Sparger Assembly for Bioprocessing Systems

Abstract

A sparger assembly for a bioprocessing system includes a base and a plurality of spargers connected to the base, each sparger including a plurality of orifices, each of the plurality of spargers having a generally cylindrical shape. Each of the plurality of spargers includes a sidewall and a top defining the cylindrical shape, and the sidewall and top each include a plurality of orifices. The orifices in the sidewall can be arranged in arrays of various heights around the periphery of the sidewall. Additionally, ridges can be disposed on the sidewall above each array of orifices.

Description

[Technical Field]

[0001] FIELD OF THE INVENTION Embodiments of the present invention relate generally to bioprocessing systems and methods, and more particularly to sparger assemblies for single-use bioreactor systems. [Background technology]

[0002] Various vessels, devices, components, and unit operations are known for performing 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 bioreactor bags and single-use mixer bags are used as such vessels. For example, biological material (e.g., animal cells and plant cells), including, for example, mammalian animal, plant, or insect cells, and microbial cultures can be processed using disposable or single-use mixers or bioreactors.

[0003] The biopharmaceutical industry is increasingly using single-use or disposable containers. Such containers can be flexible or collapsible plastic bags supported by an external rigid structure, such as a stainless steel shell or vessel. The use of sterilized disposable bags eliminates the time-consuming step of container cleaning and reduces the chance of contamination. The bag can be placed within a rigid vessel and filled with the desired fluid for mixing. An agitator assembly disposed within the bag is used to mix the fluid. Existing agitators are either top-driven (having a shaft extending downward into the bag with one or more impellers mounted thereon) or bottom-driven (having an impeller disposed at the bottom of the bag driven by a magnetic drive system or motor located outside the bag and / or vessel). Most magnetic agitator systems include a rotating magnetic drive head outside the bag and a rotating magnetic agitator (also referred to in this context as an "impeller") within the bag. The movement of the magnetic drive head enables torque transmission and thus rotation of the magnetic agitator, allowing the agitator to mix the fluid within the vessel. Magnetic coupling of the agitator inside the bag to a drive system or motor external to the bag and / or bioreactor vessel can eliminate contamination issues, allow for a fully enclosed system, and prevent leaks. Because the drive shaft does not need to penetrate the bioreactor vessel wall to mechanically rotate the agitator, a magnetically coupled system can also eliminate the need for a seal between the drive shaft and the vessel.

[0004] Depending on the fluid being processed, a bioreactor system may include several fluid lines connected to the bag for monitoring, analysis, sampling, and liquid transfer, as well as various sensors, probes, and ports. For example, harvest ports are typically located at the bottom of disposable bags and containers, allowing harvest lines to be connected to the bag for harvesting and draining the bag. Additionally, existing bioreactor systems typically utilize spargers to introduce controlled amounts of a specific gas or combination of gases into the bioreactor. The spargers output small bubbles into the liquid to agitate and / or dissolve the gas into the liquid. The delivery of gas via the sparger helps mix materials and maintain a homogeneous environment throughout the interior of the bag, which can sometimes be essential for cell growth in the bioreactor. Ideally, the sparger and agitator are in close proximity to ensure optimal distribution of the gas throughout the container.

[0005] In relation to the above, oxygen is an important substrate for growth, production, and maintenance activities in cell culture. Cells obtain their oxygen in the form of a free, non-compound form called dissolved oxygen (DO). One of the most important functions of a bioreactor is to continuously supply dissolved oxygen to cells through aeration. Aeration in a bioreactor typically occurs when oxygen diffuses through the overlay to the cell-culture medium interface and when oxygen from the sparger dissolves in the cell culture medium by convection due to agitation. Agitation disperses oxygen bubbles and promotes mass transfer of the gas bubbles across the gas-liquid (cell-culture medium) interface. The oxygen transfer rate (OTR) from the gas to the liquid interface is a function of the physicochemical properties of the cell culture medium, the geometric parameters of the bioreactor, and the presence of cells.

