JP2011152076A - Wave type culture apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a wave type culture apparatus for animal cells and the like, which can control a culture solution at a suitable temperature. <P>SOLUTION: The wave type culture apparatus A for seesawing a culture table 2 on which a culture container is loaded is characterized by having a thermometer 2b disposed at one end of the culture table to contact with the culture container 1, a driving portion 3 for seesawing the culture table in a direction orthogonal to the seesawing movements in a state that one end of the culture table is lowered, and a temperature-controller 4 for controlling the temperature of the culture container on the basis of the measurement result of the thermometer. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a wave type culture apparatus that stirs a culture solution in a culture vessel by a seesaw motion and supplies or removes oxygen and carbon dioxide.

Conventionally, as a device for culturing animal cells, insect cells and the like in large quantities, a culture device using a culture tank having a ventilator and / or a stirrer and a glass or metal bowl-shaped cylindrical structure has been used. In such a culture device, the convection generated by the rotation of the stirring blade of the stirrer, and in the case of only the aeration device, the culture solution is uniformly mixed by the rise of the bubbles in the tank and the bubbles supplied to the culture solution are passed through. Supply oxygen or supply or remove carbon dioxide.
In recent years, wave-type culture apparatuses have been used mainly for the purpose of reducing costs, improving operability, and reducing contamination. The wave type culture tank is a rock-shaped plastic bag or other culture container that contains a culture solution in a seesaw motion, so that the nutrients supplied to the culture solution can be mixed uniformly and oxygen can be supplied from the surface of the solution. Supply and carbon dioxide gas supply or removal.

One of the characteristics of this wave type culture tank is that the culturable liquid volume range is wide. Therefore, when using a vertical cylindrical structure culture tank, there is a great merit that a process can be constructed with one culture tank even in a process that requires a plurality of culture tanks. At this time, since there is a minimum cell concentration that can be proliferated, it is necessary to set the cell concentration at the start of culture to a certain level or more.
About this wave type culture apparatus, it is disclosed in the following Patent Document 1, Non-Patent Document 1, Non-Patent Document 2, and Non-Patent Document 3,

JP 2006-540323 A

Sartorius Co., Ltd. “Single Use Culture Device Biostat Cultiback RM20 / 50 Product Specification” Sartorius Co., Ltd. “Biostat Cultiback RM20 / 50 Basic -Operation Manual-” GE Healthcare Bioscience Co., Ltd. “GROWCELLS CELLCULTURE WAVEBIOREACTOR”

  By the way, the above-mentioned wave type culture apparatus of the prior art structurally deteriorates the temperature control performance when culturing in a state where the amount of the culture solution is small as compared with the case where the amount of the solution is large. This is because in a wave type culture apparatus, the temperature of the culture solution in the culture vessel is measured by a thermometer attached so as to circumscribe the center of the culture vessel. This is because the temperature of the gas in the culture vessel is measured instead of the temperature of the culture solution in the culture vessel, particularly when the amount of the culture solution is small. And if temperature control is performed based on the temperature measured in this way, naturally appropriate temperature control cannot be performed. As a result, in the wave type culture apparatus, the upper and lower limits of the culture temperature control value differ depending on whether the amount of the culture solution is large or small, and the productivity is particularly different in temperature sensitive cultures. End up.

  This invention is made | formed in view of the situation mentioned above, and aims at providing the wave type culture apparatus which can control a culture solution to a suitable temperature rather than before.

  In order to achieve the above object, in the present invention, as a first solving means related to a wave type culture apparatus, there is a wave type culture apparatus that moves a culture table on which a culture vessel is placed. A thermometer arranged at one end so as to be in contact with the culture vessel, a drive unit that moves the culture table in a direction perpendicular to the seesaw motion with one end of the culture table lowered, and measurement of the thermometer The temperature control means for controlling the temperature of the culture vessel based on the result is employed.

