KR102337372B1 - Apparatus for manufacturing artificail skin and micro plate - Google Patents

Abstract

An artificial skin manufacturing apparatus is disclosed. The artificial skin manufacturing apparatus according to the present invention includes: an incubator apparatus having a culture space and providing a culture environment for artificial skin; and a dispensing device having a dispensing space and sucking the fluid in the microplate or dispensing the fluid into the microplate; includes

Description

Artificial skin manufacturing device and microplate

The present invention relates to an artificial skin manufacturing apparatus for manufacturing artificial skin, and a microplate used in the artificial skin manufacturing apparatus.

When artificial skin is manufactured by a bioprinter or by hand, a micro plate is used for culturing cells and the like. These microplates are used in the form of inserting an insert containing cells, etc. into a plate base in which a well in which media can be contained is formed, and covering the plate cover.

In the conventional method for manufacturing artificial skin, the plate cover of the microplate is manually opened to dispense cells or collagen, and then the plate cover is closed again to be cultured in an incubator. In this way, when manually replacing the media of artificial skin being cultured in the microplate, lift the inserts one by one by hand and remove them from the wells, put the media into the wells while holding the inserts by hand, and then lower the inserts back into the wells. repeats the work placed on it.

In the process of replacing the media, the insert may be dropped or contaminated due to a user's mistake. Moreover, the whole process is time-consuming and costly.

Patent Publication No. 2017-0093105

The present invention has been devised to solve the above problems, and the process of dispensing cells and various fluids in the microplate, and the process of replacing the media are all made automatically, and a plurality of inserts can be operated at once, so that artificial skin is manufactured An object of the present invention is to provide an artificial skin manufacturing apparatus capable of reducing time and cost in the process and preventing contamination.

An artificial skin manufacturing apparatus for manufacturing artificial skin using a microplate according to an embodiment of the present invention includes: an incubator apparatus having a culture space and providing an artificial skin culture environment; and a dispensing device having a dispensing space and sucking the fluid in the microplate or dispensing the fluid into the microplate; The microplate comprises: a plate base having a plurality of wells formed thereon; an insert carrier having a plurality of carrier holes disposed on the plate base; 4 inserts, and a plate cover covering the plate base, wherein the dispensing device includes an insert carrier elevating module capable of displacing the insert carrier up and down.

According to an embodiment, the insert carrier lifting module further includes a carrier gripper gripping the insert carrier, and a carrier gripper transport module capable of vertically displacing the carrier gripper.

According to an embodiment, the carrier gripper may include a suction pad for adsorbing the insert carrier by using a suction force, and the suction pad adsorbs a portion between the carrier holes of the insert carrier.

According to an embodiment, the insert carrier elevating module further includes a drop catcher having a variable position and positioned below the carrier gripper, and a drop catcher transport module for moving the drop catcher to a position.

According to one embodiment, the dispensing device, a fluid suction / dispensing module for performing dispensing and suction of the fluid, and a container transfer module for moving the microplate between the fluid suction / dispensing module and the incubator device. include

According to one embodiment, the insert carrier lifting module is located on the position movement path of the micro plate by the container transfer module.

According to an embodiment, the container transport module includes a transport guide rail extending in at least one direction in a horizontal direction, and a container loading block positioned along the transport guide rail, wherein the container loading block includes the fluid Moving between the suction/dispensing module and the incubator device, the insert carrier lifting module includes a carrier gripper gripping the insert carrier, wherein the carrier gripper is positioned on the transport guide rail.

According to one embodiment, the fluid suction/dispensing module includes a fluid dispensing module for dispensing a fluid, an automatic pipette module for dispensing and sucking the fluid, and a module transport robot for positioning the fluid dispensing module and the automatic pipette module. include

According to an embodiment, the fluid dispensing module includes a fluid container in which a fluid is stored, a pneumatic pipe providing pneumatic pressure to the fluid container, and a cooling unit for cooling the fluid container.

According to an embodiment, the automatic pipette module includes a tip mounting protrusion capable of removably inserting a disposable tip, and the disposable tip is stored in the dispensing device.

According to one embodiment, the dispensing device further includes a tool storage module, the tool storage module, a container storage unit in which a predetermined tube container in which cells and media are stored, is used for suction and dispensing of fluid and a tip storage unit in which disposable tips are stored.

According to an embodiment, the tool storage module further includes a heating unit for heating the tube container stored in the container storage unit.

According to an embodiment, the tool storage module further includes a tip processing unit for processing the used disposable tip, and a fluid processing unit for processing the used fluid.

According to an embodiment, the incubator device includes a first housing having the culture space formed therein, a first container loading module on which the microplate is loaded, a first container carrying robot carrying the microplate, and the incubator and an environmental control module for controlling the environment within the housing.

According to an embodiment, the first housing includes a connection door provided on one side, and the dispensing device and the culture space of the incubator housing communicate with each other through the connection door.

According to an embodiment, the dispensing device further includes a second housing having the dispensing space formed therein, and a second container loading module in which the microplate is loaded, wherein the second housing includes an openable and openable main door. Including, the second container loading module is disposed on the inside of the main door.

According to an embodiment, the dispensing device includes a second container transport robot that transports the microplate in the second housing.

According to one embodiment, the control device for controlling the incubator device and the dispensing device; further includes.

The microplate used in the apparatus for manufacturing artificial skin according to an embodiment of the present invention includes: a plate base having a plurality of wells; an insert carrier placed on the plate base and having a plurality of carrier holes; an insert inserted into the well; and a plate cover covering the plate base, wherein the insert includes a body having a transparent membrane at the bottom inserted into the well, formed at the upper end of the body, and protruding in a horizontal direction to be supported on the insert carrier Includes support.

According to one embodiment, the insert further includes a through portion formed on the outer peripheral surface of the body.

According to the artificial skin manufacturing apparatus according to the present invention, the process of dispensing cells and fluids in the microplate and the process of replacing the media can all be performed automatically. In addition, a plurality of inserts can be lifted at once by the insert carrier. Therefore, time and cost can be saved in the artificial skin manufacturing process, and contamination can be prevented.

