Multi-bioreactor

Abstract

A multi-bioreactor according to the present invention comprises: a plurality of stations (10) on which culture containers (1) containing a culture medium can be placed; and a driving unit (30) configured to generate a mechanical driving force, wherein the plurality of stations (10) are spaced apart from each other in the vertical direction, and are configured to move together by receiving the driving force from the driving unit (30).

Description

multi-bioreactor

[0001] The present invention relates to a bioreactor configured in multiple stages and advantageous for mass production.

[0002] Since typical bioreactors use E. coli as their standard, they create an optimal environment for the culture bag through numerous tubes and sensors connected to the culture bag. While many large-capacity bioreactors exist for this purpose, there is currently only one bioreactor that utilizes a culture bag.

[0003] However, in the case of bacteria like Pseudomonas, there are not many places that have secured Pseudomonas strains, and few cases of commercial use exist. Therefore, suitable bioreactors are virtually nonexistent. While Pseudomonas can be cultured simply by shaking, optimized bioreactors are needed.

[0004] The purpose of the present invention is to provide a bioreactor suitable for mass cultivation of microorganisms.

[0005] A multi-bioreactor according to one aspect of the present invention comprises: a plurality of stations (10) on which a culture container (1) containing a culture solution can be placed; a driving unit (30) that generates a mechanical driving force; wherein the plurality of stations (10) are arranged vertically spaced apart from each other, and the driving force of the driving unit (30) is transmitted to the plurality of stations (10) so that the plurality of stations (10) move together.

[0006] In the above multi-bioreactor, each of the plurality of stations (10)

[0007] The station (10) may further include a connecting rod (20) that is pivotally hinged to the installed frame (50) at two facing left and right hinge points, has one end connected to the driving unit (30), and is connected to a connecting point that is a point spaced apart from the two hinge points in each of the plurality of stations (10), thereby transmitting the driving force of the driving unit (30) to each of the stations (10).

[0008] In the above multi-bioreactor, each of the stations (10) can be rotated at a certain angle by the connecting rod (20) around the two hinge points, thereby allowing each of the stations (10) to move like a seesaw.

[0009] In the above multi-bioreactor, the driving unit (30) comprises a motor (31) driven by electric energy; a reducer (32) that reduces the rotation of the motor and outputs it; and a rotary wheel (33) that is coupled to the output terminal of the reducer (32) and rotates; and one end of the connecting rod (20) can be connected to the circumference of the rotary wheel (33) to cause one end of the connecting rod (20) to rotate in a circular motion.

[0010] In the above multi-bioreactor, the driving unit (30) includes a vibrator that generates vibration, one end of the connecting rod (20) is coupled to the vibrator, and the connecting rod (20) can transmit vibration to each of the connecting points.

[0011] In the above multi-bioreactor, a heating unit (81) composed of a heating wire or a heating plate for heating the culture solution may be further provided on the upper surface of the station (10) or the bottom of the culture container (1).

[0012] In the above multi-bioreactor, Pseudomonas bacteria may be cultured.

[0013] In the above multi-bioreactor, it may include at least a sensor (70) that senses the color of the culture solution in the culture container (1); and a control unit having a machine learning model that determines the culture state from the sensing data sensed by the sensor (70).

[0014] In the above multi-bioreactor, the machine learning model may be supervised learning using a dataset including a pair of sensing data of the sensor (70) and data on the culture state.

[0015] In the above multi-bioreactor, the culture state includes an appropriate state, and when the machine learning model determines that the state is appropriate, the driving unit can be stopped or an alarm can be sent to the user.

[0016] In the above multi-bioreactor, the culture state includes an oxygen-deficient state, and when the machine learning model determines that there is an oxygen-deficient state, the control unit can increase the operating speed of the driving unit or alert the user.

[0017] According to the multi-bioreactor of the present invention, it has the advantage of being able to mass-culture microorganisms such as Pseudomonas with a very simple and low-cost structure.

[0018] According to the multi-bioreactor of the present invention, large-scale cultivation is possible, but since it does not use a rotary blade or the like, there is no cell stress or damage, there is a low possibility of cross-contamination, and there is the advantage of high process flexibility.

[0019] The multi-bioreactor of the present invention has the advantage of being very easy to scale up.

[0020] According to the multi-bioreactor of the present invention, it is easy to respond to a state of oxygen deficiency using a sensor and machine learning, and it has the advantage of being able to automatically stop upon completion of culture and provide a user alarm.

