KR101825167B1 - Bioreactor - Google Patents

Abstract

The present invention provides a bioreactor, which comprises: a chamber in which an incubation chamber is formed therein to cultivate cells, and O_2, CO_2 and N_2 are injected thereinto at a predetermined ratio and mixed; a temperature controlling part coupled to the chamber to control the temperature inside the chamber; a rocker which is coupled to the inside of the chamber, and on which a culture medium containing cells to be cultured can be placed; and a water bag which is disposed at an upper portion of the rocker and can contain the culture medium to culture the cells, and in which O_2, CO_2 and N_2 are injected thereinto at a predetermined ratio. The present invention provides the bioreactor comprising the water bag so that the cell culture can be continued without changing surrounding environment conditions while the chamber of the bioreactor is opened and closed.

Description

Bioreactor {BIOREACTOR}

The present invention relates to a bioreactor for artificially culturing cells.

A bioreactor is a system for artificially reproducing biochemical reaction processes such as decomposition, synthesis, and chemical conversion of substances in vivo, and is also called a bioreactor. Cells can be artificially cultured through continuous biological reactions at room temperature and atmospheric pressure using enzymes or microorganisms.

Because the cells are sensitive to the surrounding environment, cell culture is performed in a chamber of a bioreactor that provides optimal conditions for cell growth, such as temperature, humidity, carbon dioxide concentration, and oxygen concentration.

In the chamber of the bioreactor, a shelf is provided to allow the cells to be placed, and the chamber is provided with a heater, so that the space inside the chamber can be maintained at a temperature suitable for culturing the cells. Further, the concentration of carbon dioxide or oxygen must be kept constant depending on the kind of the cells, so that the carbon dioxide gas or the oxygen gas is uniformly supplied and discharged to the chamber.

On the other hand, the user may need to open and close the chamber door if necessary while the cells are being cultured using such a bioreactor. While opening and closing the door of the chamber, the temperature and humidity inside the chamber may change, and the concentration of carbon dioxide, oxygen, and the like may be abruptly changed. Such abrupt changes in the surrounding environment can interfere with effective cell culture.

The inventors of the present invention have endeavored to research this problem for a long time and completed the present invention.

A related art is Korean Patent Registration No. 10-1192324 (registered on October 11, 2012, Incubator for cell culture).

SUMMARY OF THE INVENTION An object of the present invention is to provide a bioreactor including a water bag so that cell culture can be continued without changing the environmental conditions even when the chamber of the bioreactor is opened and closed.

In addition, the user is provided with a bioreactor capable of selecting the cell culture inside the chamber or the cell culture in the water bag.

And, carbon dioxide or oxygen in the water bag provides a bioreactor that does not require a separate gas injection part for water bag using mixed air inside the chamber.

In order to solve the above-mentioned problems, the present invention provides a method for culturing a cell, comprising: forming a culture chamber in which a cell is cultured, a chamber in which O ₂ , CO ₂ , and N ₂ are injected and mixed at a predetermined maintenance ratio;

A temperature controller coupled to the chamber, the temperature controller adjusting a temperature inside the chamber;

A rocker coupled to the interior of the chamber and capable of being placed in a culture medium containing cells to be cultured thereon; And

And a water bag which is disposed on the rocker and into which O ₂ , CO ₂ and N ₂ can be injected at a preset ratio and is capable of culturing the cells by receiving the culture liquid.

Provide a bioreactor.

Further, the present invention may further include an air pump for sucking the mixed gas inside the chamber and moving the mixed gas into the water bag.

A suction line connecting the inside of the chamber and the air pump so that the mixed gas inside the chamber can move to the air pump; And

And a discharge line connecting the air pump and the water bag to allow the mixed gas from the air pump to move to the water bag.

The rocker can vibrate within a predetermined range with respect to the center axis.

An O ₂ injection unit, a CO ₂ injection unit, and an N ₂ injection unit, which are connected to the chamber and inject O ₂ , CO ₂ , and N ₂ into the chamber, respectively, may be formed.

