System for producing germ extract liquid

Abstract

In the present invention, a system for producing germ extract liquid (100) comprises a centrifugal separator (1), a filtration device (2), a releasing device (3) and a transportation device (4). In the centrifugal separator (1), a container (B), which contains a mixed germ liquid (GMF) obtained by mixing a germ (G) with an amino acid-containing amino acid solution (AL), is rotated while having a lid attached thereto, and the mixed germ liquid (GMF) is subjected to centrifugal separation to extract a germ extract (GEM) from the germ (G). In the filtration device (2), the mixed germ liquid (GMF) from the container (B) containing the centrifugally separated mixed germ liquid (GMF) is filtered to produce a germ extract liquid from the germ extract (GEM). The releasing device (3) releases a lid on the container (B). The transportation device (4) transports the container (B) to the centrifugal separator (1), the filtration device (2) and the releasing device (3).

Description

Germ extract production system

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

[0002] Germ extracts extracted from plant embryos are used for protein production in cell-free protein synthesis systems. Germ extracts are typically obtained from wheat, barley, rice, corn, and other grasses. The germs extracted from these plants are finely ground. The ground germs are placed in a centrifuge tube along with an amino acid solution containing various amino acids. The germ extract is extracted from the embryo by mixing the ground germ with the amino acid solution, subjecting the resulting mixture to stirring, centrifugation, and filtration, including ultrafiltration or chromatography. The germ extract extracted from the embryo is then subjected to post-processing according to the intended purpose.

[0003] 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 germ extract can be reduced.

[0004] As examples of automated manufacturing processes, devices are disclosed in Patent Document 1 (Japanese Patent Laid-Open Publication No. 6-094700) and Patent Document 2 (Japanese Patent No. 6230138). However, the devices in Patent Documents 1 and 2 produce something different from embryo extract.

[0005] Therefore, an object of the present invention is to provide an embryo extract production system that can reduce the variation in quality of embryo extract produced from embryos.

[0006] The embryo extract production system of the present invention is characterized by comprising a centrifuge device that extracts embryo extract from the embryos by rotating a lidded container containing an embryo mixture, in which embryos are mixed with an amino acid solution containing amino acids, and centrifuging the embryo mixture; a filtration device that produces embryo extract from the embryo extract by filtering the embryo mixture that comes out of 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.

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

[0008] 1 is a three-dimensional diagram showing an outline of an embryo extract liquid production system according to an embodiment, with a portion of the box omitted; FIG. 2 is a plan view showing an outline of the embryo extract liquid production system shown in FIG. 1, with a portion of the box omitted; FIG. 3 is a three-dimensional diagram of a removal unit shown in FIG. 1; FIG. 4 is a three-dimensional diagram of a filtration unit and a recovery unit shown in FIG. 1; FIG. 5 is a front view of a detachment device and a transport device shown in FIG. 1; FIG. 6 is a three-dimensional diagram showing the entire embryo extract liquid production system shown in FIG. 1; FIG. 7 is a flowchart showing the embryo extract liquid production process in an embryo extract liquid production system according to an embodiment; FIG. 8 is a diagram showing a state in which the detachment device closes the lid; FIG. 9 is a diagram showing a state in which a robot arm stirs the embryo mixture in a centrifuge tube; FIG. 10 is a diagram showing a state in which a robot arm sets a centrifuge tube in a centrifugal separator; FIG. 11 is a diagram showing an outline of an embryo extract liquid being recovered by a recovery unit over time, and a diagram showing a state in which an embryo extract is filtered and extracted by ultrafiltration or chromatography; FIG. 12 is a diagram showing an outline of an embryo extract liquid being recovered by a recovery unit over time, and a diagram showing a state in which a recovery container receives the embryo extract; 1 is a diagram showing an outline of the process of recovering an embryo extract by a recovery unit over time, and a diagram showing a state in which a recovery container that has received the embryo extract is transported by a transport device. FIG. 2 is a diagram showing a schematic state in which a freezing device freezes the embryo extract.

[0009] An embryo extract production system 100 (embryo extract production equipment) according to an embodiment of the present invention will be described with reference to FIGS. 1 to 7. FIG.