1 to 3 are views showing the structure of a microplate used in the artificial skin manufacturing apparatus according to an embodiment of the present invention.
4 is a view showing the appearance of an artificial skin manufacturing apparatus according to an embodiment of the present invention.
5 to 8 are views showing the appearance of the artificial skin manufacturing apparatus according to an embodiment of the present invention in a state in which the first housing and the second housing are separated.
9 is a view showing a first container loading module of the artificial skin manufacturing apparatus according to an embodiment of the present invention, and a first container transport robot.
10 is a view showing a second container loading module of the artificial skin manufacturing apparatus according to an embodiment of the present invention, and a portion of the second container transport robot.
11 is a view showing a tool storage module of the artificial skin manufacturing apparatus according to an embodiment of the present invention.
12 is a view showing a fluid dispensing module, an automatic pipette module, and a transport robot of the artificial skin manufacturing apparatus according to an embodiment of the present invention.
13 and 14 are views showing the fluid dispensing module of the artificial skin manufacturing apparatus according to an embodiment of the present invention.
15 is a view showing a container transfer module and an insert carrier elevating module of the artificial skin manufacturing apparatus according to an embodiment of the present invention.
16 to 18 are views showing the operation of the insert carrier lifting module of the artificial skin manufacturing apparatus according to an embodiment of the present invention.
19 and 20 are views showing a second container transport robot of the artificial skin manufacturing apparatus according to an embodiment of the present invention.

Hereinafter, with reference to the accompanying drawings, a preferred embodiment according to the present invention will be described.

Hereinafter, descriptions indicating the left-right, front-back, up-down, etc. directions in the description are based on the X-axis, Y-axis, and Z-axis illustrated in each figure. That is, the Y-axis is the front-back direction, the X-axis is the left-right direction, and the Z-axis is the up-down direction. Of course, the left-right, front-back, and up-down directions are relative concepts, and are not limited to a specific direction, respectively, and may be understood differently depending on the viewing direction.

In addition, the term "fluid" hereinafter is not a concept limited to a specific phase. That is, the "fluid" may be a liquid material, a mixture of a fluid and a solid, and may be in the form of a colloid or a gel. Therefore, in this specification, "fluid" may be understood as a general "material", and the meaning of "fluid" as "material" does not change even if the term is used differently.

<Microplate (1)>

1 to 3 show the overall structure used in the artificial skin manufacturing apparatus according to the embodiment of the present invention, Figure 2 shows a state in which the insert carrier 20 and the insert 30 are accommodated in the plate base 10. 3 shows taking out a plurality of inserts 30 using the insert carrier 20 .

Hereinafter, the microplate 1 used in the artificial skin manufacturing apparatus according to an embodiment of the present invention will be first described with reference to FIGS. 1 to 3 .

The microplate 1 includes a plate base 10 , an insert carrier 20 , an insert 30 , and a plate cover 40 .

The plate base 10 constitutes a lower part of the microplate 1 and includes a plurality of wells 12 formed on the upper surface. Each well 12 may have a predetermined depth and cross-sectional area. The plurality of wells 12 may have an MXN matrix arrangement. Various liquid media used for manufacturing artificial skin may be filled in the well 12 .

The insert carrier 20 is a plate-shaped member placed on the upper surface of the plate base 10 . The insert carrier 20 has a carrier hole 22 penetrating up and down. A plurality of carrier holes 22 are formed. The plurality of carrier holes 22 may have sizes and arrangements corresponding to the plurality of wells 12 formed in the plate base 10 . That is, the size of each carrier hole 22 may correspond (same or similar) to the size of each well 12, and the plurality of carrier holes 22 may have an MXN matrix arrangement. .

An insert 30 is a member in the form of a container that is put into each well 12 . The insert 30 has a body 32 whose bottom is made of a transparent membrane, and a support 34 provided at an upper end of the body 32 .

The body 32 is a cup-shaped part having a predetermined depth and cross-sectional area. The body 32 may have a depth and a cross-sectional area that can be inserted into the well 12 of the plate base 10 through the carrier hole 22 of the insert carrier 20 . In addition, a through portion 36 penetrating in the horizontal direction is formed on the outer circumferential surface of the body 32 .

Various cells used for manufacturing artificial skin may be contained in the body 32 . Accordingly, when the body 32 is put into the well 12 in a state in which cells, etc. are contained in the body 32, various media filled in the well 12 pass through the penetrating portion 36, and the body 32 Cells and the like within may be immersed in the media.

The support 34 is provided at the upper end of the body 32 and protrudes in the horizontal direction, and protrudes outward from the body 32 in the horizontal direction. Accordingly, when the insert 30 is inserted into the carrier hole 22 of the insert carrier 20 , the support 34 may be supported on the insert carrier 20 .

The plate cover 40 is a member that covers the plate base 10 . The insert carrier 20 is placed on the plate base 10 , and then the plate cover 40 may cover the plate base 10 in a state in which the insert 30 is inserted.

In the manufacture of artificial skin, cells and collagen, which are materials for making artificial skin, are dispensed and filled in the insert 30 , and a medium for culturing the artificial skin is filled in the well 12 . In this case, the media may be replaced with a cycle of several days.

According to the configuration as described above, the plurality of inserts 30 can be simply put into the plate base 10 , and the plurality of inserts 30 put into the plate base 10 can be easily taken out.

For example, in the case of the structure without the insert carrier 20, when the insert 30 is put into the plate base 10 or the insert 30 is taken out from the plate base 10, the inserts 30 are held one by one. Should be.

In this case, for example, when replacing the media filled in the wells 12 of the microplate 1, manually lift the inserts 30 one by one to remove them from the wells 12, and then put the media into the wells 12. The insert 30 must then be put back into the well 12 . Therefore, in the process of replacing the media, the insert 30 may be accidentally dropped by the user or contamination may occur. In addition, it takes a long time to work.

In the embodiment of the present invention, since the insert carrier 20 is provided, the media in the well 12 can be easily replaced by lifting the insert 30 at a time using the insert carrier 20 . Similarly, even when inserting the insert 30, a plurality of inserts 30 can be easily put in.