[0006] Oxygen is continuously supplied to cell cultures due to its low solubility in the liquid phase and its increasing metabolic consumption by cells over time. Oxygen supply is carefully controlled by manipulating bioreactor parameters for optimal cell growth. During batch cell culture, the oxygen utilization rate (OUR) (or oxygen transfer rate (OTR)) is initially low during the lag phase, when cells self-synthesize and there is little increase in cell density. As cell density increases during the log phase, the OUR increases until the OTR becomes limiting, as determined by the mass transfer of oxygen into the bulk liquid. The OTR and OUR rates are interrelated by the oxygen mass transfer coefficient (kLa), a volumetric mass transfer coefficient that describes the efficiency with which oxygen can be delivered to the bioreactor for given operating conditions. Thus, the OTR, through its correlation with kLa, defines the theoretical maximum cell density that could be achieved in a cell culture.

[0007] Higher oxygen utilization drives increased kLa. Increasing oxygen supply to the bioreactor drives this utilization and can be controlled by modifying the concentration (air vs. O2 enrichment) and volumetric flow rate. While high kLa values ​​are desirable, it is important to consider the actual operating conditions and their implications on cell viability and associated process costs.

[0008] For example, high airflow rates can cause cell damage due to shear forces. Excessive foam may be generated, requiring high concentrations of antifoam agents that interfere with downstream processing. Furthermore, higher airflow rates require larger exhaust filter areas, leading to increased consumable costs. Summary of the Invention [Problem to be solved by the invention]

[0009] It is therefore clear that a high performance bioreactor system must provide good bulk mixing combined with efficient gas dispersion to achieve large gas surface areas and bubble size distributions, and thus the high oxygen transfer rates and k values ​​desired in enhanced cell culture and / or microbial applications. However, improved spargers are needed to achieve high k while maintaining acceptable aeration flow rates. [Means for solving the problem]

[0010] According to a first aspect of the present invention, there is provided a sparger assembly for a bioprocessing system, the sparger assembly including a base and a plurality of spargers connected to the base, each sparger including a plurality of orifices, each of the plurality of spargers having a generally cylindrical shape.

[0011] In an embodiment, each of the plurality of spargers includes a sidewall and a top portion that define a cylindrical shape. The sidewall and the top portion each include a plurality of pores.

[0012] In embodiments, the pores in the sidewall include a first array of pores disposed at a first height above the top surface of the base. In further embodiments, the pores in the sidewall further include a second array of pores disposed at a second height above the top surface of the base, the second height being different from the first height. The second array of pores is radially offset relative to the first array of pores.

[0013] In an embodiment, the sidewall includes a first rib extending at least partially around the periphery of the sidewall, the first rib being disposed above the first array of pores. In a further embodiment, the sidewall further includes a second rib extending at least partially around the periphery of the sidewall, the second rib being disposed above the second array of pores.

[0014] In an embodiment, each of the plurality of spargers includes two mating surfaces, the two mating surfaces configured to mate with the base upon application of heat and / or a vibratory force.

[0015] According to a second aspect of the present invention, there is provided an impeller and sparger assembly for a bioprocessing system. The bioprocessing system includes an impeller and sparger assembly. The sparger assembly includes a base and a plurality of spargers connected to the base, each sparger including a plurality of orifices, each of the plurality of spargers having a generally cylindrical shape. Each of the plurality of spargers includes a sidewall and a top defining the cylindrical shape. The sidewall and top each include a plurality of orifices. In an embodiment, the orifices in the sidewall include a first array of orifices disposed at a first height from a top surface of the base. In a further embodiment, the orifices in the sidewall further include a second array of orifices disposed at a second height from a top surface of the base, the second height being different from the first height. The second array of orifices is radially offset relative to the first array of orifices. In an embodiment, the sidewall includes a first rib extending at least partially around an outer periphery of the sidewall, the first rib being disposed above the first array of perforations. In a further embodiment, the sidewall further includes a second rib extending at least partially around an outer periphery of the sidewall, the second rib being disposed above the second array of perforations. In an embodiment, each of the plurality of spargers includes two mating surfaces, the two mating surfaces configured to mate with the base upon application of heat and / or a vibratory force. The impeller assembly includes a magnetic hub connected to the base and an impeller connected to the magnetic hub.

