Sprinkler assembly for biological treatment system

Abstract

A sprinkler assembly (100) for a biological treatment system (10) includes a base (126) and a plurality of sprinklers (130) connected to the base, each sprinkler including a plurality of apertures, the plurality of sprinklers each having a generally cylindrical shape. Each of the plurality of sprayers includes a side wall and a top defining a cylindrical shape, the side wall and the top each including a plurality of apertures. The apertures of the sidewall may be arranged at a range of heights around a circumference of the sidewall. The ridges may also be located on the sidewalls over the respective array of holes.

Description

Technical Field

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

[0002] A variety of vessels, devices, components and unit operations are known for performing biochemical and / or biological processes and / or manipulating liquids and other products of such processes. In order 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 mixing bags are used as such vessels. For 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 mixers and bioreactors.

[0003] In the biopharmaceutical industry, single-use or disposable containers are increasingly used. Such containers can be flexible or collapsible plastic bags supported by external rigid structures (such as stainless steel shells or vessels). Using sterile disposable bags eliminates the time-consuming steps of cleaning vessels and reduces the chance of contamination. The bag can be positioned in a rigid vessel and filled with the fluid desired for mixing. The agitator assembly disposed in the bag is used to mix the fluid. Existing agitators are top-driven (with a shaft extending downward into the bag, one or more impellers mounted on the shaft) or bottom-driven (with an impeller disposed in the bottom of the bag, which is driven by a magnetic drive system or motor positioned 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 as "impeller" in this context) inside the bag. The movement of the magnetic drive head realizes torque transmission, and thereby realizes the rotation of the magnetic agitator, thereby allowing the agitator to mix the fluid in the vessel. Magnetic coupling of the agitator inside the bag to a drive system or motor outside the bag and / or bioreactor vessel can eliminate contamination issues, allow for a completely enclosed system, and prevent leaks. The magnetic coupling system can also eliminate the need to have a seal between the drive shaft and the vessel because there is no need to pass a drive shaft through the bioreactor vessel wall to mechanically turn the agitator.

[0004] Depending on the fluid being processed, the bioreactor system may include many fluid lines and different sensors, probes and ports coupled to the bag for monitoring, analysis, sampling and liquid transfer. For example, a harvest port is typically located at the bottom of a disposable bag and vessel, and allows a harvest line to be connected to the bag for harvesting and discharging of the bag. In addition, existing bioreactor systems typically use a sprinkler for introducing a controlled amount of a specific gas or gas combination into the bioreactor. The sprinkler outputs small bubbles into the liquid to stir the liquid and / or dissolve the gas into the liquid. The gas is delivered via the sprinkler to help mix the material, maintain a uniform environment throughout the interior of the bag, and is sometimes necessary for growing cells in a bioreactor. Ideally, the sprinkler and agitator are closely approached to ensure optimal distribution of the gas throughout the container.

[0005] In combination with the above, in cell culture, oxygen is a key matrix for growth, production and maintaining activity. Cells obtain their oxygen in a free and non-complex form, known as dissolved oxygen (DO). One of the most important functions of a bioreactor is to continuously provide dissolved oxygen to cells through aeration. When oxygen diffuses to the cell culture matrix interface through the overlay, and when the oxygen from the sparger is dissolved in the cell culture by convection with the help of stirring, aeration typically occurs in a bioreactor. Stirring disperses oxygen bubbles, and promotes the mass transfer of bubbles through the gas-liquid (cell culture matrix) interface. The oxygen transfer rate (OTR) from gas to liquid interface is a function of the physicochemical properties of the cell culture matrix, the geometric parameters of the bioreactor, and the presence of cells.

[0006] Oxygen is continuously supplied to the cell culture due to its low solubility in the liquid phase and increased consumption by cell metabolism over time. Oxygen supply is carefully controlled by manipulating bioreactor parameters for optimal cell growth. During batch cell culture, the oxygen usage rate (OUR) (or oxygen transfer rate (OTR)) is initially low during the lag phase, where cells synthesize themselves and there is a small increase in cell density. When cell density increases during the exponential phase, OUR increases until OTR becomes a limiting rate, as determined by the mass transfer of oxygen to the overall liquid. OTR and OUR rates are associated by the oxygen mass transfer coefficient kLa (volume mass transfer coefficient, which describes the efficiency at which oxygen can be delivered to the bioreactor under a given set of operating conditions). Therefore, OTR limits the theoretical maximum cell density that can be achieved in cell culture by its association with kLa.

