JP7346087B2 - Cell transfer system - Google Patents

Description

Embodiments of the invention relate to cell transfer systems.

Regenerative medicine using pluripotent stem cells such as iPS cells has already begun to be used clinically. iPS cells are established by providing reprogramming-inducing factors to highly differentiated somatic cells. During the process of establishing and culturing iPS cells, researchers who are skilled at identifying cells observe each cell one by one, and select cells that are in good condition to proceed to the next culture process. At this time, if iPS cells in good condition can be transferred cell by cell to the next culture process, the burden on researchers will be reduced.

Special Publication No. 2003-514236

The problem to be solved by the invention is to transfer iPS cells on a cell-by-cell basis.

According to embodiments, a cell transfer system includes a well plate, a transfer mechanism, and a transfer control. The well plate is provided with a plurality of wells that can accommodate iPS cells. The transfer mechanism selectively transfers the iPS cells accommodated in the well to the culture system well using an electric field. The transfer control unit controls the transfer mechanism to transfer at least one of the iPS cells accommodated in the well to the culture system well.

FIG. 1 is a diagram showing the configuration of a cell transfer system according to a first embodiment. FIG. 2 is a diagram representing a top view of the well plate shown in FIG. FIG. 3 is an enlarged view of the structure of the well plate shown in FIG. 2 near the wells. FIG. 4 is a cross-sectional view taken along line AA of the well plate shown in FIG. FIG. 5 is a sectional view taken along line BB of the well plate shown in FIG. FIG. 6 is a diagram showing another example of the movable electrode section shown in FIG. 4. FIG. 7 is a diagram showing the connection of switches when trapping iPS cells in wells of a well plate. FIG. 8 is a cross-sectional view of a well plate that has the function of efficiently trapping iPS cells. FIG. 9 is a diagram showing the connection of switches when transferring iPS cells trapped in a well. FIG. 10 is a diagram showing the operation of the movable electrode plate when a DC voltage is applied between the first electrode and the second electrode. FIG. 11 is an enlarged view of another configuration near the well shown in FIG. 3. In FIG. FIG. 12 is a cross-sectional view taken along line AA of the well plate shown in FIG. FIG. 13 is a sectional view taken along line BB of the well plate shown in FIG. 11. FIG. 14 is a diagram showing the connection of a power source and an AC power source to the well plate shown in FIGS. 11 to 13. FIG. 15 is a diagram showing the operation of the movable electrode plate when voltages of the same polarity are applied between the first electrode and the second electrode. FIG. 16 is a top view showing another configuration of the actuator shown in FIGS. 11 to 13. FIG. 17 is a sectional view taken along line AA of the actuator shown in FIG. 16. FIG. 18 is a diagram showing the configuration of a cell transfer system according to the second embodiment. FIG. 19 is an enlarged top view of the well structure of the well plate shown in FIG. 18. FIG. 20 is a cross-sectional view taken along line AA of the well plate shown in FIG. 19. FIG. 21 is a sectional view taken along line BB of the well plate shown in FIG. 19. FIG. 22 is a diagram showing the connection of a power source and an AC power source to the actuator shown in FIGS. 19 to 21. FIG. 23 is a diagram showing the operation of the movable electrode plate when a DC voltage is applied between the first electrode and the second electrode. FIG. 24 is a diagram showing a different cross section of the movable electrode plate shown in FIG. 23. FIG. 25 is a sectional view showing another configuration of the actuator shown in FIGS. 19 to 21. FIG. 26 is a diagram showing another configuration of the cell transfer system according to the second embodiment. FIG. 27 is a diagram showing contact between iPS cells pushed up by the movable electrode plate shown in FIG. 26 and a droplet held in the upper trap well plate. FIG. 28 is a different cross-sectional view of the movable electrode plate and upper trap well plate shown in FIG. 27; FIG. 29 is a diagram depicting contact between a droplet held in the upper trap well plate shown in FIG. 26 and a solution held in the culture well plate. FIG. 30 is a diagram showing another configuration of the cell transfer system according to the second embodiment. FIG. 31 is a diagram illustrating contact between a droplet held in the upper trap well roller shown in FIG. 30 and a solution held in a culture well plate.

Hereinafter, embodiments will be described with reference to the drawings.

(First embodiment)
FIG. 1 is a diagram showing an example of the configuration of a cell transfer system according to the first embodiment. The cell transfer system shown in FIG. 1 includes an array device 10 and a control device 20. FIG. 1 shows a schematic cross-sectional view of the array device 10 and a block diagram of the control device 20. The array device 10 and the control device 20 are connected, for example, by wire. Further, the control device 20 is connected to a power source 30, an AC power source 40, and a switch that opens and closes these connections.