The present invention also includes an O ₂ sensor coupled to the chamber for measuring the concentration of O _{2 in} the chamber and a CO ₂ sensor for measuring the concentration of CO _{2 in} the chamber,

And a controller for controlling the O ₂ injector, the CO ₂ injector, and the N ₂ injector according to the concentration of O ₂ and the concentration of CO ₂ measured by the O ₂ sensor and the CO ₂ sensor.

The present invention also relates to a check nozzle coupled to the chamber to assist in measuring the concentration of O ₂ and CO _{2 in} the water bag;

And a check line connecting the water bag and the check nozzle.

The temperature controller may include:

And a heater provided on six sides of the chamber.

And a blower fan coupled to the chamber to circulate the mixed gas within the chamber.

The rocker

And a BLDC motor that provides power to the vibrations.

By using the bioreactor of the present invention as described above, even if the chamber door is opened and closed, continuous and effective cell culture is possible without being affected by the surrounding environment of cell culture.

In addition, the user can select a cell culture in a chamber or a cell culture in a water bag in a chamber, thereby providing various cell culture methods.

The concentration of the air inside the water bag uses the mixed air inside the chamber, so that no separate air inflow of water only is required.

Even if the effects are not expressly mentioned here, the effects described in the following specification, which are expected by the technical characteristics of the present invention, and the provisional effects thereof are handled as described in the specification of the present invention.

1 is a view showing a bioreactor according to an embodiment of the present invention.
2 is a view showing control of mixed gas, temperature, and vibration of a rocker in a bioreactor chamber according to an embodiment of the present invention.
It is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS The present invention is capable of various modifications and various embodiments, and specific embodiments are illustrated in the drawings and described in detail in the detailed description. It is to be understood, however, that the invention is not to be limited to the specific embodiments, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

The terminology used in this application is used only to describe a specific embodiment and is not intended to limit the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In the present application, the terms "comprises" or "having" and the like are used to specify that there is a feature, a number, a step, an operation, an element, a component or a combination thereof described in the specification, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, or combinations thereof.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of a bioreactor according to the present invention will be described in detail with reference to the accompanying drawings. Referring to the accompanying drawings, the same or corresponding components are denoted by the same reference numerals, Is omitted.

1 is a view showing a bioreactor according to an embodiment of the present invention.

The bioreactor according to the present invention includes a chamber 100, a temperature controller, a rocker 300, and a water bag 400.

The chamber 100 has an incubation chamber formed therein for culturing the cells. The inner shape may be variously modified, but the inner shape may be formed in a hexahedral shape according to an embodiment of the present invention. On the front surface of the chamber 100, there is formed a door in which a cell and a culture medium for proliferation can be inserted into and removed from the inside of the chamber 100. Open the door, put the cells and culture into the incubation room, close the door, and control the temperature, humidity, carbon dioxide concentration, and oxygen concentration under certain conditions so that the cell culture can be optimized.

In this chamber 100, oxygen, carbon dioxide, and nitrogen can be injected into the furnace. In order to cultivate the cells, oxygen or carbon dioxide is required depending on the type of the cells. In some cases, an appropriate concentration of oxygen or carbon dioxide is set to optimize for cell culture.

At this time, the concentration ratio of oxygen in the culture chamber or the concentration ratio of carbon dioxide can be adjusted to the concentration of nitrogen. For example, if it is desired to adjust the carbon dioxide concentration in the culture chamber of the chamber 100 to 5%, carbon dioxide and nitrogen in the culture chamber may be injected at a ratio of 5:95. Similarly, if you want to adjust the oxygen concentration to 20%, you can inject oxygen and nitrogen into the culture chamber at a ratio of 20:80.

The nitrogen is injected to adjust the concentration of oxygen and carbon dioxide in the air in the culture chamber. The chamber 100 according to the present invention may be mixed with oxygen, carbon dioxide, and nitrogen at a predetermined ratio.

The oxygen injection unit 110, the carbon dioxide injection unit 120, and the nitrogen injection unit 130 are respectively connected to the chamber 100 for injecting oxygen, carbon dioxide, and nitrogen.

