Bioreactor Heating Device

Abstract

1. A heating device (10) for a bioreactor (70), characterized in that the heating device has a transparent, flexible body (20) that allows direct visualization of the bioreactor culture medium and is adapted to be removably coupled to one or more different types of bioreactor vessels (72) and to provide customized heating.

Description

[Technical field]

[0001] The present disclosure relates to heating devices, bioreactor systems, and related methods of use. In particular, the present disclosure deals with devices, systems, and methods for efficiently heating and regulating the temperature of a bioreactor to promote the growth and cultivation of microorganisms and other organisms. [Background technology]

[0002] A bioreactor generally refers to a device or system used to support a biologically active environment. A bioreactor may include a vessel in which a biological process, such as the cultivation of an organism or a biochemically active substance derived from an organism, is carried out. The process may be aerobic or anaerobic. A bioreactor may also refer to a device or system designed to grow cells or tissues in the context of cell culture.

[0003] Bioreactors may have cylindrical, variable diameter, or other configurations and may range in size from milliliters to cubic meters. Bioreactors can be made from a variety of materials, such as glass, stainless steel, polymers, etc. The size and configuration of a bioreactor may be determined in part by the intended mode of operation, e.g., a bioreactor configured for batch, fed-batch, continuous use, multi-use, or single-use bioprocessing activities. As an example, continuous-use bioreactors are often configured as autoclavable, reusable glass or stainless steel cylindrical vessels. In contrast, single-use bioreactors are disposable and often constructed of plastic or other polymers.

[0004] A typical bioreactor consists of the following parts: Agitator or impeller. This is used to agitate the reactor contents, keeping the "cells" in a completely homogenous state and improving the transport of nutrients and oxygen to the cells. Baffles. This is used to break up vortex formation within the vessel, but is usually undesirable as it changes the center of gravity of the system and consumes additional power without promoting agitation. Sparger. In aerobic culture processes, the purpose of the sparger is to supply the appropriate gases (such as oxygen and CO2) to the growing cells. Jacket. This provides an annular area through which hot or cold water is circulated for heat transfer.

[0005] The rate and quality of bioprocessing is directly dependent on the environmental conditions and parameters established by the bioreactor, such as nutrient levels, pH, O2 levels, and temperature. Regulation and maintenance of temperature, in particular, is a critical factor in promoting biological growth and production of biochemically active substances. The ability to regulate, regulate, and customize the temperature of a bioreactor culture and the ability to transfer heat uniformly throughout the bioreactor culture greatly impact the overall bioprocess. Existing heaters for temperature regulation typically only provide a primary heating or cooling unit adjacent to and supporting the distal base of the bioreactor vessel. Such devices do not provide uniform and consistent heat transfer throughout the culture, often resulting in temperature gradients throughout the bioreactor culture, limiting the rate of heat transfer. With such devices, pockets of bioreactor culture may be hotter or colder than the desired temperature range. Additionally, because the heat transfer surfaces of the bioreactor are not insulated, heaters are forced to operate inefficiently and must work harder to account for heat loss through non-insulated / non-heated surfaces.

[0006] Electrical heating jackets are also known that can be wrapped around a single-walled bioreactor vessel. However, these are typically simple devices with a single temperature setting and heating rate and on / off functionality. Such devices do not allow for adjustment or customization of heat transfer, nor are they configured or adapted for use with different types of bioreactor vessels that may be designed for different bioprocessing operations and have different temperature thresholds, different heat transfer characteristics, and different rates at which the bioreactor vessel can be safely and efficiently heated. Such devices are also operated independently of environmental conditions, bioprocessing data, and other information from the bioreactor. There are also no fundamental temperature limitations or feedback loops to provide for potentially destructive uses of the heating jacket, which, when used in conjunction with a bioreactor vessel constructed of a low melting point material, can cause overheating, damage, and / or melting of the heating jacket and / or bioreactor. Thus, these devices are unable to intelligently, efficiently, or effectively transfer heat to a bioreactor, especially to different types of bioreactors.

[0007] Furthermore, conventional heating jackets are typically constructed of opaque multi-layer insulating fabrics and / or rigid exteriors purposefully designed for electrical and thermal insulation. In this case, direct visualization of the bioreactor culture through the heating jacket is not possible. However, continuous, real-time visual monitoring and regulation of the bioreactor culture is a key element in managing a bioprocess, evaluating ongoing biochemical reactions, and ensuring high yield efficiency. Unhindered transmission of light through the bioreactor vessel and heating device is necessary for accurate and clear direct visual assessment of potential key bioprocess indicators such as turbidity, coloration, and tint. For example, US2016 / 184827 A1 discloses a temperature control device for controlling the temperature of the vessel, which can be conformally and flexibly positioned on the vessel wall. However, the temperature control device according to US2016 / 184827 A1 does not allow visualization of the bioreactor culture through the temperature control device. Summary of the Invention [Problem to be solved by the invention]

[0008] In view of the above-mentioned deficiencies, there is a need to develop a heating device that addresses the deficiencies of current bioreactor heating systems.

[0009] The objective of the present disclosure is to provide a heating device with a transparent body that allows direct visualization of the bioreactor culture while the heating device is connected to the bioreactor and operating.CN108998376 A discloses a dynamic cell culture device and method based on a dielectric elastomer actuation device.The dynamic cell culture device according to CN108998376 A discloses that the container body, cover, holder module and / or heating sheet compartment can be made of transparent materials.

[0010] Another object of the present disclosure is to provide a heating device that can be reusably coupled to a variety of different types of bioreactors and allows for customized heat transfer specifically adapted to the needs of the attached bioreactor and the bioreactor culture. [Means for solving the problem]

[0011] An embodiment is a heating device for a bioreactor. The heating device comprises: a transparent flexible body, a heating element coupled to the flexible body, and a sensor coupled to the flexible body. The flexible body has a transparent portion with a material having optical transparency and is removably coupleable to and substantially surrounds a sidewall defining a perimeter of a transparent bioreactor vessel containing a bioreactor culture. The heating element transfers heat to the sidewall for uniform heating of the bioreactor culture. The heating element is disposed throughout the heat transfer portion including the transparent portion of the flexible body. The heating element is configured as an electrically conductive resistive wire such that visibility through the transparent portion is substantially unimpeded. The heating element is connectable to a controller that regulates the heat transfer. The sensor detects temperature and / or temperature changes of the heating device and / or the bioreactor culture. The sensor is connectable to the controller for monitoring and / or regulating the temperature of the heating device and / or the bioreactor culture. Thus, direct visualization of the bioreactor culture is achieved while the heating device is coupled to the bioreactor. It should be noted that CN108998376 A does not disclose that only the container body, the cover, the holder module and / or the heating sheet section may be made of a transparent material, but rather that the heating sheet itself may be made of a transparent material.

[0012] An embodiment relates to a heating device as previously described, in which the sensor and the heating element are configured as an integrated unit or component of the heating device.

