Germ extract liquid production system

Abstract

To provide a germ extract liquid production system that can reduce variation in quality of germ extract liquid produced from germs.SOLUTION: A germ extract liquid production system 100 comprises a centrifugal separator 1, a filter device 2, a detaching / attaching device 3, and a carrier device 4. The centrifugal separator 1 rotates a container B containing germ mixed fluid GMF, which is formed by mixing germs G into amino acid solution AL containing amino acid, in a lidded state to centrifugally separate the germ mixed fluid GMF, and thereby extracts germ extract material GEM from the germs G. The filter device 2, by filtering the germ mixed fluid GMF coming out of the container B containing the centrifugally separated germ mixed fluid GMF, generates germ extract liquid from the germ extract material GEM. The detaching / attaching device 3 detaches / attaches the lid from / to the container B. The carrier device 4 carries the container B to the centrifugal separator 1, the filter device 2 and the detaching / attaching device 3.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to an embryo extract producing system for producing an embryo extract for cell-free protein synthesis. [Background technology]

[0002] Germ extracts extracted from plant germs are used for protein production in cell-free protein synthesis systems. The germs used to prepare germ extracts are generally harvested from wheat, barley, rice, corn, and other grasses. The germs harvested from such plants are finely ground. The ground germs are placed in a centrifuge tube together with an amino acid solution containing various types of amino acids. The germ extract is extracted from the germs by mixing the ground germs with the amino acid solution, subjecting the resulting germ mixture to stirring, centrifugation, and filtration including ultrafiltration or chromatography. The germ extract extracted from the germs is then subjected to post-treatment according to the purpose. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 6-094700 [Patent Document 2] Patent No. 6230138 Summary of the Invention [Problem to be solved by the invention]

[0004] However, since germ extract is produced manually, there is a large variation in quality after production. Therefore, if the production of germ extract is automated, the variation in quality of the germ extract can be reduced. As an example of automating the production process, the devices disclosed in Patent Documents 1 and 2 are disclosed. However, the devices in Patent Documents 1 and 2 produce something other than germ extract.

[0005] Therefore, an object of the present invention is to provide a germ extract production system that can reduce the variation in quality of germ extract produced from germs. [Means for solving the problem]

[0006] The embryo extract production system of the present invention is characterized by comprising a centrifuge device that extracts an embryo extract from the embryo by rotating a covered container containing an embryo mixture in which an embryo is mixed with an amino acid solution containing amino acids and centrifuging the embryo mixture, a filtration device that produces an embryo extract from the embryo extract by filtering the embryo mixture discharged from the container containing the centrifuged embryo mixture, a detachment device that attaches and detaches the lid to the container, and a transport device that transports the container to the centrifuge device, the filtration device, and the detachment device. Effect of the Invention

[0007] According to the embryo extract production system of the present invention, it is possible to reduce variation in the quality of the embryo extract produced from embryos. [Brief description of the drawings]

[0008] [Figure 1] 1 is a schematic three-dimensional diagram of an embryo extract production system according to an embodiment of the present invention, in which a portion of a box body is omitted. [Diagram 2] FIG. 2 is a plan view showing an outline of the embryo extract production system shown in FIG. 1, in which a part of a box body is omitted. [Diagram 3] FIG. 2 is a three-dimensional view of the removal unit shown in FIG. [Figure 4] FIG. 2 is a three-dimensional view of the filtration unit and the recovery unit shown in FIG. [Diagram 5] 2 is a front view of the installation / removal device and the transport device shown in FIG. [Figure 6] FIG. 2 is a three-dimensional view of the freezing device shown in FIG. [Figure 7] FIG. 2 is a three-dimensional view showing the entire embryo extract production system shown in FIG. 1. [Figure 8]3 is a flowchart showing the steps of producing an embryo extract in the embryo extract production system according to the embodiment. [Figure 9] 13A and 13B are diagrams showing the state in which the attachment / detachment device closes the lid. [Figure 10] FIG. 13 is a diagram showing a state in which a robot arm stirs the germ mixture in a centrifuge tube. [Figure 11] FIG. 13 is a diagram illustrating a state in which a robot arm sets a centrifuge tube in a centrifugal separator. [Figure 12] FIG. 2 is a time-course diagram showing an outline of how an embryo extract is recovered by a recovery unit, and shows how the embryo extract is filtered and extracted by ultrafiltration or chromatography. [Figure 13] FIG. 13 is a time-course diagram showing an outline of how the germ extract is recovered by the recovery unit, showing the state in which the recovery container receives the germ extract. [Figure 14] FIG. 13 is a time-series diagram showing an outline of how germ extract is recovered by the recovery unit, showing a state in which the recovery container that has received the germ extract is transported by a transport device. [Figure 15] FIG. 2 is a schematic diagram showing a state in which a freezing device freezes an embryo extract. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] An embryo extract production system 100 according to an embodiment of the present invention will be described with reference to FIGS.

[0010] 1 and 2 automates the steps required to produce an embryo extract GEF, such as a centrifugation step for the embryo mixture GMF and a filtration step for the embryo mixture GMF, including ultrafiltration or chromatography. Thus, the embryo extract production system 100 reduces the occurrence of human error, foreign matter contamination, and other variations in the quality of the embryo extract GEF that are unavoidable when producing an embryo extract GEF by manual labor.

[0011] The germ extract liquid production system 100 includes a centrifuge 1, a filtration device 2, a detachment device 3 for attaching and detaching a lid T to a container containing the germ mixture liquid GMF, a transport device 4, a post-treatment device 5 for performing post-treatment on the produced germ extract liquid GEF, and a box 6. The box 6 houses the centrifuge 1, the filtration device 2, the detachment device 3, the transport device 4, and the post-treatment device 5. The transport device 4 transports the container containing the germ mixture liquid GMF between the centrifuge 1, the filtration device 2, and the detachment device 3. For example, a centrifuge tube B for performing centrifugation is used as the container. In this way, the transport device 4 transports the centrifuge tube B containing the germ mixture liquid GMF between the centrifuge 1, the filtration device 2, and the detachment device 3, thereby producing the germ extract liquid GEF from the germ G. The germ extract liquid GEF is transported to the post-treatment device 5 by the transport device 4.

