Robot for cell collection device and cell collection method

Abstract

The present invention is a robot for a cell collection device, the robot having a terminal arm positioned at an end part of the robot, the robot being characterized in that an end part of the terminal arm has a holder for holding an object of interest, the holder has a plurality of holding modes, and, when the object is to be held in the different holding modes, the terminal arm and the object forms an angle of 0° to 180°, exclusive, theretween.

Description

[Technical Field]

[0001] The present invention relates to cell culture, and more particularly to a robot for a cell harvesting device and a cell harvesting method using the robot for a cell harvesting device. [Background technology]

[0002] In cell culture, cells cultured in various culture vessels must be recovered for passaging. In most cases, conventional cell recovery from culture vessels was performed manually by an operator. However, to produce cell-based products, a certain amount of cells is required, necessitating multiple cell culture and cell passaging procedures. However, because prolonged cell passaging can damage the cells, the passaging procedure must be completed quickly. Furthermore, to produce cells of consistent quality, the same procedures must be performed at each step. Furthermore, strict requirements for sterility during the procedure mean that manual procedures require high levels of skill, are complex, time-consuming, and prone to errors. For this reason, the inventor designed a cell recovery device that uses a robot to perform cell recovery operations. However, when using a robot, it was discovered that it was difficult to completely tilt and secure the container containing the culture medium or cell washing solution, for example, when pouring the culture medium or cell washing solution from one container to another. For example, even when using a six-axis robot with six degrees of freedom of rotation, the robot arm cannot fully mimic the flexible movements of a human, so the range of motion it can achieve is still limited. This limited range of rotation angles posed a problem, making it difficult to tilt objects. In particular, in cell culture, the operating space is limited, and many components are placed in a small space. Therefore, even if rotation angles can be achieved, flexible operation cannot be achieved due to obstacles in the robot arm's motion trajectory. Furthermore, flexible operation can be achieved by using a redundant robot with more degrees of freedom, but this method comes at a significant cost. Summary of the Invention [Problem to be solved by the invention]

[0003] The present invention has been made in view of the above-mentioned problems of the conventional technology, and aims to provide a robot for a cell recovery device and a cell recovery method that can prevent errors during cell recovery work by automating at least a portion of the work performed manually by a human using a robot in cell culture, and that can improve operability without upgrading the robot's hardware by providing the robot with different holding modes and realizing multiple holding angles.

[0004] In order to achieve the above object, the following inventions have been adopted. [Means for solving the problem]

[0005] The present invention provides a robot for a cell recovery device that has a terminal arm located at its end, the end of which has a holder for holding an object to be held, the holder having a plurality of holding modes, and when holding the object to be held in different holding modes, the terminal arm and the object form different angles that are greater than 0° and less than 180°.

[0006] Preferably, the holder has two holding modes, a first holding mode and a second holding mode, and when holding the object in the first holding mode, the terminal arm and the object form a first angle, and when holding the object in the second holding mode, the terminal arm and the object form a second angle.

[0007] More preferably, the difference between the first angle and the second angle is 90°.

[0008] More preferably, the terminal arm has a first holding portion and a second holding portion located at different positions, the first holding portion and the second holding portion are each capable of holding the same portion of the held object, and when the first holding portion holds the held object, it is in the first holding mode, and when the second holding portion holds the held object, it is in the second holding mode.

[0009] More preferably, the holder has a connection pin connected to the object to be held, and the connection pin engages with a hole to be held in the object to fix the holder and the object relative to each other.

[0010] More preferably, at least two groups of the connection pins are provided and arranged to protrude in opposite directions, and one of the two groups of the connection pins has at least two or more of the connection pins.

[0011] More preferably, two groups of said connection pins are provided, each group having two of said connection pins.

[0012] The present invention includes a medium discharging step of discharging the medium in the culture vessel; a washing step of injecting a cell washing solution into the culture vessel and discharging the cell washing solution; a detachment step of injecting a cell detachment solution into the culture vessel to detach cells in the culture vessel; a washing step of washing the cells in the culture vessel; a recovery step of discharging the cells in the culture vessel into a cell recovery bottle; a suspending step of suspending the cells in the cell collection bottle, The liquid discharging operation in each of the above steps is performed by tilting the robot for a cell recovery device according to any one of the above inventions, and the various containers to be discharged in each of the above steps are held by the robot for a cell recovery device as the objects to be held, The present invention further provides a cell recovery method in which, in the tilting operation, the liquid inside the retained objects is discharged while the retained objects are held in the different holding modes.

[0013] The present invention also provides a robot for a cell recovery device having a terminal arm, A holder for holding an object to be held is provided at the end of the terminal arm, The holder can hold the object to be held in a plurality of different holding modes, The object to be held has a central axis that serves as a reference for its posture, The tilt angle of the central axis of the object to be held in the holding mode with respect to the extending direction of the terminal arm is greater than 0° and less than 180°, The present invention provides a robot for a cell recovery device, in which the object to be held is held by the terminal arm at different inclination angles in the plurality of different holding modes.