[0013] An embodiment relates to a heating device as previously described, in which the heating element comprises one or more electrically conductive wires forming a heat transfer portion of a flexible body, the heat transfer portion of the flexible body being transparent, and the heating element is configured such that visibility of the bioreactor culture through the heat transfer portion is substantially unimpeded when the heating device is coupled to a transparent bioreactor vessel.

[0014] Certain embodiments relate to the aforementioned heating device, wherein the flexible body is configured such that when placed adjacent to a transparent bioreactor vessel around opposing exterior walls of the transparent bioreactor vessel, visibility of the bioreactor culture through the exterior walls is unobstructed.

[0015] An embodiment relates to a heating device as described above, wherein the heating device is reusably and removably coupled to a first bioreactor and provides a first heating compatible with the first bioreactor, and the heating device is reusably and removably coupled to a second bioreactor and provides a second heating compatible with the second bioreactor, the first heating and the second heating being different.

[0016] An embodiment relates to the aforementioned heating device, in which the first heating and the second heating are any of heating to a predetermined temperature or temperature range, transferring heat at a predetermined temperature, transferring heat at a predetermined heating rate, facilitating or limiting the application of heat based on a temperature threshold, facilitating or limiting the application of heat based on a temperature change, heating for a predetermined time, or applying heat according to a predetermined program.

[0017] An embodiment relates to the aforementioned heating device, in which the first heating and the second heating are different and dependent on any of the following: a type of bioreactor vessel dockable to the heating device, a configuration and / or material properties of the bioreactor vessel dockable to the heating device, an intended operation of the bioreactor vessel dockable to the heating device, or a desired temperature, temperature range, or temperature change of a bioreactor culture in the bioreactor vessel docked to the heating device.

[0018] One embodiment relates to the heating device as described above, in which the first heating and the second heating transfer heat at a predetermined heating rate, the first bioreactor is a single-use bioreactor and the second bioreactor is a multiple-use bioreactor, the heating device heats the vessel of the first bioreactor at the first predetermined heating rate, and the heating device heats the vessel of the second bioreactor at a second predetermined heating rate that is faster than the first heating rate.

[0019] An embodiment relates to a heating device as described above, in which the flexible body is configured as a heating jacket, the flexible body comprising a first flexible layer with a first transparent portion that does not impede visibility through the first flexible layer, and a second flexible layer with a second transparent portion that does not impede visibility through the second flexible layer, the heating element is disposed between the first and second flexible layers, and when the heating device is coupled to the transparent bioreactor vessel, the bioreactor culture is visible through the first and second transparent portions of the flexible body.

[0020] Another aspect of the invention is a bioreactor system comprising a heating device as described above and a controller for monitoring and / or regulating the heat transfer, the controller being connected to the heating elements and the sensor.

[0021] One embodiment relates to a bioreactor system as described above, comprising a single-use bioreactor with a plastic bioreactor vessel and a multi-use bioreactor with a glass bioreactor vessel, a heating device removably coupled to the plastic bioreactor vessel and the glass bioreactor vessel and in operative communication with the plastic bioreactor vessel and the glass bioreactor vessel, the heating device (10) providing a first heating to the plastic bioreactor vessel and a second heating to the glass bioreactor vessel, the first heating and the second heating being different.

[0022] Certain embodiments relate to a bioreactor system as described above, the bioreactor system comprising a user interface operatively associated with the controller for a user to adjust the heating of the heating device.

[0023] An embodiment relates to a bioreactor system as described above, comprising an auxiliary heater connected to a controller and coupled to the transparent bioreactor vessel for transferring heat to the transparent bioreactor vessel, the controller centrally controlling and regulating the heat transfer through the heating device and the auxiliary heater.

[0024] An embodiment relates to a bioreactor system as described above. The bioreactor system includes a first bioreactor for culturing tissue. The first bioreactor includes a first transparent bioreactor vessel containing a first bioreactor culture. A heating device is operatively associated with the first transparent bioreactor vessel, the heating device being disposed around an exterior surface of the transparent first bioreactor vessel or bioreactor vessel part, the heating device being configured to transfer heat to the first bioreactor culture and measure a temperature of the heating device and / or the first bioreactor culture and not substantially impede visibility of the first bioreactor culture, and a controller is connected to the heating device to regulate a temperature of the first bioreactor culture and heat applied by the heating device, the heating device providing a first heating in accordance with one or more parameters or conditions of the first bioreactor and a second heating in accordance with one or more parameters or conditions of the second bioreactor, the first heating and the second heating being different.

[0025] An embodiment relates to a bioreactor system as described above, further comprising an auxiliary heater coupled to the first transparent bioreactor vessel and transferring heat to the first transparent bioreactor vessel, and a controller connected to the auxiliary heater and centrally controlling and regulating the heat applied by the heating device and the auxiliary heater to regulate a temperature of the heating device and / or the first bioreactor culture.

[0026] An embodiment relates to a bioreactor system as described above, further comprising a second bioreactor, wherein the first bioreactor is a single-use bioreactor, the first transparent bioreactor vessel is a plastic transparent bioreactor vessel, the second bioreactor is a multi-use bioreactor with a second transparent bioreactor vessel, the second transparent bioreactor vessel is a glass transparent bioreactor vessel, and the heating device is removably coupled to the first transparent bioreactor vessel and the second transparent bioreactor vessel and configured to operate in association with the first transparent bioreactor vessel and the second transparent bioreactor vessel.

[0027] An embodiment relates to a bioreactor system as described above, wherein the heating device of the bioreactor system comprises: a flexible body including one or more transparent portions that allow visibility of a first bioreactor culture when the heating device is coupled to the bioreactor, a heating element configured to not substantially impede visibility of the bioreactor culture through the one or more transparent portions of the flexible body when the heating device is coupled to the first bioreactor, and a temperature sensor connected to a controller to detect a temperature or a temperature change of the flexible body and / or the first bioreactor culture.

[0028] An embodiment relates to a bioreactor system as described above, in which the heating device is integrally formed with, coupled to, attached to, or connected to a bioreactor component, which is the wall of the transparent bioreactor vessel, the bioreactor impeller, the bioreactor impeller shaft, the bioreactor dip tube, and / or the bioreactor spin filter.

[0029] Another embodiment is a method of regulating a temperature in a bioreactor, the method comprising operatively associating a heating device as described above with the bioreactor vessel and using the heating device to heat the bioreactor vessel or a bioreactor culture contained within the bioreactor vessel.

[0030] An embodiment relates to the aforementioned method, comprising detecting a state, parameter or change in said parameter of a bioreactor culture and / or a heating device using a heating device, and adjusting a temperature of the bioreactor culture and / or the heating device based on the detected state, parameter or change in said parameter of the bioreactor culture and / or the heating device.

