Cooling device for bioreactor
By using a combination of cooling gel, packaging bags and fixings on small-scale bioreactors, the problems of low cooling efficiency and poor safety of small-scale bioreactors are solved, and an efficient and safe cooling effect is achieved.
Patent Information
- Application Number
- CN202422726118.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-08
- Publication Date
- 2025-09-09
- Estimated Expiration
- 2034-11-08
AI Technical Summary
Existing small-scale bioreactors lack suitable cooling devices, resulting in long natural cooling time, safety risks of alcohol cooling, high cost and frostbite risk of dry ice cooling, and large and inconvenient refrigeration equipment.
A combination of cooling gel, packaging bags and fixings is used to achieve rapid cooling by pre-cooling the cooling gel and then fixing it on the bioreactor. The cooling gel is made of elastomeric polymer and has good heat absorption and flexibility.
It provides a low-cost, easy-to-use and efficient cooling solution for small-scale bioreactors, avoiding safety hazards and waste of resources, and meeting the cooling needs of different reactors.
Smart Images
Figure CN223316675U_ABST
Abstract
Description
Technical Field
[0001] The utility model relates to the technical field of cell culture, in particular to a cooling device for a bioreactor. Background Art
[0002] The production of therapeutic proteins such as monoclonal antibodies through mammalian cell culture is currently a common method. Culture temperature is an important parameter that affects mammalian cell growth and protein production. In the early stage of cell culture, in order to allow the cells to reach a higher cell density, the temperature in the early stage of culture is generally set to a higher level, such as 37.0℃ or 36.5℃; after the cells reach a certain density, they are generally cooled appropriately, such as to 33.0℃ or 31.0℃, so that the cells enter the protein production cycle. The specific culture temperature and whether to cool down will vary depending on product requirements, but the temperature of mammalian cell culture is generally above 30.0℃. For some more sensitive protein products, such as some proteins that are prone to aggregation or reduction during harvesting, the operation of cooling first and then harvesting can be adopted at the end of mammalian cell culture. Usually, the temperature of the culture medium in the bioreactor needs to be lowered to room temperature (such as 25.0℃) or lower temperature (such as 15.0℃) to maintain the stability of the product.
[0003] The reactors used in large-scale antibody production (typically with a volume of 50 L or more) are equipped with a temperature control unit (TCU), a specialized cooling device that utilizes condensed water to cool the reactor. However, small-scale reactors, typically 1 L, 2 L, 3 L, 5 L, 7 L, and 15 L, currently lack suitable cooling devices. Therefore, cooling methods commonly used include natural cooling, spraying with alcohol, dry ice, or using larger equipment to generate cold water. However, all of the above cooling methods have disadvantages such as safety and waste of resources: 1) Natural cooling takes a long time to wait, and it is not easy to reduce the temperature to below the ambient temperature; 2) Alcohol cooling: Spraying too much alcohol around the reactor poses a risk of flammability and explosion, and the alcohol cooling effect is poor, requiring continuous spraying around the tank, resulting in alcohol waste; 3) Dry ice cooling: Dry ice is solid carbon dioxide, which is expensive. Excessive use can easily cause oxygen deficiency safety risks in the surrounding area, and the dry ice temperature is low, making it easy to get frostbite during use; 4) Refrigeration equipment: It is relatively expensive, large in size, and takes up more laboratory space. A special water storage device is required to produce cold water during cooling, which is not convenient to operate. Therefore, in order to reduce the operation of the experimenter, improve the cooling efficiency, and reduce safety hazards, a small-scale bioreactor device with low price, easy to use, and high cooling efficiency has been developed. Utility Model Content
[0004] The purpose of the utility model is to provide a cooling device for a bioreactor, which is cheap, easy to use, and has high cooling efficiency, and is very suitable for cooling small-scale bioreactors.
[0005] To achieve this purpose, the present invention adopts the following technical solutions:
[0006] The utility model discloses a cooling device for a bioreactor, comprising: cooling gel; a packaging bag, the packaging bag is coated on the outside of the cooling gel; and a fixing piece, the fixing piece is arranged on the packaging bag and is used to fix the packaging bag to the bioreactor.
[0007] In some embodiments, the fixing element includes a Velcro provided on the packaging bag.
[0008] In some specific embodiments, the packaging bag is rectangular, and the fixing piece includes a rounded portion and a bristle portion, both of which extend along the width direction of the packaging bag and are respectively arranged at both ends of the packaging bag along its length direction.
[0009] In some specific embodiments, the fixing element is adhered to the surface of the packaging bag.