The oxygen injection unit 110, the carbon dioxide injection unit 120 and the nitrogen injection unit 130 coupled to the chamber 100 may be injected and mixed into the culture chamber of the chamber 100 by a predetermined amount.

The chamber 100 is connected to an oxygen sensor 140 and a carbon dioxide sensor 150 for measuring concentrations of oxygen and carbon dioxide. The control unit 150 coupled to the chamber 100 controls the oxygen injection unit 110, the carbon dioxide injection unit 120, and the oxygen sensor 140 according to the oxygen concentration and the concentration of the carbon dioxide measured by the oxygen sensor 140 and the carbon dioxide sensor 150, And the nitrogen injection unit 130 so that the mixed air in the culture chamber of the chamber 100 is adjusted to the predetermined oxygen concentration and the carbon dioxide concentration.

Through the configuration of the controller 150, the mixed air in the chamber 100 can be automatically adjusted to be automatically optimized for culture.

And the blower fan 700 may be coupled to the chamber 100 for circulation of the gas mixed with the mixture of oxygen, carbon dioxide, and nitrogen injected into the culture chamber of the chamber 100. The blower fan 700 can move the air in the culture chamber of the chamber 100 by rotation of the fan to better mix oxygen, carbon dioxide, and nitrogen and evenly spread the mixed air into the chamber in the chamber 100 have.

The present invention includes a temperature controller. The temperature controller is coupled to the chamber 100 to control the temperature inside the chamber 100. For culture, a constant temperature should be maintained in the incubation room. To this end, a temperature controller is coupled to the chamber 100 to control the temperature inside the chamber 100.

The temperature controller includes a heater 200 installed on all six sides of the chamber 100. In other words, the inside of the chamber 100 is formed as a hexahedron, and the heaters 200 are provided on each of the surfaces, so that the temperature in each surface can be controlled uniformly in the culture chamber. The blower fan 700 described above helps not only the mixing and circulation of air in the culture room, but also the circulation of air to eventually uniformize the temperature in the culture room.

The heaters 200 provided on the respective surfaces can be individually controlled to improve the temperature control efficiency.

The present invention includes a rocker (300).

The rocker 300 may be placed in a culture medium containing cells to be coupled into the chamber 100 and cultured thereon. The cells and the culture liquid may be accommodated in a specific container and placed in a culture chamber in the chamber 100 to allow the culture to proceed. At this time, the container containing the cells and the culture solution may be put on a shelf such as the rocker 300, and the culture may proceed.

The rocker 300 may rotate about the center axis 310. And moves up and down similarly to the seesaw motion based on the center axis 310 within a certain range. The cells and the culture liquid placed on the rocker 300 by the rotational movement of the rocker 300 can be well shaken. The rocker 300 serves as a kind of shaker.

Cells and culture medium can be cultured more efficiently if external forces such as linear motion, rotational motion, and up and down motion are applied to the container containing the cells and the culture medium, rather than culturing the cells and the culture medium in a horizontal static state. Not only makes contact between the cells and the culture medium uniform, but also increases the contact with oxygen or carbon dioxide, thereby enabling efficient and uniform culture.

In order to efficiently cultivate the rocker 300, the rocker 300 can be rotated up and down within a certain range such as a seesaw motion.

It may be the BLDC motor 320 to provide the power of the rotational motion of the rocker 300. The BLDC motor 320 is composed of a rotor and a stator, and the rotor is formed of a magnet plate and a plurality of permanent magnets disposed on the magnet plate. That is, the magnet plate is formed in a circular shape, and a plurality of permanent magnets are arranged along the circumference on the magnet plate. Also, the coil plate is formed as a circular plate of the same size corresponding to the magnetic plate. A plurality of winded coils corresponding to the plurality of magnets are arranged on the coil plate.

When a current is supplied to a plurality of winded coils, a rotating system is formed. When the magnet system formed by the rotating system and the plurality of permanent magnets are linked to each other, a rotational power may be generated in the rotor. According to this principle, the rotor can be supported and rotated by the stator.