[0031] One embodiment relates to the aforementioned method, comprising the steps of operatively associating a heating device having a transparent body with a first bioreactor vessel, providing a first heating with the heating device adapted for the first bioreactor vessel or a first bioreactor culture contained within the first bioreactor vessel, operatively associating the heating device with a second bioreactor vessel, providing a second heating with the heating device adapted for the second bioreactor vessel or a second bioreactor culture contained within the second bioreactor vessel, and directly visualizing the first bioreactor culture through the transparent body when the heating device is operatively associated with the first bioreactor vessel and directly visualizing the second bioreactor culture through the transparent body when the heating device is operatively associated with the second bioreactor vessel, wherein the first heating and the second heating are distinct. [Brief description of the drawings]

[0032] The following drawings depict exemplary embodiments and are not intended to limit the scope of the claims. For ease of illustration, similar elements may be referenced with common or similar numerals throughout the drawings. The drawings are not necessarily drawn to scale.

[0033] [Figure 1A] FIG. 1 illustrates an exemplary first heating device for a bioreactor.

[0034] [Figure 1B] FIG. 1B is an exploded view of the heating device of FIG. 1A.

[0035] [Diagram 2] FIG. 2 shows a second embodiment of a bioreactor heating device.

[0036] [Diagram 3] FIG. 1B illustrates the exemplary heating device of FIG. 1A positioned in a bioreactor.

[0037] [Figure 4] FIG. 1B illustrates an exemplary bioreactor system including the exemplary heating device of FIG. 1A.

[0038] [Diagram 5] FIG. 3 shows a third embodiment of a bioreactor heating device.

[0039] [Figure 6] FIG. 4 shows a fourth embodiment of a bioreactor heating device.

[0040] [Figure 7] FIG. 1 shows an exemplary first method of regulating the temperature of the heating device and / or bioreactor culture using a heating device.

[0041] [Figure 8] FIG. 13 illustrates a second exemplary method of using a heating device. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0042] For illustrative purposes, the general principles of the present disclosure are described with reference to various exemplary embodiments. Particular embodiments of the present disclosure are specifically described herein. However, those skilled in the art will readily appreciate that the same principles may be applied and employed in other variations and embodiments as well. The scope of the present disclosure is not limited to the particular embodiments described herein. Moreover, the terms used herein are for the purposes of description and illustration, not limitation.

[0043] Various embodiments will now be described with reference to the drawings. These drawings are intended only to facilitate the description of exemplary embodiments. They are not exhaustive and do not limit the scope of the present disclosure. The illustrated embodiments do not necessarily embody all aspects, features, or advantages of the subject matter of the present disclosure. In addition, any aspect, feature, or advantage described in connection with a particular embodiment is not necessarily limited to that embodiment and may be embodied or practiced in other embodiments, whether or not illustrated or described herein.

[0044] For purposes of this detailed description, the singular forms "a," "an," and "the" may include plural references unless the context clearly dictates otherwise. Thus, for example, a reference to a "heating element" may include a plurality of heating elements known to those of skill in the art and their equivalents. The terms "a" (or "an"), "one or more," and "at least one" may be used interchangeably herein. Additionally, the terms "comprising," "including," "composed of," and "having" may be used interchangeably.

[0045] As used herein, "bioreactor culture" refers to any contents of a bioreactor vessel or bioreactor, such as, but not limited to, a culture of organisms, cells, tissues or other biological and / or chemical components.

[0046] "Transparent" as used herein refers to a range of light transmission from complete transparency to substantial transparency or some translucent properties, meaning that the majority of light propagates through the material and is visible without substantially impeding the field of view. The operator of the bioreactor can essentially see the color, content level, agitation, homogeneity, etc., inside the bioreactor. That is, the operator can visually determine the state of the bioreaction through the heating device (as the operator could in a bioreactor without such a heating device). This can be achieved, for example, by configuring the conductive resistance (heating) wire so as not to reduce the light transmission of the heating device by more than 10%, preferably not more than 20%, more preferably not more than 30%, and most preferably not more than 50%. The conductive resistance wire can be configured, for example, to occupy 1% or less of the surface area of ​​the heat transfer area, preferably not more than 5%, more preferably not more than 10%, even more preferably not more than 20%, even more preferably not more than 30%, and most preferably not more than 50%.

[0047] As used herein, a "sensor" refers to any device, element, or article that detects a parameter, condition, characteristic, or change therein. As used herein, "detection" or "sensing" refers to any direct or indirect means for measuring, sensing, calculating, or determining. For example, a temperature sensor includes both devices that directly detect or measure temperature and devices that indirectly determine a change in temperature based on temperature or another parameter.

[0048] The present disclosure is directed to a heating device 10 for a bioreactor 70, a bioreactor system 80, and a method for heating and / or regulating the temperature of one or more bioreactors 70 and / or heating device 10. In an exemplary embodiment, the heating device 10 and bioreactor system 80 are configured for safe, efficient, customized, intelligent temperature regulation of the heating device 10 and / or one or more bioreactors 70, as well as for clear visualization of the bioreactor culture through a transparent portion 30 of the heating device 10 to facilitate bioprocessing, cultivation, and evaluation of the bioreactor culture. The heating device 10 may be configured for use in connection with different types of bioreactors 70, including single-use bioreactors as well as continuous-use bioreactors, multiple-use bioreactors, or batch-fed bioreactors. Additionally, various heat transfer parameters are customized for the corresponding bioreactor 70 and / or bioreactor culture, such as heating rate, set point temperature, temperature threshold, temperature change, heating duration, heating cycle, etc. An exemplary method for heating and / or regulating the temperature of the heating apparatus 10 and / or bioreactor 70 may include using the heating apparatus 10 to transfer heat to the bioreactor vessel 72, determining the temperature or temperature change of the heating apparatus 10 and / or the bioreactor contents, adjusting the heat transfer based on the determined temperature and / or temperature change, and monitoring the bioreactor culture and bioprocess by directly visualizing the bioreactor culture through the transparent portion 30 of the heating apparatus 10.

[0049] 1A-1B and 3-4 show an exemplary embodiment of a heating device 10 for one or more bioreactors 70. The heating device 10 has a flexible body 20 that is removably coupled to a bioreactor vessel 72 and has one or more transparent portions 30. The heating device 10 further includes one or more heating elements 40 for transferring heat to the bioreactor 70 and one or more sensors 60 for determining a state or parameter of the heating device 10 and / or the contents of the bioreactor vessel 72. In an exemplary embodiment, the heating elements 40 and the sensors 60 may be a single integrated unit or component of the heating device 10 and function as both heat transfer and temperature detection. A controller 50 connected to or otherwise operably associated with the heating elements 40 and / or sensors 60 regulates the temperature of the bioreactor vessel 72 and / or the bioreactor culture contained within the heating device 10. In an embodiment, the controller 50 is included in or otherwise operably associated with the heating device 10, a part, component, or heating device 10 of a heating device system. In another embodiment, the controller 50 may be a separate device, such as a biocontroller of the bioreactor system 80. In an exemplary embodiment, the heating apparatus 10 is reusably and reattachably matable and adapted for use with a variety of different types of bioreactors 70 requiring different heat transfer capabilities.