[0010] 1 and 2 automates the processes required to produce germ extract GEF, such as the centrifugation process for the germ mixture GMF and the filtration process for the germ mixture GMF, which includes ultrafiltration or chromatography. Therefore, the germ extract production system 100 reduces the occurrence of variations in the quality of the germ extract GEF that are unavoidable when producing germ extract GEF due to human error, foreign matter contamination, and other manual processes.

[0011] The germ extract production system 100 includes a centrifuge 1, a filtration device 2, a detachment device 3 for attaching and detaching lids T to containers containing germ mixture GMF, a transport device 4, a post-treatment device 5 for post-treating the produced germ extract 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 containers containing the germ mixture GMF between the centrifuge 1, the filtration device 2, and the detachment device 3. The containers used are, for example, centrifuge tubes B for centrifugation. In this way, the transport device 4 transports the centrifuge tubes B containing the germ mixture GMF between the centrifuge 1, the filtration device 2, and the detachment device 3, thereby producing the germ extract GEF from the germs G. The germ extract 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, thereby centrifuging the germ mixture GMF. By centrifuging the germ mixture GMF, the germ extract GEM is extracted from the germs 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 with an internal space. The opening / closing door 12 automatically opens and closes an opening that connects 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 holds the centrifuge tube B and rotates around a rotation axis 13A (see FIG. 2 ) while housed in the internal space of the main body 11. The rotating table 13 holding the centrifuge tube B rotates, centrifuging the germ mixture GMF in the centrifuge tube B.

[0013] 1 and 2, the centrifugal separator 1 may be a swing rotor type in which the holder becomes perpendicular to the rotation axis 13A due to centrifugal force, or an angle rotor type having a turntable 13 that holds the centrifuge tubes B at an angle inclined with respect 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 GMF. As shown in Figure 3, the filtration device 2 filters the germ mixture GMF discharged from centrifuge tube B containing the centrifuged germ mixture GMF. This removes germs G and other components from the germ mixture GMF. Then, as shown in Figure 4, the filtration device 2 separates the germ extract GEM from the germ mixture GMF from which the germs G have been removed, producing the germ extract 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 embryos G or the state of the embryo mixture 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 located at the destination (outlet 21A) of the germ mixed liquid GMF flowing 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 determined appropriately taking into account the size of the solid matter to be removed, etc. Preferably, there are multiple filters 212. If there are multiple filters 212, unused filters 212 can be used in each filtration step when the germ mixed liquid GMF is filtered multiple times.

[0019] The filter conveyor 213 is a device that conveys 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 depending on the progress of the manufacturing process.

[0020] The container conveyor 214 places an empty centrifuge tube B below the filter 212 into which the germ mixture 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 along a path that passes under the funnel 211 and the filter 212. The holder 215 holds each centrifuge tube B with its opening facing upward. By positioning the centrifuge tube B below the filter 212 into which the germ mixture GMF is poured, the germ mixture GMF that has passed through the filter 212 enters the centrifuge tube B through its opening. The holder 215 preferably holds multiple empty centrifuge tubes B. In this manner, the removal unit 21 can filter the germ mixture GMF multiple times without manual intervention.

[0021] 4 separates the embryo extract GEM from the solution containing the embryo 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 to the bottom, an injection section 22A, a storage section 22B that holds an ultrafiltration membrane or a stationary phase packing for chromatography and that 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 through the centrifugation and filtration processes, as well as the eluate, as described below, are injected. The injection section 22A is a cylinder with an upward and downward opening, and its diameter decreases as it goes downward. The upward opening is a spout through which the solution containing the germ extract GEM and the eluate are poured. The downward opening is an outlet through which the germ mixture liquid GMF and the eluate exit from the inside of the injection section 22A to the outside. In this way, the germ mixture liquid GMF and the eluate are poured from the wide upper opening, allowing the conveying device 4, described below, to 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 pipe 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, capturing the germ extract GEM from the solution and 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, and 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 determined appropriately depending on the type of germ extract GEM to be separated.

