System and method for adjusting filter height for bioprocess systems

Abstract

A bioreactor system is provided for use in the implementation of a biomanufacturing process. The system includes a bioreactor vessel, an exhaust filter and associated filter heater, and a height adjustment mechanism connected to the exhaust filter and associated filter heater and the bioreactor vessel. The exhaust filter is fluidly connected to a disposable bioreactor bag located inside the bioreactor vessel via at least one tube, and the height adjustment mechanism adjusts the height of the exhaust filter and associated filter heater relative to the top surface of the disposable bioreactor bag. By adjusting the height of the exhaust filter and associated filter heater, twisting of the tubes is avoided, thereby ensuring that overpressure of the disposable bioreactor bag is avoided.

Description

Technical Field

[0001] Embodiments of the present invention generally relate to bioprocess systems and methods, and more particularly, to systems and methods for adjusting filter height and related filter heat for bioprocess systems.

Background Art

[0002] Various containers, devices, components, and unit operations for performing biochemical and / or biological processes and / or for manipulating liquids and other products of such processes are known. In order to avoid the time, cost, and difficulty associated with sterilizing containers used in biopharmaceutical manufacturing processes, single-use or disposable bioreactor bags and single-use mixer bags are used as such containers. For example, biological substances (e.g., animal and plant cells) and microbial cultures, including mammalian, plant, or insect cells, can be processed using disposable or single-use mixers and bioreactors.

[0003] In the biopharmaceutical field, single-use or disposable containers are increasingly in use. Such containers may be flexible or foldable plastic bags supported by an external rigid structure such as a stainless steel outer shell or container. The use of sterile disposable bags eliminates the time-consuming container cleaning step and reduces the opportunity for contamination. The bag may be placed inside a rigid container and filled with the desired fluid for mixing. Depending on the fluid being processed, the system may include several fluid lines and various sensors, probes, and ports connected to the bag for monitoring, analysis, sampling, and fluid transfer. For example, multiple ports are usually located on the front of the bag and accessible through openings in the side walls of the container, providing connection points for sensors, probes, and / or sampling lines. In addition, the attachment of harvest ports or drain lines is usually located at the bottom of the disposable bag and configured for insertion through openings in the bottom of the container, allowing the harvest line to be connected to the bag for harvesting and draining the bag after the completion of the bioprocess.

[0004] Typically, a stirrer assembly located inside the bag is used to mix the fluid. Existing stirrers are either top-driven (having a shaft extending downward into the bag with one or more impellers mounted on the shaft) or bottom-driven (having an impeller at the bottom of the bag, driven by a magnetic drive system or motor located outside the bag and / or container). Most magnetic stirrer systems include a rotating magnetic drive head outside the bag and a rotating magnetic stirrer (also called the "impeller" in this context) inside the bag. The movement of the magnetic drive head enables torque transmission and, therefore, rotation of the magnetic stirrer, allowing the stirrer to mix the fluid in the container. Magnetic coupling of the stirrer inside the bag to the drive system or motor outside the bag and / or bioreactor container can eliminate contamination problems, enable a fully sealed system, and prevent leakage. Since there is no need for a drive shaft to penetrate the bioreactor container wall and mechanically rotate the agitator, the magnetically coupled system can eliminate the need for a seal between the drive shaft and the container.

[0005] During the cell culture process, the bag is inflated, and fluids and gases are introduced into the bag. Such gases may include air, CO2, oxygen, and N2. In addition, culture medium is probably added periodically (or continuously) throughout the culture process. Gases and fluids are also removed from the bag during the culture process. Typically, gases are removed through an exhaust line (e.g., a tube) connected to an exhaust filter attached to an external container at the top of the bag. A filter heater is usually wrapped around the filter to ensure that the concentration in the exhaust line is kept to a minimum, thereby reducing deposits on the exhaust filter. However, because the bag is inflated and gases are added to the system, the amount of inflation changes throughout the cell culture process. If the bag is overinflated, the exhaust line is pushed up. Since the exhaust filter is attached to an external container, it has a fixed height. This causes the exhaust line to bend or twist, raising the pressure in the bag above a safe level (i.e., the exhaust line is at least partially blocked, preventing gases from leaving the bag at a sufficient rate). Currently, when this occurs, the culture must be stopped or paused, otherwise the bag is likely to rupture due to overpressure. A new (or identical) exhaust filter may then be attached to the bag with a shorter exhaust line, and the culture process can then be resumed. However, these steps are cumbersome, require the culture to be paused, which may threaten cell viability, and may require additional supplies (e.g., additional tubing, connectors, etc.). [Overview of the project] [Problems that the invention aims to solve]