When the rotor rotates, the center shaft 310 coupled to the rotor rotates, and when the center shaft 310 rotates, the rocker 300 coupled to the center shaft 310 rotates.

By using the BLDC motor 320, it is possible to use the motor for rotating the rocker 300 for a long period of time with high wear resistance and durability.

According to an embodiment of the present invention, a water bag 400 may be disposed at an upper portion of the rocker 300. Cells and a culture medium are injected into the water bag 400, and cell proliferation can proceed.

Even when the user opens the door of the chamber 100 through the structure of the water bag 400, the culture can be continued in the water bag 400 without changing the environmental condition.

When the door of the chamber 100 is opened, the oxygen concentration or the carbon dioxide concentration of the culture chamber inside the chamber 100 can be drastically changed. The temperature inside the culture room may also vary. Therefore, the surrounding environment of the cells cultured inside the culture chamber may be changed, which may affect the culture of the cells.

However, if a separate water bag 400 is provided in the culture chamber as in the present invention, even if the door of the chamber 100 is opened, the concentration of oxygen or carbon dioxide in the water bag 400 is unchanged, The water bag 400 does not suddenly change. Therefore, the culture process can be continued in the water bag 400 continuously and stably.

Accordingly, the user may cultivate the cells in the culture chamber inside the chamber 100, or may cultivate the cells inside the water bag 400 inside the culture chamber. The user can select cells according to convenience and cultivate the cells.

At this time, mixed air injected into the water bag 400 can use mixed air inside the chamber 100. Therefore, no air injection unit for the separate water bag 400 is required.

To this end, the present invention may further include an air pump 500. The air pump 500 is disposed outside the incubation chamber of the chamber 100 and can suck the mixed gas inside the chamber 100 and supply the mixed gas back into the water bag 400. The mixed gas within the chamber 100 includes a suction line 510 for movement to the air pump 500.

The suction line 510 connects the inside of the chamber 100 and the air pump 500 to move the mixed gas inside the chamber 100 to the air pump 500.

And an ejection line 520 for moving the mixed gas, which has been moved to the air pump 500, to the water bag 400 again. The discharge line 520 connects the air pump 500 and the water bag 400 to move the mixed gas moving from the chamber 100 to the air pump 500 to the water bag 400 again.

By controlling the mixed gas in the chamber 100, the same gas as the mixed gas inside the chamber 100 is automatically introduced into the water bag 400 through the above-described configuration, and the gas inside the water bag 400 is separately There is no need to control. As a result, the gas inside the water bag 400 becomes sufficient to control the gas inside the chamber 100.

When the sufficient amount of mixed gas flows into the water bag 400 through the air pump 500, the operation of the air pump 500 can be stopped and the suction line or the discharge line 520 can be temporarily closed. When the air pump 500 and the gas in the chamber 100 are separated from each other, even if the door of the chamber 100 is opened, the concentration of the gas mixture (oxygen concentration, carbon dioxide concentration) It maintains a constant concentration without the influence of gas.

In an embodiment of the present invention, the concentration of the mixed gas in the water bag 400 may be separately measured.

For this, a check nozzle 600 formed outside the chamber 100 may be further included. The check line 610 may connect the water bag 400 and the check nozzle 600 to each other to move the mixed gas of the water bag 400 to the check nozzle 600.

That is, the check nozzle 600 is coupled to the chamber 100 to measure the oxygen concentration or the carbon dioxide concentration in the water bag 400. An oxygen concentration meter or a carbon dioxide concentration meter may be connected to the check nozzle 600 to check the concentration of oxygen or carbon dioxide in the water bag 400 moving on the check line 610.

2 is a view showing the control of the mixture gas in the bioreactor chamber 100, the temperature control, and the vibration of the rocker 300 according to an embodiment of the present invention.

The carbon dioxide is stored in the carbon dioxide tank, and the carbon dioxide main board can be injected into the chamber 100 by controlling the solenoid valve.

The nitrogen is stored in the nitrogen tank, the oxygen is stored in the oxygen tank, and the solenoid valve is controlled by the oxygen control board so that a predetermined amount of nitrogen and oxygen is injected into the chamber 100.