[0016] According to a third aspect of the present invention, a bioprocessing apparatus is provided. The bioprocessing apparatus includes a flexible bag, a sparger assembly, and an impeller assembly. The sparger assembly includes a base and a plurality of spargers connected to the base, each sparger including a plurality of orifices, each of the plurality of spargers having a generally cylindrical shape. Each of the plurality of spargers includes a sidewall and a top defining the cylindrical shape. The sidewall and top each include a plurality of orifices. In an embodiment, the orifices in the sidewall include a first array of orifices disposed at a first height from a top surface of the base. In a further embodiment, the orifices in the sidewall further include a second array of orifices disposed at a second height from a top surface of the base, the second height being different from the first height. The second array of orifices is radially offset relative to the first array of orifices. In an embodiment, the sidewall includes a first rib extending at least partially around the periphery of the sidewall, the first rib being positioned above the first array of perforations. In a further embodiment, the sidewall further includes a second rib extending at least partially around the periphery of the sidewall, the second rib being positioned above the second array of perforations. In an embodiment, each of the plurality of spargers includes two mating surfaces, the two mating surfaces configured to mate with the base upon application of heat and / or a vibratory force. The impeller assembly includes a magnetic hub connected to the base and an impeller connected to the magnetic hub. The base includes at least one input port, the at least one input port being in fluid communication with the plurality of spargers. The input port is connectable to a gas source such that gas from the gas source is configured to exit through the plurality of perforations and enter the flexible bag.

[0017] The invention will be better understood from the following description of non-limiting embodiments, with reference to the accompanying drawings, in which: [Brief explanation of the drawings]

[0018] [Figure 1] FIG. 1 is a cross-sectional view of a bioreactor system according to an embodiment of the present invention. [Figure 2A] FIG. 1 is a side view of a sparger assembly according to an embodiment of the present invention. [Figure 2B] FIG. 1 is a top view of a sparger assembly according to an embodiment of the present invention. [Figure 3] FIG. 2C is a perspective view of the sparger assembly of FIGS. 2A and 2B. [Figure 4] 4 is a diagram of an impeller and sparger assembly incorporating the sparger assembly of FIGS. 2A-3, in accordance with an embodiment of the present invention. FIG. [Figure 5A] FIG. 4 is a side view of a sparger of the sparger assembly of FIGS. 2A-3, in accordance with an embodiment of the present invention. [Figure 5B] FIG. 4 is a top view of a sparger of the sparger assembly of FIGS. 2A-3, in accordance with an embodiment of the present invention. [Figure 6A] FIG. 5C is a cross-sectional view of the sparger of FIGS. 5A-5B, according to an embodiment of the present invention. [Figure 6B] FIG. 6B is an enlarged view of portion A of FIG. 6A in accordance with an embodiment of the present invention. [Figure 7] FIG. 6C is a perspective view of the sparger of FIGS. 5A-6B, according to an embodiment of the present invention. [Figure 8A] FIG. 4 is a side view of a sparger of the sparger assembly of FIGS. 2A-3, according to a further embodiment of the present invention. [Figure 8B] FIG. 4 is a top view of a sparger of the sparger assembly of FIGS. 2A-3, according to a further embodiment of the present invention. [Figure 9A] 8A-8B in accordance with an embodiment of the present invention. FIG. [Figure 9B] FIG. 9B is an enlarged view of portion A of FIG. 9A in accordance with an embodiment of the present invention. [Figure 10] FIG. 9C is a perspective view of the sparger of FIGS. 8A-9B, according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0019] Reference will now be made in detail to exemplary embodiments of the 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.