[0012] The centrifuge 1 rotates the centrifuge tube B containing the germ mixture GMF with the lid T closed, and centrifuges the germ mixture GMF. By centrifuging the germ mixture GMF, the germ extract GEM is extracted from the germ G into the solvent of the germ mixture GMF. The centrifuge 1 has a main body 11, an opening / closing door 12, and a rotating table 13. The main body 11 is a box having an internal space. The opening / closing door 12 is a door that automatically opens and closes an opening that leads from the outside of the main body 11 to the internal space of the main body 11. The opening and closing of the opening / closing door 12 is performed by an actuator (not shown) that changes the position of the opening / closing door 12. The rotating table 13 is a table that holds the centrifuge tube B, and rotates around a rotating shaft 13A (see FIG. 2) while being accommodated in the internal space of the main body 11. The rotating table 13 that holds the centrifuge tube B rotates, and the germ mixture GMF in the centrifuge tube B is centrifuged.

[0013] 1 and 2, the centrifuge 1 may be of a swing rotor type in which a holder becomes perpendicular to a rotation axis 13A due to centrifugal force, or an angle rotor type having a turntable 13 that holds centrifuge tubes B at an angle inclined to the rotation axis 13A. Specifically, the turntable 13 has a plurality of holders 13B. The holders 13B are arranged on the turntable 13 so as to be symmetrical with respect to the rotation axis 13A.

[0014] The filtration device 2 shown in Figures 3 and 4 performs a filtration process including ultrafiltration or chromatography on the germ mixture liquid GMF. As shown in Figure 3, the filtration device 2 filters the germ mixture liquid GMF discharged from the centrifuge tube B containing the centrifuged germ mixture liquid GMF. This removes the germ G and other substances from the germ mixture liquid GMF. Then, as shown in Figure 4, the filtration device 2 separates the germ extract GEM from the germ mixture liquid GMF from which the germ G has been removed, to produce a germ extract liquid GEF.

[0015] The filtration device 2 has a removal unit 21, a filtration unit 22, and a recovery unit 23. However, depending on the variety of the germs G or the state of the germ mixed liquid GMF after centrifugation, the removal unit 21 may be omitted.

[0016] The removal unit 21 shown in Figure 3 removes solids from the germ mixture GMF. Solids are impurities that are undesirable for being mixed into the finely ground germs G and other germ extract GEF. The removal unit 21 separates the solution containing the germ extract GEM from solids such as germs G.

[0017] Specifically, the removal unit 21 includes a funnel 211 , a filter 212 , a filter conveyor 213 , and a container conveyor 214 .

[0018] The funnel 211 receives the germ-mixed liquid GMF and guides it to the filter 212. The filter 212 is disposed at the destination (outlet 21A) of the germ-mixed liquid GMF that flows down the funnel 211. As the germ-mixed liquid GMF passes through the filter 212, solid matter is removed from the germ-mixed liquid GMF. The mesh size of the filter 212 is appropriately determined taking into consideration the size of the solid matter to be removed. Preferably, there are multiple filters 212. If there are multiple filters 212, when the germ-mixed liquid GMF is filtered multiple times, unused filters 212 can be used in each filtration step.

[0019] The filter conveyor 213 is a device that conveys any one of the multiple filters 212 to the outlet 21A of the funnel 211. The filter conveyor 213 shown in Fig. 3 is a slider that slides on a path that passes through the outlet 21A of the funnel 211. With the filter conveyor 213, the germ mixed liquid GMF is filtered through an appropriate filter 212 according to the progress of the manufacturing process.

[0020] The container conveyor 214 places an empty centrifuge tube B under the filter 212 into which the germ-mixed liquid GMF is poured. The container conveyor 214 shown in FIG. 3 is a slider on which a holder 215 holding the empty centrifuge tube B moves on a path passing under the funnel 211 and the filter 212. The holder 215 holds each centrifuge tube B so that the mouth of the tube faces upward. By placing the centrifuge tube B under the filter 212 into which the germ-mixed liquid GMF is poured, the germ-mixed liquid GMF that has passed through the filter 212 enters the centrifuge tube B from the mouth of the tube B. It is preferable that the holder 215 holds a plurality of empty centrifuge tubes B. In this manner, the removal unit 21 can filter the germ-mixed liquid GMF multiple times without manual intervention.

[0021] 4 separates the germ extract GEM from the solution containing the germ extract GEM obtained by the removal unit 21 by ultrafiltration or chromatography. The filtration unit 22 includes a separation section 221, a supply mechanism 222, and a cooling tank 223 for the storage section.

[0022] The separation section 221 has, from the top, an injection section 22A, a storage section 22B that holds an ultrafiltration membrane or a stationary phase filler for chromatography, etc., and stores a solution containing the embryo extract GEM, a discharge passage 22C, and a valve (not shown).

[0023] The injection section 22A is a section into which the solution containing the germ extract GEM obtained by the centrifugation process and the filtration process, and the eluate, as described below, are injected. The injection section 22A is a cylinder with an upward and downward opening, and its diameter decreases toward the bottom. The upward opening is a spout into which the solution containing the germ extract GEM and the eluate are poured. The downward opening is an outlet through which the germ mixed liquid GMF and the eluate exit from the inside of the injection section 22A to the outside. In this way, the germ mixed liquid GMF and the eluate are poured from the wide upper opening, so that the conveying device 4, described below, can easily pour the solution containing the germ extract GEM and the eluate into the injection section 22A.

[0024] The storage section 22B is a cylinder having an upward and downward opening. The upward opening is connected by a tube to the outlet of the separation section 221. The downward opening of the storage section 22B is an outlet through which the liquid that has entered the storage section 22B flows from the internal space of the storage section 22B to the outside.

[0025] The storage section 22B contains an ultrafiltration membrane or a chromatography stationary phase GL material. The ultrafiltration membrane passes a solution containing the germ extract GEM through the membrane, which captures the germ extract GEM from the solution, thereby separating the germ extract GEM. In the case of chromatography, the solution containing the germ extract GEM is brought into contact with the chromatography stationary phase GL material, whereby the germ extract GEM is separated by adsorption, distribution, ion exchange, or the like. The material, type, and / or amount of the chromatography stationary phase GL are appropriately determined depending on the type of germ extract GEM to be separated.

[0026] The discharge passage 22C is connected to the outlet of the storage section 22B. A valve (not shown) is provided between the outlet of the storage section 22B and the outlet of the discharge passage 22C to temporarily block the flow of liquid from inside the storage section 22B through the discharge passage 22C to the outside. The valve opens and closes as necessary.