The injected oxygen, carbon dioxide, and nitrogen can be mixed in the chamber 100. The gas thus mixed moves into the water bag 400 through the air pump 500, and cell culture can proceed.

On the other hand, the driver board of the BLDC motor 320 can control the BLDC motor 320 to provide the rocker 300 with up-and-down turning force such as seesaw. As the rocker 300 rotates, the cells and the culture liquid placed on the rocker 300 can be more effectively and uniformly shaken. The locker 300 can function as a shaker.

The user may directly perform cell culture inside the chamber 100 using the cell culture apparatus of the present invention or may selectively perform cell culture inside the water bag 400 inside the chamber 100.

And the temperature controller controls the temperature inside the chamber 100 as a whole. The temperature inside the water bag 400 is also adjusted according to the temperature control inside the chamber 100. Since the mixed gas inside the chamber 100 is shared in the water bag 400 while being inserted into the chamber 100.

The scope of protection of the present invention is not limited to the description and the expression of the embodiments explicitly described in the foregoing. It is again to be understood that the present invention is not limited by the modifications or substitutions that are obvious to those skilled in the art.

100: chamber
110:
120: carbon dioxide injection unit
130: Nitrogen injection part
140: oxygen sensor
150: Carbon dioxide sensor
160:
200: heater
300: Rocker
310: center axis
320: BLDC motor
400: water bag
500: air pump
510: suction line
520: Discharge line
600: Check nozzle
610: Check line
700: blower fan

Claims (10)

A culture chamber is formed inside the cell so that the cells can be cultured. A door for introducing and withdrawing a culture solution containing cells to be cultured is formed. O ₂ , CO ₂ , and N ₂ are injected through the injection parts A chamber to be mixed;
A temperature controller coupled to the chamber, the temperature controller adjusting a temperature inside the chamber;
A rocker coupled to the interior of the chamber and capable of being placed in a culture medium containing cells to be cultured thereon;
A water bag which is provided in the culture chamber and is disposed on the rocker and into which O ₂ , CO ₂ and N ₂ can be injected at a predetermined ratio, the culture can be accommodated and cells can be cultured; And
And an air pump for sucking the mixed gas inside the chamber and moving the mixed gas into the water bag,
A suction line connecting the inside of the chamber and the air pump to allow the mixed gas inside the chamber to move to the air pump; And
And a discharge line connecting the air pump and the water bag so that the mixed gas from the air pump can move to the water bag,
The mixed gas injected into the chamber is used for cell culture inside the culture chamber and is also injected into the water bag through the air pump, the suction line and the discharge line, and is also used for cell culture inside the water bag doing,
Bioreactor. delete delete The method according to claim 1,
Characterized in that the rocker vibrates within a predetermined range with respect to the central axis.
Bioreactor. The method according to claim 1,
And an O ₂ injection unit, a CO ₂ injection unit, and an N ₂ injection unit, which are coupled to the chamber and inject O ₂ , CO ₂ , and N ₂ into the chamber, respectively.
Bioreactor. 6. The method of claim 5,
An O ₂ sensor coupled to the chamber for measuring the concentration of O ₂ within the chamber and a CO ₂ sensor for measuring the concentration of CO ₂ inside the chamber,
Characterized by further including the O ₂ sensor and control unit for the O ₂ injector, wherein the CO ₂ injector, wherein the N ₂ injection unit controlled according to the concentration and the concentration of CO ₂ in the O ₂ measured by the CO ₂ sensor doing,
Bioreactor. The method according to claim 1,
A check nozzle coupled to the chamber to assist in measuring the concentration of O ₂ and CO _{2 in} the water bag;
Further comprising a check line connecting the water bag and the check nozzle.
Bioreactor. The method according to claim 1,
The temperature controller may include:
And a heater provided on each of six sides of the chamber.
Bioreactor. The method according to claim 1,
Further comprising a blower fan coupled to the chamber to circulate the mixed gas within the chamber.
Bioreactor. The method according to claim 1,
The rocker
Characterized in that it comprises a BLDC motor providing power of vibration,
Bioreactor.

Images