[0020] As used herein, the terms "flexible" or "collapsible" refer to structures or materials that are pliable or capable of being folded without breaking, and may also refer to compressible or expandable materials. An example of a flexible structure is a bag made of polyethylene film. As used interchangeably herein, the terms "rigid" and "semi-rigid" describe "non-collapsible" structures, i.e., structures that do not collapse, collapse, or otherwise deform under normal forces that would substantially reduce their elongated dimensions. Depending on the context, "semi-rigid" can also refer to structures that are more flexible than "rigid" elements, such as bendable pipes or conduits, but still do not collapse longitudinally under normal conditions and forces.

[0021] As used herein, "vessel" refers, in some cases, to a flexible bag, flexible container, semi-rigid container, rigid container, or flexible or semi-rigid tubing. As used herein, the term "vessel" is intended to encompass bioreactor vessels having flexible or semi-rigid walls or wall portions, single-use flexible bags, and other containers 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 (e.g., chromatography and tangential flow filter systems), and their associated fluid paths. As used herein, the term "bag" refers to a flexible or semi-rigid container or vessel used, for example, as a bioreactor or mixer for the contents therein.

[0022] Embodiments of the present invention provide a bioreactor system and a sparger assembly for the bioreactor system. In one embodiment, a sparger assembly for a bioprocessing system includes:

[0023] 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 20. The vessel 20 may be formed, for example, from stainless steel, a polymer, a composite material, glass, or other metal, and may be cylindrical in shape, although other shapes may be utilized without departing from the broader aspects of the present invention. The vessel 20 provides support for a single-use flexible bag 30 disposed within the vessel 20. The vessel 20 may be of any shape or size, so long as it is capable of supporting the single-use flexible bioreactor bag 30. For example, according to an embodiment of the present invention, the vessel 20 is capable of receiving and supporting a 10-2000 L flexible or collapsible bioprocess bag assembly 30 and has a maximum working height H and an inner diameter D.

[0024] The vessel 20 may include one or more sight windows that allow a person to view the fluid level within the flexible bag 30, as well as a window located in a lower region of the vessel 20. The windows allow access to the interior of the vessel 20 for the insertion and placement of various sensors and probes (not shown) within the flexible bag 30, and for connecting one or more fluid lines to the flexible bag 30 for fluids, gases, etc., to be added to or withdrawn from the flexible bag 30. 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 ratio, and gas flow rate.

[0025] Flexible bag 30 contains an impeller 22 attached to a magnetic hub 24 at the bottom center of the interior of the bag, and the impeller rotates on an impeller plate 26 (also referred to herein as a "base plate" or "sparger plate") also located on the interior bottom of bag 30. Together, impeller 22 and hub 24 (and, in some embodiments, impeller plate 26) form an impeller assembly. A magnetic drive 28 external to container 20 provides the motive force to rotate magnetic hub 24 and impeller 22, mixing the contents of flexible bag 30. While FIG. 2 illustrates the use of a magnetically driven impeller, other types of impellers and drive systems are possible, including top-driven impellers.

[0026] In certain embodiments, impeller plate 26 may be configured as a sparger assembly used to introduce a particular gas or air into the fluid within bag 30 to agitate and / or dissolve the air or gas into the fluid. Accordingly, in some embodiments, the impeller and sparger and their components form a combined impeller / sparger assembly. In other embodiments, the sparger assembly and impeller assembly are separate and / or distinct components. In either implementation, as discussed in detail below, the sparger assembly and impeller assembly are in close proximity to ensure optimal distribution of the gas throughout bag 30. As discussed below, it is envisioned that the sparger assembly (which may also function as an impeller plate supporting the impeller) may take on one of a variety of configurations.