[0010] In some embodiments, the packaging bag is made of a compression-resistant nylon composite polyethylene material.
[0011] In some embodiments, the cooling gel comprises GEL biogel.
[0012] In some embodiments, the fixing element includes an adhesive layer disposed on the surface of the packaging bag.
[0013] In some embodiments, the fixing member includes a fixing ring and a binding belt, and the fixing ring and the binding belt are respectively provided at two ends of the packaging bag along the length direction thereof.
[0014] In some embodiments, there are multiple packaging bags, which are stacked and two adjacent packaging bags are connected by a connector.
[0015] In some specific embodiments, the connecting member includes Velcro.
[0016] The cooling device for bioreactors of the present invention has the following beneficial effects: the cooling gel is an elastomeric polymer with good flexibility, sliding resistance, and high-intensity heat absorption, which can effectively absorb heat. In actual use, it is only necessary to place the cooling device in a refrigerator for a specified period of time for pre-cooling, and then fix the entire cooling device to the bioreactor using the fixings provided on the packaging bag to effectively meet the cooling needs of various bioreactors at the small-scale stage. The cooling device of this embodiment only includes three parts: the cooling gel, the packaging bag, and the fixings. It has a simple structure, is easy to use, has a low manufacturing cost, and has a good cooling effect. It is very suitable for cooling small-scale bioreactors.
[0017] Additional aspects and advantages of the present invention will be given in part in the following description and will become apparent from the following description or learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] Figure 1 This is a schematic structural diagram of a cooling device for a bioreactor according to a first embodiment of the present invention;
[0019] Figure 2 This is a schematic structural diagram of a cooling device for a bioreactor according to a second embodiment of the present invention;
[0020] Figure 3 This is a schematic structural diagram of a cooling device for a bioreactor according to a third embodiment of the present invention;
[0021] Figure 4 It is a structural schematic diagram of a cooling device for a bioreactor according to a fourth embodiment of the present utility model.
[0022] Reference numerals:
[0023] 100. Cooling gel; 200. Packaging bag; 300. Fixing piece; 310. Round hair portion; 320. Bristle portion; 330. Fixing ring; 340. Strap; 400. Connecting piece. DETAILED DESCRIPTION
[0024] The present invention will be further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are intended only to illustrate the present invention and are not intended to limit the present invention. It should also be noted that, for ease of description, the accompanying drawings only illustrate portions relevant to the present invention, not all of its components.
[0025] In the description of this utility model, unless otherwise specified or limited, the terms "connected," "connect," and "fixed" should be understood in a broad sense. For example, they can refer to fixed connection, detachable connection, or integration; mechanical connection or electrical connection; direct connection or indirect connection through an intermediate medium; internal communication between two components or interaction between two components. Those skilled in the art will understand the specific meanings of the above terms in this utility model based on the specific circumstances.
[0026] In the description of this embodiment, the terms "upper," "lower," "right," and other orientations or positional relationships are based on the orientations or positional relationships shown in the accompanying drawings and are intended solely for ease of description and simplified operation. They do not indicate or imply that the devices or components referred to must have a specific orientation, be constructed, or operate in a specific orientation. Therefore, they should not be construed as limitations on the present invention. Furthermore, the terms "first" and "second" are used solely for descriptive purposes and have no special meaning.
[0027] Example 1:
[0028] The utility model discloses a cooling device for a bioreactor (hereinafter referred to as the cooling device for convenience of description), Figure 1 As shown, the cooling device includes a cooling gel 100, a packaging bag 200, and a fixing member 300. The packaging bag 200 is coated on the outside of the cooling gel 100. The fixing member 300 is disposed on the packaging bag 200 and is used to secure the packaging bag 200 to the bioreactor. It will be understood that the cooling gel 100 is an elastomeric polymer with excellent flexibility, slip resistance, and high heat absorption, which can effectively absorb heat. In actual use, the cooling device only needs to be placed in a refrigerator for a specified period of time for pre-cooling. Then, the fixing member 300 disposed on the packaging bag 200 can be used to secure the entire cooling device to the bioreactor to effectively meet the cooling needs of various small-scale bioreactors. The cooling device of this embodiment only includes three parts: the cooling gel 100, the packaging bag 200, and the fixing member 300. It has a simple structure, is easy to use, has a low manufacturing cost, and has a good cooling effect, making it very suitable for cooling small-scale bioreactors.