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

[0027] The supply mechanism 222 supplies an eluate to the separation section 221 for eluting the germ extract GEM separated in the storage section 22B, toward a collection container 234 that collects the germ extract GEM. The germ extract GEM separated in the storage section 22B is washed with the eluate, thereby producing a germ extract GEF. The components contained in the eluate and their ratios are determined appropriately 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. Figure 4 shows three storage containers 22D, 22D, and 22D. 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 depending on the type of germ extract GEM.

[0029] The pure water PW and 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 to allow a predetermined amount of eluate to accumulate in the separation section 221. Whether the predetermined amount of eluate has accumulated in the separation section 221 is determined, for example, by whether 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 or higher. The liquid level of the eluate is measured, for example, by an optical or capacitance level sensor 22L. When it is determined that the predetermined amount of 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 Figure 4 is a container that accommodates the storage unit 22B, each storage container 22D, and a refrigerant CL. The refrigerant CL, cooled by an appropriate method, cools the storage unit 22B and each storage container 22D. Therefore, when separation is performed by ultrafiltration or chromatography, the germ extract GEM, eluate, and germ extract GEF can be prevented from becoming hot and deteriorating.

[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 contained in the storage section cooling tank 223 is set so that the temperature measured by the solution temperature sensor 22F is appropriate. This prevents the liquid contained in each storage container 22D, such as the amino acid solution AL or pure water PW as the eluate, 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 extends 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 above the turntable 231. Therefore, the disposal unit 232 or the holding structure 233 can be positioned below the discharge passage 22C by rotating the turntable 231. The lower part of the turntable 231 is cooled by a collection cooling tank 235.

[0034] The waste unit 232 is a part that receives, from the separation unit 221, 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. The waste unit 232 shown in Figure 4 is a tube with a bottom that receives the liquid. Because 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 that collects 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 opening of the collection container 234 faces diagonally upward. The holding structure 233 is positioned below the discharge passage 22C before the germ extract liquid GEF emerges from the discharge passage 22C. This allows the germ extract liquid GEF that has exited the discharge passage 22C to enter the collection container 234. The amount of germ extract liquid GEF that has entered the collection container 234 is measured by an optical or ultrasonic level sensor 23B. If the measurement result of the level sensor 23B determines that a predetermined amount or more of germ extract liquid GEF is contained in the collection container 234, the collection container 234 is collected.

[0036] The recovery cooling tank 235 (an example of a cooling device) shown in Figure 4 is a container filled with a refrigerant CL. A portion of the holding structure 233 is immersed in the refrigerant CL. By immersing a portion of the holding structure 233 in the refrigerant CL, the germ extract liquid GEF contained in the recovery container 234 held by the holding structure 233 is maintained at a low temperature. As a result, the recovery cooling tank 235 prevents the germ extract liquid GEF contained in the recovery 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 GEF contained in the recovery container 234. The temperature of the germ extract GEF can be measured by bringing a temperature sensor into contact with the recovery container 234 or the holding structure 233. Alternatively, the temperature of the germ extract GEF may 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 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 GEF from rising. A thermocouple, a resistance temperature detector, or the like is used as the germ extract temperature sensor.

[0038] The detaching device 3 shown in Fig. 5 attaches and detaches the lid T to and from the centrifuge tube B. The detaching device 3 rotates the lid T placed on the opening of the centrifuge tube B, thereby screwing a threaded portion provided on the lid T into a threaded portion provided on the opening of the centrifuge tube B, thereby closing the opening of the centrifuge tube B with the lid T. Meanwhile, the detaching 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 detaching 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 opening 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 clamping it from the sides. The lid opening / closing mechanism 32 is a mechanism that grips the lid T and rotates it in a direction to open or close the lid T relative to the opening of the centrifuge tube B. The lid opening / closing mechanism 32 shown in FIG. 5 has claws that grip the lid T from three sides. The claws that grip the lid T move in directions toward or away from the opening of the centrifuge tube B.

[0040] Preferably, the detaching device 3 further includes an unused lid holder 33. The unused lid holder 33 is a holder that holds an unused lid T. An 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 filtering device 2, and the desorbing device 3 shown in Fig. 1. This allows the germ mixture GMF to be centrifuged and filtered without manual intervention. Therefore, the transport device 4 reduces variations in the production quality of the germ extract GEF that occur due to differences in operators.

