KR20210020237A - Auto medium-changing system - Google Patents

Abstract

An automatic medium-changing system is disclosed. The automatic medium-changing system of the present invention includes: a chamber in which a plurality of wells are disposed along a circumferential direction with respect to a rotation axis; a nozzle disposed over any one of the wells; an infusion pump that delivers a solution to the nozzle; and an actuator for rotating the rotation axis. According to the present invention, it is possible to provide the automatic medium-changing system configured to create various test environments in a plurality of wells.

Description

Automatic badge replacement system {AUTO MEDIUM-CHANGING SYSTEM}

The present invention relates to an automatic medium replacement system.

Cell culture is a technology for culturing cells isolated from an individual outside the individual, and such cell culture is the core of cell culture technology to consistently maintain a cultured environment similar to that of an individual's body.

Cells or spheroids with a slow growth rate require long-term cell culture in the same chamber or plate without subculture. In particular, when cells or spheroids are cultured in a plurality of wells, it is required to maintain the same environment for each well.

Delayed replenishment of the medium deteriorates the condition of the cells through insufficient supply of nutrients and acidification of the culture medium, and may lower the reliability of the results of subsequent experiments. Therefore, in order to maintain the continuity of the study, it should be possible to perform cell maintenance and drug treatment even in the absence of a researcher.

In this regard, Korean Patent Publication No. 1412083 (hereinafter referred to as'Prior Document 1') discloses a cell culture unit, a cell culture device, and a cell culture system. The cell culture system of Prior Document 1 includes a plurality of cell culture units, a plate accommodating the cell culture units, an incubator providing a temperature and an atmosphere suitable for cell growth to the cell culture units accommodated in the plate, and a sealed state. It consists of a culture medium storage container in which the furnace culture medium is stored and a lung culture medium storage container in which the lung culture medium is stored in a sealed state.

The cell culture system of Prior Document 1 can be used by attaching only the number of cell culture units required for the test to a plate. In addition, the cell culture system of Prior Literature 1 has an advantage that only the cell culture unit used at the time of completion of the test can be discarded and a new cell culture unit can be mounted on a plate to be used.

In the cell culture system of Prior Document 1, the culture solution distributor includes a divider partition wall divided into an inlet-side space and an outlet-side space, and culture solution distribution tubes connected to a plurality of outlets. That is, the cell culture system of Prior Document 1 has a disadvantage that only a simple culture test is possible in which only one type of culture medium is supplied to a plurality of wells through a culture medium divider.

Therefore, the cell culture system of Prior Document 1 has a problem in that the test period increases in proportion to the number of test conditions in order to perform a cell culture test under various test conditions (selective injection of medium and drug, change in injection amount).

(Patent Document 1) KR1412083 B

It is an object of the present invention to provide an automatic medium replacement system configured to create various test environments in a plurality of wells.

However, the technical problem to be achieved by the present invention is not limited to the problems mentioned above, and other problems that are not mentioned may be clearly understood by those of ordinary skill in the art from the following description.

The object is, in accordance with the present invention, a chamber in which a plurality of wells are disposed along a circumferential direction about a rotation axis; A nozzle disposed on one of the wells; An injection pump that sends a solution to the nozzle; And an actuator that rotates the rotating shaft.

And a discharge pump for discharging the solution in the well, wherein the chamber comprises: a discharge pipe connected to the discharge pump and formed on the rotation shaft; And a connection pipe that connects the wells to the discharge pipe, and moves the solution of the wells to the discharge pipe.

The wells and the connection pipes may be axially symmetric with respect to the rotation axis.

The connector may include a bent tube connected to a lower end of the well; And a horizontal pipe connecting the bent pipe and the discharge pipe, and some or all of the bent pipe may be formed not to be higher than the horizontal pipe.

Gear teeth are formed along the circumferential direction on the rotation shaft, and the actuator includes: a gear meshing with the gear teeth; And a motor that rotates the gear.

A support for supporting the nozzle; And a base on which the support is installed.

The rotation shaft includes a lower shaft having the gear teeth formed thereon and rotatably mounted to the base; And an upper shaft connected to the wells and detachably coupled to the lower shaft.

The support, a fixed support provided on the base; And a rotation support that is rotatably mounted on the fixed support and supports the nozzle.