<Entire structure of artificial skin manufacturing device>

4 is a view showing the appearance of an artificial skin manufacturing apparatus according to an embodiment of the present invention. 5 to 8 are views showing the appearance of the artificial skin manufacturing apparatus according to an embodiment of the present invention in a state in which the first housing 110 and the second housing 210 are separated from each other in each direction. Hereinafter, the overall structure of the artificial skin manufacturing apparatus according to an embodiment of the present invention will be described with reference to FIGS. 4 to 8 .

The artificial skin manufacturing apparatus according to an embodiment of the present invention largely includes an incubator apparatus 100 , a dispensing apparatus 200 , and a control apparatus 300 .

The incubator device 100 is a device that provides an environment in which artificial skin can be cultured. The incubator apparatus 100 includes a first housing 110 , a first container loading module 120 , a first container transport robot 130 , and an environment control module (not shown).

The dispensing device 200 is a device capable of dispensing various media, cells, collagen, etc. in the microplate 1 . The dispensing device 200 includes a second housing 210 , a second container loading module 220 , a tool storage module 230 , a fluid dispensing module 240 , an automatic pipette module 250 , and a module transport robot 260 . , the container transport module 270 , the insert carrier elevating module 280 , and a second container transport robot 290 .

The control device 300 is a device capable of controlling the operation of the incubator device 100 and the dispensing device 200 . The control device 300 may include a predetermined CPU, an output means, and an input means. The control device 300 receives a user's signal, processes various commands, and controls the operation of the incubator device 100 and the dispensing device 200 . For example, the control device 300 may control an environment control module (not shown) of the incubator device 100 to create an environment suitable for culturing artificial skin in the incubator device 100.\

<Incubator device 100>

9 is a view showing the first container loading module 120, and the first container transport robot 130 in the incubator device 100 of the artificial skin manufacturing apparatus according to an embodiment of the present invention. Hereinafter, the incubator apparatus 100 will be described with reference to FIGS. 4 to 9 .

The incubator apparatus 100 may include a first housing 110 , a first container loading module 120 , a first container transport robot 130 , and an environment control module (not shown).

The first housing 110 is composed of a predetermined housing having a space therein. The space in the first housing 110 is composed of a culture space 112 equipped with a cell culture environment. The first housing 110 may have a structure and material suitable for blocking the exchange of gas, humidity, and temperature between the culture space 112 and the outside. Accordingly, the culture space 112 may be configured to maintain a cell culture environment.

A connection door 114 is provided on one side of the first housing 110 . Through the connection door 114 , the culture space 112 in the first housing 110 may communicate with the dispensing space 212 in the dispensing device 200 . The connection door 114 may include an openable and openable door, or may be configured as a communication space without a separate door.

The first container loading module 120 is a device capable of loading the microplate (1). The first vessel loading module 120 is embedded in the culture space 112 of the first housing 110 .

The first container loading module 120 may be configured as a tower-type multi-layer shelf capable of loading a plurality of microplates 1 . The first container loading module 120 may have a plurality of accommodation spaces 121 . Each micro plate 1 may be loaded in the storage space 121 . The accommodating space 121 is opened to one side, and the microplate 1 can be inserted or removed from the accommodating space 121 .

The first container transport robot 130 includes a first gripper module 131 , a transport module 132 capable of moving the first gripper module 131 in a three-dimensional space, and a shaft driving device 136 . include

The first gripper module 131 is a device for gripping the microplate 1 . The configuration of the first gripper module 131 is not limited. For example, as shown in the drawings, the first gripper module 131 may have a predetermined support panel that can be moved by supporting the bottom surface of the microplate 1 .

The transport module 132 is a device capable of moving the first gripper module 131 in a three-dimensional space. A specific shape of the transport module 132 is not limited. For example, as in the embodiment, it may be a three-axis motion device having three guide beams 133 , 134 , 135 extending in an X-axis, a Y-axis, and a Z-axis, respectively.

The shaft driving device 136 may rotate the first gripper module 131 . According to an embodiment, the first gripper module 131 may be rotated about the Z axis.

The first gripper module 131 may be moved in a three-dimensional space by the transport module 132 . In addition, it is rotatable about the Z-axis by the shaft drive device 136 .

By the operation of the transport module 132 and the shaft drive device 136 , the microplate 1 may be transported to the outside (dispensing space 212 ) through the connection door 114 , and the first container is loaded It may be accommodated in the module 120 .

The environment control module (not shown) is a device capable of controlling the environment of the culture space 112 in the incubator device 100 . Here, the environment includes gas, humidity, temperature, and the like, and is not limited to specific factors.

The culture space 112 in the incubator device 100 must maintain an environment suitable for cell culture. Therefore, it is preferable that an inert gas (eg, CO ₂ gas), humidity, and temperature (eg, 37° C.) are constantly maintained inside the culture space 112 . Accordingly, the environment control module (not shown) may include a gas control unit, a humidity control unit, and a temperature control unit. The gas control unit may supply an inert gas, the humidity control unit may control humidity to a specific level, and the temperature control unit may maintain the temperature at a specific temperature (eg, 37° C.).

<Dispensing device 200>

Hereinafter, the dispensing device 200 will be described with reference to FIGS. 4 to 8 .

The dispensing device 200 is a device capable of dispensing various media, cells, collagen, etc. in the microplate 1 . The dispensing device 200 includes a second housing 210 , a second container loading module 220 , a tool storage module 230 , an automatic pipette module 250 , a fluid dispensing module 240 , and a module transport robot 260 . , the container transport module 270 , the insert carrier elevating module 280 , and a second container transport robot 290 .

The second housing 210 is composed of a predetermined housing having a space therein. The space in the second housing 210 is formed of a dispensing space 212 in which dispensing of a fluid or the like can be performed.

The second housing 210 may have a structure and material suitable for blocking the exchange of gas, humidity, and temperature between the dispensing space 212 and the outside. Accordingly, it is possible to prevent the dispensing space 212 from being contaminated by the external environment. The dispensing space 212, like the culture space 112, may maintain a constant temperature, humidity, and a state filled with an inert gas, but is not limited thereto.

