holes along a longitudinal extent of the sparge tube between the opposite distal ends, and a central hub coupled to the sparge tube at a location intermediate the opposite distal ends of the sparge tube, the central hub having a fluid passage in fluid communication with the sparge tube through the inlet opening. In an embodiment, the central hub is overmolded around the sparge tube. In an embodiment, the plurality of sparge holes is located at an upper portion of the sparge tube, and the inlet opening is located at a lower portion of the sparge tube. In an embodiment, the sparger apparatus also includes a cap at at least one of the opposite distal ends of the sparge tube, the cap having a through hole in fluid communication with the central passage of the sparge tube. In an embodiment, the through hole is an axial through hole oriented to direct sparge gas exiting the through hole in a direction generally perpendicular to the sparge gas exiting through the plurality of sparge holes. In an embodiment, the through holes are oriented to direct sparge gas exiting the through holes in a direction generally parallel to the sparge gas exiting through the plurality of sparge holes. In an embodiment, the through holes include an angle of approximately 90 degrees. In an embodiment, opposite distal ends of the sparge tube taper to a point, and each opposite distal end includes an axial opening for the passage of sparge gas.

[0038] In another embodiment, a method of manufacturing a sparger apparatus is provided. The method includes providing a tube having opposing distal ends and an inlet opening in a sidewall of the first tube between the opposing distal ends, inserting a pin into the inlet opening, overmolding around the pin and the tube to form a central hub, and removing the pin to form a feed passage in the central hub, the feed passage fluidly communicating with the interior of the tube through the inlet opening. In an embodiment, the tube includes a plurality of radial holes along a longitudinal extent of the tube. In an embodiment, the pin has a tapered tip. In an embodiment, the pin has an outer diameter larger than a diameter of the inlet opening of the tube such that the pin forms an interference fit when inserted into the inlet opening. In an embodiment, the method also includes inserting a cap into each of the opposing distal ends of the tube. In an embodiment, the cap includes an axial hole oriented to direct sparge gas exiting the axial hole in a direction generally perpendicular to the sparge gas exiting through the plurality of radial holes. In an embodiment, the cap includes holes oriented to direct sparge gas exiting the holes in a direction generally parallel to the sparge gas exiting through the plurality of radial holes, hi an embodiment, the cap is attached to the tube by at least one of a press fit, an adhesive, and / or a weld.

[0039] In yet another embodiment, a bioprocessing system is provided. The bioprocessing system includes a vessel, a flexible bioprocessing bag positionable within the vessel, and a sparger apparatus coupled to a fluid port in the flexible bioprocessing bag, the sparger apparatus including a sparge tube having opposite distal ends, an inlet opening, and a plurality of sparge holes along a longitudinal extent of the sparge tube between the opposite distal ends, and a central hub coupled to the sparge tube at a location intermediate the opposite distal ends of the sparge tube, the central hub having a fluid passage in fluid communication with the sparge tube through the inlet opening. In an embodiment, the sparger apparatus is T-shaped. In an embodiment, the sparger apparatus further includes a cap at at least one of the opposite distal ends of the sparge tube, the cap having a through hole in fluid communication with the central passage of the sparge tube. In an embodiment, the through hole is an axial through hole oriented to direct sparge gas exiting the through hole in a generally perpendicular direction to sparge gas exiting through the plurality of sparge holes. In an embodiment, the through-holes are oriented to direct sparge gas exiting the through-holes in a direction generally parallel to the sparge gas exiting through the plurality of sparge holes.

[0040] In yet another embodiment, a sparger apparatus is provided. The sparger apparatus includes at least one sparge tube having a distal end and a plurality of sparge holes along a longitudinal extent of the sparge tube, a hub coupled to the sparge tube, the hub having a fluid passage in fluid communication with a central passage of the sparge tube for providing gas to the sparge tube, and a cap at the distal end of the sparge tube, the cap having a through hole in fluid communication with the central passage of the sparge tube. In an embodiment, the through hole is an axial through hole oriented to direct sparge gas exiting the through hole in a direction generally perpendicular to the sparge gas exiting through the plurality of sparge holes. In an embodiment, the through hole is oriented to direct sparge gas exiting the through hole in a direction generally parallel to the sparge gas exiting through the plurality of sparge holes.