In addition, the object is, according to the present invention, a chamber in which a plurality of wells are disposed along a circumferential direction about a rotation axis; A nozzle disposed on one of the wells; An injection pump that sends a solution to the nozzle; And an actuator that rotates the rotating shaft, and a control unit for controlling the operation of the actuator and the injection pump so that the solution falls from the nozzle to each of the wells. do.

In addition, the object is, in accordance with the present invention, a chamber in which a plurality of wells are arranged along a circumferential direction about a rotation axis; A nozzle disposed on one of the wells; An injection pump that sends a solution to the nozzle; And an actuator that rotates the rotation shaft, wherein the injection pump is provided in plural, and the nozzle is provided in plural and is respectively connected to the infusion pump.

According to the present invention, it is possible to provide an automatic medium replacement system configured to create various test environments in a plurality of wells by selectively injecting a solution for each well while the chamber rotates.

1 is a plan view of an automatic badge replacement system according to an embodiment of the present invention.
2 is a perspective view showing a chamber, a nozzle, and an actuator of the automatic badge replacement system of FIG. 1.
3 is a plan view showing a chamber, a nozzle, and an actuator of the automatic badge replacement system of FIG. 1.
FIG. 4 is a side view showing a chamber, a nozzle, and an actuator of the automatic badge replacement system of FIG. 1.
5 is a side view showing a well, a connection pipe, and a discharge pipe of the automatic medium replacement system of FIG. 1.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, in describing the present invention, a description of a function or configuration that is already known will be omitted in order to clarify the gist of the present invention.

The automatic medium replacement system of the present invention is made to create various test environments in a plurality of wells.

1 is a plan view of an automatic badge replacement system according to an embodiment of the present invention, FIG. 2 is a perspective view showing a chamber, a nozzle, and an actuator of the automatic badge replacement system of FIG. 1, and FIG. 3 is the automatic badge replacement system of FIG. Is a plan view showing the chamber, the nozzle and the actuator of FIG. 4 is a side view showing the chamber, the nozzle and the actuator of the automatic badge replacement system of FIG. 1, and FIG. 5 is It is a side view showing.

As shown in Figure 1, the automatic medium replacement system 10 according to an embodiment of the present invention is made so that cells isolated from tissues or organs of an individual are cultured outside the individual, the chamber 100, the nozzle 200 ), an injection pump 300, a discharge pump 400, an actuator 500, a support 600, a base 700, and a control unit 800.

2 and 3, the nozzle 200 is configured to supply a solution to the well 110, and includes a first nozzle 210, a second nozzle 220, and a third nozzle 230 It is composed by

The first nozzle 210 is configured to supply a medium to the well 110. The second nozzle 220 is configured to supply a washing liquid to the well 110. The third nozzle 230 is configured to supply a chemical solution to the well 110.

The first nozzle 210, the second nozzle 220, and the third nozzle 230 are mounted on the rotation support 620. The first nozzle 210, the second nozzle 220, and the third nozzle 230 are disposed together on any one of the wells 110 by the rotation support 620.

As shown in FIG. 1, the injection pump 300 is configured to send a solution to the nozzle 200, and includes a first injection pump 310, a second injection pump 320, and a third injection pump 330 It is composed by

The first injection pump 310 is configured to send a medium to the first nozzle 210. The first injection pump 310 is connected by a medium tank and a tube 311. In addition, the first injection pump 310 is connected by the first nozzle 210 and the tube 312.

The second injection pump 320 is configured to send the washing liquid to the second nozzle 220. The second injection pump 320 is connected by a washing liquid tank and a tube 321. In addition, the second injection pump 320 is connected by the second nozzle 220 and the tube 322.

The third injection pump 330 is configured to send a drug to the third nozzle 230. The third injection pump 330 is connected by a drug tank and a tube 331. In addition, the third injection pump 330 is connected to the third nozzle 230 and the tube 332.

The discharge pump 400 is configured to discharge the solution existing in the well 110. The discharge pump 400 is connected by a waste tank and a tube 401. In addition, the third injection pump 330 is connected by the discharge pipe 140 and the tube 402.

The first injection pump 310, the second injection pump 320, the third injection pump 330, and the discharge pump 400 are operated under the control of the controller 800.