[0027] The supply mechanism 222 supplies an eluate for eluting the germ extract GEM separated in the storage section 22B to the separation section 221 toward a collection container 234 that collects the germ extract GEM. The germ extract GEM separated in the storage section 22B is washed away with the eluate, thereby generating an germ extract GEF. The components contained in the eluate and the ratio of the components are appropriately determined depending on the type of ultrafiltration membrane or chromatography stationary phase GL and / or the type of germ extract GEM to be separated. Specifically, the supply mechanism 222 has a storage container 22D and a pump 22E.

[0028] The storage container 22D stores pure water PW or amino acid solution AL. The pure water PW is used to wash the ultrafiltration membrane or the chromatography stationary phase GL. The amino acid solution AL is used as an eluent. Three storage containers 22D, 22D, 22D are shown in FIG. 4. Each storage container 22D is provided with a different type of liquid, such as pure water PW or amino acid solution AL. The type and number of liquids to be stored are not limited to pure water PW or amino acid solution AL, but are determined according to the type of germ extract GEM.

[0029] The pure water PW and the amino acid solution AL stored in each storage container 22D are supplied to the injection section 22A by a pump 22E connected to each storage container 22D. When the eluate is supplied to the storage section 22B, the valve is closed in order to store a predetermined amount of the eluate in the separation section 221. Whether or not the predetermined amount of the eluate has accumulated in the separation section 221 is determined, for example, by whether or not the liquid level of the eluate in the liquid passage connecting the injection section 22A and the storage section 22B has reached a predetermined level. The liquid level of the eluate is measured, for example, by an optical or capacitive level sensor 22L. When it is determined that the predetermined amount of the eluate has accumulated, the valve is opened.

[0030] The storage unit cooling tank 223 cools the storage unit 22B and each storage container 22D. The storage unit cooling tank 223 shown in Fig. 4 is a container that accommodates the storage unit 22B, each storage container 22D, and a refrigerant CL. The refrigerant CL, which has been cooled by an appropriate method, cools the storage unit 22B and each storage container 22D. This prevents the germ extract GEM, the eluate, and the germ extract GEF from becoming hot and deteriorating when separation is performed by ultrafiltration or chromatography.

[0031] Preferably, each storage container 22D has a solution temperature sensor 22F. The solution temperature sensor 22F measures the temperature of the liquid stored in each storage container 22D. The solution temperature sensor 22F is, for example, a thermocouple or a resistance temperature detector. The temperature of the refrigerant CL in the storage section cooling tank 223 is set so that the temperature measured by the solution temperature sensor 22F is appropriate. Therefore, it is possible to prevent the liquid stored in each storage container 22D, such as the amino acid solution AL as the eluent or the pure water PW, from becoming too hot and deteriorating.

[0032] The recovery unit 23 recovers the germ extract GEF produced in the filtration unit 22. Specifically, the recovery unit 23 includes a rotary table 231, a disposal section 232, a holding structure 233, a recovery container 234, and a recovery cooling tank 235.

[0033] The turntable 231 is a disk that can rotate around an axis 23A that is aligned in the vertical direction. The turntable 231 is disposed below the discharge passage 22C. A disposal unit 232 and a holding structure 233 that holds a collection container 234 are provided on the upper portion of the turntable 231. Therefore, the disposal unit 232 or the holding structure 233 can be disposed below the discharge passage 22C by rotating the turntable 231. The lower portion of the turntable 231 is cooled by a collection cooling tank 235.

[0034] The waste unit 232 is a part that receives the liquid obtained by removing the germ extract GEM from the solution containing the germ extract GEM, or the pure water PW used to wash the ultrafiltration membrane or the chromatography stationary phase GL, from the separation unit 221. The waste unit 232 shown in Fig. 4 is a tube with a bottom that receives the liquid. Since the waste unit 232 opens upward, it can receive the liquid from the discharge passage 22C by being placed below the discharge passage 22C.

[0035] The holding structure 233 holds a collection container 234 for collecting the germ extract liquid GEF. The holding structure 233 shown in FIG. 4 is a holder that holds the collection container 234 so that the mouth of the collection container 234 faces diagonally upward. The holding structure 233 is disposed under the discharge passage 22C before the germ extract liquid GEF comes out of the discharge passage 22C. As a result, the germ extract liquid GEF that comes out of the discharge passage 22C enters the collection container 234. The amount of the germ extract liquid GEF that enters the collection container 234 is measured by an optical or ultrasonic level sensor 23B. If it is determined from the measurement result of the level sensor 23B that a predetermined amount or more of the germ extract liquid GEF is in the collection container 234, the collection container 234 is collected.

[0036] 4 is a container containing a refrigerant CL. A part of the holding structure 233 is immersed in the refrigerant CL. By immersing a part of the holding structure 233 in the refrigerant CL, the germ extract liquid GEF contained in the collection container 234 held by the holding structure 233 is held at a low temperature. As a result, the recovery cooling tank 235 prevents the germ extract liquid GEF contained in the collection container 234 from becoming too hot and deteriorating.

[0037] Preferably, the recovery unit 23 has a germ extract temperature sensor (not shown) that measures the temperature of the germ extract liquid GEF contained in the recovery container 234. The temperature of the germ extract liquid GEF can be measured by contacting a temperature sensor with the recovery container 234 or the holding structure 233. The temperature of the germ extract liquid GEF may also be measured indirectly by measuring the temperature of the refrigerant CL contained in the recovery cooling tank 235. If the temperature of the germ extract liquid GEF recovered by the recovery unit 23 can be measured, the temperature of the refrigerant CL in the recovery cooling tank 235 can be adjusted to prevent the temperature of the germ extract liquid GEF from increasing. A thermocouple, a resistance temperature detector, or the like is used as the germ extract temperature sensor.

[0038] The detachment device 3 shown in Fig. 5 attaches and detaches the lid T to and from the centrifuge tube B. The detachment device 3 rotates the lid T placed at the mouth of the centrifuge tube B to screw a threaded portion of the lid T into a threaded portion of the mouth of the centrifuge tube B, thereby closing the mouth of the centrifuge tube B with the lid T. Meanwhile, the detachment device 3 grasps the lid T attached to the centrifuge tube B and rotates it in a direction that loosens the screw, thereby removing the lid T from the centrifuge tube B.