[0014] The present invention provides a robot for a cell recovery device that has a terminal arm located at the terminal, the end of which has a holder for holding a target object, and the holder has multiple holding modes. When holding a target object in different holding modes, the terminal arm and the target object form different angles greater than 0° and less than 180°. Using this robot for a cell recovery device instead of manual labor reduces the number of workers required for cell recovery in cell culture and prevents errors during cell recovery. Furthermore, by holding the target object in multiple cell recovery modes, the target object can assume different postures relative to the robot. Therefore, if a certain posture does not provide sufficient tilting effect, simply switching to another holding mode effectively adjusts the tilting angle. This is advantageous for tasks such as tilting and rocking during the cell recovery process. This eliminates the need for expensive robots and allows flexible operation using a standard robot. [Effects of the Invention]

[0015] According to the present invention, operability can be improved. [Brief explanation of the drawings]

[0016] [Figure 1] Fig. 1 is a schematic front view showing a cell recovery device using a robot according to the present invention, in which a safety cabinet is omitted. [Figure 2] 2 is a schematic plan view showing a cell recovery device using a robot according to the present invention, in which the safety cabinet is omitted. [Figure 3]FIG. 3 shows the first bottle held in the container body holder. [Figure 4] FIG. 4 shows the state in which the first bottle is held by the container body holder. [Figure 5] FIG. 5 shows a state in which the container body holder holding the first bottle is held by the robot holder. [Figure 6] FIG. 6 shows the state in which the second bottle is held by the container body holder. [Figure 7] FIG. 7 shows the state in which the second bottle is held by the container body holder. [Figure 8] FIG. 8 shows the state in which the container body holder holding the second bottle is held by the robot holder. [Figure 9] FIG. 9 shows the state in which the third bottle is held by the container body holder. [Figure 10] FIG. 10 shows the state in which the container body holder holding the third bottle is held by the robot holder. [Figure 11] FIG. 11 shows the state in which the fourth bottle is held by the container body holder. [Figure 12] FIG. 12 shows the state in which the container body holder holding the fourth bottle is held by the robot holder. [Figure 13] Fig. 13 is a schematic front view showing the safety cabinet of the cell recovery device shown in Fig. 1. Fig. 13 is a schematic view showing the exterior of the safety cabinet. [Figure 14] Fig. 14 is a schematic side view showing the safety cabinet of the cell collection device shown in Fig. 2. The schematic side view of Fig. 14 shows the interior of the safety cabinet. DETAILED DESCRIPTION OF THE INVENTION

[0017] Hereinafter, exemplary embodiments of the present invention will be described with reference to the drawings. It should be understood that these specific descriptions are intended merely to teach those skilled in the art how to implement the present invention, and do not enumerate all possible embodiments of the present invention, nor are they intended to limit the scope of the present invention. In this specification, the term "vertical direction" refers to the direction of gravity (the up-down direction in FIG. 1 ), and the term "horizontal direction" refers to the horizontal direction in a plane perpendicular to the vertical direction (the left-right direction in FIG. 1 ). Furthermore, "tilting" primarily refers to the process of tilting the central axis of a container at a certain angle relative to the vertical direction via a movable container (described below). "Tapping" primarily refers to the reciprocating motion of the container via a movable container (described below) at a predetermined posture and frequency within a predetermined range for a predetermined time, thereby achieving reciprocating vibration of the container. "Shaking" primarily refers to the combined motion process of reciprocatingly shaking and rocking the container within a certain range via a robot (described below). During this motion process, the centerline of the container may extend along the vertical direction, the horizontal direction, or may not extend along a specific direction.

[0018] The structure of a cell recovery device using a robot according to the present invention will be described below with reference to the drawings. (Structure of a cell recovery device using a robot according to the present invention)

[0019] As shown in Figures 1 to 14, a cell recovery device using a robot (robot for cell recovery device) according to the present invention includes a safety cabinet 6, a control unit CU provided outside the safety cabinet 6, and a plurality of containers C, a stage 1, a mounting member 2, a capper 3, a pipette member 4, and a robot 5 provided inside the safety cabinet 6.

[0020] In this embodiment, the containers C contain fluids such as cell recovery culture media and cell solutions, and can be grasped by the robot 5 and moved to various positions. As shown in Figures 3, 4, 6, 7, 9, and 11, each container C has a container body CB that forms a storage space, a cap CL for closing the opening of the container body CB, and a container body holder CH that securely holds the container body CB. Specifically, in this embodiment, the containers C are divided into a first bottle C1, a second bottle C2, a third bottle C3, and a fourth bottle C4.

[0021] The first bottle C1 has a square cross section of the container body CB, a volume of 125 ml, and is a bottle containing a cell washing solution or a cell detachment solution. The cell washing solution may be, for example, PBS (phosphate buffered saline), and the cell detachment solution may be, for example, trypsin. Before the cell recovery device of the present invention begins operation, the first bottle C1 is accommodated in a corresponding one of the placement positions formed by the movable container unit 212. The movable container unit 212 is capable of rotating around an axis extending along the vertical direction V and of linear displacement along the vertical direction V. The container body holder CH of the first bottle C1 is provided with a gripping portion that is gripped by the container holder 542 of the robot 5.

[0022] The second bottle C2 has a circular container body CB with a volume of 500 ml. The lower half of the container body CB of the second bottle C2 tapers toward the bottom. The second bottle C2 may be a container, such as a centrifuge tube for cell collection. The second bottle C2 may further have other structures that are advantageous for concentration, flow, distribution, and collection of the cell solution. Before the cell collection device according to the present invention starts operating, the second bottle C2 may be accommodated in the mounting position of the movable container 212 or the fixed container 211. For example, before the cell collection device starts operating, the second bottle C2 is accommodated at position Pa (see FIG. 2). The container body holder CH of the second bottle C2 is provided with a gripping portion that is gripped by the container holder 542 of the robot 5.