[0029] It should be noted that in actual use, the cooling device of the present invention is first pre-cooled in a -21°C refrigerator overnight (for at least 8 hours) and then directly wrapped around the bioreactor. Of course, the specific pre-cooling temperature and pre-cooling time can be modified according to the cooling requirements. If a lower cooling temperature or faster cooling effect is required, it can also be achieved by alternating the use of two or more cooling devices at the same time, which is convenient and quick to operate.
[0030] refer to Figure 1As shown, the fixing member 300 comprises a Velcro strip disposed on the packaging bag 200. It will be appreciated that the Velcro strip allows the cooling device to be wrapped around the bioreactor and secured thereto during use, without the need for straps or adhesive. This provides a very simple and convenient fixing method.
[0031] Optionally, the packaging bag 200 is rectangular, and the fixing member 300 includes a bristle portion 310 and a bristle portion 320. Both the bristle portion 310 and the bristle portion 320 extend along the width of the packaging bag 200 and are respectively located at both ends of the packaging bag 200 along its length. It is understood that a bioreactor is typically a barrel-shaped structure. The packaging bag 200 of this embodiment is rectangular. During actual use, the packaging bag 200 is attached to the outer wall of the barrel-shaped structure, and after a complete circle, the bristle portion 310 and the bristle portion 320 are attached. This not only increases the contact area between the packaging bag 200 and the bioreactor, thereby improving the cooling effect of the cooling device on the bioreactor, but also facilitates the installation and removal of the cooling device.
[0032] Optionally, the fixing member 300 is bonded to the surface of the packaging bag 200. It is understood that in actual operation, the fixing member 300 can be bonded to a reasonable position on the surface of the packaging bag 200 according to the shape of the bioreactor. On the one hand, this allows the packaging bag 200 to be securely wrapped around bioreactors of different shapes. On the other hand, it prevents the fixing member 300 from falling off the surface of the packaging bag 200, ensuring the stability of the connection between the fixing member 300 and the packaging bag 200.
[0033] Optionally, the packaging bag 200 is made of a pressure-resistant nylon composite polyethylene material. As will be appreciated, the pressure-resistant nylon composite polyethylene material has high strength, is lightweight, and has excellent heat transfer performance. Using the pressure-resistant nylon composite polyethylene material as the packaging bag 200 prevents leakage of the cooling gel 100 due to damage to the packaging bag 200, thereby improving the reliability and service life of the cooling device. Furthermore, it ensures rapid heat exchange between the bioreactor and the cooling gel 100, thereby improving the cooling performance of the cooling device.
[0034] Optionally, the packaging bag 200 is sealed by melting. This ensures that the interior of the packaging bag 200 is sealed, preventing external contaminants from entering the packaging bag 200 and contaminating the cooling gel 100. It also prevents leakage of the cooling gel 100. It should be noted that the length and width of the packaging bag 200 can be modified based on the size of the bioreactor, allowing the cooling device of this embodiment to meet the cooling needs of a wider range of bioreactor models.
[0035] Of course, in other embodiments of the present invention, the packaging bag 200 may also be made of other suitable materials according to actual needs and is not limited to the above description.
[0036] Optionally, the cooling gel 100 includes a GEL biogel. GEL biogel is generally a soft gel material made of a polymer (such as silicone, polyester, polyurethane, etc.). GEL biogel is an elastomeric polymer with an ultra-soft softness rating, good flexibility, sliding resistance, and high-intensity heat absorption. It contains up to 80% water molecules, can effectively absorb heat, and is 100% safe and non-toxic. In addition, the GEL biogel will not freeze at -25.0°C, so it can change its shape arbitrarily even if it is pre-cooled at -21.0°C for more than 8 hours, which can well meet the cooling needs of various bioreactors in the small-scale stage. Of course, in other embodiments of the present invention, the cooling gel 100 can also select other suitable materials according to actual needs, and is not limited to the above description.
[0037] Example 2:
[0038] refer to Figure 2 As shown, the cooling device of this embodiment is substantially the same as that of the first embodiment, except that the fixing member 300 of the cooling device of this embodiment is not a Velcro strip, but an adhesive layer provided on the surface of the packaging bag 200. Adhesive bonding the cooling device to the bioreactor via the adhesive layer can enhance the firmness of the cooling device and the bioreactor container, thereby improving the cooling effect on the bioreactor.
[0039] Example 3:
[0040] refer to Figure 3 As shown, the cooling device of this embodiment is substantially the same as that of the first embodiment, except that the fixing member 300 of the cooling device of this embodiment is not a Velcro strip, but instead includes a fixing ring 330 and a binding strap 340. The fixing ring 330 and the binding strap 340 are respectively provided at both ends of the packaging bag 200 along its length. It can be understood that the fixing ring 330 and the binding strap 340 can enhance the secure connection between the cooling device and the bioreactor container, thereby improving the cooling effect on the bioreactor.