As shown in FIG. 1, the first injection pump 310, the second injection pump 320, the third injection pump 330, and the discharge pump 400 may be mounted on the controller 800. The first injection pump 310, the second injection pump 320, the third injection pump 330, and the discharge pump 400 may be provided as a peristaltic pump.

The first infusion pump 310, the second infusion pump 320, the third infusion pump 330, and the discharge pump 400 do not directly contact the sterilized medium, washing liquid, and drugs, but a small amount of solution Should be able to control precisely.

In a metering pump, the motor squeezes the tube, so the solution in the tube does not contact the pump. A stepper motor is used in the metering pump. The stepper motor has the advantage of being able to control the number of revolutions very precisely.

As shown in FIG. 2, the base 700 is a configuration in which the chamber 100, the actuator 500, and the support 600 are installed, and forms a plate or plate-shaped block shape. A groove (hereinafter, referred to as'shaft hole') into which the lower end of the lower shaft 131 is rotatably inserted is formed in the base 700.

A mounting portion 710 is formed on the base 700. The mounting portion 710 protrudes upward from the upper surface of the base 700. A hole through which the bolt head is caught is formed in the mounting portion 710. The motor 510 is fixed to the upper surface of the base 700 by bolts inserted into the mounting portion 710.

As shown in FIGS. 2 to 4, the actuator 500 is configured to rotate the rotation shaft 130 and includes a motor 510 and a gear 520.

The gear 520 is provided as a shaft of a worm gear. A gear tooth meshing with the gear 520 is formed in the gear part 131A of the rotation shaft 130. The axes of the gear 520 and the gear portion 131A are orthogonal to each other. The gear 520 may transmit rotational force to the rotation shaft 130, but the lower rotation shaft 130 cannot rotate the gear 520.

The gear 520 is rotated by the motor 510. The motor 510 is provided as a step motor. The motor 510 rotates at a certain angle under the control of the controller 800. The motor 510 may rotate in a forward direction and a reverse direction under the control of the controller 800 to rotate the rotation shaft 130 in both directions.

As shown in FIGS. 2 to 4, the support 600 is a configuration supporting the nozzle 200 and is installed on the base 700. The support 600 is configured to include a fixed support 610 and a rotating support 620.

The fixing support 610 is provided on the base 700. The fixing support 610 protrudes upward from the upper surface of the base 700. A hole into which the lower end of the rotation support 620 is rotatably inserted is formed in the upper end of the fixing support 610.

The rotation support 620 is a configuration that supports the nozzle 200 and is rotatably mounted on the fixed support 610. The lower end of the rotary support 620 is rotatably inserted into a hole formed at the upper end of the fixed support 610.

As shown in FIG. 4, a researcher performing cell culture may rotate the rotating support 620 to position the nozzles 200 outside the chamber 100. The upper shaft 132 and the lower shaft 131 may be coupled or separated while the nozzles 200 are positioned outside the chamber 100.

A tube support part 621 into which tubes are inserted may be formed in the rotation support 620. The tubes may be disposed inside the tube support 621.

2 to 4, the chamber 100 is a configuration that forms a plurality of wells 110, the well 110, the connecting member 120, the rotation shaft 130, the discharge pipe 140 and the connection It is configured to include a tube 150.

The wells 110 form a culture space in which cells are cultured. The wells 110 form a cylindrical shape of the same size. The wells 110 are disposed along the circumferential direction around the rotation shaft 130. The wells 110 may be made of a transparent plastic material such as polydimethylsiloxane (PDMS), polystyrene (PS), and polyethylene (PE).

As illustrated in FIG. 5, an insert 111 may be inserted into the well 110. As disclosed in Registered Patent Publication No. 1367855 Cell Culture Device, since the insert 111 inserted into the well 110 is a known technology, a detailed description thereof will be omitted.

2 and 3, the connecting member 120 is a configuration that connects the wells 110 and forms a ring shape. The wells 110 are arranged along the circumferential direction by the connecting member 120.

The connection member 120 may be formed of the same material as the wells 110. The connecting member 120 and the well 110 may be integrally manufactured by injection molding. Alternatively, the connecting member 120 and the well 110 may be formed and then combined by thermal bonding.

As shown in FIG. 4, the rotation shaft 130 is configured to form an axis of the chamber 100, and includes a lower shaft 131 and an upper shaft 132.