[0039] Specifically, the attachment / detachment device 3 has a container holder 31 and a lid opening / closing mechanism 32. The container holder 31 holds the centrifuge tube B so as not to cover the mouth of the centrifuge tube B. The container holder 31 shown in FIG. 5 is a pair of claws that hold the centrifuge tube B by pinching it from the sides. The lid opening / closing mechanism 32 is a mechanism that rotates the lid T in a direction to open the lid T or in a direction to close the lid T with respect to the mouth of the centrifuge tube B while gripping the lid T. The lid opening / closing mechanism 32 shown in FIG. 5 has claws that pinch the lid T from three sides. The claws that grip the lid T move in a direction to approach or move away from the mouth of the centrifuge tube B.

[0040] Preferably, the detachment device 3 further includes an unused lid holder 33. The unused lid holder 33 is a holder that holds an unused lid T. The unused lid T is a lid T that has not yet been used in the production process of the embryo extract production system 100. If the mouth of the centrifuge tube B is not closed with a lid T, the lid opening / closing mechanism 32 grasps the unused lid T held by the unused lid holder 33 and attaches it to the mouth of the centrifuge tube B.

[0041] The transport device 4 transports the centrifuge tube B to the centrifugal separator 1, the filtration device 2, and the desorber 3 shown in Fig. 1. In this way, the germ mixture liquid GMF is centrifuged and filtered without relying on human hands. Therefore, the transport device 4 reduces the variation in the production quality of the germ extract liquid GEF that occurs depending on the operator.

[0042] Preferably, the transport device 4 has a robot arm 41 and an imager 42. The robot arm 41 is a device that can grasp objects such as centrifuge tubes B. Specifically, the robot arm 41 shown in FIG. 5 is a device that has a pair of claws for grasping objects at the tip of an arm having multiple joints. The pair of claws holds the centrifuge tube B by pinching it from the sides. Such a robot arm 41 can transport the centrifuge tube B three-dimensionally without employing a special structure. As a result, not only is the structure of the embryo extract production system 100 simplified, but the centrifuge tube B can be transported in a versatile manner within the embryo extract production system 100.

[0043] Furthermore, the robot arm 41 stirs the germ mixed liquid GMF contained in the centrifuge tube B by changing the posture of the centrifuge tube B over time. Therefore, the transport device 4 can stir the germ mixed liquid GMF in a fixed procedure each time, thereby reducing the variation in the quality of the germ extract liquid GEF. In addition, the robot arm 41 can be set to have a wider range of motion than a human arm. Therefore, the robot arm 41 can stir the germ mixed liquid GMF more efficiently than a human hand by changing the posture of the centrifuge tube B to a posture that cannot be achieved by hand.

[0044] The imager 42 captures an image of the periphery of the claws of the robot arm 41. Based on the image captured by the imager 42, the robot arm 41 can operate in accordance with the status of the centrifugal separator 1 or the filtering device 2 shown in FIG.

[0045] Preferably, the conveying device 4 further includes a case 43 and a coolant 44, as shown in FIG. 1. The case 43 houses the centrifuge tube B containing the germ mixture liquid GMF. The coolant 44 is housed in the case 43 together with the centrifuge tube B to cool the germ mixture liquid GMF. Specifically, the case 43 shown in FIG. 1 is provided with a holding part (not shown) that holds the two centrifuge tubes B, B in an upright position side by side. The two centrifuge tubes B, B and the holding part are housed in the case 43 together with the coolant 44. The coolant 44 is, for example, ice or other solid that can cool the centrifuge tube B. Such a coolant 44 has a low risk of penetrating into the centrifuge tube B or leaking out of the case 43, unlike the liquid coolant 44.

[0046] Furthermore, preferably, as shown in FIG. 5, the transport device 4 further includes a holding table 45. The holding table 45 is a table that temporarily holds the centrifuge tube B so that the robot arm 41 can hold the centrifuge tube B in various positions. The holding table 45 shown in FIG. 5 has a structure that holds the centrifuge tube B in a state in which the surface of the centrifuge tube B for the claws of the robot arm 41 to hold the centrifuge tube B from the side protrudes from the holding table 45. Therefore, the claws of the robot arm 41 can hold the centrifuge tube B held on the holding table 45 from the side. With such a holding table 45, the robot arm 41 can hold the centrifuge tube B in a position suitable for transporting the centrifuge tube B to each of the centrifuge device 1, the filtration device 2, and the detachment device 3. In addition, the centrifuge tube B can be accurately held by the robot arm 41 by passing through the holding table 45 when being transported between each of the centrifuge device 1, the filtration device 2, and the detachment device 3. In particular, a device that applies an external force to the centrifuge tube B via the lid T, such as the attachment / detachment device 3, causes a shift (misalignment) in the position of the centrifuge tube B relative to the robot arm 41. Even if such a misalignment occurs, the robot arm 41 can correct the misalignment. As a result, the robot arm 41 can transport the centrifuge tube B to the next device without any problems.

[0047] 1 and 2 performs a predetermined post-treatment on the germ extract GEF recovered in the recovery container 234. The post-treatment includes a treatment for utilizing the produced germ extract GEF and a treatment for preserving the produced germ extract GEF.

[0048] An example of an apparatus for performing processing using the produced embryo extract GEF is an apparatus for mixing the embryo extract GEF with mRNA (messenger RiboNucleic Acid). Such a post-processing apparatus 5 can synthesize a desired protein immediately after producing the embryo extract GEF, thereby reducing the risk of deterioration in the quality of the embryo extract GEF due to storage.

[0049] An example of an apparatus for preserving the produced germ extract GEF is a freeze-drying apparatus that freeze-dries the collection container 234. FIG. 6 shows a freezing apparatus 51 as an example of the post-processing apparatus 5. The freezing apparatus 51 is an apparatus capable of freezing the collection container 234 containing the germ extract GEF. Preferably, the conveying apparatus 4 shown in FIG. 1 conveys the collection container 234 to the freezing apparatus 51. If an operator conveys the collection container 234 to the freezing apparatus 51, there is a risk that the quality of the germ extract GEF will deteriorate due to human error or the like. However, by conveying the collection container 234 containing the germ extract GEF to the freezing apparatus 51 by the conveying apparatus 4, the risk of the production quality of the germ extract GEF being deteriorated due to human error or the like can be reduced. In detail, the robot arm 41 conveys the collection container 234 from the filtration apparatus 2 via the holding table 45 and the detaching apparatus 3 to the freezing apparatus 51. As a result, the collection container 234 with the lid T closed by the detachment device 3 is transported to the freezing device 51. Even if the position of the collection container 234 relative to the robot arm 41 is shifted in the detachment device 3, the position shift is corrected by the holding table 45.