[0006] From the above perspective, a mechanism is needed to adjust the height of the exhaust filter and associated filter heater to prevent the bag from over-inflating and twisting the exhaust line. [Means for solving the problem]

[0007] A first aspect of the present invention relates to a method for adjusting the height of an exhaust filter and associated filter heater. The method includes the steps of: attaching the exhaust filter and associated filter heater to a height adjustment mechanism; attaching the height adjustment mechanism to a bioreactor container; fluidly connecting the exhaust filter to a disposable bioreactor bag located inside the bioreactor container via at least one tube; and adjusting the height of the exhaust filter and associated filter heater relative to the top surface of the disposable bioreactor bag. According to the embodiment, the step of adjusting the distance between the exhaust filter and associated filter heater and the top surface of the disposable bioreactor bag to increase occurs after the disposable bioreactor bag has been inflated, thereby straightening at least one tube. By straightening the tube, overpressure generated inside the disposable bioreactor bag due to twisting of at least one tube is relieved.

[0008] In the embodiment, the height adjustment mechanism includes at least one rail, and the adjustment step includes sliding the exhaust filter and associated filter heater along the rail. The height adjustment mechanism further includes at least one clamp and at least one plunger, wherein the step of sliding the exhaust filter and associated filter heater along the rail includes rotating the plunger in a first direction so that the plunger is released from the rail, and moving the exhaust filter and associated filter heater along the rail. After the exhaust filter and associated filter heater have been moved along the rail, the method further includes rotating the plunger in a second direction to lock the plunger into a slot in the rail.

[0009] In a further embodiment, the height adjustment mechanism includes a feed screw located in a channel of at least one rail, and a knob located on a first end of the feed screw, wherein the step of sliding the exhaust filter and associated filter heater along the rail includes the step of rotating the knob.

[0010] According to any embodiment, the height of the exhaust filter and associated filter heater relative to the top surface of the disposable bioreactor bag is automatically adjusted based on the height of the top surface of the disposable bioreactor bag or the detected pressure inside the disposable bioreactor bag. In one embodiment, the automatic adjustment step includes activating a motor when the detected pressure exceeds a threshold.

[0011] A second aspect of the present invention relates to a bioreactor system, the bioreactor system comprising a bioreactor vessel, an exhaust filter and associated filter heater, and a height adjustment mechanism connected to the exhaust filter and associated filter heater and the bioreactor vessel, wherein the exhaust filter is fluidly connected via at least one tube to a disposable bioreactor bag located inside the bioreactor vessel, and the height adjustment mechanism adjusts the height of the exhaust filter and associated filter heater relative to the top surface of the disposable bioreactor bag.

[0012] In the embodiment, the height adjustment mechanism includes at least one rail, and the height of the exhaust filter and associated filter heater is adjusted by sliding along the at least one rail. The height adjustment mechanism further includes at least one clamp and at least one plunger, wherein rotation of the plunger in a first direction releases the plunger from the rail so that the exhaust filter and associated filter heater can move along the rail. Rotation of the plunger in a second direction locks the plunger in a slot in the rail so that the exhaust filter and associated filter heater cannot move along the rail.

[0013] In a further embodiment, the height adjustment mechanism further includes a feed screw located within a channel of at least one rail, and a knob located on a first end of the feed screw, the height of the exhaust filter and associated filter heater being adjusted by rotating the knob.

[0014] According to any embodiment, the system further includes a motor and at least one sensor configured to determine the height of the top surface or the detected pressure inside a disposable bioreactor bag, the height of the exhaust filter and associated filter heater being automatically adjusted by the motor when the detected pressure or top surface height exceeds a threshold.