One side of the second housing 210 may be connected to the connection door 114 of the incubator device 100 . Accordingly, the culture space 112 in the incubating housing and the dispensing space 212 in the dispensing device 200 may communicate with each other through the connection door 114 .

An openable and openable main door 214 may be provided in front of the second housing 210 . The main door 214 may be opened and closed by a user.

Hereinafter, each configuration in the dispensing device 200 will be described.

<Second container loading module 220>

10 is a view showing a portion of the second container loading module 220, and the second container transport robot 290 of the artificial skin manufacturing apparatus according to an embodiment of the present invention.

The second container loading module 220 is a device capable of loading the microplate (1). The second container loading module 220 is embedded in the dispensing space 212 of the second housing 210 .

The second container loading module 220 may be configured as a tower-type multi-layer shelf on which a plurality of microplates 1 can be loaded. The second container loading module 220 may have a plurality of accommodation spaces 221 . Each of the microplates 1 may be loaded in the storage space 221 .

According to the embodiment, the storage space 221 may be opened in the front-rear direction. In addition, an opening/closing door 223 for opening and closing the rear of the storage space 221 may be provided in front of the second container loading module 220 . In addition, according to the embodiment, the second container loading module 220 may be located in the front in the dispensing space 212 , and the second container loading module 220 may be located in the rear of the main door 214 .

Accordingly, the microplate 1 may be transported from the rear of the second container loading module 220 and put into the storage space 221 . In addition, when the main door 214 provided in the front of the second housing 210 is opened, the second container loading module 220 is exposed, and the opening/closing door 223 provided in the second container loading module 220 is opened. The user can take out the micro plate 1 in the storage space 221 .

Also, according to the embodiment, the opening portions 222 may be formed on both sides of the storage space 221 to be opened in the lateral direction. Both sides of the microplate 1 put into the accommodation space 221 through the open part 222 may be exposed. Accordingly, the grip guide 293 of the container transport robot 260, which will be described later, can grip both sides of the microplate 1 through the open part 222 .

<Tool storage module 230>

11 is a view showing the tool storage module 230 of the artificial skin manufacturing apparatus according to an embodiment of the present invention.

The tool storage module 230 is configured to store various tools used for storage, dispensing, suction, and processing of various means used for manufacturing artificial skin, such as fluids, cells, and media. The tool storage module 230 may include a module housing 231 , a container storage unit 232 , a heating unit 234 , a tip storage unit 235 , a tip processing unit 237 , and a fluid processing unit 238 . have.

The module housing 231 may have a three-dimensional shape of a long direction as a whole. A container storage unit 232 , a heating unit 234 , a tip storage unit 235 , a tip processing unit 237 , and a fluid processing unit 238 are provided in the module housing 231 . Accordingly, the container storage unit 232 , the heating unit 234 , the tip storage unit 235 , the tip processing unit 237 , and the fluid processing unit 238 may integrally constitute one module.

The container storage unit 232 is a means for storing a container in which cells or media for making artificial skin are contained. The container may be, for example, a C-tube container, and the C-tube container may be seated and stored in the container storage unit 232 . A plurality of support grooves 233 may be formed on the upper surface of the container storage unit 232 . The plurality of support grooves 233 are arranged, for example, in a matrix of M×N, and a C-tube container may be seated in each support groove 233 .

Meanwhile, a plurality of container storage units 232 may be provided to store different types of C-tube containers. For example, a first container storage unit 232A for storing the first C-tube container (C-A) and a second container storage part 232B for storing the second C-tube container (C-B) may be provided. In this case, the media may be contained in the first C-tube container (C-A), and cells may be contained in the second C-tube container (C-B). However, the present invention is not limited thereto.

The heating unit 234 is a means for providing heat at a constant temperature to the C-tube vessel seated in the vessel storage unit 232 . The cells or media in the C-tube vessel need to be kept at a constant temperature (37° C.). Accordingly, the heating unit 234 may provide adequate heat to constantly maintain the temperature of the cells or media contained in the C-tube container. The heating unit 234 may include, for example, a temperature sensor, a heater, and a temperature controller for controlling the heater.

The tip storage unit 235 is a means in which a disposable tip (T) can be seated and stored. The disposable tip T is a member in the form of a straw that can be used for suction and dispensing of a fluid. A plurality of fitting grooves 236 may be formed on the upper surface of the tip storage unit 235 . The plurality of fitting grooves 236 may be arranged, for example, having a matrix of M×N, and a disposable tip T may be inserted and stored in each fitting groove 236 .

The tip processing unit 237 is a place where the used disposable tip (T) is thrown away. The tip processing unit 237 may be a box-shaped portion having an upwardly open collection space. The tip processing unit 237 may be taken out by the user. Therefore, it is possible to remove the disposable tip (T) in the tip processing unit (237).

The fluid processing unit 238 is a place where the used fluid is discarded. The fluid processing unit 238 may be a box-shaped part having a collection space open upward. The fluid processing unit 238 may be taken out by a user. Accordingly, the fluid in the fluid processing unit 238 may be removed.

As the tool storage module 230 is provided as described above, various tools and fluids used for manufacturing artificial skin can be stored integrally in one module.

<Fluid dispensing module 240, automatic pipette module 250, module transport robot 260>

12 is a view showing the fluid dispensing module 240, the automatic pipette module 250, and the transport robot 260 of the artificial skin manufacturing apparatus according to an embodiment of the present invention. 13 and 14 are views showing the fluid dispensing module 240 of the artificial skin manufacturing apparatus according to an embodiment of the present invention.

The fluid dispensing module 240 , the automatic pipette module 250 , and the module transport robot 260 are devices involved in suction and/or dispensing of various fluids. Accordingly, it can be said that the fluid dispensing module 240 , the automatic pipette module 250 , and the module transport robot 260 constitute one module (fluid suction/dispensing module).

The fluid dispensing module 240 includes a fluid container 241 , a pneumatic pipe 242 , a fixing part for the fluid container 241 , and a cooling part 245 .

The fluid container 241 is a container in which a predetermined fluid (eg, collagen, etc.) can be contained. The fluid container 241 is mounted in the fluid dispensing module 240 .