[0023] The third bottle C3 is a bottle whose container body CB has a rectangular cross section. Before the cell recovery device according to the present invention starts operating, the third bottle C3 is accommodated in a corresponding mounting position of the fixed storage section 211, and is thereby fixed to the stage 1. For example, before the cell recovery device starts operating, the third bottle C3 is accommodated in position Pb (see FIG. 2). The third bottle C3 serves as a culture vessel to accommodate culture medium and grown cells. The cells are eventually concentrated in the second bottle C2. The container body holder CH of the third bottle C3 is provided with a gripping portion that is gripped by the container holder 542 of the robot 5.

[0024] The fourth bottle C4 has a square cross section of the container body CB and a volume of 2000 ml. Before the cell recovery device according to the present invention starts operating, the fourth bottle C4 is accommodated in a corresponding mounting position of the fixed storage unit 211, and is thereby fixed to the stage 1. For example, before the cell recovery device starts operating, the fourth bottle C4 is accommodated in position Pc (see FIG. 2). The fourth bottle C4 is a bottle that accommodates the discharged culture medium, and all of the culture medium discharged from the third bottle C3 is collected in the fourth bottle C4.

[0025] The container body holders CH for the four bottles C1, C2, C3, and C4 described above may be dedicated resin brackets or artificially formed silicone rubber brackets. In this way, the bottles will not fall even if they are inverted. Furthermore, because the bottles C1, C2, C3, and C4 are made of plastic, when the robot 5 directly grips the container body CB, bending can make it difficult to operate the caps and the bottles are prone to falling. However, the container body holders CH can avoid these problems.

[0026] In this embodiment, as shown in FIGS. 1 and 2, the stage 1 is installed on a work table 62 (see FIG. 14) inside a safety cabinet 6. The stage 1 has a work surface 1a extending along the horizontal direction H. A mounting member 2, a capper 3, a pipette member 4, and a robot 5 are installed on the work surface 1a.

[0027] Specifically, in this embodiment, the mounting member 2 is for mounting the container body CB and cap CL of the container C. The mounting member 2 has a container body accommodating section 21 and a cap mounting section 22. The container body accommodating section 21 and the cap mounting section 22 form mounting positions corresponding to the container body CB and cap CL of the container C, respectively, a temporary storage position for temporarily storing the container C, and a tilting / swinging position for tilting the container body CB of the container C (usually in a state where the cap CL is not engaged) or performing a reciprocating motion (i.e., tapping) (usually in a state where the cap CL is engaged).

[0028] Furthermore, the container body accommodating section 21 accommodates the container body CB of the corresponding container C and has an accommodating space that matches the cross-sectional shape of the container body CB. The multiple container body accommodating sections 21 are distributed on the stage 1 so as to surround the robot 5, thereby facilitating the robot 5 to operate on the container C inside the container body accommodating section 21. The container body accommodating section 21 has a fixed accommodating section 211 that cannot move relatively and a movable accommodating section 212 that can move relatively. Note that the "corresponding container C" refers to the container C accommodated in the container body accommodating section 21, such as a bottle C1.

[0029] The fixed storage part 211 holds its corresponding container body CB so that it is fixed relative to the work surface 1a. In this embodiment, the fixed storage part 211 holds its corresponding container body CB so that its central axis Sf is perpendicular to the work surface 1a. In other words, the central axis Sf of the container body CB extends along the vertical direction V. In this way, the opening of the container body CB stored in the fixed storage part 211 always faces upward in the vertical direction V. The fixed storage part 211 forms the above-mentioned placement position and temporary storage position. Note that the "corresponding container body CB" refers to the container body CB of the container C held by the fixed storage part 211, for example, the container body CB of the bottle C4.

[0030] The movable container 212 holds the corresponding container body CB so that it can rotate relative to the work surface 1a. In this embodiment, the movable container 212 for accommodating the first bottle C1 is rotatable about an axis extending along the vertical direction V and linearly displaceable along the vertical direction V, allowing the first bottle C1 to be positioned at different positions in a predetermined vertical direction V and different positions in the horizontal direction H. If necessary, containers C other than the first bottle C1 can be placed in the movable container 212, allowing each container C to be moved to a position convenient for manipulation by the robot 5. Furthermore, the movable container 212 also forms the tilting / swinging position, allowing the container C moved to the tilting / swinging position by the robot 5 to perform desired tilting and / or reciprocating motion in the movable container 212. The movable container 212 for forming the tilting / swinging position accommodates a specific container C only when necessary, thereby tilting the central axis Sf of the container body CB of the container C relative to the horizontal work surface 1a and / or performing a reciprocating motion of the container C within a predetermined range, thereby promoting uniform mixing and distribution of the solution in the container C. Note that the "corresponding container body CB" refers to the container body CB of the container C held by the movable container 212, for example, the container body CB of the bottle C1.