[0050] In the exemplary embodiment of FIGS. 1A-1B and 3, the flexible body 20 of the heating device 10 is configured to be adjustably positioned around and in direct contact with the exterior surface of the transparent cylindrical bioreactor vessel 72 to completely surround the periphery of the sidewall of the bioreactor vessel 72 for efficient and uniform heat transfer. The flexible body 20 may be configured as a wrap, jacket, blanket, or other configuration adapted to substantially or completely conform to, surround, and insulate the periphery and exterior wall of the bioreactor 70. In one embodiment, a substantial portion, majority, or the entirety of the sidewall or surface of the bioreactor vessel 72 is surrounded by the heating device 10. The shape of the flexible body 20 is preferably compatible with the bioreactor vessel 72 and facilitates a secure attachment. For example, the flexible body 20 and heating device 10 may have a generally rectangular configuration adapted to conform to and surround the exterior wall of a cylindrical bioreactor, or may have a trapezoidal or asymmetric configuration to conform to a conical or other variable diameter bioreactor. In an embodiment, the flexible body 20 may have a prefabricated three-dimensional structure, such as a cylindrical, conical, or curved configuration, to facilitate attachment to the bioreactor vessel 72. In the embodiment shown in Figures 1A, 1B, and 3, the flexible body 20 may have multiple shapes or configurations, such as a flattened configuration to facilitate storage (Figure 1A), a cylindrical configuration to completely surround the circumference of the outer wall of the cylindrical bioreactor vessel 72 (Figure 3), other shapes and / or configurations to conform to the exterior surface of the bioreactor vessel 72, etc. The flexible body 20 may also include one or more cutouts 28 along its length to facilitate positioning the heating device 10 around a bioreactor power cord, connector, sampling port, or other components that protrude from the surface of the bioreactor vessel 72. The heating device 10 and flexible body 20 may be configured to fit different sizes of bioreactor vessels 72, including small laboratory benchtop bioreactors with volumes less than 1000 mL or in the range of 250 mL to 1000 mL.In other embodiments, the heating device 10 and flexible body 20 may be sized to fit 1 L, 2 L, 3 L or larger sized bioreactors.

[0051] As shown in FIGS. 1A-1B, the flexible body 20 may include one or more fasteners or fastener portions 26 for adjustably positioning and securing the flexible body 20 to the bioreactor 80. The fasteners 26 are preferably designed to allow the heating device 10 and the flexible body 20 to be releasably coupled to the reusable bioreactor 80. In one embodiment, the fasteners or fastener portions 26a, 26b may be located on or near opposing ends of the flexible body 20 (FIG. 1A). A user may wrap and secure the flexible body 20 about the bioreactor vessel 72 by overlapping and attaching a first fastener 26a to a second fastener 26b (FIG. 3). The fasteners 26 may be configured as hook and loop fasteners, reusable adhesives, hooks, clips, clamps, snaps, or other types of fasteners.

[0052] The flexible body 20 may include one or more transparent portions 30 that provide clear visualization of the bioreactor culture within the transparent bioreactor vessel 72 when enclosed within the heating device 10. Such direct visualization of the bioreactor culture allows for bioprocess analysis, evaluation, monitoring and cultivation of the bioreactor culture. In one embodiment, the flexible body 20 is entirely transparent, including the transparent fastener portion 26, allowing visualization through all surfaces of the heating device 10. In an alternative embodiment, the flexible body 20 has one or more opaque portions, such as the opaque fastener portion 26, as well as one or more transparent portions 30a, 30b, 30c positioned or arranged to provide visibility through most or a substantial portion of the heating device 10. Preferably, the transparent portion 30 is positioned and arranged such that when the heating apparatus 10 is attached to the bioreactor vessel 72, the bioreactor culture can be clearly viewed through one or more pairs of opposing outer walls, surfaces, or portions of the flexible body 20 adjacent to the opposing outer walls of the transparent bioreactor vessel 72 such that a user has a direct line of sight through the opposing outer walls of the transparent bioreactor vessel 72 and through the opposing outer walls of the heating apparatus 10 surrounding the bioreactor vessel 72. The unobstructed transmission of light and clear visualization of the bioreactor culture through the opposing transparent outer walls of the bioreactor vessel 72 and the heating apparatus 10 improves visual evaluation of the bioreactor culture and allows for analysis that may not be easily discerned otherwise. For example, accurate evaluation of turbidity, coloration, and / or hue to measure the progress and / or status of the bioreactor culture is preferably evaluated when there is a direct path / transmission of light through the bioreactor vessel 72 and the heating apparatus 10. In another embodiment, the transparent portion 30 is positioned to be visible through multiple adjacent and / or opposing exterior surfaces or faces of the flexible body 20. In another embodiment, the transparent portion 30 comprises at least 50% or at least 75% of the flexible body 20.In another embodiment, when the heating device 10 is attached to and substantially or completely surrounded by a sidewall of the transparent bioreactor vessel 72, at least 50% or at least 75% of the sidewall of the transparent bioreactor vessel 72 that is surrounded by the heating device 10 allows for direct visualization of the bioreactor culture.

[0053] In the embodiment shown in FIG. 1B, the flexible body 20 can have a multi-layer material structure including a first layer 22, 24 having one or more transparent portions 30 and a second layer 24 including a corresponding one or more transparent portions 30. The first and second layers can be configured as sheets made of a polymeric material, preferably a heat-resistant polymeric material such as silicone. In another embodiment, the layers 22, 24 can be made of a transparent metal. The transparent portions 30 of the first and second layers 22, 24 can likewise be made of a transparent polymeric material, preferably a heat-resistant polymeric material such as silicone, or a transparent metal. In one embodiment, the first and second layers 22, 24 are comprised of a transparent polymeric material that defines a substantial extent or the entirety of the flexible body 20 and allows visualization throughout the first and second layers 22, 24 that form the flexible body 20. In another embodiment, the flexible body 20 is further defined by one or more fastener portions 26 that can be attached to and adjacent the first and second layers 22, 24. Alternatively, the fasteners 26 may be constructed of the same or similar transparent polymeric material as the first and second layers 22, 24, allowing complete visibility throughout the entire flexible body 20. Alternatively, one or more of the fastener portions 26 may be opaque, but preferably form only a small portion of the flexible body 20.

[0054] The heating device 10 and flexible body 20 further include one or more heating elements 40. The heating elements 40 are disposed on, embedded in, attached to, coupled to, or otherwise operatively associated with the flexible body 20. The heating elements 40 are configured and adapted to transfer heat through the flexible body 20 to a bioreactor vessel 72 adjacent to or otherwise coupled to the heating device 10. Specifically, the heating elements 40 are configured and adapted to transfer heat to the bioreactor culture through a sidewall of the bioreactor vessel 72. In one embodiment, the heating elements 40 may be configured, arranged, and adapted to apply heat uniformly to the sidewall of the bioreactor vessel 72. The heating element 40 may be configured and adapted to transfer heat to different types of bioreactors 70, including, but not limited to, single-use bioreactors having a bioreactor vessel 72 made from a transparent plastic material, or multiple-use or continuous-use bioreactors having a bioreactor vessel 72 made from glass. The heating apparatus 10 may further be configured and programmed to provide different heating, e.g., different applied heating rates, different temperature thresholds and / or set points, different heating durations, different heating profiles, cycles or programs, etc., for each bioreactor 70 to provide customized, safe heating of the bioreactor vessel 72, its contents and the heating apparatus 10.