  In the present invention, as the second solving means related to the wave type culture apparatus, in the first solving means, a plurality of thermometers are provided at one end of the culture table, and the temperature control means is an average of the plurality of thermometers. A means of controlling the temperature of the culture vessel based on the value is adopted.

  According to the present invention, the wave-type culture apparatus is a wave-type culture apparatus that moves a culture table on which a culture vessel is placed on a seesaw, and includes a thermometer arranged at one end of the culture table so as to be in contact with the culture vessel. And a drive unit that moves the culture table in a direction orthogonal to the seesaw motion with one end of the culture table lowered, and temperature control means for controlling the temperature of the culture vessel based on the measurement result of the thermometer.

  As a result, the culture solution is in a state of being closer to one end, and since the thermometer can always be adjacent to the culture solution L via the culture vessel, the conventional thermometer has been arranged at the center of the culture vessel. The temperature of the culture solution can be accurately measured even if the amount of the culture solution is small compared to that. In the wave type culture apparatus, the culture solution can be controlled to a more appropriate temperature based on the measurement result of the thermometer.

It is a perspective view which shows the external appearance of the wave type culture apparatus A which concerns on one Embodiment of this invention. It is a perspective view of the culture stage 2 of the wave type culture apparatus A which concerns on one Embodiment of this invention. It is front sectional drawing of the thermometer 2b arrange | positioned at the culture stand 2 of the wave type culture apparatus A which concerns on one Embodiment of this invention. It is a right view which shows the seesaw motion of the culture stage 2 of the wave type culture apparatus A which concerns on one Embodiment of this invention.

  Hereinafter, an embodiment of the present invention will be described with reference to the drawings. The present embodiment relates to a wave type culture apparatus that stirs a culture solution by swinging a culture vessel containing the culture solution by a seesaw motion.

  First, a schematic configuration of the wave type culture apparatus A according to the present embodiment will be described with reference to FIG. FIG. 1 is a perspective view showing an appearance of a wave type culture apparatus A according to the present embodiment. The wave type culture apparatus A is used, for example, for the production of pharmaceutical antibodies, and cultivates cells by using microorganisms and animal / plant cells. That is, the wave type culture apparatus A is a device for culturing cells while supplying oxygen into the culture solution L, mixing the dissolved oxygen and nutrients uniformly, and further supplying or removing carbon dioxide gas. It is.

As shown in FIG. 1, the wave type culture apparatus A includes a culture vessel 1, a culture table 2, a drive unit 3, a controller 4, an intake tube 5, and an exhaust tube 6.
The culture vessel 1 is a plastic bag made of a plastic member such as polypropylene or polyethylene, and stores the culture solution L therein. The culture vessel 1 is preferably in the shape of a pillow, but may have other shapes, and the dimensions can be appropriately changed according to the user's request. Such a culture container 1 can be disposable and is excellent in reducing production costs in industrial use.

  As shown in FIG. 1, the culture vessel 1 is connected to an intake tube 5 and an exhaust tube 6, and oxygen or carbon dioxide gas is supplied through the intake tube 5 and the inside is not required through the exhaust tube 6. Gas is exhausted. In addition, the culture vessel 1 can be attached to and detached from the culture table 2, and when the culture table 2 performs a seesaw motion while the culture vessel 1 is fixed to the culture table 2, a wave is generated in the culture medium L inside. And the culture solution L in the culture container 1 is stirred by the said wave, oxygen and a carbon dioxide gas are supplied or removed, and a nutrient is mixed uniformly. In addition, the said culture solution L contains the nutrient source etc. which are needed when culturing the said cell with the cell used as culture | cultivation object.

Next, the culture table 2 will be described with reference to FIG. FIG. 2 is a perspective view of the culture table 2 of the wave type culture apparatus A according to the present embodiment.
The culture table 2 generates a wave in the culture solution L of the culture vessel 1 fixed to itself by performing seesaw motion back and forth (movement in the direction of a double arrow in FIG. 2) under the control of the controller 4. Stir L. As shown in FIG. 1, the culture table 2 is in a state of being lowered to the right end side.