[0031] Furthermore, the cap placing unit 22 forms a placing position for placing the cap CL by placing the cap CL removed from the container C. In this embodiment, the cap placing unit 22 has a cap receiving member 221 that can be clamped by the robot. The cap receiving member 221 is formed with a plurality of recesses 222 that match the shape of each cap CL, so that the recesses 222 can accommodate the corresponding cap CL, and each recess 222 corresponds to the placing position of one cap CL. The cap receiving member 221 can be moved from the stage 1 to the capper 3 by the robot 5, and the cap receiving member 221 places the cap CL in the recess 222 by aligning the corresponding recess 222 with the cap CL removed by the capper 3. In addition, the cap receiving member 221 can be moved from the stage 1 to the capper 3 by the robot 5, and the cap receiving member 221 aligns the cap CL placed thereon with the capper 3, and further engages the capper 3 with the cap CL before fastening the cap CL to its corresponding container body CB.

[0032] In this embodiment, the capper 3 operates the cap CL of a different container C to engage and separate the cap CL from its corresponding container body CB. The capper 3 has an engagement claw 31 that can engage with the cap CL of the container C and rotate in two directions around the vertical direction V. The engagement claw 31 has three claw portions 311 evenly distributed around the circumferential direction of the cap CL, allowing it to fasten or remove the cap CL of the container C. After engaging with the cap CL attached to the container body CB of the container C from the outside, the engagement claw 31 can be rotated in one direction to remove the cap CL from the container body CB and separate the cap CL from the container body CB. Meanwhile, the engagement claw 31 can close the opening of the container body CB by engaging the cap CL with the container body CB.

[0033] The capper 3 also has a cap state detector (not shown) that detects whether the opening of the container C is covered with the cap CL. The cap state detector may be an optical sensor. In the cell recovery method described below, after performing the engagement or separation operation for all caps CL, the cap state detector detects whether the caps CL have been securely engaged with or separated from the container body CB. If it is detected that the desired state has not been achieved, the control unit CU controls the buzzer to issue an alarm and stops the operation.

[0034] The capper 3 may also be provided with a clamping module that clamps the container body CB of the container C. The clamping module has two clamping sections that approach or separate from each other, thereby fixing and holding the container body CB of the container C with the two clamping sections and relatively fixing the container body CB. In this way, when the capper 3 operates the cap CL of the container C to engage or separate the cap CL from the container body CB, the container body CB does not rotate freely due to the operation of the engagement claw 31 of the capper 3. Furthermore, the inner peripheral wall of the engagement claw 31 may be formed with engagement portions having two or more inner diameters. This allows the engagement claw 31 to engage with caps CL of different diameter ranges, thereby enabling it to clamp caps CL of different diameter ranges. For example, if the inner diameters of the engagement portions on the inner peripheral wall of the engagement claw 31 are 5 cm and 7 cm, it can engage with caps CL with diameters of 5 to 6 cm and also with caps CL with diameters of 7 to 8 cm. Of course, any design may be used as long as the inner diameter dimensions are different, and the specific dimensional range can be adjusted as needed.

[0035] In this embodiment, the pipette member 4 includes an assembled pipette (50 ml), a silicone hose, and a glass syringe. The pipette enters the container body CB and directly aspirates and dispenses the solution in the container body CB. The silicone hose is located between the pipette and the glass syringe and has a certain degree of flexibility. It serves to airtightly connect the pipette and the glass syringe, thereby preventing the pipette from being hindered from moving in the vertical direction V due to the inability of the connection to deform. The pipette and silicone hose are both disposable. The glass syringe functions as a piston, providing power for the aspirating and dispensing operations. In this way, the pipette member 4 suspends the cells in the cell solution collected in the second bottle C2 (dispersing, homogenizing, and suspending the cells). The pipette member 4 performs the above-mentioned suspension process by aspirating (aspirating) the solution from the container body CB of the container C or dispensing (dispensing) the solution into the container body CB of the container C in different amounts.

[0036] In this embodiment, the robot 5 has a mechanical structure with six degrees of freedom for moving the container body CB of the container C and the cap receiving member 221. The robot 5 includes multiple arms 51, 52, 53, and 54 connected in series. Among these, the fourth arm 54, which is the terminal arm, has a container holder 542 at the end thereof, which can hold the container C in at least two positions (corresponding to a first holding mode and a second holding mode). Specifically, the fourth arm 54 has two different container holders 542 in different positions, i.e., a first container holder 542 (first holding portion) and a second container holder 542 (second holding portion). The first holding mode is when the first container holder 542 holds the container C. When the container holder 542 holds the container C in the first holding mode, the container holder 542 of the fourth arm 54 forms a first angle with the central axis Sf of the container body CB of the container C. The second holding mode is when the second container holder 542 holds a container C, and when the container holder 542 holds a container C in the second holding mode, the holder 542 of the fourth arm 54 and the central axis Sf of the container body CB of the container C form a second angle. The difference between the first angle and the second angle may be any value greater than 0° and less than 180°, and causes the container C to perform a predetermined movement (linear displacement movement and swinging).