[0055] In one embodiment, the heating element 40 is disposed on, embedded in, attached to, coupled to, or otherwise operatively associated with any portion of the first and / or second layers 22, 24, including the transparent portion 30 and / or the mounting portion 26. In another embodiment, the heating element 40 may be disposed on, embedded in, attached to, coupled to, or otherwise operatively associated with a third layer having the same or similar structure and material composition and properties as the first and second layers 22, 24. In one embodiment, the heating element 40 and / or the third layer including the heating element 40 is preferably disposed between and insulated by the first and second layers 22, 24.

[0056] The heating element 40 may be configured as any type of element that allows for heat transfer and does not substantially impede transparency and visualization through the flexible body 20, specifically through one or more transparent portions 30. In the embodiment of Figs. 1A-1B, the heating element 40 is configured as an electrically conductive resistive wire that emits heat when an electric current is passed through the wire. In an embodiment, the wire may be prefabricated and positioned, disposed, embedded, bonded, glued, molded together, or otherwise bonded to a portion of the flexible body 20. In another embodiment, the wire is printed, etched, or otherwise formed on and attached to the flexible body 20. The wire may be configured as a thin or fine wire, even if densely positioned on or within a portion of the transparent portion 30, such that the view through such transparent area is substantially unobstructed and the bioreactor culture can be clearly viewed through the transparent portion 30. In an embodiment, the wire may be made of copper, aluminum, nickel, platinum, alloys thereof, transparent metals, or similar conductive materials. The wires may be preformed and bonded to the flexible body 20, or the conductive heat transfer circuit may be formed by cutting, etching, deposition, or other methods. The wires may have a circular cross section, for example, although square, triangular, or other cross sections are also contemplated. Preferably, one or more heating elements 40 are positioned in relation to the flexible body 20 to allow substantially uniform heating throughout the heat transfer area of ​​the flexible body 20. In an embodiment, the heat transfer area of ​​the flexible body 20 includes the transparent portion 30. In the embodiment shown in FIG. 1A, the heating elements 40 are densely positioned over the continuously arranged rows and columns and / or over the spirals throughout the heat transfer portion of the flexible body 20. The one or more heating elements 40 are densely positioned and span the entire heat transfer area of ​​the flexible body 20, including the transparent portion 30, while the heat transfer area of ​​the flexible body 20 and the transparent portion 30 remains completely or substantially transparent, as shown in FIG. 3.

[0057] The heating device 10 and the flexible body 20 further include one or more sensors 60. The sensor 60 is disposed or positioned on, embedded in, attached to, coupled to, or otherwise operably associated with the flexible body 20 to measure, sense, detect, and / or determine one or more parameters or conditions of the heating device 10 and / or the coupled bioreactor 70. The sensor 60 may be any type of sensor that facilitates operation of the heating device 10, heat transfer regulation, and / or bioprocessing. In an embodiment, the sensor 60 may be a temperature sensor, a capacitive sensor, a photoelectric sensor, an ultrasonic sensor, and / or other sensor. In an exemplary embodiment, the sensor 60 may be used to directly or indirectly determine the temperature of the flexible body 20 and / or the bioreactor culture, and may be configured as a thermocouple, a thermistor, or a resistance temperature detector. Multiple sensors 60 may be coupled to the flexible body 20 and / or distributed throughout the flexible body 20. Preferably, multiple integrated temperature sensors may be disposed throughout the flexible body 20. As shown in the exemplary embodiment of FIGS. 1A-1B, the heating element 40 and the temperature sensor 60 may be configured as a single integrated component or unit. For example, the heating element 40 may be a conductive resistive wire configured to transfer heat and determine the temperature of the flexible body 20 and / or the bioreactor culture based on a measured voltage and / or a determined change in resistance of the wire. In another embodiment, in addition to or as an alternative to a temperature sensor, the heating device 10 may include a sensor 60 that may detect material properties of the bioreactor vessel 72, the size and / or configuration of the bioreactor vessel 72, or potentially the cell concentration or density of the bioreactor culture.

[0058] In an alternative exemplary embodiment, as shown in Figures 5-6, the heating device 10 may be integrated with components of the bioreactor 70 and / or bioreactor vessel 72. In an embodiment, the heating device 10 may have a body integrally formed with, attached to, or coupled to the bioreactor 70 and / or bioreactor vessel 72. In an embodiment, the body of the heating device 10 may be configured as a flexible body 20, such as a silicone film or layered construction, constructed from a biocompatible material and coupled to, attached to, or otherwise operably associated with one or more heating elements 40 and one or more sensors 60. For example, the heating elements 40 and sensors 60 may be embedded in or otherwise insulated by the flexible body 20. In another embodiment, the heating element 40 and the sensor 60 are not supported by a carrier or body, but instead are integrally formed with, attached to, or coupled to the bioreactor 70 and / or bioreactor vessel 72. In the embodiment shown in FIG. 5, the heating device 10 and the heating element 40 and the sensor 60 are attached, attached, integrated, or otherwise operably associated with one or more portions of the impeller 72, including, but not limited to, the impeller shaft and / or impeller blades, the spin filter 75, the dip tube 76, or the bioreactor culture sensor 78. In the embodiment shown in FIG. 6, the heating device 10 and the heating element 40 and the sensor 60 may be attached, attached, integrated, or otherwise operably associated with a transparent sidewall of the bioreactor vessel 72 (FIG. 6). Such an arrangement allows a user to clearly view the contents of the bioreactor 72 while the heating device 10 is operating. In exemplary embodiments, these bioreactor components may be substantially or completely transparent and may be made from transparent materials such as glass or clear plastic, and the heating device 10 and heating device body may be substantially or completely transparent.This provides additional visibility of the contents within the bioreactor vessel, allowing a user to view the bioreactor culture through one or more bioreactor components and the heating device 10.

[0059] The connector 62 of the heating device 10 connects the heating element 40 and / or the sensor 60 to a controller 50 and / or a power source for operating the heating device 10. The heating element 40 and the sensor 60 are connected to and / or otherwise operably associated with the controller 50 for regulating heat transfer and / or temperature of the heating device 10 and / or the contents of the bioreactor vessel 72. In an embodiment, the controller 50 may be part of, integral with, and / or operably associated with the heating device 10. For example, the controller 50 may be an integral component of the connector 62, which also functions to connect the heating element 40 and / or the sensor 60 with a power source. In the exemplary embodiment shown in FIG. 4, the heating element 40 and the sensor 60 are connected via the connector 62 to the controller 50 configured as a biocontroller that is part of the bioreactor system 80.