The lower shaft 131 is rotatably mounted on the base 700. The lower end of the lower shaft 131 is rotatably inserted into a shaft hole formed in the base 700. The lower shaft 131 is formed with a gear portion 131A and an insertion groove 131H.

The gear part 131A is configured to receive the rotational force of the actuator 500 and forms a gear tooth along the circumferential direction around the lower shaft 131.

As described above, the rotational force of the motor 510 is transmitted to the gear unit 131A through the gear 520. When the motor 510 rotates at a certain angle under the control of the controller 800, the lower shaft 131 also rotates at a certain angle.

The upper shaft 132 is detachably coupled to the lower shaft 131. An insertion groove 131H into which the lower portion of the upper shaft 132 is inserted is formed in the lower shaft 131. A rubber ring 132R is coupled to the lower portion of the upper shaft 132.

When the upper shaft 132 is inserted into the insertion groove 131H, the rubber ring 132R is compressed between the upper shaft 132 and the inner surface of the insertion groove 131H. The upper shaft 132 and the lower shaft 131 form a coupling force by the elasticity and frictional force of the rubber ring 132R.

As shown in FIGS. 4 and 5, the discharge pipe 140 forms a single outlet for discharging the solution discharged from the wells 110 to the outside of the chamber 100. The discharge pipe 140 is formed on the upper shaft 132. The discharge pipe 140 and the upper shaft 132 may be integrally manufactured by injection molding. Alternatively, the discharge pipe 140 and the upper shaft 132 may be respectively molded and then joined by thermal bonding.

The connection pipe 150 connects the wells 110 to the upper end of the single discharge pipe 140, respectively. The connection pipes 150 form a passage through which the solution of the wells 110 moves to the single discharge pipe 140. The connection pipes 150 and the wells 110 form a one-to-one correspondence structure.

When the discharge pump is operated, the solutions in the wells 110 move to the single discharge pipe 140 through the connection pipe 150 at the same time by the negative pressure formed in the single discharge pipe 140.

As shown in FIG. 3, the connection pipes 150 form a radial shape around the upper end of the single discharge pipe 140. The upper end of the discharge pipe 140 is located at the center of the rotation shaft 130. Therefore, the wells 110 and the connection pipe 150 form an axisymmetric structure with respect to the rotation shaft 130.

The upper shaft 132 is mechanically connected to the wells 110 by a connection pipe 150. That is, the wells 110 and the upper shaft 132 behave integrally due to the rigidity of the connection pipe 150. The upper shaft 132 and the connection pipe 150 may be integrally manufactured by injection molding. Alternatively, the upper shaft 132 and the connection pipe 150 may be respectively molded and then joined by thermal bonding.

As shown in FIG. 5, the connection pipe 150 includes a bent pipe 151 and a horizontal pipe 152.

The bent tube 151 is connected to the lower end of the well 110. When the discharge pump 400 is operated, the solution in the well 110 first moves to the bent tube 151. The horizontal pipe 152 connects the bent pipe 151 and the discharge pipe 140 in a horizontal direction. Accordingly, when the discharge pump 400 is operated, the solution in the well 110 moves to the discharge pipe 140 by sequentially passing through the bent pipe 151 and the horizontal pipe 152.

As shown in FIG. 5, some or all of the bent pipe 151 is not higher than the horizontal pipe 152. Accordingly, the solution remaining in the bent tube 151 (hereinafter, “remaining solution”) does not move to the horizontal tube 152 only by gravity.

Therefore, even if the discharge pump 400 is turned off immediately after the solution in the well 110 is discharged to the connection pipe 150, a certain amount of the solution can always be left in the bent pipe 151. Thereafter, when the injection pump 300 is operated to supply a new solution to the well 110, the new solution is filled into the well 110 on top of the remaining solution.

As shown in FIG. 1, the controller 800 is a component that controls the operation of the injection pump 300, the discharge pump 400, and the actuator 500. The controller 800 controls the operation of the infusion pump 300, the discharge pump 400, and the actuator 500 to periodically replenish the fresh medium and chemical solution to each well 110 during a long cell culture period.

The controller 800 controls the operation of the infusion pump 300, the discharge pump 400, and the actuator 500 so that any one or more of a medium, a washing liquid, and a drug fall from the nozzle 200 to each of the wells 110. I can.