[0050] As shown in Fig. 6, the freezing device 51 includes a freezing container 511 and a holder 512. The freezing container 511 is a container that contains a liquid freezing refrigerant IL. The freezing refrigerant IL is a substance having a boiling point below room temperature, such as liquid nitrogen. The type of freezing refrigerant IL is appropriately determined according to the temperature at which the target germ extract liquid GEF is stored. The centrifuge tube B is placed inside the freezing container 511 through an opening provided at the top of the freezing container 511.

[0051] The holder 512 is a device by which the transport device 4 holds the collection container 234. The holder 512 deforms in response to the buoyant force that the centrifuge tube B receives from the freezing refrigerant IL. Specifically, the holder 512 shown in FIG. 6 has a gripping portion 513, a following portion 514, and a holding portion 515. The gripping portion 513 is a portion that is gripped by the transport device 4. In addition, a part of the gripping portion 513 is inserted into the inside of the freezing container 511 through the mouth of the freezing container 511. The gripping portion 513 shown in FIG. 6 is in the shape of a long, thin rod.

[0052] The holding portion 515 is connected to the tip of the gripping portion 513 via the following portion 514. The holding portion 515 is a portion that holds the collection container 234. Specifically, the holding portion 515 is two plates that curve outward. The following portion 514 is a portion that changes the posture of the holding portion 515 by following the force that the collection container 234 held by the holding portion 515 receives. Specifically, the following portion 514 is a hinge that rotates the holding portion 515 toward the gripping portion 513 around the tip of the gripping portion 513. When the collection container 234 held by the holding portion 515 comes into contact with the liquid surface of the freezing refrigerant IL in the freezing container 511, the collection container 234 receives buoyancy from the freezing refrigerant IL. Due to the buoyancy that the collection container 234 receives from the freezing refrigerant IL, the following portion 514 deforms so that the collection container 234 floats on the liquid surface of the freezing refrigerant IL. Therefore, the recovery container 234 is in a position where the side surface floats on the liquid surface. This position increases the surface area of ​​the germ extract liquid GEF, so that the thawing process can be shortened.

[0053] Preferably, the freezing device 51 has a load cell (not shown). The load cell measures the weight of the freezing container 511 and the freezing refrigerant IL contained in the freezing container 511. In this way, the control device 7 described below can determine, based on the measurement result of the load cell, whether or not the freezing container 511 contains a sufficient amount of freezing refrigerant IL for freezing the germ extract liquid GEF contained in the collection container 234.

[0054] As shown in FIG. 7, the box 6 houses a centrifugation device 1, a filtration device 2, a desorption device 3, a transport device 4, and a freezing device 51 which is an example of a post-processing device 5. This makes it possible to prevent an operator from intervening in the centrifugation process, the filtration process, and the freezing process which is an example of a post-processing process. For example, the box 6 can prevent an operator from interfering with the operation of the transport device 4 which transports the centrifuge tube B. As a result, the box 6 can reduce deterioration in the quality of the embryo extract GEF due to human error or the like.

[0055] Preferably, the box 6 has a temperature adjustment device 61 that adjusts the temperature inside the box 6. The temperature adjustment device 61 can prevent deterioration in the quality of the germ extract liquid GEF due to an increase in temperature of the germ mixed liquid GMF or the germ extract liquid GEF during production by the germ extract liquid production system 100.

[0056] Preferably, the box 6 has an air blower 62 and an exhaust port 65. The air blower 62 blows clean air F1 toward the centrifugal separator 1, the filtering device 2, the desorption device 3, the transport device 4, and the freezing device 51, which is an example of the post-processing device 5. In FIG. 6, the air blower 62 is provided on the ceiling of the box 6. The air blower 62 blows clean air F1 from top to bottom. For this purpose, the air blower 62 has a fan 63 for blowing air and a HEPA (High Efficiency Particle Area) filter 64 through which the air F1 generated by the fan 63 passes. As a result, foreign matter such as dust is kept away from the centrifugal separator 1, the filtering device 2, the desorption device 3, the transport device 4, and the freezing device 51, which is an example of the post-processing device 5, by the clean air F1 and F2.

[0057] The exhaust port 65 exhausts the air F2 sent by the blower 62 to the outside of the box body 6. The exhaust port 65 shown in FIG. 7 is provided on the side of the box body 6 at a position lower than the filter device 2, the desorption device 3, and the transport device 4. Therefore, foreign matter such as dust is exhausted from the exhaust port 65 to the outside of the box body 6 together with the air F2 sent by the blower 62. As a result, foreign matter is prevented from being mixed into the germ extract GEF. In addition, the exhaust port 65 is provided at a position lower than the opening into which the centrifuge tube B is inserted in the freezing device 51, which is an example of the centrifugal separator 1 and the post-processing device 5. The opening into which the centrifuge tube B is inserted is the opening of the holder 13B in the centrifugal separator 1, and is the mouth portion provided at the top of the freezing container 511 in the freezing device 51. In this way, the air F2 sent by the blower 62 reaches the opening, so that foreign matter such as dust can be reliably kept away from the opening of the centrifugal separator 1 and the post-processing device 5.

[0058] The control device 7 controls the operations of the centrifuge 1, the filtration device 2, the detachment device 3, the conveyance device 4, the post-processing device 5, and the box body 6. The control device 7 has a storage unit 71 and a control unit 72. The storage unit 71 stores a control program for controlling the operations of the centrifuge 1, the filtration device 2, the detachment device 3, the conveyance device 4, the post-processing device 5, and the box body 6, and measurement results of various sensors provided in the embryo extract production system 100. The storage unit 71 includes, for example, a storage device such as a memory. The control unit 72 controls the operations of the centrifuge 1, the filtration device 2, the detachment device 3, the conveyance device 4, the post-processing device 5, and the box body 6 according to the control program stored in the storage unit 71. The control unit 72 includes a calculation device such as a central processing unit. The control unit 72 may control some of the functions of the centrifuge 1, the filtration device 2, the detachment device 3, the conveyance device 4, the post-processing device 5, and the box body 6.