[0007] Higher oxygen availability drives an increase in kLa. Increased oxygen supply to the bioreactor drives this availability and can be controlled by modifying the concentration (enrichment of air relative to O2) and volumetric flow rate. While high kLa values ​​are desirable, it is important to consider actual operating conditions and the impact on cell viability and associated process costs.

[0008] For example, high air flow rates may cause cell damage due to shear forces. Excessive foaming may also be generated, requiring high concentrations of defoamers, which may hinder downstream processing. In addition, higher air flow rates require larger exhaust filtration areas, driving up consumable costs.

[0009] It is therefore clear that a high performance bioreactor system must provide good overall mixing combined with efficient gas dispersion in order to achieve high gas surface area and bubble size distribution and thereby provide the high oxygen transfer rates and kLa values ​​desired in intensified cell culture and / or microbial applications. However, there is a need for an improved sparger that provides high kLa while maintaining acceptable aeration flow rates. Summary of the invention

[0010] According to a first aspect of the present invention, a sprinkler assembly for a biological treatment system is provided, wherein the sprinkler assembly comprises: a base; and a plurality of sprinklers connected to the base, each sprinkler comprising a plurality of holes; wherein each of the plurality of sprinklers has a substantially cylindrical shape.

[0011] In an embodiment, each of the plurality of sprinklers includes a sidewall and a top defining a cylindrical shape. The sidewall and the top each include a plurality of holes.

[0012] In an embodiment, the holes of the sidewall include a first array of holes located at a first height from the top surface of the base. In a further embodiment, the holes of the sidewall further include a second array of holes located at a second height from the top surface of the base, the second height being different from the first height. The holes of the second array are radially offset relative to the holes of the first array.

[0013] In an embodiment, the sidewall includes a first ridge extending at least partially around the circumference of the sidewall, the first ridge being located above the holes of the first array. In a further embodiment, the sidewall also includes a second ridge extending at least partially around the circumference of the sidewall, the second ridge being located above the holes of the second array.

[0014] In an embodiment, each of the plurality of sprinklers includes two bonding surfaces configured to bond with the base upon application of heat and / or vibrational forces.

[0015] According to a second aspect of the present invention, an impeller and sprinkler assembly for a biological treatment system is provided. The biological treatment system includes an impeller and a sprinkler assembly. The sprinkler assembly includes: a base; and a plurality of sprinklers connected to the base, each sprinkler including a plurality of holes; wherein each of the plurality of sprinklers has a generally cylindrical shape. Each of the plurality of sprinklers includes a sidewall and a top, which define a cylindrical shape. The sidewall and the top each include a plurality of holes. In an embodiment, the holes of the sidewall include a first array of holes located at a first height from the top surface of the base. In another embodiment, the holes of the sidewall also include a second array of holes located at a second height from the top surface of the base, the second height being different from the first height. The holes of the second array are radially offset relative to the holes of the first array. In an embodiment, the sidewall includes a first ridge extending at least partially around the circumference of the sidewall, the first ridge being located above the holes of the first array. In another embodiment, the sidewall also includes a second ridge extending at least partially around the circumference of the sidewall, the second ridge being located above the holes of the second array. In an embodiment, each of the plurality of sprinklers includes two engagement surfaces configured to engage with the base upon application of heat and / or vibrational forces.The impeller assembly includes: a magnetic hub coupled to the base; and an impeller coupled to the magnetic hub.