Then, as shown in FIG. 2, a heater 2a is embedded in the culture table 2, and a thermometer 2b is disposed. FIG. 3 is a front cross-sectional view (cross-sectional view in the front direction of FIG. 1) of the thermometer 2b arranged on the culture table 2 of the wave type culture apparatus A according to the present embodiment.
As shown in FIG. 2, the heater 2 a is embedded in one surface of the culture table 2, and controls the culture medium L to an optimum temperature for culture by heating the culture vessel 1 from below under the control of the controller 4. .

  As shown in FIG. 2, the thermometer 2 b is disposed at the right end of the culture table 2 so as to contact the right end of the culture vessel 1. As shown in FIG. 3, the thermometer 2b includes a temperature sensor 2b-1 at the center, and the temperature sensor 2b-1 measures the temperature of the culture medium L via the culture vessel 1.

The temperature sensor 2b-1 outputs a temperature detection signal indicating the measured temperature to the controller 4. The temperature sensor 2b-1 is provided with a heat insulating material on the lower side thereof so as not to be directly affected by the heat of the heater 2a embedded below the thermometer 2b.
Then, the controller 4 determines the temperature of the culture solution L based on the temperature detection signal input from the temperature sensor 2b-1, and controls the temperature of the heater 2a so that the culture solution L becomes an appropriate temperature.

The drive unit 3 is in a state where the right side is lowered, and vibrates back and forth while drawing a fan shape under the control of the controller 4. The drive unit 3 repeats this back-and-forth vibration, thereby causing the culture table 2 to continuously perform seesaw motion.
The controller 4 includes a control circuit and an operation display unit that are constituted by a CPU (Central Processing Unit), a ROM (Read Only Memory), a RAM (Random Access Memory), and the like, and a control program stored in the ROM. The entire operation of the wave type culture apparatus A is controlled based on the temperature detection signal input from the temperature sensor 2b-1 of the thermometer 2b and the operation instruction received by the operation display unit.

The operation display unit includes a touch panel and displays various screens and operation buttons for receiving operation instructions. The details of the operation of the controller 4 will be described below as the operation of the wave type culture apparatus A.
The heater 2a and the controller 4 constitute the temperature control means of this embodiment.

  The intake tube 5 is attached to the upper side of the culture vessel 1 and supplies oxygen into the culture vessel 1. Further, the exhaust tube 6 is attached to the upper side of the culture vessel 1 so as to be aligned with the intake tube 5, and discharges unnecessary gas in the culture vessel 1 to the outside. Further, for example, a 0.22 μm filter is attached to the intake tube 5 and the exhaust tube 6, and contaminants contained in the gas passing through the filter are removed.

Next, the operation of the wave type culture apparatus A according to the present embodiment configured as described above will be described in detail with reference to FIG. FIG. 4 is a right side view showing the seesaw motion of the culture table 2 of the wave type culture apparatus A according to the present embodiment. In addition, the thick arrow of FIG. 4 shows the moving direction of the culture stand 2. FIG.
First, the user who wants to culture presses the culture start button on the operation display section of the controller 4 of the wave type culture apparatus A.

  The controller 4 causes the drive unit 3 to start the seesaw motion of the culture table 2 when the operation display unit receives a culture start instruction by pressing the culture start button. When the seesaw motion is started, the culture table 2 repeats the operations of (a) and (b) of FIG. 4, that is, the seesaw motion is performed back and forth around the drive unit 3. In this way, the front and back of the culture table 2 are alternately lifted, so that waves as shown in FIGS. 4A and 4B are generated and stirred in the culture solution L in the culture vessel 1.

And the controller 4 makes the heater 2a heat the culture container 1 with the start of the seesaw motion of the culture stand 2, and makes the thermometer 2b start the measurement of the temperature of the culture solution L.
In the wave type culture apparatus A, when the seesaw motion is performed back and forth while the culture stage 2 is lowered to the right end side, the culture solution L is shifted to the right side, but the thermometer 2b is in contact with the right end of the culture vessel 1. Therefore, the thermometer 2b is always adjacent to the culture solution L through the culture vessel 1.