[0042] Preferably, the transport device 4 includes a robot arm 41 and an image capture device 42. The robot arm 41 is a device capable of grasping objects such as centrifuge tubes B. Specifically, the robot arm 41 shown in FIG. 5 is a device having a pair of claws for grasping objects at the tip of an arm with 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 in three dimensions without employing a special structure. As a result, not only is the structure of the embryo extract production system 100 simplified, but centrifuge tubes B can also be transported in a versatile manner within the embryo extract production system 100.

[0043] Furthermore, the robot arm 41 agitates the germ mixture GMF contained in the centrifuge tube B by changing the position of the centrifuge tube B over time. Therefore, the transport device 4 can agitate the germ mixture GMF using a set procedure each time, reducing variation in the quality of the germ extract GEF. In addition, the robot arm 41 can be set with a wider range of motion than a human arm. Therefore, the robot arm 41 can agitate the germ mixture GMF more efficiently than a human hand by changing the position of the centrifuge tube B to a position that cannot be achieved manually.

[0044] The image capturer 42 captures an image of the area around the claws of the robot arm 41. The image captured by the image capturer 42 enables the robot arm 41 to operate in accordance with the status of the centrifugal separator 1 or the filtering device 2 shown in FIG.

[0045] Preferably, the transport device 4 further includes a case 43 and a coolant 44, as shown in FIG. 1 . The case 43 houses a 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 component (not shown) that holds two centrifuge tubes B, B in an upright position side-by-side. The two centrifuge tubes B, B and the holding component are housed in the case 43 together with the coolant 44. The coolant 44 is, for example, ice or another solid capable of cooling the centrifuge tube B. Unlike liquid coolant 44, such coolant 44 has a low risk of penetrating the centrifuge tube B or leaking out of the case 43.

[0046] Preferably, as shown in FIG. 5 , the transport device 4 further includes a holder 45. The holder 45 temporarily holds the centrifuge tube B so that the robot arm 41 can grasp the centrifuge tube B in various positions. The holder 45 shown in FIG. 5 has a structure that holds the centrifuge tube B with the surface of the centrifuge tube B, which the claws of the robot arm 41 use to grasp the centrifuge tube B from the side, protruding from the holder 45. Therefore, the claws of the robot arm 41 can grasp the centrifuge tube B held on the holder 45 from the side as well. This holder 45 allows the robot arm 41 to 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 desorbing device 3. Furthermore, by passing the holder 45 when the centrifuge tube B is transported between each of the centrifuge device 1, the filtration device 2, and the desorbing device 3, the robot arm 41 can accurately grasp the centrifuge tube B. In particular, a device such as the attachment / detachment device 3 that applies an external force to the centrifuge tube B via the lid T causes a deviation (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 collected in the collection 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 processing the produced embryo extract GEF is an apparatus for mixing mRNA (messenger ribonucleic acid) with the embryo extract GEF. 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 embryo 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 a post-processing apparatus 5. The freezing apparatus 51 is capable of freezing the collection container 234 containing the embryo extract GEF. Preferably, the transport apparatus 4 shown in FIG. 1 transports the collection container 234 to the freezing apparatus 51. If an operator transports the collection container 234 to the freezing apparatus 51, there is a risk of the quality of the embryo extract GEF deteriorating due to human error or the like. However, by having the transport apparatus 4 transport the collection container 234 containing the embryo extract GEF to the freezing apparatus 51, the risk of the production quality of the embryo extract GEF deteriorating due to human error or the like can be reduced. Specifically, the robot arm 41 transports the collection container 234 from the filtration apparatus 2 via the support table 45 and the detachment apparatus 3 to the freezing apparatus 51. As a result, the collection container 234 with the lid T closed by the detaching 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 detaching device 3, the position shift is corrected by the holding table 45.