[0027] 2A-3 illustrate an embodiment of a sparger assembly 100 that can be utilized with the flexible bag 30 and bioreactor system 10. As shown therein, the sparger assembly 100 includes a base plate 126 and a plurality of spargers 130 connected to the base plate 126. The spargers 130 are each generally cylindrically shaped and are concentrically arranged around the periphery of the base plate 126. Each sparger 130 is connected to a fluid input port 160 so that gas / fluid can be introduced into the flexible bag 30 through the sparger 130. In embodiments, the sparger 130 and the base plate 126 can be manufactured as a single, integrated component. In other embodiments, the sparger 130 can be manufactured as a separate component that can be coupled to the base plate 126. 2A-3 show eight spargers 130 equidistantly spaced around base plate 126, more or fewer spargers 130 (e.g., one to seven or more than eight) are within the scope of the present invention. Sparger 130 includes an array of pores so that when gas is input through input port 160, the gas exits sparger 130 and forms bubbles of controlled size. As FIG. 4 shows, the bubbles created by sparger 130 are then dispersed by impeller 122 as the impeller is rotated due to magnetic forces generated by magnetic drive 28, which rotates magnetic hub 124.

[0028] As explained in more detail below, conventional spargers are planar in nature (e.g., flat disk or ring-shaped), thus limiting the amount of gas that can be introduced into a cell culture. This limitation ultimately leads to an inadequate amount of gas being delivered to the bioreactor. As a result, the bioreactor cannot achieve sufficient oxygen kLa and / or CO2 stripping, resulting in poor performance (e.g., high cell death and lower cell density). Compared to conventional spargers, the present invention advantageously finds that by fabricating the sparger in a three-dimensional shape (e.g., cylindrical shape), additional pores can be implemented, thereby enabling the formation of a greater number of smaller bubbles when gas is introduced into the sparger (when the bag is filled with a fluid, such as cell culture medium). The higher bubble density with smaller bubble size results in more surface area contact between the sparged gas and the fluid, thereby further improving oxygen kLa or CO2 stripping. Additionally, the sparger design of the present invention reduces bubble coalescence (i.e., bubbles joining together to form larger bubbles) to help ensure that many small bubbles are uniformly dispersed in the cell culture medium during bioprocessing (e.g., cell culture) operations in a bioreactor.

[0029] 5A-7 show side, top, cross-sectional, and perspective views of a sparger 130 according to an embodiment of the present invention. The sparger 130 includes a base 131 with a sidewall 133 that projects upward from the top surface of the base 131 by a height H1. The sidewall 133 terminates at a top 135 that is a generally flat surface. As shown in these figures, the base 131 is generally circular in shape, and the sidewall 133 is cylindrically shaped and has a diameter that is smaller than the diameter of the base 131 (the diameters of the sidewall 133 and the base 131 may be the same, or the diameter of the sidewall 133 may be larger than the diameter of the base 131). The sidewall 133 includes pores 137 to allow introduced gas to bubble out of the sparger 130. In certain embodiments, the sidewall 133 has a height H p1 includes an array of pores 137 in a circular pattern. In an alternative embodiment, the array of pores 137 in the sidewalls has varying heights from the base. Furthermore, the top 135 includes an array of pores 137 in a circular pattern around its periphery, along with an additional central pore. It is noted that the pores 137 arranged around the periphery of the top 135 are radially offset from the pores arranged in the sidewalls (see, for example, FIG. 6A). By radially offsetting the pores, gas bubbles are less likely to coalesce. In other words, as gas bubbles form and exit the sidewalls 133, they travel vertically upward. These gas bubbles are less likely to encounter gas bubbles formed by the pores in the top because the pores in the top 135 are radially offset from one another (i.e., not arranged parallel to the longitudinal axis of the sparger 130), thus reducing the likelihood of coalescence. In one particular embodiment, it is known that there are seven circumferential pores and one central pore in the top portion 135, although more or fewer pores are within the scope of the present invention. p Although seven pores are shown in a circular pattern in Figure 1, additional or fewer pores are within the scope of the present invention.