[0016] According to a third aspect of the present invention, a bioprocessing device is provided. The bioprocessing device includes a flexible bag, a spray assembly, and an impeller assembly. The spray assembly includes: a base; and a plurality of sprayers connected to the base, each sprayer including a plurality of holes; wherein each of the plurality of sprayers has a generally cylindrical shape. Each of the plurality of sprayers includes a side wall and a top, which define a cylindrical shape. The side wall and the top each include a plurality of holes. In an embodiment, the holes of the side wall include a first array of holes located at a first height from the top surface of the base. In another embodiment, the holes of the side wall also include a second array of holes located at a second height from the top surface of the base, the second height being different from the first height. The holes of the second array are radially offset relative to the holes of the first array. In an embodiment, the side wall includes a first ridge extending at least partially around the circumference of the side wall, the first ridge being located above the holes of the first array. In another embodiment, the side wall also includes a second ridge extending at least partially around the circumference of the side wall, the second ridge being located above the holes of the second array. In an embodiment, each of the plurality of sprinklers includes two engagement surfaces configured to engage with the base when heat and / or vibration forces are applied. 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 in fluid communication with the plurality of sprinklers. The input port is connectable to a gas source such that gas from the gas source is configured to exit through the plurality of holes and enter the flexible bag. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0018] Figure 1 is a cross-sectional view of a bioreactor system according to an embodiment of the present invention.

[0019] Figure 2A and Figure 2B A side view and a top view of a spray assembly according to an embodiment of the present invention are shown.

[0020] Figure 3 Show Figure 2A and Figure 2B A perspective view of a spray assembly.

[0021] Figure 4 An impeller and a sprinkler assembly according to an embodiment of the present invention are shown, which are combined Figure 2A-3 Spray components.

[0022] Figure 5A and Figure 5B The embodiment according to the present invention is shown Figure 2A-3 Side view and top view of the sprinkler of the spray assembly.

[0023] Fig. 6A The embodiment according to the present invention is shown Figure 5A-5B Cross-sectional view of a sprinkler.

[0024] Figure 6B According to an embodiment of the present invention Fig. 6A Magnified view of section A of FIG.

[0025] Figure 7 According to an embodiment of the present invention Figures 5A-6B Perspective view of a sprinkler.

[0026] Fig. 8A and Figure 8B Another embodiment according to the present invention is shown Figure 2A-3 Side view and top view of the sprinkler of the spray assembly.

[0027] Fig.9A The embodiment according to the present invention is shown Figures 8A-8B Cross-sectional view of a sprinkler.

[0028] Fig. 9B According to an embodiment of the present invention Fig.9A Magnified view of section A of FIG.

[0029] Fig.10 According to an embodiment of the present invention Figures 8A-9B Perspective view of a sprinkler. DETAILED DESCRIPTION

[0030] Reference will now be made in detail to exemplary embodiments of the present invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference symbols are used throughout the drawings to refer to the same or like parts.

[0031] As used herein, the terms "flexible" or "collapsible" refer to structures or materials that are pliable or capable of bending without breaking, and may also refer to compressible or expandable materials. 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 "non-collapsible" structures, that is, structures that do not fold, collapse, or otherwise deform to significantly reduce their extended dimensions under the action of normal forces. Depending on the context, "semi-rigid" may also refer to structures that are more flexible than "rigid" elements, such as bendable tubes or catheters, but are still structures that do not collapse longitudinally under normal conditions and forces.

[0032] As used herein, "vessel" means a flexible bag, a flexible container, a semi-rigid container, a rigid container, or a flexible or semi-rigid tube, as the case may be. As used herein, the term "vessel" is intended to include 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, matrix / buffer preparation systems, and filtration / purification systems, such as chromatography and tangential flow filtration systems, and their associated flow paths. As used herein, the term "bag" means a flexible or semi-rigid container or vessel, which is used, for example, as a bioreactor or mixer for the contents therein.

[0033] Embodiments of the present invention provide a bioreactor system and a sparger assembly for a bioreactor system. In an embodiment, a sparger assembly for a bioprocessing system includes.

[0034] refer to Figure 1 and Figure 2, showing a bioreactor system 10 according to an embodiment of the present invention. The bioreactor system 10 includes a substantially rigid bioreactor vessel or support structure 20. The vessel 20 may be formed, for example, of stainless steel, a polymer, a composite, glass, or other metal, and may be cylindrical in shape, although other shapes may be used 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 as long as it is capable of supporting a single-use flexible bioreactor bag 30. For example, according to one embodiment of the present invention, the vessel 20 is capable of accepting and supporting a 10-2000L flexible or collapsible bioprocessing bag assembly 30 and has a maximum working volume height H and an inner diameter D.