[0059] Preferably, the box 6 further includes a box internal temperature sensor (not shown). The box internal temperature sensor measures the temperature inside the box 6. The box internal temperature sensor is, for example, a thermocouple or a resistance temperature detector. If there is a box internal temperature sensor in addition to the solution temperature sensor 22F and the germ extract temperature sensor, the control unit 72 can monitor the temperatures of the germ mixture GMF, the germ extract GEM, the solution containing the germ extract GEM, the eluate, and the germ extract GEF. Specifically, the measurement results of the solution temperature sensor 22F, the germ extract temperature sensor, and the box internal temperature sensor are transmitted to the control unit 72. When the measurement result of any of the solution temperature sensor 22F, the germ extract temperature sensor, and the box internal temperature sensor exceeds a set value, the control unit 72 controls the device to be controlled to stop operating. The set value of each temperature sensor is, for example, a temperature at which the quality of the germ extract GEF to be produced is assumed to deteriorate. Therefore, the control unit 72 can prevent the germ mixture GMF, the germ extract GEM, the solution containing the germ extract GEM, the eluate, and the germ extract GEF from becoming too hot, which can result in the production of germ extract GEF of degraded quality.

[0060] The control unit 72 also determines whether the measurement result of the load cell is equal to or greater than a predetermined value. The predetermined value of the load cell is a value for determining whether the freezing container 511 contains a sufficient amount of freezing refrigerant IL for freezing the germ extract liquid GEF contained in the collection container 234. When the measurement result of the load cell is less than the predetermined value, the control unit 72 controls the controlled device to stop operation. Therefore, the control unit 72 can prevent the germ extract liquid GEF contained in the collection container 234 from being insufficiently frozen due to an insufficient amount of freezing refrigerant IL contained in the freezing container 511.

[0061] The memory unit 71 records the measurement results of at least the temperature sensor inside the box, the temperature sensor for the solution 22F, and the temperature sensor for the germ extract liquid over time. This allows workers and other related parties to check the temperatures of the germ mixture liquid GMF, the germ extract GEM, the solution containing the germ extract GEM, the eluate, and the germ extract liquid GEF after production of the germ extract liquid GEF. The memory unit 71 also records the measurement results of each temperature sensor when an abnormality occurs. An abnormality may occur, for example, when an apparatus constituting the germ extract liquid production system 100 is operating abnormally, when the temperature measured by each temperature sensor suddenly changes, or when the temperature measured by each temperature sensor changes to a temperature outside the set range.

[0062] The control performed by the control unit 72 of the embryo extract production system 100 will be described with reference to Figures 3, 5, and 7 to 13. Figure 8 shows the steps of producing embryo extract GEF. The steps of producing embryo extract GEF performed in the embryo extract production system 100 include steps P1 to P6.

[0063] In step P1, as shown in FIG. 7, the operator places the centrifuge tube B containing the germ mixture GMF in the case 43 with the mouth closed with the lid T. For example, two centrifuge tubes B, B are placed in the case 43. After the two centrifuge tubes B, B are placed in the case 43, the operator spreads the coolant 44 around the centrifuge tube B. The case 43 containing the centrifuge tube B and the coolant 44 is placed inside the box 6. After this, the door (not shown) of the box 6 is closed so that the operator cannot put his hands inside the box 6. Here, temperature-adjusted air F1, F2 is flowing inside the box 6 by the blower 62. Therefore, in the subsequent manufacturing steps of the germ extract manufacturing system 100, the temperatures of the germ mixture GMF, the solution containing the germ extract GEM, and the germ extract GEF are kept below a certain level. Furthermore, the inclusion of foreign matter in the germ mixture liquid GMF, the solution containing the germ extract GEM, and the germ extract liquid GEF is also prevented.

[0064] In step P2, the robot arm 41 removes one of the centrifuge tubes B, B housed in the case 43 from the case 43 and sets it in the attachment / detachment device 3 as shown in FIG. 9. Specifically, the robot arm 41 grips the lid T attached to one of the centrifuge tubes B housed in the case 43 shown in FIG. 7 with a claw, and transports the centrifuge tube B with the lid T attached from the case 43 to the holding table 45 shown in FIG. 5. The centrifuge tube B transported to the holding table 45 is released from the robot arm 41 and temporarily held by the holding table 45. The robot arm 41 grips the centrifuge tube B held by the holding table 45 from the side, and transfers the centrifuge tube B to the container holder 31. The lid opening / closing mechanism 32 rotates the lid T that closes the mouth of the centrifuge tube B held by the container holder 31 in a closing direction, and further tightens the lid T of the centrifuge tube B. This reduces the risk of the liquid in the centrifuge tube B leaking from the lid T when the robot arm 41 transports the centrifuge tube B or when the robot arm 41 stirs the germ mixed liquid GMF. The centrifuge tube B with the lid T retightened is set to its original position in the case 43 by the robot arm 41. Thereafter, the lid T of the other centrifuge tube B housed in the case 43 is also transported by the robot arm 41 to the lid opening / closing mechanism 32. Then, after the lid T of the other centrifuge tube B is also retightened by the lid opening / closing mechanism 32, it is returned to its original position in the case 43 by the robot arm 41.

[0065] 10, the robot arm 41 grasps the case 43 and changes the attitude of the case 43 over time. This stirs the germ mixed liquid GMF contained in the two centrifuge tubes B, B housed in the case 43. By stirring the germ mixed liquid GMF, the germs G are reliably precipitated in the germ mixed liquid GMF.

[0066] In step P4, as shown in FIG. 11, the robot arm 41 takes out two centrifuge tubes B, B housed in the case 43 one by one and sets them in the centrifugal separator 1. In order for the robot arm 41 to set the centrifuge tube B in the centrifugal separator 1, an image P of the imager 42 is used. As shown in FIG. 11, the imager 42 captures an image of the rotating table 13 and extracts a contour image (not shown) of the rotating shaft 13A and the holder 13B. The contour image is compared with a reference image RF, which is a reference position of the holder 13B relative to the rotating shaft 13A. If the contour image is out of the reference image RF, it can be determined that the holder 13B is not in the reference position. If the contour image is out of the reference image RF, the robot arm 41 rotates the rotating table 13 before setting the centrifuge tube B on the rotating table 13 so that the contour image captured over time by the imager 42 overlaps with the reference image RF. Here, the reference position is a position of the holder 13B at which the centrifuge device 1 and other devices constituting the embryo extract production system 100 are not positioned on the path between the holder 13B, which holds the centrifuge tube B on the turntable 13, and the robot arm 41. The orientation of the turntable 13 is always set to the reference position, so that the robot arm 41 can set the centrifuge tube B on the turntable 13 without interfering with other parts.