[0015] The present invention will be better understood by referring to the accompanying drawings and reading the following description of non-limiting embodiments. [Brief explanation of the drawing]

[0016] [Figure 1] This is a perspective view of a bioprocess system according to embodiments of the present invention. [Figure 2] This is a perspective view of a component management device for a bioprocess system shown in Figure 1, according to an embodiment of the present invention. [Figure 3A] This is an assembled view of a height adjustment mechanism according to an embodiment of the present invention. [Figure 3B] This is an exploded view of a height adjustment mechanism according to an embodiment of the present invention. [Figure 4A] Figures 3A and 3B show the operation of a height adjustment mechanism for adjusting the height of an exhaust filter and associated filter heater according to an embodiment of the present invention. [Figure 4B] Figures 3A and 3B show the operation of a height adjustment mechanism for adjusting the height of an exhaust filter and associated filter heater according to an embodiment of the present invention. [Figure 4C] Figures 3A and 3B show the operation of a height adjustment mechanism for adjusting the height of an exhaust filter and associated filter heater according to an embodiment of the present invention. [Figure 4D] Figures 3A and 3B show the operation of a height adjustment mechanism for adjusting the height of an exhaust filter and associated filter heater according to an embodiment of the present invention. [Figure 5] This is a diagram of an alternative height adjustment mechanism according to an embodiment of the present invention. [Figure 6A] A diagram showing how the operation of the height adjustment mechanism straightens a twisted tube connected to an exhaust filter according to an embodiment of the present invention. [Figure 6B] A diagram showing how the operation of the height adjustment mechanism straightens a twisted tube connected to an exhaust filter according to an embodiment of the present invention.

Mode for Carrying Out the Invention

[0017] Exemplary embodiments of the present invention are referred to in detail below. Examples of the present invention are shown in the accompanying drawings. As far as possible, the same reference numerals used throughout the drawings refer to the same or similar components.

[0018] As used herein, the terms "flexible" or "foldable" refer to a structure or object that is easily bent or can be bent without breaking, and also refer to a compressible or expandable object. An example of a flexible structure is a bag formed of a polyethylene film. The terms "rigid" and "semi-rigid" are used interchangeably herein to describe a structure that is "non-foldable", i.e., cannot be folded, crushed, or deformed by normal forces so as to substantially shorten its own elongated dimension. Depending on the situation, "semi-rigid" may also indicate a structure that is more flexible than a "rigid" element, such as a tube or pipes that can be bent, but further, a structure that does not collapse longitudinally under normal situations and forces.

[0019] As used herein, the term "container" may in some cases mean a flexible bag, a flexible container, a semi-rigid container, a rigid container, or a flexible or semi-rigid tubing. The term "container" as used herein is intended to include, for example, bioreactor containers having flexible or semi-rigid walls or wall portions commonly used in biological or biochemical processes, including cell culture / purification systems, mixing systems, media / buffer preparation systems, and filtration / purification systems (such as chromatography systems and tangential flow filter systems, as well as their associated flow paths), single-use flexible bags, and other containers or conduits. The term "bag" as used herein means a flexible or semi-rigid container or vessel, for example, used as a bioreactor or mixer for the contents therein. The term "consumable" or "consumable component" as used herein means a device or component that is intended to be replaced periodically due to wear or use.

[0020] Embodiments of the present invention provide a bioprocess system, and in particular, provide an exhaust filter height adjustment mechanism for a bioreactor system. In an embodiment, the bioprocess system includes a container defining an internal space for receiving a flexible bioprocess bag, the container having an access door in a side wall of the container to provide access to the internal space, and a component management device attached to the side wall of the container and having a mounting frame for attaching at least one consumable component of the bioprocess system.

[0021] Referring to Figure 1, a bioprocess system 10 (also referred to herein as a bioreactor system 10) according to an embodiment of the present invention is shown. The bioreactor system 10 includes a substantially rigid bioreactor container or support structure 12 having a plurality of legs 16 and mounted on a base 14. The container 12 may be formed from, for example, stainless steel, polymer, composite material, glass, or other metal, and may be cylindrical in shape, but other shapes may also be used without departing from a broader embodiment of the present invention. The container 12 can be any shape or size, as long as it can support a single-use flexible bioreactor bag within its internal space 18. For example, according to one embodiment of the present invention, the container 12 can accept and support flexible or foldable bioprocess bags of 10 L to 2000 L.