[0021] Figure 1 is a conceptual diagram (side view) illustrating an outline of a multi-bioreactor according to the present invention.

[0022] Figure 2 is a conceptual diagram (side view) showing an outline of a state in which a multi-bioreactor according to the present invention operates like a seesaw.

[0023] FIG. 3 is a perspective view illustrating the structure of a multi-bioreactor according to one embodiment of the present invention.

[0024] FIG. 4 is a perspective view illustrating a driving unit in a multi-bioreactor according to one embodiment of the present invention.

[0025] FIG. 5 is a conceptual diagram (side view) illustrating a multi-bioreactor according to another embodiment of the present invention.

[0026] Figure 6 is a conceptual diagram (front view) illustrating a multi-bioreactor according to another embodiment of the present invention.

[0027] Fig. 1 is a conceptual diagram (side view) illustrating an outline of a multi-bioreactor according to the present invention. Fig. 2 is a conceptual diagram (side view) illustrating an outline of a state in which a multi-bioreactor according to the present invention operates like a seesaw. Fig. 3 is a perspective view illustrating the structure of a multi-bioreactor according to an embodiment of the present invention. Fig. 4 is a perspective view illustrating a driving unit in a multi-bioreactor according to an embodiment of the present invention.

[0028] A multi-bioreactor according to one embodiment of the present invention is configured to include a plurality of stations (10), a connecting rod (20), a driving unit (30), a plurality of hinges (41), a plurality of rotating connecting units (42), a frame (50), a base (60), and a sensor (70).

[0029] A plurality of stations (10) are arranged vertically apart from each other, and each of the stations (10) can place a culture container (1) containing a culture solution. The culture container (1) is a culture bag or a culture tank that can hold and maintain a culture solution (2) during culture. The culture container (1) may further be provided with a filter communicating with the outside on its upper portion, and a sensor capable of sensing the dissolved oxygen concentration of the culture solution (2) may be installed in the culture container (1).

[0030] The station (10) is shaped like a square plate or a square frame, etc., on which a culture container (1) can be placed, and may further have guides formed along the edges to prevent the culture container (1) from moving outward. The frame (50) is a pillar installed vertically based on a base (60) on the floor surface, and at least two are installed, one on each of the left and right sides of the station (10). The frame (50) becomes a vertical pillar that supports and bears the weight of the culture containers (1) despite the movement of the station (10).

[0031] Each of the stations (10) is hinged to the installed frame (50) in a manner that it can rotate relative to the frame (50) while being fixed thereto using two hinges (41) at the two facing left and right hinge points of the station (10). The hinges (41) are positioned on each side of the station (10) in the left and right directions (X direction perpendicular to the drawing) for each station (10), so that the station (10) can rotate around them.

[0032] Each of the stations (10) is rotatable around two hinge points on both sides, and the stations (10) are moved like a seesaw by a connecting rod (20) driven by a driving unit (30).

[0033] The connecting rod (20) is connected at one end to the driving unit (30), and is connected to each of the stations (10) at each of the rotational connecting portions (42) in the plurality of stations (10) so as to enable relative rotation. The stations (10) and the connecting rod (20) are connected using the rotational connecting portions (42) at a connection point that is spaced apart from the two hinge points of the stations (10), and accordingly, the driving force of the driving unit (30) is transmitted to each of the stations (10).

[0034] In Fig. 1, the connecting rod (20) is a straight bar shape, but may not be so. As shown in Fig. 3, the connecting rod may be configured as a plurality of rods including a first connecting rod (20a) connecting the driving unit (30) and the first station (10), and a second connecting rod (20b) connecting the second station (10) and the remaining stations (10).

[0035] The driving unit (30) generates physical and mechanical driving force, and transmits the driving force of the driving unit (30) to a plurality of stations (10), thereby causing the plurality of stations (10) to move together.

[0036] A driving unit (30) according to the first embodiment comprises a motor (31; see FIG. 4) driven by electric energy, a reducer (32) that reduces the rotation of the motor and outputs it, and a rotary wheel (33) that rotates by being coupled to the output end of the reducer (32). One end of a connecting rod (20) is connected to the circumference of the rotary wheel (33) so that one end of the connecting rod (20) rotates circularly according to the rotation of the rotary wheel (30).