The pneumatic pipe 242 is a pipe having a predetermined length, and one end is connected to a predetermined pneumatic control unit (not shown) for dispensing, and the other end is connected to the fluid container 241 mounted in the fluid dispensing module 240. Can be connected have. Through the pneumatic pipe 242, air pressure provided from the pneumatic control unit (not shown) for dispensing may be transmitted to the fluid container 241 . Accordingly, the fluid in the fluid container 241 may be dispensed to the outside by the air pressure provided by the pneumatic control unit for dispensing (not shown).

The fixing guide 243 may be a predetermined fixing means for fixing a portion of the pneumatic pipe 242 . The fixing guide 243 may maintain the connection between the fluid container 241 injected into the dispensing module and the pneumatic pipe 242 .

The fixing pin 244 may be a predetermined pin for fixing the fluid container 241 mounted in the fluid dispensing module 240 .

The fixing guide 243 and the fixing pin 244 are an example of fixing means for fixing the fluid container 241 mounted in the fluid dispensing module 240 and the pneumatic pipe 242, and the shape is limited. I never do that.

The cooling unit 245 is a means for providing cold air to the fluid container 241 mounted in the fluid dispensing module 240 . The fluid container 241 may contain collagen for manufacturing artificial skin, and since the collagen hardens at room temperature, the temperature must be maintained at a constant temperature (eg, 10° C. or less). Accordingly, the cooling unit 245 may provide cold air to cool the collagen contained in the fluid container 241 . The cooling unit 245 may include, for example, a temperature sensor, a Peltier element, and a temperature controller for controlling the Peltier element.

The dispensing needle 246 may be provided to protrude from the lower end of the fluid dispensing module 240 . For example, when the fluid container 241 is mounted on the fluid dispensing module 240 , the lower end of the fluid container 241 may be connected to the dispensing needle 246 . Of course, the dispensing needle 246 may be integrally provided at the lower end of the fluid container 241 . When air pressure is transmitted to the fluid container 241 through the pneumatic pipe 242 , the fluid in the fluid container 241 may be dispensed downward through the dispensing needle 246 .

The automatic pipette module 250 is a device capable of sucking and dispensing a fluid. The automatic pipette module 250 has a tip mounting protrusion 251 protruding downward. A disposable tip T may be mounted on the tip mounting protrusion 251 . Accordingly, the automatic pipette module 250 may perform dispensing after sucking the fluid using the disposable tip T. The specific configuration of the automatic pipette module 250 is not limited, and any device capable of suctioning and dispensing a fluid by inserting a disposable tip T may be used.

The module transport robot 260 is a device capable of moving the automatic pipette module 250 and the fluid dispensing module 240 in a three-dimensional space. A specific form of the module transport robot 260 is not limited. For example, as in the embodiment, the module transport robot 260 includes three guide beams 261 , 262 , and 263 extending in the X-axis, Y-axis, and Z-axis, respectively, and the guide beams 261 and 262 , 263) may be a three-axis motion device for changing positions of the automatic pipette module 250 and the fluid dispensing module 240 in a three-dimensional space.

Since the automatic pipette module 250 and the fluid dispensing module 240 can be displaced within the movable range of the module transport robot 260 , suction and dispensing of fluid can be performed within the movable range of the module transport robot 260 . have. That is, the movable range of the module transport robot 260 may be understood as a fluid dispensing and suction area.

At this time, the automatic pipette module 250 and the fluid dispensing module 240 may move integrally in the X-axis and Y-axis directions, but may be separately displaced in the Z-axis direction. For example, a moving block 264 movable in the X-axis and Y-axis directions is provided, and the automatic pipette module 250 is connected to one side of the moving block 264, and the fluid dispensing module 240 is connected to the other side. have. In addition, the automatic pipette module 250 and the fluid dispensing module 240 are connected to the moving block 264 to each independently displace in the Z-axis.

By having the above configuration, the means for operating the automatic pipette module 250 and the fluid dispensing module 240 are reduced, and simple control can be achieved.

<The container transfer module 270 and the insert carrier elevating module 280>

15 is a view showing the container transfer module 270 and the insert carrier lifting module 280 of the artificial skin manufacturing apparatus according to an embodiment of the present invention. In addition, 16 to 18 are views showing the operation of the insert carrier lifting module 280 of the artificial skin manufacturing apparatus according to an embodiment of the present invention.

The container transfer module 270 includes a transfer guide rail 271 and a container loading block 272 disposed on the transfer guide rail 271 and movable along the transfer guide rail 271 .

The transport guide rail 271 may be a predetermined beam extending in the uniaxial direction and having a guide line. An extension direction of the transfer guide rail 271 may be an X-axis direction.

One end of the transfer guide rail 271 may be adjacent to the connection door 114 , and the other end may be adjacent to a position within the fluid dispensing and suction area (movable range of the transport robot 260 ). In addition, the transfer guide rail 271 passes through the insert carrier elevating module 280 .

The container loading block 272 is a predetermined block in which the microplate 1 can be loaded. One or more microplates 1 may be loaded on the container loading block 272 . The container loading block 272 is disposed on the transport guide rail 271 . The container loading block 272 is movable along the transfer guide rail 271 in the X-axis direction.

As described above, one end of the transfer guide rail 271 is adjacent to the connection door 114 of the incubator device 100 , and the other end is adjacent to a position in the fluid dispensing and suction area. In addition, the transfer guide rail 271 may pass through the insert carrier elevating module 280 . Accordingly, the container loading block 272 can move between the connecting door 114 and the fluid dispensing and suction area, and also pass through the insert carrier lifting module 280 .

The insert carrier lifting module 280 includes a stand 281 , a carrier gripper 282 , a carrier gripper transport module 283 for moving the carrier gripper 282 , a drop catcher 284 , and a drop catcher transport module 285 .

The stand 281 is an upright bar-shaped part. The stand 281 is located on one side of the path through which the transfer guide rail 271 of the container transfer module 270 passes.

The carrier gripper 282 is a device capable of gripping the insert carrier 20 . The carrier gripper 282 is connected to the stand 281 through the carrier gripper transport module 283 and is located on a path through which the transport guide rail 271 passes.