[0022] The container 12 may include one or more viewing windows 20 that allow an operator to view the fluid level in a flexible bag located within the internal space 18, and a window 22 located in the lower region of the container 12. The window 22 allows access to the interior of the container 12 for the insertion and placement of various sensors and probes (not shown) within the flexible bag, and for connecting one or more fluid lines to the flexible bag for fluids, gases, etc., to be added to or drawn from the flexible bag. Sensors / probes and control devices for monitoring and controlling important processing parameters include any one or more of the following and combinations, such as temperature, pressure, pH, dissolved oxygen (DO), dissolved carbon dioxide (pCO2), mixing ratio, and gas flow rate.

[0023] In embodiments, the container 12 includes an access door 24 that is hinged or pivotably connected to the side wall of the container 12, allowing access to the internal space 18. The door 24 may include a handle 26 that facilitates movement of the door between an open position and a closed position. In embodiments, the door 24 may be configured or positioned such that, when the door 24 is in the closed position, the lower edge of the door 24 forms the upper edge or boundary of the window 22, and / or the side edge of the door 24 forms the edge or boundary of the window 20. By defining the boundaries of one or more windows 20, 22 with the edge of the door 24, when the door 24 is in the open position, an adjacent, unobstructed access opening in the side wall of the container is formed by the opening 20, the opening 22, and the open door 24 (i.e., the opening into which the door is received). Thus, the area of ​​adjacent access openings formed in the side wall of the container 12 is equal to the combined area of ​​the door 24, window 22, and window 20 when the door is in the open position. This results in greater openness and access to the interior space 18 than would be possible if the door and window were separated by the side wall portion of the container 12.

[0024] Referring further to Figure 1, the inner side wall of the container 12 may include one or more vertical baffles 28 projecting into the internal space 18. The baffles 28 may have a substantially triangular cross-section, but shapes and structures known in the art may also be used without departing from a broader embodiment of the present invention. The baffles 28 are configured to contact the flexible bag and, for purposes known in the art, to bias it inward (when placed in the internal space 18) during bioprocess operation.

[0025] As further shown in Figures 1 and 2, the bioreactor system 10 also includes a component management device 100. The device 100 includes a frame 102 used to connect various components to a flexible bag. The frame 102 can generally take the form of a semicircular or curved rail that mimics the outer diameter of the container 12. Specifically, Figure 2 shows how an exhaust filter 134 with an associated filter heater can be attached to the frame 102. As shown, each exhaust filter and associated filter heater 134 can be attached to a frame portion 124 by a height adjustment mechanism 140. Specifically, as best shown in Figures 2, 3 and 5, each exhaust filter and associated filter heater 134 is attached to the height adjustment mechanisms 140, 150 by fasteners 146 which are attached to the frame 102 by fasteners 139. As these figures show, the height adjustment mechanisms 140, 150 can be attached to the rail (Figure 5) or directly to the protruding portion (e.g., flange) 124 of the frame 102.

[0026] As will be discussed in more detail below, the height adjustment mechanisms 140, 150 are configured to adjust the height of the exhaust filter and associated filter heater 134 relative to the frame 102 and container 12 so that the distance between the exhaust filter and associated filter heater 134 and the single-use bag can be adjusted before, during, and / or after the cell culture process is carried out in the single-use bag. Specifically, the exhaust filter and associated filter heater 134 are fluidly connected to the single-use bag via at least one tube so that the gas introduced (and generated) during the cell culture process can exit the single-use bag. The height of the exhaust filter and associated filter heater 134 can be changed to accommodate changes in the expansion of the single-use bag due to changes in the amount of gas entering (or generated) in the single-use bag. This ensures that the integrity of the fluid connection between the single-use bag and the exhaust filter is properly maintained.