[0041] Example 4:
[0042] refer to Figure 4 As shown, the cooling device of this embodiment comprises multiple packaging bags 200, which are stacked and connected by connectors 400, which include Velcro. This embodiment is suitable for bioreactors with relatively high cooling requirements. Connecting multiple packaging bags 200 together with Velcro can improve the cooling effect of the bioreactor.
[0043] Taking the cooling device in Example 1 as an example, a 3L bioreactor was used to evaluate the cooling effect of the cooling device and dry ice under the conditions of commonly used upstream mammalian cell culture temperatures (33.0°C and 31.0°C) and harvest volume (1.8L).
[0044] The specific method is:
[0045] 1) The day before the experiment, the cooling device of this embodiment was placed in a -21°C refrigerator for pre-cooling for no less than 8 hours;
[0046] 2) Raise the temperature of 1.8 L of cell culture medium in two 3 L bioreactors to 33.0°C or 31.0°C;
[0047] 3) Remove the heating blanket from the bioreactor and wrap the periphery of the bioreactor tank with the cooling device of this embodiment that has been pre-cooled overnight and an appropriate amount of dry ice;
[0048] 4) Record the cooling time and rate of the bioreactor from 33.0°C or 31.0°C to 25.0°C (25.0°C is the commonly used harvest temperature for upstream cell culture).
[0049] Effect comparison:
[0050] Table 1 Comparison of cooling data
[0051]
[0052] Refer to the table above:
[0053] 1) When the temperature drops from 33.0°C to 25.0°C, the cooling effect of the cooling device is comparable to that of the dry ice condition, and both take about 35 minutes; 2) When the temperature drops from 31.0°C to 25.0°C, the cooling effect of the cooling device of the present invention is significantly better than that of the dry ice condition, and the cooling time is only 20 minutes.
[0054] Throughout this specification, references to "some embodiments," "other embodiments," and the like indicate that the specific features, structures, materials, or characteristics described in conjunction with that embodiment or example are included in at least one embodiment or example of the present invention. In this specification, schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
[0055] Obviously, the above-described embodiments of the present invention are merely examples for the purpose of clearly illustrating the present invention and are not intended to limit the manner in which the present invention is to be implemented. A person skilled in the art would be able to make various obvious changes, readjustments, and substitutions without departing from the scope of protection of the present invention. It is not necessary and impossible to enumerate all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the claims of the present invention.
Claims
1. A cooling device for a bioreactor, characterized in that: include: Cooling gel (100); A packaging bag (200), the packaging bag (200) being wrapped around the outside of the cooling gel (100); A fixing member (300) is provided on the packaging bag (200) and is used to fix the packaging bag (200) to the bioreactor.
2. The cooling device for a bioreactor according to claim 1, characterized in that: The fixing member (300) comprises a Velcro provided on the packaging bag (200).
3. The cooling device for a bioreactor according to claim 2, characterized in that: The packaging bag (200) is rectangular, and the fixing piece (300) comprises a rounded bristle portion (310) and a burr portion (320). Both the rounded bristle portion (310) and the burr portion (320) are extended along the width direction of the packaging bag (200) and are respectively arranged at two ends of the packaging bag (200) along its length direction.
4. The cooling device for a bioreactor according to claim 2, characterized in that: The fixing member (300) is bonded to the surface of the packaging bag (200).
5. The cooling device for a bioreactor according to claim 1, characterized in that: The packaging bag (200) is made of a pressure-resistant nylon composite polyethylene material.
6. The cooling device for a bioreactor according to claim 1, characterized in that: The cooling gel (100) comprises GEL biogel.
7. The cooling device for a bioreactor according to claim 1, characterized in that: The fixing member (300) comprises an adhesive layer arranged on the surface of the packaging bag (200).
8. The cooling device for a bioreactor according to claim 1, characterized in that: The fixing member (300) comprises a fixing ring (330) and a binding belt (340), and the fixing ring (330) and the binding belt (340) are respectively arranged at two ends of the packaging bag (200) along the length direction thereof.
9. The cooling device for a bioreactor according to claim 1, characterized in that: There are a plurality of packaging bags (200), and the plurality of packaging bags (200) are stacked and arranged, and two adjacent packaging bags (200) are connected via a connector (400).
10. The cooling device for a bioreactor according to claim 9, characterized in that: The connecting piece (400) comprises Velcro.