The specific shape of the carrier gripper 282 is not limited. As an example, the carrier gripper 282 may include a suction pad for adsorbing the insert carrier 20 , a suction pump and a suction valve providing suction force to the suction pad. Accordingly, the carrier gripper 282 may grip the insert carrier 20 by using negative pressure. The adsorption pad may adsorb the insert carrier 20 by sucking a portion between the respective carrier holes 22 formed in the insert carrier 20 .

As another example, the carrier gripper 282 may be a means capable of lifting by supporting at least a portion of the insert carrier 20 .

The carrier gripper transport module 283 is a device capable of moving the carrier gripper 282 . The carrier gripper transport module 283 may position the carrier gripper 282 in an up-down direction (Z-axis direction). Accordingly, the carrier gripper transport module 283 may be a uniaxial motion robot capable of moving the carrier gripper 282 in the Z-axis direction.

The drop catcher 284 may be any bowl-like device. The drop catcher 284 may have a predetermined area, and according to an embodiment, may have an area equal to or greater than that of the microplate 1 . The drop catcher 284 may be positioned on the same line as the carrier gripper 282 in the Y-axis direction.

The drop catcher transport module 285 is a device capable of moving the drop catcher 284 . The drop catcher transport module 285 can position the drop catcher 284 in a horizontal direction (eg, the Y-axis direction) on a predetermined height (eg, between the container loading block 272 and the carrier gripper 282 ). have. Accordingly, the drop catcher transport module 285 may be a uniaxial motion robot capable of moving the drop catcher 284 in the Y-axis direction.

The operation of the insert carrier elevating module 280 will be described as follows.

As described above, the insert carrier elevating module 280 may be located at one position between both ends of the transfer guide rail 271 of the container transfer module 270 . Accordingly, the insert carrier lifting module 280 is positioned on the movement path of the container loading block 272, and when the container loading block 272 moves along the transfer guide rail 271, the insert carrier lifting module 280 is moved. can pass

X along the transfer guide rail 271 of the container transfer module 270 in a state where the microplate 1 with the plate cover 40 removed is placed on the container loading block 272 of the container transfer module 270 It can move in the axial direction. When the container loading block 272 is positioned at the point where the insert carrier lifting module 280 is located, the container loading block 272 is stopped.

In this state, the carrier gripper 282 moves downward in the Z-axis direction to adsorb the insert carrier 20 . Subsequently, the carrier gripper 282 moves upward while adsorbing and gripping the insert carrier 20 .

Then, the drop catcher 284 is moved in the Y-axis direction by the drop catcher transport module 285 . Accordingly, the drop catcher 284 is positioned under the carrier gripper 282 and the insert carrier 20 , and at the same time positioned on the plate base 10 of the microplate 1 . Accordingly, the insert carrier 20 lifted by the insert carrier 20 and various liquids falling from the insert 30 fall on the drop catcher 284 . Therefore, contamination by the liquid can be prevented.

The operation of the carrier gripper 282 and the operation of the drop catcher 284 are as shown in FIGS. 16 to 18 . That is, the carrier gripper 282 raises and lowers the insert carrier 20 and the insert 30 as shown by the arrow A in FIGS. 16 to 18 , and then the drop catcher 284 moves as shown by the arrow B to move the insert carrier 20 and The liquid falling from the insert 30 falls on the drop catcher 284 .

<Second container transport robot 290 >

19 and 20 are views showing the second container transport robot 290 of the artificial skin manufacturing apparatus according to an embodiment of the present invention.

The second container transport robot 290 includes a gripper module 291 and a transport module 292 that can position the gripper module 291 in a three-dimensional space.

The gripper module 291 is a device for gripping the microplate 1 (or at least a portion of the microplate 1 ). For example, the gripper module 291 includes a grip guide 293 having a variable width, an operating means 294 for varying the width of the grip guide 293, and a rotating gripper module 291 . A shaft drive device 295 is included.

A plurality of grip guides 293 may be provided. The actuating means 294 may vary the distance between the grip guides 293 . Accordingly, a transport object such as the microplate 1 may be gripped between the two grip guides 293 .

The shaft driving device 295 may rotate the grip guide 293 about the central axis C. According to the embodiment, the grip guide 293 may be rotated about the Z axis. Although it has been described in this description that the grip guide 293 is rotated, the entire gripper module 291 may be rotated, and in the drawings, the entire gripper module 291 is shown to be rotatable about the central axis C. .

The transport module 292 is a device capable of moving the gripper module 291 in a three-dimensional space. A specific shape of the transport module 292 is not limited. For example, as in the embodiment, it may be a three-axis motion device having three guide beams 296 , 297 , 298 extending in the X-axis, Y-axis, and Z-axis respectively.

The gripper module 291 may be moved in a three-dimensional space by the transport module 292 .

The second container transport robot 290 may position the microplate 1 within the dispensing space 212 of the dispensing device 200 . Accordingly, various operations can be performed.

For example, the second container transport robot 290 is located between the tool storage module 230 and the connection door 114 in the X-axis direction, and the second container loading module 220 and the container in the Y-axis direction. It may be located between the transfer modules 270 .

Accordingly, an operation of placing the microplate 1 in the second container loading module 220 or opening and closing the plate cover 40 of the microplate 1 placed on the container transfer module 270 can be performed. have.

<Collagen dispensing for artificial skin production>

Hereinafter, collagen dispensing for the production of artificial skin will be described.

First, the microplate 1 loaded on the first container loading module 120 in the incubator device 100 is transported by the first container transport robot 130 . By the first container transport robot 130 , the microplate 1 is transferred to the container loading block 272 of the container transfer module 270 in the dispensing device 200 through the connection door 114 .

Next, the plate cover 40 of the microplate 1 is opened. In this case, the plate cover 40 of the microplate 1 may be opened using the gripper module 291 of the second container transport robot 290 in the dispensing device 200 .

Then, the container transfer module 270 moves the container loading block 272 along the transfer guide rail 271 . Accordingly, the container loading block 272 and the microplate 1 loaded on the container loading block 272 (the plate cover 40 open state) is the movable range of the transport robot 260 (fluid dispensing and suction area). transported to be located within.