[0027] According to embodiments of the present invention, the height adjustment mechanism 140 includes a back plate 141 attached by fasteners 142 to a mounting plate 135 for an exhaust filter and associated filter heater 134. The height adjustment mechanism 140 further includes a rail 143 attached to a frame 102 by clamps 145 attached to the back plate 141 by fasteners 139 and clamps 146. As best shown in Figures 3A to 4B, the rail 143 generally has an inverted "T" shape, with a slot 144 located within its vertical portion. The clamp 145 is molded so that the vertical portion of the rail 143 can slide within a recess in the clamp 145. The height adjustment mechanism 140 further includes a plunger 147 inserted into a hole in the clamp 145. The length of the plunger 147 is such that it penetrates the clamp 145 and enters the slot 144. A nut 148 is screwed onto the plunger 147. The slot 144 includes an array of projections 149 (e.g., toothed) (best shown in Figures 4C and 4D) so that the plunger 147 can be located within a recess (circular cutout) in the rail 143. Thus, when the handle of the plunger 147 is rotated in a first direction (e.g., clockwise), the plunger 147 is advanced into the slot 144 and located within one of the recesses (see Figure 4D), thereby engaging the exhaust filter and associated filter heater 134 and preventing their movement relative to the rail 143. Similarly, when the handle of the plunger is rotated in a second direction (e.g., counterclockwise), the plunger 147 is retracted out of the recess and the rail 143 (see Figure 4C), thereby releasing the exhaust filter and associated filter heater 134 and allowing their movement relative to the rail 143.

[0028] With such a configuration, the height adjustment mechanism 140 can adjust the height of the exhaust filter and associated filter heater 134. Specifically, the exhaust filter and associated filter heater 134 are slidable along the length of the rail 143. To accomplish this, as shown in Figures 4A to 4D, the user rotates the handle of the plunger 147 counterclockwise (as indicated by the arrow in Figure 4A). This releases the height adjustment mechanism 140. The user can then slide the exhaust filter and associated filter heater 134 along the rail 143 to the desired height (as indicated by the arrow in Figure 4B). To prevent further movement of the exhaust filter and associated filter heater 134, the user then rotates the handle clockwise, thereby positioning the plunger in the desired recess in the rail 143, and thereby locking the height of the exhaust filter and associated filter heater 134.

[0029] Figure 5 shows an alternative embodiment of the height adjustment mechanism 150. As shown, the height adjustment mechanism 150 also includes a rail 155 having a substantially inverted "T" shape. The lower part of the rail 155 is fixed to the frame 102 by fasteners 139, as previously described. The rail 155 has a channel 152 formed along at least part of its length, and a lead screw 153 extends along the length of the channel 152. The uppermost part of the lead screw terminates at a knob 151 located at the top of the rail 155. A back plate 154, fixed to the mounting plate 135 (and thereby fixed to the exhaust filter and associated filter heater 134), has a portion into which the lead screw 153 is screwed and protrudes into the channel. Specifically, the portion of the back plate 154 is configured to fit into the channel 152 and includes a through hole into which the lead screw is screwed. Thus, the portion of the back plate 154 functions as a nut into which the lead screw 153 is screwed. To adjust the height of the exhaust filter and associated filter heater 134, the user rotates the knob 151. Specifically, the user rotates the knob 151 in a first direction (e.g., clockwise) and also rotates the lead screw 153 in the first direction, thereby moving the back plate 154 upward along the channel due to its engagement with the lead screw 153. Similarly, by rotating the knob 151 in a second direction (e.g., counterclockwise), the back plate 154 moves downward along the channel. In this way, the user can adjust the height of the exhaust filter and associated filter heater 134 by rotating the knob 151.

[0030] While the embodiments described above illustrate a height adjustment mechanism having components of a specific geometric shape / design, the present invention is not limited in this respect. For example, the T-shaped rail can have other structures (e.g., a roughly plate-like shape, a rod shape, etc.) as long as the rail can be attached to the frame of the outer container. Furthermore, the length of the rail can be changed based on the specific application (i.e., the required height adjustment length). According to one embodiment, the length of rails 143, 152 is about 50 to 200 mm, and in one preferred embodiment, the length is about 80 mm.