[0030] The sparger 130 also includes ridges 138 that extend at least partially around the periphery of the sidewall 133. The ridges 138 are positioned above an array of perforations 137 disposed in the sidewall 133 and act as a mechanism for directing the bubbles formed by the perforations 137. Specifically, as the bubbles form and exit the sidewall 133, they contact the bottom of the ridges 138 and are directed away from the sidewall. This provides two major benefits. First, because the ridges 138 help direct the bubbles away from each other, this is an additional mechanism for reducing coalescence. Second, it gives the bubbles more time to build themselves up before they float up and are mixed by the impeller assembly. By allowing the bubbles more time to form (i.e., increasing the resonance time before mixing), the bubble shape solidifies, thereby further helping to reduce coalescence as the bubbles are dispersed throughout the fluid in the flexible bag 30.

[0031] As shown, the ribs 138 extend radially a distance away from the sidewall 133 and are positioned adjacent to, but above, the perforations 137 in the sidewall. The distance the ribs extend from the sidewall 133 is such that, in embodiments, the ribs 138 have a diameter smaller than the diameter of the base 131. In further embodiments, the ribs extend such that they have a diameter equal to or greater than the diameter of the base 131. The ribs may also have a curved or otherwise chamfered surface that contacts the sidewall 133. Having a curve / chamfer rather than a right angle helps direct the air bubbles away from the sparger 130 so that they are more easily dispersed into the fluid in the flexible bag 30.

[0032] 6, base 131 includes a mating surface 139 on which there are two circular regions having a generally triangular cross-section, as shown. When manufacturing sparger assembly 100, each sparger 130 is placed on base plate 126, and heat and / or vibratory force is applied to sparger 130. The lower point of the triangle focuses this energy so that sparger 130 mates with base plate 126 on both mating surfaces 139.

[0033] 8A-10 show side, top, cross-sectional, and perspective views of a sparger 130′ according to a further embodiment of the present invention. The sparger 130′ includes a base 131′ with a sidewall 133′ projecting upward from the top surface of the base 131′ by a height H2. The sidewall terminates at a top 135′ that is a generally flat surface. As these figures show, the base 131′ is generally circular in shape, and the sidewall 133′ is cylindrically shaped and has a diameter smaller than that of the base 131′ (the diameters of the sidewall 133′ and the base 131′ may be the same, or the diameter of the sidewall 133′ may be larger than that of the base 131′). The sidewall 133′ includes pores 137′ to allow introduced gas to bubble out of the sparger 130′. In certain embodiments, the sidewall 133′ has a height H p 1, a first array of pores 137′ in a circular pattern and a height H p2, in a circular pattern, and a second array of pores 137′, where H p 2>H p In a further embodiment, the two arrays of pores 137′ have a height H p 1 and height H p 2, but may have variable heights from base 131'. Additionally, top portion 135' includes an array of perforations 137' in a circular pattern around its periphery, along with an additional central perforation. Top portion 135' may optionally include an indentation or protrusion 136' that serves as a visual reference point to ensure that sparger 130' is installed on base plate 126' in the proper orientation.

[0034] As best seen in Figure 8A, the height H p The pores 137′ arranged in the 1st row have a height H p 2. By radially offsetting the pores, the possibility of bubbles coalescing is lower. In other words, the height H p At 1, as the bubbles form and exit sidewall 133', they travel vertically upward. Because their pores are radially offset from one another (i.e., not aligned parallel along the longitudinal axis of sparger 130'), these bubbles rise to a height H p The pores 137' around the circumference of the top 135' are less likely to encounter bubbles formed by the pores 137' at height H for the same reason. p 2. In one particular embodiment, it is known that there are seven circumferential slots and one central slot in the top portion 135', although more or fewer slots are within the scope of the invention. p 1 and H p In 2, seven pores are shown in a circular pattern, although additional or fewer pores are within the scope of the present invention.