[0037] One end of the connecting rod (20) is connected to the rotary wheel (30) and is connected to each of the stations (10) at each connecting point located in the middle of the connecting rod (20). As one end of the connecting rod (20) rotates along the circumference of the rotary wheel (30), the connecting points (rotary connecting portions (42)) can move on an arc centered on each hinge (41), and each of the stations (10) moves together like a seesaw. Each of the stations (10) at the connecting points is rotated within a limited, constant angle, thereby moving like a seesaw.

[0038] The driving unit (30) according to the second embodiment includes a vibrator that generates vibrations. One end of a connecting rod (20) is coupled to the vibrator, and the connecting rod (20) transmits vibrations to each of the connection points. The driving unit (30) according to the second embodiment has the advantage of having a smaller movement of the station (10) than the driving unit (30) according to the first embodiment, but does not require a reducer or the like.

[0039]

[0040] FIG. 5 is a conceptual diagram (side view) illustrating a multi-bioreactor according to another embodiment of the present invention.

[0041] A multi-bioreactor according to another embodiment of the present invention is characterized by further including a heating unit (81) compared to the multi-bioreactor described through FIGS. 1 to 4. The heating unit (81) is formed on the upper surface of the station (10) or the bottom of the culture container (1) and is configured as a heating wire or a heating plate for heating the culture solution in the culture container (1). The heating unit (81) can be controlled by a control unit to control whether or not it generates heat and the heating temperature.

[0042]

[0043] Figure 6 is a conceptual diagram (front view) illustrating a multi-bioreactor according to another embodiment of the present invention.

[0044] According to another embodiment of the present invention, a multi-bioreactor is not only vertically stacked with a plurality of stations as illustrated in FIGS. 1 to 5, but also has a plurality of vertically arranged stations (hereinafter also referred to as “station columns”) arranged in the left and right directions to form a two-dimensional array. Two adjacent stations in the left and right directions can be configured by sharing a single frame (50). Since the stations belonging to each station column are driven together by a single driving unit (30), the number of driving units (30) corresponding to the number of station columns is sufficient.

[0045] According to the present invention, there is an advantage in that a number of stations and culture containers can be densely arranged in a narrow space, and the culture start time and culture level can be set separately for each station column.

[0046] The multi-bioreactor according to the present invention is optimized for culturing Pseudomonas bacteria. Pseudomonas bacteria can be used as a raw material for peptide cosmetics and health functional foods, or for adsorbing mercury compounds in wastewater and reducing them to metallic mercury.

[0047] The control unit (not shown) controls the driving speed of the driving unit (30) to control the speed at which the connecting rod (20) rises and falls vertically, and the station operates like a seesaw, so that the culture solution (2) in the culture container (1) moves back and forth, and a wave-like flow of the culture solution is generated, which comes into contact with air and injects dissolved oxygen into the culture solution.

[0048] The sensor (7) senses the color of the culture solution in the culture container (1), and may be a color sensor that senses the color of the received light, or a camera that photographs an object to obtain a color video or a color image. The control unit (not shown) has a machine learning model that receives the sensing data sensed by the sensor (70) and determines the culture state from the sensing data. The machine learning model is learned in advance using a learning dataset. The machine learning model is supervised learning using a dataset that includes pairs of sensing data of the sensor (70) and data on the culture state.

[0049] As the culture progresses normally, the cultured bacteria (Pseudomonas bacteria) gradually change from colorless to pink, and then from pink to purple. As the culture progresses, the color gradually changes, and it is recommended to stop the culture when it reaches a certain color (color range). As time passes and the culture progresses, the color of the culture solution changes. However, the problem is that the time and the degree of cultivation are not always directly proportional, so the color must be continuously observed and the culture must be stopped when it reaches a certain color.

[0050] In the dataset for pre-learning, the 'culture state' can be divided into multiple culture stages, for example, stages 1 to 6, and a specific stage (for example, stage 4) among them can be configured as an 'optimal state'. The sensing data can be a color image from a sensor (70) that captured the culture solution. In the pre-supervised learning for the machine learning model, a data pair of [color image of culture solution - specific culture state] can be used as training data. A large number of such data pairs are secured as a dataset and then the machine learning model is subjected to supervised learning.

[0051] The control unit receives sensing data from the sensor (70) and inputs it into a trained machine learning model, and the machine learning model can output the cultivation status. If the machine learning model determines (outputs) that the condition is 'appropriate', the control unit can stop the driving unit or alert the user.