[0050] As shown in Figure 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 such as liquid nitrogen that has a boiling point below room temperature. The type of freezing refrigerant IL is determined appropriately depending on the temperature at which the target germ extract GEF is to be 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 used by the transport device 4 to hold the collection container 234. The holder 512 deforms in response to the buoyancy of the centrifuge tube B, which is exerted by 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 portion of the gripping portion 513 is inserted into the freezing container 511 through the opening 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 follower 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 follower portion 514 is a portion that changes the posture of the holding portion 515 in response to a force applied to the collection container 234 held by the holding portion 515. Specifically, the follower 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 is subjected to buoyancy from the freezing refrigerant IL. Due to the buoyancy applied to the collection container 234 from the freezing refrigerant IL, the follower portion 514 deforms so that the collection container 234 floats on the liquid surface of the freezing refrigerant IL. Therefore, the side of the collection container 234 is in a position where it floats on the liquid surface. This position increases the surface area of ​​the germ extract GEF, thereby shortening the time required for the thawing process.

[0053] Preferably, the freezing device 51 has a load cell (not shown) that 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 later) can determine, based on the measurement result of the load cell, whether the freezing container 511 contains a sufficient amount of freezing refrigerant IL to freeze the embryo extract GEF contained in the collection container 234.

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

[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 a decrease in the quality of the germ extract GEF due to an increase in the temperature of the germ mixture GMF or the germ extract GEF during production by the germ extract production system 100.

[0056] Preferably, the box 6 has a blower 62 and an exhaust port 65. The blower 62 blows clean air F1 toward the centrifugal separator 1, the filtering device 2, the desorbing device 3, the conveying device 4, and the freezing device 51, which is an example of a post-processing device 5. In FIG. 6 , the blower 62 is provided on the ceiling of the box 6. The blower 62 blows clean air F1 from top to bottom. For this purpose, the blower 62 has a fan 63 that blows air and a HEPA filter (High Efficiency Particulate Air 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 desorbing device 3, the conveying device 4, and the freezing device 51, which is an example of a post-processing device 5, by the clean air F1 and F2.

[0057] The exhaust port 65 exhausts the air F2 sent by the air blower 62 to the outside of the box 6. The exhaust port 65 shown in FIG. 7 is located on the side of the box 6, below the filtering device 2, the desorption device 3, and the conveying device 4. Therefore, foreign matter such as dust is exhausted to the outside of the box 6 through the exhaust port 65 along with the air F2 sent by the air blower 62. As a result, foreign matter is prevented from being mixed into the germ extract GEF. Additionally, in the centrifugal separator 1 and the freezing device 51, which is an example of a post-processing device 5, the exhaust port 65 is located below the opening through which the centrifuge tube B is inserted. In the centrifugal separator 1, the opening through which the centrifuge tube B is inserted is the opening of the holder 13B, and in the freezing device 51, the opening is the opening provided at the top of the freezing container 511. In this way, the air F2 sent by the air blower 62 reaches the opening, thereby reliably keeping foreign matter such as dust away from the openings 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 transport device 4, the post-processing device 5, and the box 6. The control device 7 includes a memory unit 71 and a control unit 72. The memory unit 71 stores control programs for controlling the operations of the centrifuge 1, the filtration device 2, the detachment device 3, the transport device 4, the post-processing device 5, and the box 6, as well as measurement results from various sensors provided in the embryo extract production system 100. The memory unit 71 includes 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 transport device 4, the post-processing device 5, and the box 6 in accordance with the control programs stored in the memory unit 71. The control unit 72 includes a computing device such as a central processing unit. Note that the control unit 72 may control some of the functions of the centrifuge 1, the filtration device 2, the detachment device 3, the transport device 4, the post-processing device 5, and the box 6.

[0059] Preferably, the box 6 further includes an internal box temperature sensor (not shown). The internal box temperature sensor measures the temperature inside the box 6. The internal box temperature sensor is, for example, a thermocouple or a resistance temperature detector. The presence of an internal box temperature sensor in addition to the solution temperature sensor 22F and the germ extract temperature sensor allows the control unit 72 to 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 internal box temperature sensor are transmitted to the control unit 72. If the measurement results of any of the solution temperature sensor 22F, the germ extract temperature sensor, and the internal box temperature sensor exceed a set value, the control unit 72 controls the device to be controlled to stop operation. The set value of each temperature sensor is, for example, a temperature at which the quality of the produced germ extract GEF is expected 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 would result in the production of a germ extract GEF of deteriorated quality.