[0060] The controller 50 may be used to monitor the temperature and / or temperature change of the heating device 10 and / or the contents of the bioreactor vessel 72, and the heat transfer therebetween. In an exemplary embodiment, the controller 50 and heating device 10 are preferably configured, programmed and adapted to provide customized heat transfer specific to and targeted to the unique requirements and / or limitations of different types of bioreactors 70, different bioreactor cultures and different bioprocessing applications. For example, the desired and allowed heating activity, heat transfer behavior or heat transfer function for a single-use bioreactor 70 and corresponding single-use clear plastic bioreactor vessel 72, which requires a lower heat transfer rate, has a lower maximum temperature threshold / lower melting point and has a shorter heating allowable time, may be different than a multiple-use or continuous-use bioreactor 70 including a glass bioreactor vessel 72, which requires a higher heat transfer rate, a higher maximum temperature threshold / higher melting point and a longer heating allowable time. Thus, customized heating and heat transfer using the heating device 10 allows for efficient and safe operation of the heating device 10 as well as effective heating to the attached bioreactor 70.In one embodiment, the heating device 10 and controller 50 are configured and programmed to adjust the heating and / or temperature regulation based on a variety of different factors, including, but not limited to, the type of bioreactor 70 coupled to the heating device 10, the configuration and / or material properties of the bioreactor vessel 72 coupled to the heating device 10, the material properties of the heating device 10 and / or the flexible body 20, the intended bioprocessing operation of the bioreactor 70, the intended yield or bioprocessing result, the desired temperature or temperature change of the bioreactor culture, the desired temperature or temperature change of the heating device 10, the detected temperature or temperature change of the heating device 10 or the bioreactor culture, the detected heat introduced from the bioreactor system components and actuators (such as the agitator motor of the impeller 74), the detected turbidity or clarity of the bioreactor culture, the detected color or hue of the bioreactor culture, the detected cell concentration or density of the bioreactor culture, or user input / user specified parameters. In any situation, the controller 50 and heating apparatus 10 can take the above factors into account in determining the heating activity, heat transfer action or heat transfer function, etc., such as the applied heating rate, heating temperature, heating time, heating cycle profile program, initial, final, and / or intermediate temperature set points, etc. to provide customized, efficient, high yield and safe heating for different bioreactors 70, different bioreactor vessels 72, different bioreactor cultures, and / or different bioprocess applications.

[0061] One or more sensors 60 operatively associated with the controller 50 provide a feedback loop that facilitates continuous real-time monitoring and evaluation of the conditions of the bioreactor culture and the heating apparatus 10, or adjusting the heat transfer function of the heating apparatus 10 based on data from multiple sensors 60, allowing for customized and efficient bioprocessing.

[0062] In an exemplary embodiment, the heating device 10 and controller 50 are pre-programmed to require minimal setup and / or oversight by the user when using the heating device. The heating device 10, controller 50 and / or bioreactor system 80 may be configured as smart devices and systems, such that the heating device 10, upon connection with the controller 50 and / or coupling with the bioreactor 70, may automatically detect and determine the appropriate heating activity or function based on the following information received from the controller 50: pre-programmed heat transfer functions and settings for different applications and bioreactor devices; environmental or physical parameters or conditions detected by sensors 60 associated with the bioreactor 70, bioreactor vessel 72 and / or heating device 10; and / or information input / instructed by the user. In one embodiment, the heating device 10 automatically detects and performs an initial heating function specifically adapted for the corresponding bioreactor 70, bioreactor vessel 72, bioreactor culture and / or intended bioprocessing application upon coupling the heating device 10 to the bioreactor vessel 72, bioreactor 70 and / or controller 50. Alternatively, the heating device 10 limits heating functions that are detrimental and / or adverse to the heating device 10, bioreactor 70, bioreactor vessel 72 and / or bioreactor culture. For example, the heating device 10 and controller 50 may be pre-programmed with heat transfer functions and operations adapted for different types of bioreactors, different types of bioreactor vessels, different bioreactor cultures and / or intended bioprocessing applications, etc. The sensor 60 may function to determine which of the pre-programmed options is best suited for the intended application upon coupling the heating device 10 to the bioreactor vessel 72.Similarly, the pre-programmed heating operations and heat transfer functions may be further sorted and filtered upon receiving user input from the controller 50 regarding the intended bioprocessing application, the type of bioreactor culture being cultivated, and other information, to determine a recommended course of action for heating using the heating device 10. Bioreactor Systems

[0063] The heating device 10 of the present disclosure may be part of a novel bioreactor system 80. In one embodiment, the bioreactor system 80 may include any of the previously described embodiments of the heating device 10, a controller 50, and one or more bioreactors 70. In one embodiment, the bioreactor system 80 may include two or more different types of bioreactors 70, such as a single-use bioreactor, a multiple-use bioreactor, or a continuous-use bioreactor. Additionally, the bioreactor system 80 may include two bioreactor vessels 72 made from different materials, such as glass and clear plastic. In one embodiment, the bioreactor vessels 72 may be clear. In another embodiment, the bioreactor vessels 72 may be opaque but may change color based on the pH value of the bioreactor culture contained therein.

[0064] 4, the bioreactor system 80 may include a heating device 10, a controller 50, one or more bioreactors 70, and a display and / or user interface 82. Optionally, the bioreactor system 80 may further include a base heater 84, which may be connected to the controller 50. The controller 50 can then centrally regulate the temperature of the bioreactor culture in one or more bioreactor vessels 72 by controlling heat transfer through both the heating device 10 and the base heater 82.

[0065] The heating device 10 and bioreactor system 80 provide several benefits and advantages, namely, enhanced monitoring capabilities and customized, adjustable, efficient, effective and safe temperature regulation. In particular, the heating device 10 is reusable and adapted for use in connection with a variety of different bioreactors 70, bioreactor vessels 72, bioreactor systems 80 and bioreactor cultures, thereby eliminating the need for multiple customized heating devices for specific bioreactors, bioreactor systems or intended bioprocessing applications. The heating device 10 is further configured to provide heat transfer capabilities specifically tailored to the associated bioreactor. The sensor 60 further provides a continuous feedback loop of the conditions and parameters of the heating device 10 and / or bioreactor culture, facilitating continuous real-time monitoring, evaluation and adjustment of bioprocessing conditions and parameters, including but not limited to adjustment of heat transfer from the heating device 10. The transparent portion 30 of the heating device 10 allows for immediate and clear visualization of the bioreactor culture, further aiding in monitoring, evaluation and adjustment of bioprocessing conditions and parameters as needed. Method for heating a bioreactor

[0066] The present disclosure is further directed to a method for heating a bioreactor 70 using the heating device 10. In an exemplary embodiment shown in FIG. 7, the method includes the steps of: heating a bioreactor vessel 72 operatively associated with the heating device 10 using any of the heating devices 10 described above; determining a condition, parameter or change thereof of the bioreactor culture and / or the heating device 10; and adjusting heat transfer using the heating device 10 based on the determined condition, parameter or change thereof of the bioreactor culture and / or the heating device 10. The heating device 10 may be operatively associated with the bioreactor 70 using any of the methods of the present disclosure, such as by removably and reusably attaching the heating device 10 to surround an exterior wall of the bioreactor vessel 72. In an embodiment, the method further includes removing the heating device 10 from a first bioreactor vessel 72, such as a single-use plastic bioreactor vessel, and reusably attaching the heating device 10 to a different second bioreactor vessel, such as a multiple-use or continuous-use glass bioreactor vessel.