[0052] Cultivation may not proceed normally, and if the culture medium is red, it indicates a state of oxygen deficiency. When a machine learning model is supervised with a dataset including pairs of sensor (70) sensing data and culture status data, the color image of the red culture medium and the culture status of 'oxygen deficiency' can be matched and included in the dataset.

[0053] The present invention provides a mass-production bioreactor capable of simultaneously shaking multiple culture plates. According to one embodiment of the present invention, when a machine learning model of a control unit determines that an oxygen deficiency condition exists during operation of a multi-bioreactor, the control unit increases the operating speed of the drive unit or alerts the user to take action. Increasing the operating speed of the drive unit increases shaking and the amount of dissolved oxygen.

[0054]

[0055] According to the multi-bioreactor of the present invention, it has the advantage of being able to mass-culture microorganisms such as Pseudomonas with a very simple and low-cost structure.

[0056] Meanwhile, single, large-capacity bioreactors are fixed and require the use of devices such as rotary blades, which leads to significant cell stress and damage, increased risk of cross-contamination, and low process flexibility. In contrast, the multi-bioreactor of the present invention enables large-scale culture but does not use devices such as rotary blades, resulting in no cell stress and damage, low risk of cross-contamination, and high process flexibility. Since the culture medium is separated for each culture container, contamination and problems in a specific drainage container do not spread to other culture containers.

[0057] In addition, according to the multi-bioreactor of the present invention, in order to increase capacity, a new column can be combined with an existing column as shown in Fig. 6, so it has the advantage of being very easy to scale up while maintaining space efficiency.

Claims

1. Multiple stations (10) on which culture containers (1) containing culture solution can be placed; Including a driving unit (30) that generates mechanical driving force; The above plurality of stations (10) are arranged vertically spaced apart from each other, It is characterized in that the driving force of the driving unit (30) is transmitted to the plurality of stations (10) so that the plurality of stations (10) move together. Multi bioreactor.

2. In claim 1, Each of the above multiple stations (10) At the two facing left and right hinge points of the above station (10), it is pivotally hinged to the installed frame (50), First, it is connected to the driving unit (30) and further includes a connecting rod (20) that is connected to a connecting point that is a point spaced apart from the two hinge points in each of the plurality of stations (10) and transmits the driving force of the driving unit (30) to each of the stations (10). Multi bioreactor.

3. In claim 2, Each of the above stations (10) The connecting points are rotated at a certain angle by the connecting rod (20) around the two hinge points, so that each of the stations (10) moves like a seesaw. Multi bioreactor.

4. In claim 3, The above driving unit (30) is A motor driven by electric energy (31); A reducer (32) that reduces the rotation of the above motor and outputs it; and It is configured to include a rotating wheel (33) that is coupled to the output terminal of the above reducer (32) and rotates; One end of the above connecting rod (20) is connected to the circumference of the above rotating wheel (33) so that one end of the above connecting rod (20) moves in a circular motion. Multi bioreactor.

5. In claim 2, The above driving unit (30) includes a vibrator that generates vibration, One end of the above connecting rod (20) is coupled to the vibrator, and the connecting rod (20) transmits vibration to each of the connecting points. Multi bioreactor.

6. In claim 1, The upper surface of the above station (10) or the bottom of the above culture container (1) further includes a heating unit (81) composed of a heating wire or a heating plate for heating the culture solution. Multi bioreactor.

7. In claim 1, Cultivating Pseudomonas bacteria, Multi bioreactor.

8. In claim 1, At least a sensor (70) for sensing the color of the culture solution in the culture container (1); A control unit including a machine learning model that determines the culture state from the sensing data sensed by the above sensor (70); Multi bioreactor.

9. In claim 8, The above machine learning model is, Supervised learning is performed using a dataset that includes pairs of sensing data and culture status data of the above sensor (70). Multi bioreactor.

10. In claim 9, The above culture condition includes an appropriate condition, If the machine learning model determines that the above is in an appropriate state, the driving unit is stopped or an alarm is sent to the user. Multi bioreactor.

11. In claim 9, The above culture condition includes an oxygen-deficient condition, If the machine learning model determines that there is an oxygen deficiency, the control unit increases the operating speed of the driving unit or alerts the user. Multi bioreactor.

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