[0060] The control unit 72 also determines whether the load cell measurement result is equal to or greater than a predetermined value. The predetermined load cell value is a value for determining whether the freezing container 511 contains a sufficient amount of freezing refrigerant IL to freeze the germ extract GEF contained in the collection container 234. If the load cell measurement result 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 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 (stores) over time the measurement results of at least the box interior temperature sensor, the solution temperature sensor 22F, and the germ extract temperature sensor. This allows workers and other relevant personnel to check 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 after the germ extract GEF has been produced. The memory unit 71 also records (stores) the measurement results of each temperature sensor when an abnormality occurs. An abnormality may occur, for example, when a device constituting the germ extract production system 100 malfunctions, when the temperature measured by each temperature sensor suddenly changes, or when the temperature measured by each temperature sensor falls 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 for producing the embryo extract GEF. The steps for producing the embryo extract GEF performed by the embryo extract production system 100 include steps P1 to P6.

[0063] In step P1, as shown in FIG. 7 , an operator places centrifuge tube B containing germ mixture GMF in case 43 with its opening closed with lid T. For example, two centrifuge tubes B and B are placed in case 43. After the two centrifuge tubes B and B are placed in case 43, the operator spreads coolant 44 around centrifuge tube B. Case 43 containing centrifuge tube B and coolant 44 is placed inside box 6. A door (not shown) of box 6 is then closed to prevent the operator from reaching inside box 6. Temperature-controlled airflow F1 and F2 is blown through box 6 by air blower 62. Therefore, in the subsequent production processes of the germ extract production system 100, the temperatures of the germ mixture GMF, the solution containing germ extract GEM, and the germ extract GEF are maintained below a certain level. Furthermore, the inclusion of foreign matter in the germ mixture GMF, the solution containing the germ extract GEM, and the germ extract GEF is 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 uses its claws to grasp the lid T attached to one of the centrifuge tubes B housed in the case 43 shown in FIG. 7, and transports the centrifuge tube B with the lid T attached from the case 43 to the holder 45 shown in FIG. 5. The centrifuge tube B transported to the holder 45 is released from the robot arm 41 and temporarily held on the holder 45. The robot arm 41 grasps the centrifuge tube B held on the holder 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, which has closed the opening of the centrifuge tube B held in the container holder 31, in a direction to close the lid T, thereby further tightening the lid T of the centrifuge tube B. This reduces the risk of 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 mixture fluid GMF. The centrifuge tube B with the lid T retightened is set back 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 position of the case 43 over time. This causes the germ mixture GMF contained in the two centrifuge tubes B, B housed in the case 43 to be stirred. By stirring the germ mixture GMF, the germs G are reliably precipitated in the germ mixture 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. To set the centrifuge tube B in the centrifugal separator 1, the robot arm 41 uses an image P captured by the image capture device 42. As shown in FIG. 11 , the image capture device 42 captures an image of the turntable 13 and extracts a contour image (not shown) of the rotation axis 13A and the holder 13B. The contour image is compared with a reference image RF, which represents the reference position of the holder 13B relative to the rotation axis 13A. If the contour image deviates from the reference image RF, it can be determined that the holder 13B is not in the reference position. If the contour image deviates from the reference image RF, the robot arm 41 rotates the turntable 13 so that the contour images captured over time by the image capture device 42 overlap with the reference image RF before setting the centrifuge tube B on the turntable 13. Here, the reference position is a position of the holder 13B on the turntable 13 where the centrifuge device 1 and other devices constituting the embryo extract production system 100 are not positioned on the path between the holder 13B, where the centrifuge tube B is set, and the robot arm 41. By positioning the turntable 13 at the reference position every time, the robot arm 41 can set the centrifuge tube B on the turntable 13 without interfering with other components.