[0067] After one of the centrifuge tubes B is set on the turntable 13, the robot arm 41 rotates the turntable 13 half a turn. Then, if the contour image is out of the reference image RF, the robot arm 41 rotates the turntable 13 so that the contour image overlaps with the reference image RF. This allows the robot arm 41 to set the other centrifuge tube B in the holder 13B that is diagonally opposite the holder 13B in which the one centrifuge tube B is set, across the rotation shaft 13A. This reduces the risk of the turntable 13 of the centrifugal separator 1 swinging significantly when it rotates.

[0068] After the two centrifuge tubes B, B are set on the turntable 13, the opening and closing door 12 is closed by the actuator. When the opening and closing door 12 is closed, the turntable 13 starts to rotate. When the turntable 13 rotates, the germ extract GEM is extracted from the germ G into the solvent of the germ mixture liquid GMF. The turntable 13 stops after rotating at a predetermined speed for a predetermined time. Whether the rotation of the turntable 13 has stopped can be determined by images captured by the imager 42 over time. For example, if the centrifuge device 1 is provided with a display that displays the rotation speed of the turntable 13, it can be determined whether the turntable 13 has stopped from the value of the rotation speed displayed on the display. Note that the germ extract liquid production system 100 can also be configured to send a signal having information on the operating state of the centrifuge device 1, including whether the rotation of the turntable 13 has stopped, from the centrifuge device 1 to the control device 7. With this configuration, the control device 7 can determine whether the rotation of the turntable 13 has stopped based on the information included in the signal received from the centrifuge device 1. When the turntable 13 stops, the actuator opens the door 12 and the centrifugation process is completed.

[0069] When the centrifugation process of the germ mixture GMF is completed, the robot arm 41 removes the centrifuge tube B from the turntable 13 and sets it in the container holder 31 shown in FIG. 9. The lid opening / closing mechanism 32 removes the lid T of the centrifuge tube B. The centrifuge tube B from which the lid T has been removed is transported by the robot arm 41 to the removal unit 21 shown in FIG. 3. When the centrifuge tube B is transported, the removal unit 21 is in a state in which the filter 212 and the empty centrifuge tube B are placed under the funnel 211. The robot arm 41 tilts the centrifuge tube B to pour the germ mixture GMF into the funnel 211. As a result, the liquid from which solids such as the germ G have been removed, i.e., the solution containing the germ extract GEM, is poured into the empty centrifuge tube B placed in the removal unit 21.

[0070] The robot arm 41 sets the centrifuge tube B containing the solution containing the germ extract GEM in the container holder 31 shown in FIG. 9. Then, the lid opening / closing mechanism 32 takes out an unused lid T from the unused lid holder 33 and closes the mouth of the centrifuge tube B set in the container holder 31 with the lid T. After this, the robot arm 41 sets the centrifuge tube B whose mouth is closed with the lid T again in the centrifugal separator 1 shown in FIG. 11. The centrifugal separator 1 can perform a centrifugation process on the centrifuge tube B that has been set again. The germ extract liquid production system 100 performs a set of a centrifugation process and a filtration process at least once to extract the germ extract GEM from the germ G and remove the germ G from the germ mixture liquid GMF. The number of sets of a centrifugation process and a filtration process performed by the germ extract liquid production system 100 is not limited to one, but is appropriately determined depending on the type of germ G, etc.

[0071] In step P5, the filtration unit 22 and the recovery unit 23 perform ultrafiltration or chromatography on the solution containing the embryo extract GEM obtained in the centrifugation step and the filtration step.

[0072] The robot arm 41 transports the centrifuge tube B containing the solution containing the germ extract GEM to the filtration unit 22. The robot arm 41 pours the solution containing the germ extract GEM from the centrifuge tube B into the separation section 221 shown in FIG.

[0073] The solution containing the germ extract GEM poured into the separation section 221 flows into the storage section 22B. As a result, the liquid containing the germ extract GEM passes through the ultrafiltration membrane or the chromatography stationary phase GL. The ultrafiltration membrane or the chromatography stationary phase GL separates the germ extract GEM from the solution containing the germ extract GEM. The liquid excluding the germ extract GEM is then discharged to the waste section 232. The supply mechanism 222 may supply pure water PW to the separation section 221 before the solution containing the germ extract GEM is poured into the separation section 221. By doing so, before the solution containing the germ extract GEM is poured into the separation section 221, the substances attached to the ultrafiltration membrane or the chromatography stationary phase GL are washed away by the pure water PW into the waste section 232. As a result, it is possible to prevent the substances attached to the ultrafiltration membrane or the chromatography stationary phase GL from being mixed into the germ extract liquid GEF to be generated before the solution containing the germ extract GEM is poured into the separation section 221.

[0074] After the liquid excluding the germ extract GEM is discharged to the waste section 232, the robot arm 41 grasps the shaft 23A and rotates the turntable 231 in order to place the collection container 234 under the discharge passage 22C. The valve of the discharge passage 22C is also closed. Then, the supply mechanism 222 operates the pump 22E to supply the amino acid solution AL as the eluate to the injection section 22A. As a result, the eluate is supplied to the storage section 22B.

[0075] The valve opens when the measurement result of the level sensor 22L reaches or exceeds a predetermined level. In this manner, the germ extract GEM can be sufficiently dissolved in the eluate. When the valve opens, as shown in FIG. 13, the germ extract GEM is dissolved in the eluate and the germ extract liquid GEF produced is collected in the collection container 234. After this, the robot arm 41 rotates the turntable 231 so that the holding structure 233 holding the empty collection container 234 is positioned under the discharge passage 22C. Then, in the same manner as above, the germ extract GEF is produced from the solution containing the germ extract GEM contained in the remaining centrifuge tube B and collected in another empty collection container 234.