[0037] The first angle and the second angle will be explained in more detail. The container C (or the container body CB) is an example of a held object. The container C has an opening that is closed by the cap CL, and the orientation of the opening serves as the reference for the container's posture. That is, a virtual line that passes through the center of the opening and extends in the longitudinal direction of the container body CB is the central axis Sf, and the central axis Sf serves as the reference for the container's posture. The first angle (tilt angle) is the angle of the central axis Sf of the container C when held in the first holding mode relative to the extension direction of the fourth arm 54 (base 541, described below). This angle is greater than 0° and less than 180°. The second angle (tilt angle) is the angle of the central axis Sf of the container C when held in the second holding mode relative to the extension direction of the fourth arm 54 (base 541, described below). This angle is greater than 0° and less than 180°, and is different from the first angle.

[0038] The fourth arm 54 has a base 541 extending along a first direction and a container holder 542 extending along a second direction perpendicular to the first direction. The base 541 and the container holder 542 are fixedly connected. The base 541 is connected to the third arm 53 described below, and the container holder 542 is provided to hold a container C. The container holder 542 can hold the container C so that the central axis Sf of the container C coincides with the first direction or the second direction, thereby holding the container C via the container body holder CH in the first holding mode or the second holding mode. In this case, the difference between the first angle and the second angle is 90°. When the central axis Sf of the container C coincides with the first direction (for example, the configurations shown in Figures 5, 8, 10, and 12), the robot 5 mainly moves the container C horizontally linearly with its opening facing upward, i.e., moves the container C between different positions. When the central axis Sf of the container C coincides with the first direction or the second direction, the robot 5 can tilt the solution in the container body CB by tilting the opening of the container C at any angle relative to the vertical direction V, or can hold and shake the container C to uniformly mix the solution in the container C.

[0039] In this way, tilting the solution in container C in two relative postures is equivalent to holding container C at different angles. Specifically, if the solution in container C cannot be completely drained in the first holding mode due to limited degrees of freedom of the robot arm of robot 5 or due to obstacles on the movement trajectory when the robot arm achieves a certain tilt angle and position, the solution is drained as much as possible in the first holding mode. Then, container C can be held in the second holding mode and the solution in container C can be drained again. This allows for a sufficient tilt angle and operational operability to be obtained, allowing the solution in container C to be tilted more completely and preventing excessive residual solution. Furthermore, by rocking container C in two relative postures, the solution in container C can be mixed more uniformly.

[0040] In this embodiment, as described above, the fourth arm 54 (terminal arm) has two different container holders 542 located at different positions, i.e., a first container holder 542 (first holding portion) and a second container holder 542 (second holding portion). The first container holder 542 and the second container holder 542 can each hold the same portion of a container C. When the first container holder 542 holds a container C (held object), it is in the first holding mode, and when the second container holder 542 holds a container C (held object), it is in the second holding mode. Furthermore, the container holder 542 has connection pins 542P that are connected to the container C, and holds the container C by clamping the connection pins 542P. The connection pins 542P can engage with holding holes that are pre-formed in the container C, so that the holder 542 is fixed relative to the container C. In this embodiment, two connection pins 542P are provided for each group of connection pins 542P, and the connection pins 542P of one group are arranged to protrude in the opposite direction to the connection pins 542P of the other group. In this way, even if one connection pin 542P of one group of connection pins 542P fails to engage due to an unexpected situation, the other connection pin 542P of the same group can still perform the function of securely gripping the container C.

[0041] Furthermore, to further improve operational operability, whether the robot arm uses the first holding part or the second holding part, two different holding postures can be realized by holding the robot arm in the forward direction and the reverse direction, respectively, which actually corresponds to realizing more holding modes.

[0042] Furthermore, excluding the fourth arm 54, the multiple arms 51, 52, and 53 of the robot 5 include a first arm 51 having one end attached to the stage 1 of the cell recovery device, a second arm 52 connected to the first arm 51, and a third arm 53 connected to the second arm 52. The first arm 51 extends along a vertical direction V and is rotatable around the vertical direction V. The second arm 52 extends linearly and has one end connected to the other end of the first arm 51 via a first joint 51J, which provides the second arm 52 with at least one degree of rotational freedom relative to the first arm 51. The third arm 53 extends linearly and has one end connected to the other end of the second arm 52 via a second joint 52J, which provides the third arm 53 with at least one degree of rotational freedom relative to the second arm 52. The fourth arm 54 is connected to the third arm 53 via a third joint 53J, and the third joint 53J provides the fourth arm 54 with at least one degree of rotational freedom relative to the third arm 53. Specifically, the first joint 51J is provided with a first axis extending along the horizontal direction H, and the second arm 52 is rotatable around the first axis. The second joint 52J is provided with a second axis extending along the horizontal direction H, and the third arm 53 is rotatable around the second axis. The third joint 53J is provided with a third axis extending along the horizontal direction H, and the fourth arm 54 is rotatable around the third axis. Furthermore, the third arm 53 and the fourth arm 54 are both rotatable around their respective central axes. In this way, the robot 5 can achieve six degrees of freedom of movement.

[0043] According to the above-described invention, the robot 5 has a mechanical structure with six degrees of freedom, which enables it to hold other members in desired positions and complete tasks such as linear displacement, rotation, tilting, and swinging of the container C. Specifically, the robot 5 can smoothly complete each desired task by moving each container C to the capper 3, aligning each recess 222 of the cap receiving member 221 with the removed cap CL, and moving each container C to a placement position, a temporary storage position, a tilted position, etc.