  Then, when the temperature detection signal is input from the thermometer 2b, the controller 4 causes the heater 2a to heat the culture medium L to a preset temperature based on the temperature detection signal of the thermometer 2b.

In the wave type culture apparatus A according to this embodiment as described above, the seesaw motion is performed back and forth while the culture table 2 is lowered to the right end side, and the thermometer 2b is disposed so as to contact the right end of the culture vessel 1. The
As a result, the culture medium L is shifted to the right side, and the thermometer 2b can always be adjacent to the culture medium L via the culture container 1, so that the conventional thermometer 2b is arranged at the center of the culture container 1. Compared with what has been done, the temperature of the culture solution L can be accurately measured even if the amount of the culture solution L is small. And in the wave type culture apparatus A, the controller 4 can control the culture solution to a more appropriate temperature by controlling the heater 2a based on the measurement result of the thermometer 2b.

As mentioned above, although one Embodiment of this invention was described, this invention is not limited to the said embodiment, For example, the following modifications can be considered.
(1) In the above-described embodiment, the seesaw motion is performed back and forth while the culture table 2 is lowered to the right end side, and the thermometer 2b is arranged so as to contact the right end of the culture vessel 1. It is not limited to.

  For example, the thermometer 2b may be disposed in contact with the left end of the culture vessel 1 with the culture table 2 in the state where the left end side is lowered. Alternatively, the thermometer 2b may be disposed so as to be in contact with the front end of the culture vessel 1 while the culture table 2 is moved left and right while the front end side is lowered, or the culture table 2 is in a state where the rear end side is lowered. However, the thermometer 2b may be disposed so as to contact the rear end of the culture vessel 1 by moving the seesaw from side to side.

  Furthermore, when the culture medium L is extremely small, it is tilted so that any one of the four corners of the culture table 2 is lowered, and the thermometer 2b is disposed so as to contact the end of the culture container 1 in the tilted direction. However, the culture table 2 may be caused to see-saw so that it does not move so much in the culture vessel 1.

(2) In the above embodiment, one thermometer 2b is arranged so as to contact the right end of the culture vessel 1, but the present invention is not limited to this.

  For example, not only one but also a plurality of thermometers 2b are provided on the right end side of the culture table 2, and the controller 4 calculates the average value of the measurement results of the plurality of thermometers 2b, and based on the average value, the heater You may make it control 2a.

(3) In the above embodiment, the seesaw motion is performed back and forth while the culture table 2 is lowered to the right side, and the thermometer 2b is disposed so as to contact the right end of the culture vessel 1, but the present invention is not limited thereto. It is not limited.
For example, when a rail for arranging the thermometer 2b is provided on the culture table 2 and the culture table 2 is tilted to the right side, the thermometer 2b moves to the right end of the culture table 2 along the rail. Thereby, the trouble of having to reposition the position of the thermometer 2b according to the direction in which the culture table 2 is tilted can be saved.

A ... Wave type culture device, 1 ... Culture vessel, 2 ... Culture table, 2a ... Heater, 2b ... Thermometer, 3 ... Drive unit, 4 ... Controller, 5 ... Intake tube, 6 ... Exhaust tube

Claims (2)

A wave type culture apparatus for seesaw motion of a culture table on which a culture vessel is placed,
A thermometer disposed at one end of the culture table so as to contact the culture vessel;
A drive unit that moves the culture table in a direction perpendicular to the seesaw motion with one end of the culture table lowered;
And a temperature control means for controlling the temperature of the culture vessel based on the measurement result of the thermometer. The wave type according to claim 1, wherein a plurality of thermometers are provided at one end of the culture table, and the temperature control means controls the temperature of the culture vessel based on an average value of the plurality of thermometers. Culture device.

Images