[0067] After one centrifuge tube B is set on the turntable 13, the robot arm 41 rotates the turntable 13 half a revolution. Then, if the contour image deviates from the reference image RF, the robot arm 41 rotates the turntable 13 so that the contour image overlaps the reference image RF. This allows the robot arm 41 to set the other centrifuge tube B in the holder 13B diagonally across the rotation axis 13A from the holder 13B in which the one centrifuge tube B is set. This reduces the risk of the turntable 13 of the centrifuge device 1 shaking significantly when it rotates.

[0068] After the two centrifuge tubes B, B are placed on the turntable 13, the door 12 is closed by the actuator. Closing the door 12 causes the turntable 13 to begin rotating. As the turntable 13 rotates, the germ extract GEM is extracted from the germs G into the solvent of the germ mixture GMF. The turntable 13 rotates at a predetermined speed for a predetermined period of time and then stops. Whether the rotation of the turntable 13 has stopped can be determined from images captured over time by the image capture device 42. For example, if the centrifuge device 1 is equipped with a display that displays the rotation speed of the turntable 13, whether the turntable 13 has stopped can be determined from the rotation speed value displayed on the display. The germ extract production system 100 can also be configured so that the centrifuge device 1 sends a signal containing information about the operating status of the centrifuge device 1, including whether the rotation of the turntable 13 has stopped, 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 contained in the signal received from the centrifuge device 1. When the turntable 13 stops, the actuator opens the door 12, completing the centrifugation process.

[0069] When the centrifugation process for the germ mixture GMF is complete, 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 from 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 has been transported, the removal unit 21 is in a state in which the filter 212 and the empty centrifuge tube B are positioned below 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 places a centrifuge tube B containing a solution containing the germ extract GEM in the container holder 31 shown in FIG. 9 . The lid opening / closing mechanism 32 then removes an unused lid T from the unused lid holder 33 and closes the opening of the centrifuge tube B placed in the container holder 31 with the lid T. The robot arm 41 then places the centrifuge tube B, whose opening is closed with the lid T, back into the centrifuge device 1 shown in FIG. 11 . The centrifuge device 1 can then perform a centrifugation step on the centrifuge tube B that has been placed back into the centrifuge device 1. The germ extract production system 100 performs a set of a centrifugation step and a filtration step at least once to extract the germ extract GEM from the germs G and remove the germs G from the germ mixture GMF. Note that the number of sets of the centrifugation step and the filtration step performed by the germ extract production system 100 is not limited to one and can be determined as appropriate 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 from which the germ extract GEM has been removed is then discharged into the waste section 232. The supply mechanism 222 may also supply pure water PW to the separation section 221 before the solution containing the germ extract GEM is poured into the separation section 221. In this way, any substances adhering to the ultrafiltration membrane or the chromatography stationary phase GL are washed away into the waste section 232 by the pure water PW before the solution containing the germ extract GEM is poured into the separation section 221. As a result, substances adhering to the ultrafiltration membrane or the chromatography stationary phase GL before the solution containing the embryo extract GEM is poured into the separation section 221 can be prevented from being mixed into the embryo extract liquid GEF that is produced.

[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 to position the collection container 234 below the discharge passage 22C. The valve of the discharge passage 22C is also closed. The supply mechanism 222 then operates the pump 22E to supply the amino acid solution AL as the eluate to the injection section 22A. This supplies the eluate to the storage section 22B.

[0075] The valve opens when the measurement result of the level sensor 22L reaches or exceeds a predetermined level. This allows the germ extract GEM to 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 resulting germ extract liquid GEF is collected in a collection container 234. The robot arm 41 then rotates the turntable 231 so that the holding structure 233 holding the empty collection container 234 is positioned below the discharge passage 22C. Then, in the same manner as above, germ extract liquid GEF is produced from the solution containing the germ extract GEM in the remaining centrifuge tube B and collected in another empty collection container 234.