[0041] As used herein, elements or steps referred to in the singular and elements or steps preceded by the words "a" or "an" should be understood as not excluding a plurality of said elements or steps, unless expressly stated otherwise. Furthermore, references to "one embodiment" of the invention are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the claimed features. Furthermore, unless expressly stated to the contrary, embodiments "comprising," "including," or "having" an element or elements having a particular property may include additional such elements that do not have that property.

[0042] This written description uses examples to disclose some embodiments of the invention, including the best mode, and to enable one of ordinary skill in the art to practice embodiments of the invention, including making any device or system, using any device or system, and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those of ordinary skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the claim language, or if they include equivalent structural elements with insubstantial differences from the claim language. [Explanation of symbols]

[0043] 10. Biological reaction systems 12 Bioreactor vessel and support structure 14 Basics 16 Legs 18 Lifting Structure 20 Flexible biological reaction bag, bioprocess bag assembly 22 Visual Window 24 Windows 28 Impeller 30 Magnetic Hub 34 Magnetic drive unit 36 Gas supply piping 100 Sparger equipment, spraying equipment 102 First tube, distribution tube 104 Second pipe, supply pipe 106 Center aisle 108 Spray hole 110 Center entrance opening 112 Center supply passage 114 Large diameter part 116 Small diameter part 118 Shoulder 120 Sleeve 140 type 142 Mold forming area 150 core pins 152 Tip 154 Large diameter part 156 Small diameter part 158 Shoulder 200 Cap 202 Main body part 204 Recess 206 Through holes, holes 300 Cap 302 Main body part 304 Recess 306 Through hole 400 tapered distal end 402 Axial opening

Claims

1. a single sparge tube (102) having opposed distal ends, an inlet opening (110), and a plurality of sparge holes (108) along a longitudinal extent of the sparge tube (102) between the opposed distal ends; a central hub (104) coupled to the sparge tube (102) at a location intermediate the opposed distal ends of the sparge tube (102), the central hub (104) having a fluid passageway (112) in fluid communication with the sparge tube (102) through the inlet opening (110); a cap (200) fitted to each end of the sparge tube (102), the cap (200) having a central through hole (206) aligned with a longitudinal axis of the sparge tube (102); Equipped with The sparger assembly (100), wherein the central hub (104) is overmolded around the sparger tube (102).

2. said plurality of sparging holes (108) being located on said single sparging tube (102); The sparger apparatus (100) of claim 1, wherein the inlet opening (110) is located in a lower portion of the sparger tube (102).

3. A method of manufacturing a sparger apparatus (100), comprising the steps of: providing a single sparge tube (102) having opposed distal ends and an inlet opening (110) in a sidewall of the sparge tube (102) between the opposed distal ends; Inserting a pin (150) into said entrance opening (110); overmolding around the pin (150) and the distribution tube (102) to form a central hub (104); removing the pin (150) to form a supply passage (112) in the central hub (104), the supply passage (112) in fluid communication with an interior of the single tube (102) through the inlet opening (110); fitting a cap (200) to each of the opposed distal ends of the sparging tube (102), the cap (200) including a central throughbore (206) aligned with a longitudinal axis of the sparging tube (102); The method includes:

4. The method of claim 3, wherein the single tube (102) includes a plurality of radial holes (108) along a longitudinal extent of the single tube (102).

5. The method of claim 3 or 4, wherein the pin (150) has a tapered tip (152).

6. 6. The method according to claim 3, wherein the pin (150) has an outer diameter larger than a diameter of the inlet opening (110) of the distribution tube (102) so as to form an interference fit when the pin (150) is inserted into the inlet opening (110).

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