[0035] The vessel 20 may include one or more viewing windows that allow one to observe the fluid level within the flexible bag 30, and a window positioned at a lower region of the vessel 20. The window allows access to the interior of the vessel 20 for inserting and positioning 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 adding fluids, gases, etc. to or removing them from the flexible bag 20. Sensors / probes and controllers for monitoring and controlling important process parameters include any one or more of the following and combinations thereof: for example, temperature, pressure, pH, dissolved oxygen (DO), dissolved carbon dioxide (pCO2), mixing rate, and gas flow rate.

[0036] The flexible bag 20 contains an impeller 22 attached to a magnetic hub 24 at the bottom center of the inside of the bag, which rotates on an impeller plate 26 (also referred to herein as a "base plate" or "sprayer plate"), which is also located on the inside bottom of the bag 20. The impeller 22 and the hub 24 (and in some embodiments, the impeller plate 26) together form an impeller assembly. A magnetic drive 28 external to the vessel 20 provides power for rotating the magnetic hub 24 and impeller 22 to mix the contents of the flexible bag 30. Although FIG. 2 shows the use of a magnetically driven impeller, other types of impellers and drive systems are possible, including top-driven impellers.

[0037] In an embodiment, the impeller plate 26 may be configured as a sprinkler assembly, which is used to introduce a specific gas or air into the fluid within the bag 30 so as to stir the fluid and / or dissolve the air or gas into the fluid. Therefore, in some embodiments, the impeller and sprinkler and components thereof form a combined impeller / sprayer assembly. In other embodiments, the sprinkler assembly and the impeller assembly may be separate and / or discrete components. In any embodiment, the sprinkler assembly and the impeller assembly are closely adjacent to ensure optimal distribution of the gas throughout the bag 30, as discussed in detail below. As discussed below, it is contemplated that the sprinkler assembly (which may also serve as an impeller plate supporting the impeller) may adopt one of a variety of configurations.

[0038] For example, Figure 2A-3An embodiment of a sparger assembly 100 that can be used with a flexible bag 30 and a bioreactor system 10 is shown. 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 cylindrical in shape and are concentrically positioned around the periphery of the base plate 162. Each sparger 130 is connected to a fluid input port 160 so that gas / fluid can be introduced through the spargers 130 and introduced into the flexible bag 30. In embodiments, the spargers 130 and base plate 126 can be manufactured as an integral, single component. In other embodiments, the spargers 130 can be manufactured as a separate component that can be coupled to the base plate 126. Although Figure 2A-3 Eight sprinklers 130 are shown spaced equally around the substrate 126, but more or fewer sprinklers 130 (e.g., one to seven or more than eight) are within the scope of the present invention. The sprinklers 130 include holes in an array so that when gas is input through the input port 160, the gas exits the sprinklers 130 and forms bubbles of controlled size. Figure 4 As shown, the bubbles generated by the sprinkler 130 are then dispersed by the impeller 122 as it rotates (due to the magnetic force of the rotating magnetic hub 124 generated by the magnetic drive 28).

[0039] As will be described in more detail below, conventional spargers are essentially planar (e.g., in the form of a flat disk or ring) and are therefore limited in the amount of gas that can be introduced into the cell culture. This limitation results in an insufficient amount of gas supplied to the bioreactor. As a result, the bioreactor cannot provide sufficient oxygen, kLa and / or CO2 stripping, resulting in poor performance (e.g., high cell mortality and low cell density). Compared to conventional spargers, the present invention advantageously finds that by making the spargers into a three-dimensional shape (e.g., a cylindrical shape), additional holes can be implemented, which allow a larger number of smaller bubbles to be formed when the gas is introduced into the spargers (when the bag is filled with a fluid such as a cell culture matrix). Higher bubble density and smaller bubble size provide greater surface area contact between the sparged gas and the fluid, which further improves oxygen, kLa or CO2 stripping. In addition, the design of the spargers of the present invention reduces bubble agglomeration (i.e., bubbles combine to form larger bubbles), which helps to ensure that many small bubbles are evenly dispersed into the cell culture matrix during the bioprocessing operation (e.g., cell culture) in the bioreactor.