[0044] In the specific embodiment described above, the fourth arm 54 (terminal arm) has a first container holder 542 (first holding portion) and a second container holder 542 (second holding portion) located at different positions, the first container holder 542 and the second container holder 542 are each capable of holding the same portion of the container C, and the robot is in the first holding mode when the first container holder 542 holds the container C (object to be held), and in the second holding mode when the second holding portion holds the object to be held. However, the robot according to the present invention is not limited to this. For example, the following alternative forms may be adopted.

[0045] In one alternative embodiment, the terminal arm (e.g., the fourth arm 54) has only one holding portion (e.g., the container holder 542) that can grip different locations (held portions) of the container C, and when one holding portion engages with different held portions of the container C, the first holding mode and the second holding mode can be realized. In this embodiment, the holding portion may be formed with two insertion portions arranged in parallel, and the different held portions may be formed with insertion holes corresponding to the two insertion portions. In this way, when the insertion portions engage with different insertion holes, the first holding mode and the second holding mode can be realized. Furthermore, since different held portions can share some of the insertion holes, processing costs can be saved.

[0046] In another alternative embodiment, the terminal arm (e.g., the fourth arm 54) has only one holding portion, and the container C has only one held portion. The holding portion and the held portion move relative to each other (e.g., rotate relative to each other) to achieve different engagement states, thereby realizing the first or second holding mode when the holding portion of the terminal arm engages with the held portion of the container C. In this embodiment, for example, the holding portion may have an insertion portion with a ridge portion having a cross-shaped cross section, and the held portion may have a radial insertion hole formed in a cross- or cross-like shape corresponding to the width and length of the cross-shaped ridge portion of the insertion portion. This allows the insertion portion to reliably engage with the insertion hole even when rotated at different phases relative to the insertion hole. In this way, the insertion portion can rotate relative to the insertion hole and then engage, thereby realizing the first or second holding mode.

[0047] In this embodiment, the control unit CU includes a CPU, memory, etc., and is connected to the robot 5 via a wired or wireless connection so as to be able to send and receive control signals. The control unit CU controls the robot 5 to perform various operations on the container C, controls the engagement and separation operations of the capper 3, and can control the selective suction and discharge operations of the pipette member 4, in accordance with a predetermined program stored in the memory. Although not clearly explained in this embodiment, the control unit CU may have multiple control means for controlling the operation of each member, thereby completing each of the above operations in accordance with the predetermined program.

[0048] 13 and 14, the safety cabinet 6 is provided to provide a sterile working environment. The stage 12 may be installed on a detachable work table 62 inside the safety cabinet 6, or may be the same member as the work table 62. The safety cabinet 6 has a housing 61, an exhaust module 63, a measurement module 64, a sterilization module 65, an illumination module 66, and a movement adjustment module 67.

[0049] Specifically, in this embodiment, the housing 61 has a cubic shape and forms a sterile working environment therein. The work table 62 is attached within the housing 61 and is arranged horizontally.

[0050] Furthermore, in this embodiment, the exhaust module 63 is provided to communicate between the inside and outside of the housing 61. The exhaust module 63 has an air inlet 631 and an exhaust outlet 635 provided in the housing 61, an air intake filter 632 (two in this embodiment) provided in the housing 61 and positioned at the air inlet 631, and an exhaust filter 634 (one in this embodiment) provided in the housing 61 and positioned at the exhaust outlet 635, thereby filtering out dust, particles, etc. during gas exchange between the inside and outside of the housing 61. The exhaust module 63 further has a blower 633 provided inside the exhaust outlet 635. The blower 633 is provided to promote the exhaust of air inside the housing 61 to the outside. The exhaust module 63 also has an exhaust filter differential pressure gauge 636 that monitors the pressure difference of the exhaust filter 634.

[0051] Furthermore, in this embodiment, the measurement module 64 is for measuring predetermined parameters within the housing 61. Specifically, the measurement module 64 has a particle counter 641 that measures the concentration of dust and particles within the housing 61, and a PAO (polyalphaolefin) inlet side measurement valve 642 that measures the input of PAO, thereby making it possible to provide the user with desired parameter information.

[0052] Furthermore, in this embodiment, the sterilization module 65 is provided in the housing 61 and is intended to sterilize the interior of the housing 61. Specifically, the sterilization module 65 has two germicidal lamps (15 W) provided on the side walls of the housing 61, thereby enabling the internal space of the housing 61 to be effectively sterilized.

[0053] Furthermore, in this embodiment, the lighting module 66 is for illuminating the inside of the housing 61. Specifically, the lighting module 66 includes three LEDs provided at the top of the internal space of the housing 61.

[0054] Furthermore, in this embodiment, the movement adjustment module 67 is disposed under the housing 61 to move the housing 61 and adjust the angle between the housing 61 and the ground. Specifically, the movement adjustment module 67 has a plurality of rollers 671, a plurality of adjusters 672, and a plurality of support legs 673. The rollers 671 are advantageous for the housing 61 to move along the ground when moving. The adjusters 672 are for supporting the housing 61 while adjusting the angle between the housing 61 and the ground. The support legs 673 perform a supporting function for the housing 61 after being placed down.

[0055] Furthermore, in this embodiment, the operation display unit 68 is arranged on the outer wall of the housing 61 to display parameters within the housing 61 and to input operation commands that control the operation of each component of the safety cabinet 6.