[0076] In step P6, the embryo extract GEF is freeze-dried or frozen. The freezing step is shown as an example. As shown in FIG. 14 , the robot arm 41 removes the collection container 234 from the holding structure 233. The removed collection container 234 is set in the container holder 31 shown in FIG. 9 by the robot arm 41. The lid opening / closing mechanism 32 then closes the opening of the collection container 234 with the lid T. The collection container 234, whose opening is closed with the lid T, is set in the holding portion 515 of the holder 512 shown in FIG. 15 by the robot arm 41. The collection container 234 held in the holding portion 515 is inserted into the freezing container 511 through the opening 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 surface of the freezing refrigerant IL due to the buoyancy of the freezing refrigerant IL. As a result, the collection container 234 and the embryo extract 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 embryo extract GEF is removed from the embryo extract production system 100. Thereafter, the collection container 234 containing the embryo extract GEF is removed from the embryo extract production system 100 by an operator.

[0079] In steps P1 to P6 described above, the memory unit 71 records (stores) 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 steps to be determined. With such a memory unit 71, when a germ extract GEF of unusual quality is produced, workers and other related personnel can check, after production of the germ extract GEF, information that allows the time required for transportation between steps to be determined, in addition to the measurement results of each temperature sensor.

[0080] In the above embodiment, it has been explained that the lids T of the centrifuge tubes B are opened and closed by the detaching device 3, which is a dedicated device for opening and closing the lids T of the centrifuge tubes B. However, the opening and closing of the lids T of the centrifuge tubes B may also be performed by the robot arm 41. If the robot arm 41 can open and close the lids T of the centrifuge tubes B, the number of devices required for the embryo extract production system 100 can be reduced, thereby simplifying the structure of the embryo extract production system 100.

[0081] The embodiments are illustrative in all respects and are not limiting. The scope of the present invention is defined by the claims rather than 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 an embodiment of the invention is optional and can be deleted or modified as appropriate.

Claims

1. A system for producing an embryo extract comprising: a centrifuge device that extracts an embryo extract from an embryo by rotating a covered container containing a germ mixture in which germs are mixed with an amino acid solution containing amino acids and centrifuging the germ mixture; a filtration device that produces an embryo extract from the embryo extract by filtering the germ mixture discharged from the container containing the centrifuged germ 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.

2. The embryo extract liquid producing system of claim 1, wherein the filtration device comprises: a filtration unit that separates the embryo extract from a solution containing the embryo extract by using an ultrafiltration membrane or a chromatography stationary phase; and a supply mechanism that supplies an eluate to the filtration unit, through which the embryo extract separated by the ultrafiltration membrane or the chromatography stationary phase flows, toward a collection container for collecting the embryo extract; and the embryo extract liquid is produced by dissolving the embryo extract separated by the filtration unit into the eluate supplied by the supply mechanism.

3. A germ extract production system as described in claim 1 or claim 2, wherein the filtration device has a recovery unit that recovers the germ extract, and the recovery unit includes a holding structure that holds a recovery container, and a cooling device that cools the recovery container held by the holding structure.

4. A system for producing an embryo extract as described in claim 3, further comprising a post-treatment device that performs a predetermined post-treatment on the embryo extract contained in the collection container, and the transport device transports the collection container to the post-treatment device.

5. The embryo extract production system 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 germ extract liquid production system of claim 5, wherein the freezing device has a freezing container containing a liquid freezing refrigerant and a holder for holding the collection container on the transport device, and the holder deforms in response to the buoyancy force that the collection container receives from the freezing refrigerant.

7. The embryo extract production system according to claim 4, further comprising a box in which the centrifugal separation device, the filtration 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 adjustment device for adjusting the temperature inside the box.

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

10. The germ extract liquid manufacturing system of claim 7, wherein the box body has a blower device that blows clean air toward the centrifuge device, the filtration device, the removal device, and the conveying device, and an exhaust port that exhausts the air blown by the blower device outside the box body.

11. The embryo extract production system of claim 1, wherein the transport device has a robot arm, and the robot arm agitates the embryo mixture in the container by changing the container into various postures over time.

12. The germ extract liquid manufacturing system of claim 11, wherein the conveying device has a case for housing a container containing the germ mixture and a coolant contained in the case for cooling the container containing the germ mixture, and the robot arm agitates the germ mixture by changing the posture of the container containing the germ mixture and the case containing the coolant.

Images