[0040] Figure 5A-71 and 2 show a side view, a top view, a cross-sectional view, and a perspective view of a sprinkler 130 according to an embodiment of the present invention. Sprinkler 130 includes a base 131, whose sidewall 133 protrudes upward from the top surface of base 131 by a height H1. Sidewall 133 terminates at top 135, which is a generally planar surface. As shown in these figures, base 131 is generally circular in shape, and sidewall 133 is cylindrical in shape, which has a smaller diameter than the diameter of base 131 (but the diameters of sidewall 133 and base 131 can be the same, or the diameter of sidewall 133 can be larger than that of base 131). Sidewall 131 includes holes 137 so that introduced gas can bubble outside sprinkler 130. In a specific embodiment, sidewall 133 includes holes 137 at a height H1. p 1. In an alternative embodiment, the array of holes 137 in the sidewalls have varying heights from the bottom. Additionally, the top 135 includes an array of holes 137 in a circular pattern around its perimeter, with an additional center hole. Note that the holes 137 positioned around the perimeter of the top 135 are radially offset from the holes located in the sidewalls (see, e.g., FIG. 1 ). Fig. 6A ). By radially offsetting the holes, bubbles are less likely to coalesce. In other words, as bubbles form and exit sidewall 133, they travel vertically upward. These bubbles are less likely to encounter bubbles formed by holes in top 135 because they are radially offset from one another (i.e., not positioned parallel to the longitudinal axis of sparger 130), thus reducing the likelihood of coalescence. While it is noted that in one particular embodiment, there are seven circumferential holes and one central hole in top 135, more or fewer holes are within the scope of the present invention. Similarly, while the figures show seven circumferential holes and one central hole at height H, the bubbles are less likely to coalesce. p 1, but additional or fewer holes are within the scope of the invention.

[0041] Sprinkler 130 also includes ridges 138 extending at least partially around sidewall 133. Ridges 138 are located above the array of holes 137 located in sidewall 133 and serve as a mechanism for guiding bubbles formed by holes 137. Specifically, as bubbles form and leave sidewall 133, they contact the bottom surface of ridges 138 and are pushed away from the sidewall. This provides two major advantages. First, this is an additional mechanism to reduce agglomeration because ridges 138 help push bubbles away from each other. Second, it gives bubbles more time to establish themselves before they float up and are mixed by the impeller assembly. By giving bubbles more time to form (i.e., increasing the resonance time before mixing), the bubble shape solidifies, which further helps reduce agglomeration once the bubbles are dispersed in the fluid of flexible bag 30.

[0042] As shown, the ridge 138 extends radially a distance away from the sidewall 133 and is positioned proximate to the hole 137 of the sidewall, but above the hole 137. In an embodiment, the distance that the ridge extends from the sidewall 133 is such that the diameter of the ridge 138 is less than the diameter of the base 131. In other embodiments, the ridge extends such that it has a diameter equal to or greater than the diameter of the base 131. The ridge may also have a curved or otherwise chamfered surface where it meets the sidewall 131. As opposed to a right angle, having a curvature / chamfer helps direct the bubbles away from the sprinkler 130, making it easier to disperse into the fluid of the flexible bag 30.

[0043] Special reference Figure 6B , base 131 includes bonding surfaces 139, which, as shown, are two circular areas having a generally triangular cross-section. When manufacturing sprinkler assembly 100, each sprinkler 130 is placed on substrate 126, and heat and / or vibration forces are applied to sprinkler 130. The lower point of the triangle concentrates the energy, causing sprinkler 130 to bond to substrate 162 at the two bonding surfaces 139.