[0056] The above is a description of the structure of the cell recovery device using a robot according to the present invention. Below, we will explain the automated operation steps of the cell recovery device using examples. The following operation steps can all be automatically completed by the cell recovery device according to the present invention in accordance with a predetermined program. (Example of operation steps of a cell recovery device using a robot according to the present invention)

[0057] The operation steps of the cell recovery device using the robot according to the present invention are as follows: a culture medium discharging step of discharging most of the culture medium in the third bottle C3, which is a culture vessel, into the fourth bottle C4 via the robot 5; a washing step in which the cell washing solution contained in the first bottle C1 is poured into the third bottle C3 via the robot 5 to completely wash the remaining culture medium with the cell washing solution, and then the cell washing solution is discharged into the first bottle C1, in which the third bottle C3 needs to be tilted to one side via the movable container 212 to facilitate the tilting operation when the cell washing solution is poured into the third bottle C3; a detachment step in which the cell detachment solution contained in the first bottle C1 is poured into the third bottle C3 via the robot 5 to detach the cells in the third bottle C3, in which the third bottle C3 needs to be tilted to one side via the movable container 212 to facilitate the tilting operation when the cell detachment solution is poured into the third bottle C3; a washing step of washing the cells with the cell washing solution by injecting the cell washing solution into a third bottle C3 via the robot 5; a recovery step of discharging the cell detachment solution and cells in the third bottle C3 into the second bottle C2, which is a cell recovery bottle, via the robot 5; and a suspending step of suspending the cells in the second bottle C2 via the pipette member 4.

[0058] Furthermore, the cell recovery method further includes a supplementary recovery step after the recovery step and before the suspension step, in which a cell washing solution is injected into the third bottle C3, and then the remaining cells washed with the cell washing solution are injected into the second bottle C2, thereby recovering the cells remaining in the third bottle C3 as completely as possible into the second bottle C2.

[0059] Furthermore, in all of the above-described washing step, peeling step, recovery step, and replenishment / recovery step, the third bottle C3 is rocked via the robot 5. The rocking is performed with the thickness direction of the third bottle C3 aligned substantially vertically, and the culture vessel is inverted upside down at least once during the rocking operation. This upside-down inversion is performed so as not to affect the substantially vertical state of the thickness direction. In the above-described recovery step and replenishment / recovery step, the third bottle C3 can be placed on the movable container 212 during the rocking operation by the robot 5, and the third bottle C3 can be reciprocally displaced via the movable container 212. The reciprocating displacement is a reciprocating vibration operation that continues for, for example, 10 seconds or more, with one to two reciprocating movements per second. In this vibration operation, the reciprocating movement is suddenly stopped after accelerating, simulating a tapping-like effect, allowing the cells in the third bottle C3 to fully enter the solution and thoroughly mixing the solution in the third bottle C3, thereby achieving complete recovery.

[0060] Furthermore, the tilting operation of the robot 5 is performed in each of the above-described steps. In the tilting operation, the liquid in the container C is drained while the container C is held in the first holding mode and the second holding mode, respectively. In this way, the liquid in the container C can be drained as completely as possible. Furthermore, in each of the above-described steps, it is preferable to provide an operation of moving the robot 5 to a reset position between all of the robot 5's operations. This is advantageous for setting the robot 5 to the reset position for the next operation and for troubleshooting if the robot 5 malfunctions. After the malfunction is resolved, the next operation can be performed from the predetermined reset position for that operation. Here, although an operation of moving the robot 5 to a reset position is provided between all of the robot 5's operations, an operation of moving the robot 5 to a reset position may be provided only between some of the robot 5's operations. Furthermore, during most of the suspension process, the pipette member 4 enters below the surface of the liquid in the second bottle C2 to perform the aspirating and dispensing operations, thereby performing the suspension process. At the end of the suspension process, the pipette member 4 is moved away from the liquid surface in the second bottle C2, but by continuing to perform the suction and discharge operations even in the air, the cells remaining in the pipette member 4 can be completely injected into the second bottle C2.

[0061] Therefore, the present invention provides a novel cell collection device, which is not limited to the examples described in the above specific embodiments, and further includes the following supplementary explanation.

[0062] (i) In the specific embodiment described above, the working surface 1a of the stage 1 is horizontal, but this is not limited to the present invention. If necessary, the working surface 1a may be set to form a predetermined angle with respect to the horizontal plane.

[0063] (ii) In the specific embodiment described above, the structure of the safety cabinet 6 of the cell collection device according to the present invention has been described, but the present invention is not limited to this. The safety cabinet 6 may have a desired power socket and power cord. Furthermore, the housing 61 may have a detachable structure for maintenance and a transparent structure for easy observation of the internal space.

[0064] (iii) In the specific embodiment described above, the robot 5 of the cell recovery device according to the present invention has six degrees of freedom, but this is not limited to this. The robot 5 may be a redundant robot with seven degrees of freedom. Furthermore, if more flexible operation can be achieved by adjusting the holding mode, a robot with fewer degrees of freedom may be used.

[0065] (iv) In the specific embodiment described above, an example was described in which the cap CL is gripped via the engaging claws 31, but the member for gripping the cap CL of the capper 3 is not limited to a claw and may be another type of gripping portion. The other type of gripping portion may be set to have multiple inner diameters that can be applied to multiple gripping size ranges.