[0076] In step P6, the embryo extract GEF is lyophilized or frozen. The freezing step is shown as an example. The robot arm 41 removes the collection container 234 from the holding structure 233 as shown in FIG. 14. The removed collection container 234 is set in the container holder 31 shown in FIG. 9 by the robot arm 41. Then, the lid opening / closing mechanism 32 closes the mouth of the collection container 234 with the lid T. The collection container 234 with its mouth closed with the lid T is set in the holding part 515 of the holder 512 shown in FIG. 15 by the robot arm 41. The collection container 234 held in the holding part 515 is inserted into the inside of the freezing container 511 from the mouth of the freezing container 511 by the robot arm 41.

[0077] The collection container 234 inserted into the freezing container 511 by the robot arm 41 comes into contact with the liquid freezing refrigerant IL, and floats on the liquid surface of the freezing refrigerant IL due to the buoyancy of the freezing refrigerant IL. As a result, the collection container 234 and the germ extract liquid GEF contained in the collection container 234 are frozen from the sides.

[0078] The frozen collection container 234 is transported by the robot arm 41 to a position (not shown) where the produced germ extract GEF is removed from the germ extract production system 100. Thereafter, the collection container 234 containing the germ extract GEF is removed from the germ extract production system 100 by an operator.

[0079] In steps P1 to P6 described above, the memory unit 71 records the measurement results of each temperature sensor over time. The memory unit 71 may also store information that allows the time required for each step and / or the time required for transportation between each step to be determined. With such a memory unit 71, when an embryo extract liquid GEF of unusual quality is produced, workers or other related parties can check information that allows the time required for transportation between each step to be determined after the production of the embryo extract liquid GEF, in addition to the measurement results of each temperature sensor.

[0080] In the above embodiment, it has been described that the lid T of the centrifuge tube B is opened and closed by the attachment / detachment device 3, which is a dedicated device for opening and closing the lid T of the centrifuge tube B. However, the opening and closing of the lid T of the centrifuge tube B may be performed by the robot arm 41. If the robot arm 41 can open and close the lid T of the centrifuge tube B, the number of devices required for the embryo extract production system 100 can be reduced, and the structure of the embryo extract production system 100 can be simplified.

[0081] However, the embodiments are illustrative and not restrictive in all respects. The scope of the present invention is indicated by the claims, not by the above description, and is intended to include all modifications within the meaning and scope of the claims. Any configuration other than that described as the embodiment of the invention is an optional configuration and can be deleted or modified as appropriate. [Explanation of symbols]

[0082] 1. Centrifugation equipment 2. Filtration equipment 3. Detachable device 4. Conveyor 5 Aftertreatment Device 6 box body 21 Removal Unit 22 Filtration unit 23 Recovery Unit 41 Robot Arm 43 cases 44 Coolant 51 Freezing equipment 62 Blower 65 Exhaust port 72 Memory section 100 Germ extract production system 222 Supply mechanism 233 Retention structure 234 Collection container 235 Recovery cooling tank (an example of a cooling device) 512 Holder 514 Follower B Centrifuge tube T-lid AL Amino Acid Solution GMF germ mixture GEF germ extraction fluid GEM Germ Extract

Claims

1. a centrifuge for extracting a germ extract from the germ by rotating a container, in a lidded state, containing a germ mixture in which germs are mixed with an amino acid solution containing amino acids, and centrifuging the germ mixture; a filtering device for filtering the germ mixture discharged from a container containing the centrifuged germ mixture to produce a germ extract from the germ extract; A lid attaching / detaching device for attaching and detaching a lid to the container; An embryo extract production system comprising the centrifugal separator, the filtration device, and a transport device that transports the container to the desorption device.

2. The filtration device comprises: a filtration unit for separating the germ extract from the solution containing the germ extract by using an ultrafiltration membrane or a chromatographic stationary phase; a supply mechanism for supplying an eluate for passing the embryo extract separated by the ultrafiltration membrane or the chromatography stationary phase to the filtration unit toward a collection container for collecting the embryo extract, 2. The embryo extract production system according to claim 1, wherein the embryo extract is produced by dissolving the embryo extract separated in the filtration unit into the eluate supplied by the supply mechanism.

3. The filtration device has a recovery unit for recovering the embryo extract, The recovery unit comprises: A holding structure for holding the collection container; The embryo extract production system according to claim 1 or 2, further comprising a cooling device that cools the collection container held by the holding structure.

4. a post-treatment device that performs a predetermined post-treatment on the embryo extract in the collection container; The embryo extract production system according to claim 3 , wherein the transport device transports the collection container to the post-treatment device.

5. 5. The system for producing an embryo extract according to claim 4, wherein the post-treatment device is a freezing device capable of freezing the embryo extract contained in the collection container.

6. The freezing device comprises: A freezing container containing a liquid freezing refrigerant; a holder for holding the collection container on the transport device, 6. The system for producing embryo extract according to claim 5, wherein the holder is deformed in response to a buoyant force that the collection container receives from the freezing refrigerant.

7. 5. The embryo extract production system according to claim 4, further comprising a box in which the centrifugal separation device, the filtering device, the detachment device, the transport device, and the post-treatment device are housed.

8. The system for producing germ extract according to claim 7 , wherein the box has a temperature adjusting device for adjusting a temperature inside the box.

9. The box has an inside temperature sensor that measures the temperature inside the box, the supply mechanism has a solution temperature sensor that measures the temperature of the elution solution, The recovery unit has a germ extract temperature sensor that measures the temperature of the germ extract contained in the recovery container, 9. The germ extract liquid producing system according to claim 8, further comprising a memory unit that records the measurement results of at least the temperature sensor inside the box, the temperature sensor for the solution, and the temperature sensor for the germ extract liquid over time and / or when an abnormality occurs.

10. The box body is a blower that blows clean air toward the centrifugal separator, the filtering device, the detaching device, and the conveying device; 8. The system for producing germ extract according to claim 7, further comprising an exhaust port for exhausting the air blown by the air blower to the outside of the box body.

11. The transport device has a robot arm, 2. The system for producing an embryo extract according to claim 1, wherein the robot arm agitates the embryo mixture contained in the container by changing the posture of the container into various postures over time.

12. The conveying device is A case for accommodating a container containing the germ mixture; a cooling agent contained in the case for cooling the container containing the germ mixture liquid; 12. The system for producing germ extract according to claim 11, wherein the robot arm agitates the germ mixture by changing a posture of the container containing the germ mixture and the case containing the coolant.

Images