The controller 800 may control the operation of the discharge pump 400 so that the discharge pump 400 simultaneously discharges the solution in the wells 110 at a specific time.

Then, the controller 800 may control the operation of the actuator 500 so that the nozzle 200 is positioned above the specific well 110 among the plurality of wells 110. The control unit 800 rotates the motor 510 in both directions to position the nozzle 200 above the specific well 110 in the shortest time.

Thereafter, the controller 800 may control the operation of the infusion pump 300 so that at least one of a medium, a washing solution, and a drug is supplied to the specific well 110.

Although not shown in detail, the controller 800 may include an Arduino and a pump driver. In addition, the controller 800 may include an input button and a display panel. A researcher performing cell culture may input a fresh medium, a washing solution, a replenishment cycle, and a replenishment amount for each well 110 through an input button.

According to the present invention, it is possible to provide an automatic medium replacement system configured to create various test environments in a plurality of wells by selectively injecting a solution for each well while the chamber rotates.

In the above, although specific embodiments of the present invention have been described and illustrated, the present invention is not limited to the described embodiments, and various modifications and variations can be made without departing from the spirit and scope of the present invention. It is self-evident to those who have. Therefore, such modifications or variations should not be individually understood from the technical spirit or point of view of the present invention, and the modified embodiments should be said to belong to the claims of the present invention.

10: replacement system
100: chamber 300: injection pump
110: well 310: first injection pump
111: insert 320: second injection pump
120: connecting member 330: third injection pump
130: rotary shaft 400: discharge pump
131: lower shaft 500: actuator
131A: gear unit 510: motor
131H: insertion groove 520: gear
132: upper shaft 600: support
132R: rubber ring 610: fixed support
140: discharge pipe 620: rotating support
150: connector 621: tube support
151: bending pipe 700: base
152: horizontal pipe 710: mounting part
200: nozzle 800: control unit
210: first nozzle
220: second nozzle
230: third nozzle
311,312,321,322,331,332,401,402: Tube

Claims (10)

A chamber in which a plurality of wells are disposed along a circumferential direction about a rotation axis;
A nozzle disposed on one of the wells;
An injection pump that sends a solution to the nozzle; And
Automatic badge replacement system comprising an actuator that rotates the rotating shaft. The method of claim 1,
It includes a discharge pump for discharging the solution in the well,
The chamber,
A discharge pipe connected to the discharge pump and formed on the rotation shaft; And
And a connection pipe for connecting the wells to the discharge pipe, and for transferring the solution of the wells to the discharge pipe. The method of claim 2,
The wells and the connection pipes are automatic medium replacement system, characterized in that the axisymmetric with respect to the rotation axis. The method of claim 2,
The connecting pipe,
A bent tube connected to the lower end of the well; And
It includes a horizontal pipe connecting the bent pipe and the discharge pipe,
Automatic badge replacement system, characterized in that some or all of the bent pipe is not higher than the horizontal pipe. The method of claim 1,
Gear teeth are formed along the circumferential direction on the rotation shaft,
The actuator,
A gear meshing with the gear; And
Automatic badge replacement system comprising a motor that rotates the gear. The method of claim 5,
A support for supporting the nozzle; And
Automatic badge replacement system comprising a base on which the support is installed. The method of claim 6,
The rotating shaft,
A lower shaft having the gear teeth formed and rotatably mounted to the base; And
And an upper shaft connected to the wells and detachably coupled to the lower shaft. The method of claim 6,
The support,
A fixed support provided on the base; And
Automatic badge replacement system, characterized in that it is rotatably mounted on the fixed support, and includes a rotating support for supporting the nozzle. A chamber in which a plurality of wells are disposed along a circumferential direction about a rotation axis;
A nozzle disposed on one of the wells;
An injection pump that sends a solution to the nozzle; And
Including an actuator that rotates the rotation shaft,
And a control unit for controlling the operation of the actuator and the injection pump so that the solution falls from the nozzle to each of the wells. A chamber in which a plurality of wells are disposed along a circumferential direction about a rotation axis;
A nozzle disposed on one of the wells;
An injection pump that sends a solution to the nozzle; And
Including an actuator that rotates the rotation shaft,
The injection pump is provided in plurality,
The automatic medium replacement system, characterized in that a plurality of nozzles are provided and are respectively connected to the injection pump.

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