[0066] (v) In the specific embodiment described above, an example is described in which the movable housing portion 212 can realize a reciprocating vibration motion that imitates tapping and can also realize a tilting motion, but the movable housing portion 212 may also realize different movements using different members.

[0067] (vi) In the specific embodiment described above, an example was described in which the cap mounting portion 22 has the recess 222, but the cap CL may be mounted directly on a flat position without providing the recess 222. Furthermore, the cap CL may be mounted integrally with the portion on which it is mounted, or may be a separate portion. [Explanation of symbols]

[0068] 1 stage, 1a work surface, 2 Mounting member, 21 Container body storage section, 211 Fixed storage section, 212 Movable storage section, 22 Cap mounting section, 221 Cap receiving member, 222 Recessed section, 3 capper, 31 engaging claw, 331 claw portion, 4 pipette parts, 41 pipette tips, 5 Robot, 51 First arm, 51J First joint, 52 Second arm, 52J Second joint, 53 Third arm, 53J Third joint, 54 Fourth arm, 541 Base, 542 Holder, 542P Connecting pin, 6 Safety cabinet, 61 Housing, 62 Work table, 63 Exhaust module, 631 Air intake port, 632 Air intake filter, 633 Blower, 634 Exhaust filter, 635 Exhaust port, 636 Exhaust filter differential pressure gauge, 64 Measurement module, 641 Particle counter, 642 PAO inlet side measurement valve, 65 Sterilization module, 66 Lighting module, 67 Movement adjustment module, 671 Roller, 672 Adjuster, 673 Support leg, 68 Operation display unit, C container, C1 first bottle, C2 second bottle, C3 third bottle, C4 fourth bottle, CB container body, CL cap, CH container body holder, V Vertical direction, H Horizontal direction, CU Control unit

Claims

1. A robot for a cell recovery device having a terminal arm located at an end, A holder for holding an object to be held is fixedly connected to the terminal arm, the object to be held includes a container body and a container body holder that surrounds and holds the container body, The container body has a central axis that serves as a reference for its posture, The holder has a plurality of holding modes, and when gripping and holding the container body holder in different holding modes, the terminal arm and the object to be held form different angles that are greater than 0° and less than 180°, the angle is an angle of the central axis relative to the extension direction of the terminal arm, the holder has a plurality of connection pins connected to the container body holder, the container body holder has a plurality of retained holes that engage with the plurality of connection pins, A robot for a cell recovery device, characterized in that the multiple connection pins are arranged opposite each other on either side of the container body, and the multiple connection pins engage with the multiple held holes to fix the holder and the held object relative to each other.

2. The robot for a cell recovery device according to claim 1, characterized in that the holder has two holding modes, a first holding mode and a second holding mode, and when holding the object in the first holding mode, the terminal arm and the container body form a first angle, and when holding the object in the second holding mode, the terminal arm and the container body form a second angle.

3. 3. The robot for use in a cell recovery device according to claim 2, wherein the difference between the first angle and the second angle is 90 degrees.

4. the holder has two holding modes, a first holding mode and a second holding mode; 4. A robot for a cell recovery device according to claim 1, wherein the terminal arm has a first holding portion and a second holding portion located at different positions, the first holding portion and the second holding portion are each capable of holding the same portion of the object to be held, and the robot is in the first holding mode when the first holding portion holds the object to be held, and in the second holding mode when the second holding portion holds the object to be held.

5. A robot for a cell recovery device described in any one of claims 1 to 4, characterized in that at least two groups of connection pins are provided, protruding in opposite directions, and one of the two groups of connection pins has at least two or more of the connection pins.

6. 6. The robot for a cell recovery device according to claim 5, wherein two groups of said connection pins are provided, each group having two of said connection pins.

7. a medium discharge step of discharging the medium in the culture vessel; a washing step of injecting a cell washing solution into the culture vessel and discharging the cell washing solution; a detachment step of injecting a cell detachment solution into the culture vessel to detach cells in the culture vessel; a washing step of washing the cells in the culture vessel; a recovery step of discharging the cells in the culture vessel into a cell recovery bottle; a suspending step of suspending the cells in the cell collection bottle, The liquid discharging operation in each of the above steps is performed by tilting the robot for a cell recovery device according to any one of claims 1 to 6, and the various containers to be discharged in each of the above steps are held by the robot for a cell recovery device as the objects to be held, A cell recovery method characterized in that, in the tilting operation, the liquid inside the retained object is discharged while the retained object is held in each of the different holding modes.

8. A robot for a cell collection device having a terminal arm, A holder for holding an object to be held is fixedly connected to the end of the terminal arm, the object to be held includes a container body and a container body holder that surrounds and holds the container body, The holder can hold the container body holder in a plurality of different holding modes for the object to be held, The container body has a central axis that serves as a reference for its posture, an inclination angle of the central axis of the container body in a state held in the holding mode with respect to an extending direction of the terminal arm is greater than 0° and less than 180°; In the plurality of different holding modes, the object to be held is held by the terminal arm at different inclination angles, the holder has a plurality of connection pins connected to the container body holder, the container body holder has a plurality of retained holes that engage with the plurality of connection pins, A robot for a cell recovery device, in which the multiple connection pins are arranged opposite each other on either side of the container body, and the multiple connection pins engage with the multiple held holes to fix the holder and the held object relative to each other.

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