[0031] Although two embodiments of the height adjustment mechanism 140 and 150 have been described above, the present invention is not limited in this way, and other variations are also within the scope of the present invention. For example, the height adjustment mechanism may include an array of hooks, ledges, or projections positioned at various heights along the rail, while the mounting plate 135 includes corresponding hooks or mounting points so that the mounting plate 135 can be hung or attached to the rail at various heights. Furthermore, the back plate 154 and the rail may each be made from or include at least one magnet or ferromagnetic material so that the two are magnetically attracted to each other. In this way, the back plate and the rail can be magnetically coupled at various heights along the rail.

[0032] According to any embodiment of the present invention, the height adjustment of the exhaust filter and associated filter heater 134 can be automated. For example, a motor can be attached to a knob 151 (or directly to a lead screw 153) and used to rotate the knob 151 in a desired direction to move the exhaust filter and associated filter heater 134 upward and downward along a rail 155. Furthermore, the operation of the motor can be automated by a feedback loop. For example, if the tubing attached to the exhaust filter twists as described above, the pressure inside the single-use bag increases. This pressure increase can be measured by a pressure sensor inside the single-use bag, and if the pressure exceeds a threshold, a signal can be generated, triggering the operation of a motor, which in turn rotates the knob 151 (or lead screw 153) and lifts the exhaust filter and associated filter heater 134. Furthermore, the height of the top surface of the single-use bag can be monitored by, for example, an optical sensor or camera, and if the height of the top surface increases by a predetermined amount, a signal can be generated that triggers the motor to operate and raise the exhaust filter and associated filter heater 134.

[0033] Figures 6A and 6B show the operation of height adjustment mechanisms 140, 150 for straightening at least one tube connected to the exhaust filter. As described above, when cell culture is performed in a single-use bag 104, gases and fluids are added to the bag to accelerate the culture process. At various points in the process, the single-use bag 104 may over-expand. If such over-expanding occurs, the distance between the top surface of the single-use bag 104 and the bottom surface of the exhaust filter decreases, thereby bending the tube 106 that fluidly connects the bag to the filter. If the over-expanding is sufficient, the tube 106 will bend to the extent that twisting or blockage 108 occurs in the tube 106 (see, for example, Figure 6A). This increases the pressure inside the single-use bag 104 and threatens the integrity of the bag. The present invention is advantageous in that it allows the user to untwist or prevent blockage by raising the height of the exhaust filter and associated filter heater (see, for example, Figure 6B). The alternative method, by raising the exhaust filter and associated filter heater 134 (see the arrow shown in Figure 6B), allows the height adjustment mechanism disclosed herein to straighten the tube connecting the single-use bag to the exhaust filter, thereby ensuring that the gas flows out of the bioreactor system 10 in the correct amount and preventing overpressure of the system.

[0034] It should be noted that the above description describes a height adjustment mechanism for adjusting the height of an exhaust filter and associated filter heater. However, the present invention is not limited to adjusting such components, and the height adjustment mechanisms described herein may be implemented to adjust the height of any component on a bioreactor system that requires adjustment.

[0035] In this specification, any element or step described in the singular and beginning with the word "a" or "an" should be understood not to exclude the plural form of such element or step (unless such exclusion is explicitly stated). Furthermore, the reference to "one embodiment" of the present invention is not intended to be construed as excluding the existence of further embodiments that also incorporate the described features. Moreover, unless otherwise explicitly stated, an embodiment that "includes," "companies," or "has" an element or a number of elements having a particular characteristic may include further such elements that do not possess that characteristic.

[0036] This specification discloses several embodiments of the invention, including the best mode, with examples, and enables a person skilled in the art to practice embodiments of the invention, including making and using any device or system, and carrying out any incorporated method. The patentable scope of the invention is defined by the claims and may include other examples that a person skilled in the art can conceive. Such other examples are intended to be within the claims if they have structural elements that are not different from the language of the claims, or if they include equivalent structural elements that are not substantially different from the language of the claims. [Explanation of symbols]

[0037] 10. Bioprocess systems, bioreactor systems 12. Bioreactor container, support structure 14 Base 16 Legs 18 Interior space 20. View windows, openings 22 Windows, openings 24 Access Doors 26 handle 28 Vertical baffle 100 Component management device 102 frames 104 Single-use bags 106 tube 108 Obstruction 124 Frame part, protruding part 134 Exhaust filters and related filter heaters 135 Mounting plate 139, 142 Fasteners 140, 150 Height adjustment mechanism 141 Back plate 143, 155 rails 144 slots 145 Clamp 146 Fasteners 147 Plunger 148 nuts 149 Protrusion 151 Knob 152 channels 153 Lead screw 154 Back plate