[0035] The sparger 130' also includes a first ridge 138' that extends at least partially around the periphery of the sidewall 133'. The ridge 138' has a height H p The second ridge 138′ is disposed above the array of pores 137′ disposed in the sidewall 133′. p Second, the ribs 138' are positioned above an array of perforations 137' disposed in the sidewall 133'. These ribs 138' act as a mechanism to guide the bubbles formed by the perforations 137'. Specifically, as the bubbles form and exit the sidewall 133', they come into contact with the bottom of the ribs 138' and are directed away from the sidewall. This provides two major benefits. First, because the ribs help direct the bubbles away from each other, this is an additional mechanism for reducing coalescence. Second, it gives the bubbles more time to build themselves up before they float up and are mixed by the impeller assembly. By giving the bubbles more time to form (i.e., increasing the resonance time before mixing), the bubble shape solidifies, which further helps reduce coalescence as the bubbles are dispersed throughout the fluid in the flexible bag 30.

[0036] As shown, the ribs 138′ extend radially a distance away from the sidewall 133′ and are positioned adjacent to, but above, the perforations 137′ in the sidewall 133′. The distance the ribs extend from the sidewall 133′ is such that, in embodiments, the ribs 138′ have a diameter smaller than the diameter of the base 131′. In further embodiments, the ribs have a diameter equal to or greater than the diameter of the base 131′. The ribs 138′ can also have a curved or otherwise chamfered surface, where the ribs contact the sidewall 133′. Having a curve / chamfer rather than a right angle helps direct air bubbles away from the sparger 130′ so that they are more easily dispersed into the fluid in the flexible bag 30.

[0037] 8A-10 show two arrays of perforations 137′ and two respective ridges 138′, the invention is not so limited. Additional arrays of perforations 137′ (e.g., three or more) and additional ridges 138′ (e.g., three or more) are within the scope of the invention. Note that the height H2 of the sparger 130′ can be varied to accommodate as many arrays of perforations 137′ and ridges 138′ as desired, but the maximum height of H2 is constrained by the bottom surface of the impeller 122 (i.e., the top 135′ of the sparger 130′ cannot contact the impeller 122).

[0038] 9B, base 131' includes mating surfaces 139', which are two circular regions having a generally triangular cross-section, as shown. When manufacturing sparger assembly 100, each sparger 130' is placed on base plate 126', and heat and / or vibratory force is applied to sparger 130'. The lower point of the triangle focuses this energy so that sparger 130' bonds to base plate 126' on both mating surfaces 139'.

[0039] Referring to the previous embodiment, height H2 is greater than H1 such that sparger 130' is greater than sparger 130.

[0040] While the above-described embodiments show and describe spargers having generally cylindrical sidewalls, other shapes are within the scope of the present invention. For example, the sidewalls could curve outward so that the diameter of the sparger increases. It is contemplated that the sparger could have a mushroom-like shape with a narrow lower stem that expands into a dome-like shape. Furthermore, the sidewalls need not have a circular cross-sectional shape, but could take other shapes, such as oval, square, rectangular, triangular, etc.

[0041] As provided above, embodiments of the sparger assembly disclosed herein provide increased kLa for bioreactor systems (i.e., achieve more efficient gas distribution) to support enhanced cell culture and / or microbial applications. Compared to prior art designs, the three-dimensional sparger of the present invention provides a means to create a higher density of small bubbles that are less likely to coalesce. By ensuring a small bubble size with a higher density and greater surface area between bubbles, cell culture media are obtained, providing higher oxygen transfer and CO2 stripping within the media.

[0042] It is specified that the sparger assemblies disclosed herein may be utilized in connection with some existing impeller assemblies.