[0044] Figure 8A-10 A side view, a top view, a cross-sectional view, and a perspective view of a sprinkler 130' according to another embodiment of the present invention are shown. Sprinkler 130' includes a base 131', and a side wall 133' protrudes upward from the top surface of base 131' by a height H2. The side wall terminates at a top 135', which is a generally planar surface. As shown in these figures, base 131' is generally circular in shape, and side wall 133' is cylindrical in shape, which has a smaller diameter than the diameter of base 131' (but the diameter of side wall 133' and base 131' can be the same, or the diameter of side wall 133' can be larger than that of base 131'). Side wall 131' includes a hole 137' so that the introduced gas can bubble outside sprinkler 130'. In a specific embodiment, side wall 133' includes a hole 137' at a height H2. p 1 in a circular pattern of holes 137' and at a height H p 2 in a second array of holes 137' in a circular pattern, where H p 2>H p 1. In other embodiments, the holes 137' of the two arrays do not have to be located at the height H p 1 and H p 2, but may have varying heights from base 131'. In addition, top 135' includes an array of holes 137' in a circular pattern around its perimeter, with an additional center hole. Top 135' may optionally include notches or protrusions 136' that serve as visual reference points to ensure that sprinkler 130 is mounted on base 162 with the proper geometry.

[0045] like Fig. 8A shown in the figure, located at a height H p The hole 137' at 1 is radially offset from the hole at height H p 2. By radially offsetting the holes, the bubbles are less likely to coalesce. In other words, when the bubbles are at height H p 1 and leave the side wall 133', they travel vertically upward. These bubbles are unlikely to encounter p The bubbles formed by the holes 137' at the height H2 are radially offset from each other (i.e., not positioned parallel to the longitudinal axis of the sprinkler 130), thereby reducing the likelihood of coalescence. In addition, for the same reason, the holes 137' around the circumference of the top 135' are radially offset from the holes 137' located at the height H2. p 2. Although it is noted that in one particular embodiment, there are seven circumferential holes and one central hole in the top 135', more or fewer holes are within the scope of the present invention. Similarly, although the figures show seven circumferential holes and one central hole in the top 135', more or fewer holes are within the scope of the present invention. p 1 and H p 2, but additional or fewer holes are within the scope of the invention.

[0046] Sprinkler 130' also includes a first ridge 138' extending at least partially around sidewall 133'. Ridge 138' is located at a height H p 1 is located above the array of holes 137' in the side wall 133'. The second ridge 138' is located at a height H p 138'. These ridges 138' act as a mechanism to guide the bubbles formed by the holes 137'. Specifically, as the bubbles form and leave the side wall 133', they contact the bottom surface of the ridges 138' and are pushed away from the side wall. This provides two major advantages. First, this is an additional mechanism to reduce agglomeration because the ridges help push the bubbles away from each other. Second, it gives the bubbles more time to establish themselves 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 agglomeration once the bubbles are dispersed within the fluid of the flexible bag 30.

[0047] As shown, the ridge 138' extends radially a distance away from the sidewall 133' and is positioned proximate to the hole 137' of the sidewall 133', but above the hole 137'. In an embodiment, the distance that the ridge extends from the sidewall 133' is such that the diameter of the ridge 138' is less than the diameter of the base 131'. In other embodiments, the ridge has a diameter equal to or greater than the diameter of the base 131'. The ridges 138' may also have a curved or otherwise chamfered surface where they meet the sidewall 131'. As opposed to a right angle, having a curvature / chamfer helps direct the bubbles away from the sprinkler 130', making it easier to disperse into the fluid of the flexible bag 30.

[0048] Note that although Figure 8A-10 Two arrays of holes 137' and two corresponding ridges 138' are shown, but the invention is not so limited. Additional arrays of holes 137' (e.g., three or more) and ridges 138' (e.g., three or more) are within the scope of the invention. The height H2 of the sprinkler 130' can be varied to accommodate as many arrays of holes 137' and ridges 138 as desired, noting that the maximum height of H2 is constrained by the bottom surface of the impeller 122 (i.e., the top 135' of the sprinkler 130' cannot make contact with the impeller 122).

[0049] Special reference Fig. 9B , base 131' includes bonding surfaces 139', which, as shown, are two circular areas having a generally triangular cross-section. When manufacturing sprinkler assembly 100, each sprinkler 130' is placed on substrate 126', and heat and / or vibration forces are applied to sprinkler 130'. The lower point of the triangle concentrates the energy, causing sprinkler 130' to bond to substrate 162 at the two bonding surfaces 139'.