Claims

1. A method for adjusting the height of an exhaust filter and associated filter heater, The steps include attaching the exhaust filter and associated filter heater to the height adjustment mechanism, The steps include attaching the height adjustment mechanism to the bioreactor container, The steps include: fluidly connecting the exhaust filter to a disposable bioreactor bag located inside the bioreactor container via at least one tube; The steps include adjusting the height of the exhaust filter and associated filter heater relative to the upper surface of the disposable bioreactor bag, Methods that include...

2. The method according to claim 1, further comprising the step of inflating the disposable bioreactor bag, wherein the adjusting step occurs after the disposable bioreactor bag has been inflated.

3. The method according to claim 2, wherein the distance between the exhaust filter and associated filter heater and the top surface of the disposable bioreactor bag is increased so that at least one of the tubes is straightened, thereby reducing the overpressure generated in the disposable bioreactor bag due to the twisting of at least one of the tubes.

4. The height adjustment mechanism includes at least one rail, The method according to any one of claims 1 to 3, wherein the adjusting step includes sliding the exhaust filter and associated filter heater along the rail.

5. The aforementioned height adjustment mechanism is At least one clamp and At least one plunger, Including, The step of sliding the exhaust filter and associated filter heater along the rail is: Rotating the plunger in a first direction so that the plunger is released from the rail, Moving the exhaust filter and associated filter heater along the rail, The method according to claim 4, including the method described in claim 4.

6. The method according to claim 5, further comprising the step of rotating the plunger in a second direction after the exhaust filter and associated filter heater have moved along the rail to lock the plunger into a slot in the rail.

7. The aforementioned height adjustment mechanism is A feed screw located within the channel of at least one of the rails, A knob positioned on the first end of the lead screw, wherein the step of sliding the exhaust filter and associated filter heater along the rail includes the step of rotating the knob, The method according to claim 4, further comprising:

8. The method according to any one of claims 1 to 7, wherein the height of the exhaust filter and associated filter heater relative to the top surface of the disposable bioreactor bag is automatically adjusted based on the height of the top surface of the disposable bioreactor bag or the pressure detected inside the disposable bioreactor bag.

9. The method according to claim 8, wherein the automatic adjustment step includes activating the motor when the detected pressure exceeds a threshold.

10. Bioreactor container, Exhaust filter and associated filter heater, The exhaust filter and associated filter heater, and the height adjustment mechanism connected to the bioreactor container, Includes, The exhaust filter is fluidly connected via at least one tube to a disposable bioreactor bag located inside the bioreactor container. The height adjustment mechanism adjusts the height of the exhaust filter and associated filter heater relative to the top surface of the disposable bioreactor bag in a bioreactor system.

11. The height adjustment mechanism includes at least one rail, The system according to claim 10, wherein the height of the exhaust filter and associated filter heater is adjusted by sliding along the at least one rail.

12. The aforementioned height adjustment mechanism is At least one clamp and At least one plunger and It further includes, The system according to claim 11, wherein the rotation of the plunger in a first direction releases the plunger from the rail so that the exhaust filter and associated filter heater can move along the rail.

13. The system according to claim 12, wherein the rotation of the plunger in a second direction locks the plunger into a slot in the rail so that the exhaust filter and associated filter heater cannot move along the rail.

14. The aforementioned height adjustment mechanism is A feed screw located within at least one rail channel, A knob positioned on the first end of the lead screw, wherein the height of the exhaust filter and associated filter heater is adjusted by rotating the knob, The system according to claim 10, further comprising:

15. The aforementioned system At least one sensor configured to determine the height of the upper surface or the detected pressure inside the disposable bioreactor bag, motor and It further includes, The system according to claim 14, wherein the height of the exhaust filter and associated filter heater is automatically adjusted by the operation of the motor when the detected pressure or the height of the upper surface exceeds a threshold.

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