[0067] In another embodiment, the heating device 10 may be integrally formed with components of a bioreactor 70, such as the transparent sidewall of the bioreactor vessel 72, the impeller 74, the impeller shaft, the impeller blades, the spin filter 75, the dip tube 76, or the bioreactor sensor 78 (FIGS. 5-6). The heating device 10 and the integrally coupled bioreactor components may be reusably coupled by being removably coupled to a first bioreactor 70 or bioreactor vessel 72, such as a single-use clear plastic bioreactor vessel, and then removably coupled to another second bioreactor 70 or bioreactor vessel 72, such as a multiple-use or continuous-use glass bioreactor vessel. For example, the integrated heating device 10 and bioreactor components may be inserted through and / or removably coupled to the bioreactor lid 71 of a first single-use clear plastic bioreactor vessel 72 and then removed and reusably inserted and coupled through a second lid 71 of a second multi-use or continuous-use glass bioreactor vessel 72.

[0068] The heating device 10 may be used to perform a different heating function for a first bioreactor 70 and / or bioreactor vessel 72 than the heating function performed for a second bioreactor 70 and / or bioreactor vessel 72. The heating function performed may be customized or specifically adapted for the correspondingly attached bioreactor 70 and / or bioreactor vessel 72. In one embodiment, the method includes adjusting the applied heat from the heating device 10 and / or the temperature of the bioreactor culture and / or the heating device 10 based on various detected conditions, parameters or changes therein of the bioreactor culture contained within the heating device 10 and / or bioreactor 72, as described above.

[0069] In one embodiment, the method further includes the step of directly visualizing the bioreactor culture through the transparent portion 30 of the heating device 10. For example, if the heating device 10 is configured as a heating wrap or jacket that is placed around and surrounds the transparent bioreactor vessel 72, the user can directly view the bioreactor culture through the transparent sidewalls of the bioreactor vessel 72 and the transparent sidewalls of the heating device 10 that surround the periphery of the bioreactor vessel 72. In another embodiment, the bioreactor 70 and / or components of the bioreactor vessel 72, such as the impeller 72 or spin filter 75, may be transparent and integrated with a transparent heating device 10 integrated therewith. The user can then view the bioreactor culture through the transparent components of the bioreactor 70 and bioreactor vessel 72 and the transparent heating device 10.

[0070] As shown in FIG. 8, another exemplary method may include the steps of: operatively associating a heating device 10 having a transparent body with a first bioreactor vessel 72; using the heating device 10 to provide a first heating specific or adapted to the first bioreactor vessel 72 or the second bioreactor culture; operatively associating the heating device 10 with a second bioreactor vessel 72; using the heating device 10 to provide a second heating specific or adapted to the second bioreactor vessel 72 or the second bioreactor culture, where the first heating and the second heating are different; and directly visualizing the contents of the first and second bioreactor vessels 72 through the transparent body of the heating device 10 when the heating device 10 is operatively associated with the first and second transparent bioreactor vessels 72.

[0071] The above method is particularly advantageous for culturing and promoting the growth of bioreactor cultures that require customized temperature regulation. Exemplary applications of the method may include performing bioprocess experiments where the bioprocess experiments are particularly sensitive to biopharmaceutical bioprocess and temperature conditions, require substantial temperature customization and regulation, where the ideal temperature conditions are unknown / yet to be evaluated / determined, and where visual indicators are important in monitoring and controlling the bioprocess.

[0072] Certain methods may be described with steps presented in a particular order. However, as will be understood by one of ordinary skill in the art, in many cases these steps may be performed in any order. Thus, the methods of the present disclosure are not limited to the particular order of steps described herein.

[0073] Although specific embodiments have been shown and described, they are not intended to limit the scope of the claims of this application. It will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the claims. The claims are intended to cover alternatives, modifications, and equivalent embodiments.

[0074] The foregoing disclosure has been presented for purposes of illustration and description only and is not to be construed as limiting the scope of the claims in any manner. [Explanation of symbols]

[0075] 10 Heating device 20 Flexible body of heating device 22 First layer of flexible body 24 Second layer of flexible body 26 Fasteners, fastener parts of flexible bodies 28 Flexible body cutout 30 Transparent part of flexible body 40 Heating Element 50 Controller 60 Temperature Sensor 62 Connector 70 Bioreactor 71 Bioreactor Lid 72 Bioreactor vessel 74 Bioreactor Agitator 75 Bioreactor Spin Filter 76 Bioreactor Dip Tube 78 Bioreactor Sensor 80 Bioreactor System

Claims

1. A heating device (10) for a bioreactor having a transparent bioreactor vessel (72) containing a bioreactor culture, comprising: a transparent flexible body (20); a heating element (40) coupled to said flexible body (20); a temperature sensor (60) coupled to the flexible body (20); Equipped with The flexible body (20) has a transparent portion (30), Further, the flexible body (20) is removably coupled to a sidewall of the transparent bioreactor vessel (72) to define a perimeter of the transparent bioreactor vessel (72); the transparent portion (30) of the flexible body (20) surrounds at least a major portion of the periphery of the transparent bioreactor vessel (72); the heating element (40) transfers heat to the sidewall of the transparent bioreactor vessel (72) to heat the bioreactor culture; the heating element (40) comprises a resistive wire disposed across the transparent portion (30) of the flexible body (20); the heating element (40) is configured to provide unobstructed visibility through the transparent portion (30) of the flexible body (20); The heating element (40) is connectable to a controller (50) for regulating heat transfer; 10. A heating device according to claim 9, wherein the temperature sensor (60) is connectable to the controller (50) to provide feedback for regulating the transfer of heat to the bioreactor culture.

2. A heating device as described in claim 1, characterized in that the heating element is removably connected to the side wall of the transparent bioreactor vessel (72) so that the transparent portion of the flexible body (20) surrounds the transparent bioreactor vessel (72).

3. 3. The heating device according to claim 1, wherein the temperature sensor (60) and the heating element (40) are configured as integral components of the heating device (10).

4. 2. The heating device of claim 1, wherein the flexible body (20) is configured such that when placed adjacent to the transparent bioreactor vessel (72) around opposing outer walls of the transparent bioreactor vessel (72), visibility of the bioreactor culture through the outer walls is not obstructed.