[0050] With reference to the previously described embodiments, height H2 is greater than H1 , such that sprinkler 130 ′ is taller than sprinkler 130 .

[0051] Although the aforementioned embodiments show and describe a sprinkler having a generally cylindrical sidewall, other shapes are within the scope of the present invention. For example, the sidewall may be curved outwardly so that the diameter of the sprinkler increases. The sprinkler may have a mushroom-like shape, with a narrow lower stem that expands into a dome-like shape. Furthermore, the sidewall need not have a circular cross-sectional shape, but may take other shapes, such as oval, square, rectangular, triangular, etc.

[0052] As provided in the above disclosure, embodiments of the sparger assembly disclosed herein provide an increased kLa for a bioreactor system (i.e., achieving 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 of producing a higher density of vesicles that are less likely to coalesce. By ensuring a high density of vesicle sizes, a larger surface area is obtained between the vesicle and the cell culture matrix, providing higher oxygen transfer and CO2 stripping within the culture matrix.

[0053] It is expressly noted that the sprinkler assemblies disclosed herein may be used in conjunction with many existing impeller assemblies.

[0054] As used herein, an element or step described in the singular and beginning with the word "one" or "a kind of" should be understood as not excluding a plurality of said elements or steps, unless such exclusion is explicitly stated. In addition, reference to "one embodiment" of the present invention is not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the described features. In addition, unless explicitly stated to the contrary, an embodiment that "includes," "contains," or "has" one or more elements having a particular property may include additional such elements that do not have that property.

[0055] This written description uses examples to disclose several embodiments of the invention, including the best mode, and also to enable one of ordinary skill in the art to practice the 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 one 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 literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.

Claims

1. A sprinkler assembly for a biological treatment system, comprising: base; a plurality of sprinklers connected to the base, each sprinkler comprising a plurality of apertures; Wherein, each of the plurality of sprinklers has a generally cylindrical shape.

2. The sprinkler assembly of claim 1, wherein: Each of the plurality of sprinklers includes a sidewall and a top defining the cylindrical shape.

3. The sprinkler assembly of claim 1 or 2, wherein: The sidewall and the top each include a plurality of holes.

4. A sprinkler assembly according to claim 2 or 3, wherein: The apertures of the sidewall include a first array of apertures located at a first height from a top surface of the base.

5. The sprinkler assembly of claim 4, wherein: The apertures of the sidewall include a second array of apertures located at a second height from the top surface of the base, the second height being different than the first height.

6. The sprinkler assembly of claim 5, wherein: The apertures of the second array are radially offset relative to the apertures of the first array.

7. The sprinkler assembly of any one of claims 2 to 6, wherein: The sidewall includes a first ridge extending at least partially around a circumference of the sidewall, the first ridge being located over a first array of apertures.

8. The sprinkler assembly of claim 7, wherein: The sidewall includes a second ridge extending at least partially around a circumference of the sidewall, the second ridge being located over the second array of apertures.

9. A sprinkler assembly according to any one of the preceding claims, wherein: Each of the plurality of sprinklers includes two bonding surfaces configured to bond with the base upon application of heat and / or vibrational forces.

10. An impeller and sprinkler assembly for a biological treatment system, comprising: A sprinkler assembly according to any one of claims 1 to 9; as well as An impeller assembly is attached to the base.

11. The impeller and sprinkler assembly of claim 10, wherein: The impeller assembly includes a magnetic hub connected to the base; and An impeller is connected to the magnetic hub.

12. A biological treatment device comprising: Flexible bags; The spray assembly of any one of claims 1-9, wherein the base is coupled to the flexible bag such that the plurality of sprayers are located within the flexible bag; as well as An impeller assembly is attached to the base such that the impeller assembly is located within the flexible bag.

13. The bioprocessing apparatus according to claim 12, wherein: The base includes at least one input port in fluid communication with the plurality of sprinklers.

14. The biological treatment system of claim 13, wherein: The at least one input port is connectable to a gas source.

15. The biological treatment system of claim 14, wherein: Gas from the gas source is configured to exit through the plurality of holes and enter the flexible bag.

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