The module transport robot 260 then moves the fluid dispensing module 240 onto the container loading block 272 . The fluid dispensing module 240 dispenses collagen in the fluid container 241 into the insert 30 of the microplate 1 .

When the dispensing of collagen is completed, the container transfer module 270 operates to move the container loading block 272 along the transfer guide rail 271 . Accordingly, the container loading block 272 moves in the direction in which the connecting door 114 is located.

Then, the plate cover 40 is covered on the microplate 1 . In this case, the plate cover 40 may be covered on the microplate 1 on the container loading block 272 using the second container transport robot 290 . Accordingly, the insert 30 in which collagen is dispensed is covered by the plate cover 40 .

The first container transport robot 130 transports the microplate 1 to the first container loading module 120 to be loaded back into the first container loading module 120 .

<Cell dispensing for artificial skin production>

Hereinafter, cell dispensing for the production of artificial skin will be described.

First, the microplate 1 loaded on the first container loading module 120 in the incubator device 100 is transported by the first container transport robot 130 . By the first container transport robot 130 , the microplate 1 is transferred to the container loading block 272 of the container transfer module 270 in the dispensing device 200 through the connection door 114 .

Next, the plate cover 40 of the microplate 1 is opened. In this case, the plate cover 40 of the microplate 1 may be opened using the gripper module 291 of the second container transport robot 290 in the dispensing device 200 .

Then, the container transfer module 270 moves the container loading block 272 along the transfer guide rail 271 . Accordingly, the container loading block 272 and the microplate 1 (the plate cover 40 open state) loaded on the container loading block 272 are transported so as to be positioned within the movable range of the transport robot 260 .

Then, the module transport robot 260 moves the automatic pipette module 250 onto the tool storage module 230 to suck the cells in the C-Tube of the tool storage module 230 . At this time, the automatic pipette module 250 may insert the disposable tip T into the tip mounting protrusion 251 before suctioning the cells.

When the automatic pipette module 250 completes cell aspiration, the transport robot 260 moves the automatic pipette module 250 onto the container loading block 272 . The automatic pipette module 250 dispenses cells into the insert 30 of the microplate 1 .

When the cell dispensing is completed, the container transfer module 270 operates to move the container loading block 272 along the transfer guide rail 271 . Accordingly, the container loading block 272 moves in the direction in which the connecting door 114 is located.

Then, the plate cover 40 is covered on the microplate 1 . In this case, the plate cover 40 may be covered on the microplate 1 on the container loading block 272 using the second container transport robot 290 . Accordingly, the insert 30 in which the cells are dispensed is covered by the plate cover 40 .

The first container transport robot 130 transports the microplate 1 to the first container loading module 120 to be loaded back into the first container loading module 120 .

<Explanation of media replacement operation>

Hereinafter, replacement of the media in the well 12 of the microplate 1 is demonstrated.

First, the microplate 1 loaded on the first container loading module 120 in the incubator device 100 is transported by the first container transport robot 130 . The artificial skin being cultured is contained in the microplate (1). By the first container transport robot 130 , the microplate 1 is transferred to the container loading block 272 of the container transfer module 270 in the dispensing device 200 through the connection door 114 .

Next, the plate cover 40 of the microplate 1 is opened. In this case, the plate cover 40 of the microplate 1 may be opened using the gripper module 291 of the second container transport robot 290 in the dispensing device 200 .

Then, the container transfer module 270 moves the container loading block 272 along the transfer guide rail 271 . When the container loading block 272 and the microplate 1 (the plate cover 40 open state) loaded on the container loading block 272 are positioned at the position where the insert carrier lifting module 280 is located, the container transfer module 270 it stops

Next, the insert carrier 20 is lifted by using the carrier gripper 282 of the insert carrier lifting module 280 . At this time, as described in the description of the microplate 1 above, when the insert carrier 20 is lifted, the insert 30 is also lifted together.

As the insert carrier 20 and the insert 30 are lifted in this way, the micro plate 1 on the container loading block 272 remains only the plate base 10 . At this time, the drop catcher transport module 285 may operate so that the liquid falling from the insert carrier 20 and the insert 30 may fall on the drop catcher 284 .

Then, the container transfer module 270 moves the container loading block 272 along the transfer guide rail 271 again. Accordingly, the container loading block 272 and the microplate 1 (a state in which only the plate base 10 remains) loaded on the container loading block 272 are transported so as to be positioned within the movable range of the transport robot 260 .

Next, the transport robot 260 moves the automatic pipette module 250 onto the microplate 1 , sucks the existing media filled in the well 12 of the microplate 1 , and then the fluid processing unit (238) and discarded. At this time, the automatic pipette module 250 may insert the disposable tip T into the tip mounting protrusion 251 before suctioning the media. The transport robot 260 then moves the automatic pipette module 250 onto the tool storage module 230 to aspirate fresh media in the C-tube container of the tool storage module 230 .

When the automatic pipette module 250 completes aspiration of the media, the transport robot 260 moves the automatic pipette module 250 onto the container loading block 272 . The automatic pipette module 250 dispenses fresh media into the wells 12 of the plate base 10 . Thus, a replacement of the media in the well 12 is made.

When the dispensing of the media is completed, the container transfer module 270 operates to move the container loading block 272 along the transfer guide rail 271 .

When the container loading block 272 is again positioned at the position where the insert carrier lifting module 280 is located, the insert carrier lifting module 280 lowers the insert 30 and the insert carrier 20 onto the plate base 10 . . Of course, at this time, the drop catcher 284 is displaced from the position below the carrier gripper 282 . The insert carrier 20 is placed on the plate base 10 , and the insert 30 is put back into the well 12 .

Subsequently, the container transport module 270 moves the container loading block 272 in the direction in which the connection door 114 is located, and the second container transport robot 290 moves on the microplate 1 on the container loading block 272 . cover the plate cover (40).

The first container transport robot 130 transports the microplate 1 to the first container loading module 120 to be loaded back into the first container loading module 120 .