[0043] As used herein, elements or steps described in the singular and preceded by the word "a" or "an" should be understood not to exclude a plurality of such elements or steps, unless such exclusion is expressly stated. 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 recited features. Furthermore, unless expressly stated to the contrary, embodiments that "comprise," "comprise," or "have" an element or elements having a particular characteristic may include additional such elements that do not have that characteristic.

[0044] This written description uses examples to disclose certain embodiments of the invention, including the best mode, and also enables those skilled in the art to practice embodiments of the invention, including making and using any devices or systems 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 skilled 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 literal language of the claims, or if they include equivalent structural elements that have insubstantial differences from the literal language of the claims. [Explanation of symbols]

[0045] 10 Bioreactor System 20 Bioreactor vessel, support structure 22, 122 impeller 24, 124 magnetic hub 26 Impeller plate 28 Magnetic drive unit 30 Flexible Bags, Flexible Bioreactor Bags, Collapsible Bioprocess Bag Assemblies 100 Sparger Assembly 126, 126′ base plate 130, 130' Sparger 131, 131' (Sparger's) base 133, 133′ (Sparger) side wall 135, 135′ (Top of sparger) 136' Notch, protrusion 137, 137′ pores 138 Ridge 138' First furrow, second furrow, furrow 139, 139′ joint surface 160 input ports A Part (of Figure 6A), Part (of Figure 9A) H (of vessel 20) maximum working height H1, H2, H p 1. H p 2 Height D (inner diameter of container 20)

Claims

1. 1. A sparger assembly for a bioprocessing system, comprising: With the base, a plurality of spargers connected to the base, each sparger including a plurality of orifices; Including, a sparger assembly, wherein each of the plurality of spargers has a cylindrical shape.

2. Each of the plurality of spargers includes a sidewall and a top that define the cylindrical shape. The sparger assembly of claim 1 .

3. The sparger assembly of claim 1 or 2, wherein the sidewall and the top each include a plurality of perforations.

4. 4. The sparger assembly of claim 2 or 3, wherein the perforations in the sidewall include a first array of perforations disposed at a first height from a top surface of the base.

5. 5. The sparger assembly of claim 4, wherein the perforations in the sidewall include a second array of perforations disposed at a second height from the top surface of the base, the second height being different from the first height.

6. The sparger assembly of claim 5 , wherein the second array of perforations is radially offset relative to the first array of perforations.

7. 7. The sparger assembly of claim 2, wherein the sidewall includes a first rib extending at least partially around a periphery of the sidewall, the first rib being disposed above a first array of perforations.

8. 8. The sparger assembly of claim 7, wherein the sidewall includes a second rib extending at least partially around a periphery of the sidewall, the second rib being disposed above a second array of perforations.

9. 9. The sparger assembly of claim 1, wherein each of the plurality of spargers includes two mating surfaces, the two mating surfaces configured to mate with the base upon application of heat and / or a vibratory force.

10. 1. An impeller and sparger assembly for a bioprocessing system, comprising: A sparger assembly according to any one of claims 1 to 9; an impeller assembly attached to the base; an impeller and sparger assembly including:

11. The impeller and sparger assembly of claim 10 , wherein the impeller assembly includes a magnetic hub connected to the base and an impeller connected to the magnetic hub.

12. Flexible bags and 10. The sparger assembly of claim 1, wherein the base is joined to the flexible bag such that a plurality of the spargers are disposed within the flexible bag; an impeller assembly attached to the base, the impeller assembly being disposed within the flexible bag; 1. A bioprocessing device comprising:

13. 13. The bioprocess apparatus of claim 12, wherein the base includes at least one input port, the at least one input port in fluid communication with the plurality of spargers.

14. 14. The bioprocess apparatus of claim 13, wherein the at least one input port is connectable to a gas source.

15. 15. The bioprocess apparatus of claim 14, wherein gas from the gas source is configured to exit through the plurality of perforations and into the flexible bag.

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