5. the heating device (10) is reusably and removably coupled to the first bioreactor and provides first heating adapted to the first bioreactor; the heating device (10) is reusably and removably coupled to a second bioreactor and provides a second heating adapted to the second bioreactor; 2. The heating device according to claim 1, wherein the first heating and the second heating are different.

6. 6. The heating device of claim 5, wherein the first heating and the second heating are any of heating to a predetermined temperature or temperature range, transferring heat at a predetermined temperature, transferring heat at a predetermined heating rate, accelerating or limiting the application of heat based on a temperature threshold, accelerating or limiting the application of heat based on a temperature change, heating for a predetermined time, or applying heat according to a predetermined program.

7. 6. The heating device of claim 5, wherein the first heating and the second heating vary depending on and are dependent on any of the following: a type of bioreactor vessel (72) connectable to the heating device (10), a configuration and / or material properties of the bioreactor vessel (72) connectable to the heating device (10), an intended operation of the bioreactor vessel (72) connectable to the heating device (10), or a desired temperature, temperature range, or temperature change of a bioreactor culture in the bioreactor vessel (72) connected to the heating device (10).

8. the first heating and the second heating transfer heat at a predetermined heating rate; the first bioreactor is a single-use bioreactor; the second bioreactor is a multi-use bioreactor; the heating device heats the first bioreactor vessel at a predetermined first heating rate; 6. The heating device of claim 5, wherein the heating device heats the second bioreactor vessel at a second predetermined heating rate that is faster than the first heating rate.

9. The flexible body (20) is configured as a heating jacket; The flexible body (20) a first flexible layer (22) having a first transparent portion (30) that does not obstruct visibility through the first flexible layer (22); a second flexible layer (24) having a second transparent portion (30) that does not obstruct visibility through the second flexible layer (24); Equipped with the heating element (40) is disposed between the first flexible layer (22) and the second flexible layer (24); 2. The heating device of claim 1, wherein the bioreactor culture is visible through the first and second transparent portions of the flexible body when the heating device is coupled to the transparent bioreactor vessel.

10. 2. The heating device of claim 1, wherein the heating elements (40) are densely arranged in successively arranged rows and columns and / or in spirals throughout the heat transfer portion of the flexible body (20).

11. A heating device (10) according to claim 1; a controller (50) for monitoring and / or regulating the heat transfer; Equipped with The bioreactor system is characterized in that the controller (50) is connected to the heating element (40) and the temperature sensor (60).

12. a single-use bioreactor comprising a plastic bioreactor vessel; a multi-use bioreactor comprising a glass bioreactor vessel; Equipped with the heating device (10) is removably coupled to the plastic bioreactor vessel and the glass bioreactor vessel and is in operative communication with the plastic bioreactor vessel and the glass bioreactor vessel; The heating device (10) provides a first heat to the plastic bioreactor vessel and a second heat to the glass bioreactor vessel; 12. The bioreactor system of claim 11, wherein the first heating and the second heating are different.

13. 12. The bioreactor system of claim 11, further comprising a user interface (82) connected to the controller (50) for a user to adjust the heating of the heating device (10).

14. an auxiliary heater (84) connected to the controller (50) and coupled to the transparent bioreactor vessel (72) for transferring heat to the transparent bioreactor vessel (72); 12. The bioreactor system of claim 11, wherein the controller (50) regulates heat transfer through the heating device (10) and the auxiliary heater (84).

15. a first bioreactor (70) for culturing tissue; the first bioreactor (70) comprises a first transparent bioreactor vessel (72) containing a first bioreactor culture; the heating device (10) is connected to the sidewall of the first transparent bioreactor vessel (72); the heating device (10) is configured to transfer heat to the first bioreactor culture and to provide visibility of the first bioreactor culture; the controller (50) is connected to the heating device (10) to regulate the temperature of the first bioreactor culture and the heat applied by the heating device (10); the heating device (10) provides first heating based on one or more parameters for the first bioreactor and second heating based on one or more parameters for the second bioreactor; 12. The bioreactor system of claim 11, wherein the first heating and the second heating are different.

16. further comprising an auxiliary heater (84); the auxiliary heater (84) is coupled to the first transparent bioreactor vessel (72) and transfers heat to the first transparent bioreactor vessel (72); 16. The bioreactor system of claim 15, wherein the controller (50) is connected to the auxiliary heater (84) and adjusts the heat applied by the heating device (10) and the auxiliary heater (84) to regulate the temperature of the first bioreactor culture.

17. further comprising a second bioreactor; the first bioreactor is a single-use bioreactor, and the first transparent bioreactor vessel is a plastic transparent bioreactor vessel; the second bioreactor is a multi-use bioreactor comprising a second transparent bioreactor vessel, the second transparent bioreactor vessel being a glass transparent bioreactor vessel; 16. The bioreactor system of claim 15, wherein the heating device (10) is removably coupled to the first and second transparent bioreactor vessels and connected to the first and second transparent bioreactor vessels.

18. a flexible body (20) with one or more transparent portions; A heating element; a temperature sensor connected to the controller; Equipped with the transparent portion allows the first bioreactor culture to be viewed when the heating device is coupled to the bioreactor; the heating element is configured such that visibility of the first bioreactor culture through the transparent portion of the flexible body is not obstructed when the heating device (10) is coupled to the first bioreactor; 16. The bioreactor system of claim 15, wherein the temperature sensor detects the temperature of the first bioreactor culture.

19. the heating device is integrally formed with, coupled to, attached to, or connected to a component of the bioreactor; 16. The bioreactor system of claim 15, wherein the bioreactor components are a transparent bioreactor vessel wall, an impeller of the bioreactor, an impeller shaft of the bioreactor, a dip tube of the bioreactor, and / or a spin filter of the bioreactor.

20. 1. A method for regulating the temperature of a bioreactor, comprising: connecting a heating device (10) according to claim 1 to a bioreactor vessel (72); heating the bioreactor vessel (72) or a bioreactor culture contained within the bioreactor vessel (72) using the heating device (10); A method comprising:

21. using said heating device (10) to detect a condition, parameter or change in said parameter of said bioreactor culture and / or said heating device (10); adjusting the temperature of the bioreactor culture based on the detected conditions, parameters or changes in said parameters of the bioreactor culture and / or the heating device (10); 21. The method of claim 20, comprising:

22. connecting a heating device (10) having a transparent body (20) to a first bioreactor vessel; providing a first heating using the heating device (10) adapted to the first bioreactor vessel or a first bioreactor culture contained in the first bioreactor vessel; connecting said heating device (10) to a second bioreactor vessel; providing a second heating using the heating device (10) adapted to the second bioreactor vessel or a second bioreactor culture contained in the second bioreactor vessel; directly visualizing the first bioreactor culture through the transparent body (20) when the heating device (10) is connected to the first bioreactor vessel, and directly visualizing the second bioreactor culture through the transparent body (20) when the heating device (10) is operatively connected to the second bioreactor vessel; Including, 21. The method of claim 20, wherein the first heating and the second heating are different.

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