According to the artificial skin manufacturing apparatus according to the present invention, the process of dispensing cells and fluids in the microplate 1, or sucking the fluid, and the process of replacing the media can all be performed automatically. In addition, a plurality of inserts 30 can be lifted at once by the insert carrier 20 . Therefore, time and cost can be saved in the artificial skin manufacturing process, and contamination can be prevented.

Although preferred embodiments have been illustrated and described above, the present invention is not limited to the specific embodiments described above, and common knowledge in the technical field to which the present invention pertains without departing from the gist of the present invention as claimed in the claims is not limited. Various modifications are possible by the possessor, of course, and these modifications should not be individually understood from the technical spirit or prospect of the present invention.

1: Microplate
10: plate base
12: well
20: insert carrier
22: carrier hole
30: insert
32: body
34: support
36: penetrating part
40: plate cover
100: incubator device
110: first housing
112: culture space
114: connecting door
120: first container loading module
121: storage space
130: first container transport robot
131: first gripper module
132: transport module
133, 134, 135: guide beam
136: shaft drive device
200: dispensing device
210: second housing
212: busy space
214: main door
220: second container loading module
221: storage space
222: open part
223: opening and closing door
230: tool storage module
231: module housing
232: container storage unit
233: support groove
234: heating unit
235: tip storage unit
236: fitting groove
237: tip processing unit
238: fluid handling unit
240: fluid dispensing module
241: fluid container
242: pneumatic piping
243: fixing guide
244: fixing pin
245: cooling unit
246: busy needle
250: automatic pipette module
251: tip mounting protrusion
260: modular transport robot
261, 262, 263: guide beam
264: move block
270: vessel transfer module
271: transport guide rail
272: container loading block
280: insert carrier lifting module
281: stand
282: carrier gripper
283: carrier gripper transport module
284: drop catcher
285: drop catcher transport module
290: second container transport robot
291: gripper module
292: transport module
293: grip guide
294: actuation means
295: shaft drive
296, 297, 298: guide beam
300: control unit

Claims (20)

In the artificial skin manufacturing apparatus for manufacturing artificial skin using a microplate,
The artificial skin manufacturing apparatus,
an incubator device having a culture space and providing an artificial skin culture environment; and
a dispensing device having a dispensing space and sucking the fluid in the microplate or dispensing the fluid into the microplate; includes,
The microplate is
A plate base having a plurality of wells formed therein;
an insert carrier placed on the plate base and having a plurality of carrier holes formed therein;
a plurality of inserts introduced into the well and at least a portion of which is supported on the insert carrier; and
a plate cover covering the plate base;
The dispensing device is
an insert carrier elevating module capable of vertically displacing the insert carrier;
a fluid suction/dispensing module for dispensing and suctioning the fluid; and
A container transfer module for moving the microplate between the fluid suction/dispensing module and the incubator device; includes,
The insert carrier elevating module,
It is located on the position movement path of the microplate by the container transfer module,
The container transfer module,
a transport guide rail extending in at least one direction in a horizontal direction;
And a container loading block for moving the position along the transport guide rail,
The container loading block moves between the fluid suction / dispensing module and the incubator device,
The insert carrier lifting module includes a carrier gripper for gripping the insert carrier, wherein the carrier gripper is located on the transfer guide rail artificial skin manufacturing apparatus. According to claim 1,
The insert carrier elevating module,
a carrier gripper gripping the insert carrier, and
The artificial skin manufacturing apparatus further comprising a carrier gripper transport module capable of vertically displacing the carrier gripper. 3. The method of claim 2,
The carrier gripper,
and a suction pad for adsorbing the insert carrier using suction force,
The suction pad is an artificial skin manufacturing device for adsorbing a portion between the carrier hole of the insert carrier. 3. The method of claim 2,
The insert carrier elevating module,
a drop catcher variable in position and capable of being positioned below the carrier gripper; and
Artificial skin manufacturing apparatus further comprising a drop catcher transport module for moving the drop catcher position. delete delete delete According to claim 1,
The fluid suction / dispensing module,
a fluid dispensing module for dispensing a fluid;
an automatic pipette module for dispensing and aspirating fluid; and
An artificial skin manufacturing apparatus comprising a module transport robot for moving the fluid dispensing module and the automatic pipette module. 9. The method of claim 8,
The fluid dispensing module,
a fluid container in which the fluid is stored;
a pneumatic tubing providing pneumatic pressure to the fluid container; and
Artificial skin manufacturing apparatus comprising a cooling unit for cooling the fluid container. 9. The method of claim 8,
The automatic pipette module comprises:
a tip mounting protrusion capable of removably inserting the disposable tip;
The disposable tip is
An artificial skin manufacturing device stored in the dispensing device. According to claim 1,
The dispensing device is
It further comprises a tool storage module,
The tool storage module,
A container storage unit in which a predetermined tube container in which cells and media are stored,
An artificial skin manufacturing device including a tip storage unit in which disposable tips used for suction and dispensing of fluid are stored. 12. The method of claim 11,
The tool storage module,
Artificial skin manufacturing apparatus further comprising a heating unit for heating the tube container stored in the container storage unit. 12. The method of claim 11,
The tool storage module,
a tip processing unit in which the used disposable tip is processed; and
Artificial skin manufacturing apparatus further comprising a fluid processing unit to which the used fluid is processed. According to claim 1,
The incubator device,
a first housing in which the culture space is formed;
a first container loading module on which the microplate is loaded;
a first container transport robot that transports the microplate, and
Artificial skin manufacturing apparatus including an environment control module for controlling the environment in the incubator housing. 15. The method of claim 14,
The first housing includes a connection door provided on one side,
An artificial skin manufacturing device in which the dispensing device and the culture space of the incubator housing communicate through the connection door. According to claim 1,
The dispensing device is
a second housing in which the dispensing space is formed; and
Further comprising a second container loading module on which the microplate is loaded,
The second housing includes an openable and openable main door,
An artificial skin manufacturing apparatus in which the second container loading module is disposed inside the main door. 17. The method of claim 16,
The dispensing device is
Artificial skin manufacturing apparatus including a second container transport robot for transporting the microplate in the second housing. According to claim 1,
The artificial skin manufacturing device further comprising; a control device for controlling the incubator device and the dispensing device. delete delete

Images