The array device 10 is a device that accommodates iPS cells and can transfer the accommodated iPS cells to subsequent cell culture system wells. The array device 10 includes a well plate 11 for accommodating iPS cells, a lid part 12 that seals the well plate 11, and a culture system well plate 13 for transferring the iPS cells.

FIG. 2 shows an example of a top view of the well plate 11 according to the first embodiment. Note that the cross-sectional view shown in FIG. 1 represents the AA cross-section of the well plate 11 taken along the dashed line shown in FIG. The well plate 11 has a plurality of recesses (holes) called wells formed in the upper surface thereof, for example, in a grid shape. This can be said to mean that a well array is formed in the well plate 11. The opening of the well is formed to be approximately circular. The diameter of the opening of the well is about 15 μm to 20 μm, which is larger than the diameter of the iPS cells.

The well plate 11 is made of, for example, PDMS (polydimethylsiloxane) or Si. Inside the well plate 11, a trap mechanism for trapping iPS cells in the wells and a transport mechanism for selectively transporting the iPS cells trapped in the wells using an electric field are formed. The trap mechanism and the transfer mechanism are realized by, for example, a first electrode 111, a second electrode 112, and a third electrode 113 formed inside the well plate 11.

Specifically, inside the well plate 11, the first electrode 111, the second electrode 112, and the third electrode 113 are each formed in a preset direction. For example, in the example shown in FIG. 2, the first electrode 111 is represented by a broken line and is formed near one side of the well along the y-axis direction. The second electrode 112 and the third electrode 113 are represented by dashed lines and are formed along the x-axis direction so as to sandwich the well. The distance between the second electrode 112 and the third electrode 113, which are formed across the well, is shorter than the diameter of the well.

The first electrode 111 and the second electrode 112 are connected to the power source 30 via a switch 31 and a switch 32, respectively, so that a potential difference can be generated between the first electrode 111 and the second electrode 112. Further, the second electrode 112 and the third electrode 113 are connected to the AC power source 40 via a switch 41 and a switch 42, respectively, so that a potential difference can be generated between the second electrode 112 and the third electrode 113. ing.

FIG. 3 is an enlarged view of the structure near the wells of the well plate 11 shown in FIG. 2. As shown in FIG. Further, FIG. 4 shows an example of a cross-sectional view taken along line AA of the well plate 11 shown in FIG. Further, FIG. 5 shows an example of a cross-sectional view taken along line BB of the well plate 11 shown in FIG.

The first electrode 111 is disposed above the second electrode 112 and the third electrode 113. The first electrode 111 has a drive electrode portion 1111 at a position intersecting a region sandwiched between the second electrode 112 and the third electrode 113. For example, a portion of the drive electrode portion 1111 is exposed to a space provided within the well plate 11. The portions of the drive electrode portion 1111 that are exposed to the internal space are, for example, triangular prism portions 1112 and 1113. The triangular prism portions 1112 and 1113 have a columnar shape with a triangular cross section. The triangular prism portions 1112 and 1113 are formed parallel to each other along the y-axis direction. Since the drive electrode portion 1111 has the triangular prism portions 1112 and 1113, it is possible to effectively apply electrostatic force. Note that the drive electrode section 1111 does not necessarily have to have the triangular prism sections 1112 and 1113.

The second electrode 112 includes a movable electrode plate 1121, a torsion rod 1122, and a fixed part 1123. The movable electrode plate 1121 is formed for each well so as to serve as a partition plate within the well. A movable electrode plate 1121 functions as the bottom of each well. The movable electrode plate 1121 is connected to a fixed part 1123 via a conductive torsion rod 1122. A space is formed around the movable electrode plate 1121 in the well plate 11 so that the movable electrode plate 1121 can rotate around the torsion rod 1122. The movable electrode plate 1121, the torsion rod 1122, and the fixed part 1123 form an electrostatic rotary actuator as a transfer mechanism for each well.

Note that the cross section of the movable electrode plate 1121 may have a shape as shown in FIG. 6, for example. That is, the tip of the movable electrode plate 1121 may be chamfered to have a slope in the vertical direction. By devising the shape of the movable electrode plate 1121, it becomes possible to transfer iPS cells more efficiently.

Furthermore, an insulating layer may be provided on the surface of the triangular prism portion 1113 on the inner space side. By providing the insulating layer, it is possible to prevent conduction between the first electrode 111 and the second electrode even when the movable electrode plate 1121 rotates.

The distance between the second electrode 112 and the third electrode 113 that are formed across the well is shorter than the diameter of the well, and parts of the second electrode 112 and the third electrode 113 are exposed inside the well. . When a voltage is applied between the second electrode 112 and the third electrode 113 while the array device 10 is filled with a buffer solution, a dielectrophoretic force is generated in the direction toward the inside of the well, as shown in FIG. do. A trap mechanism is realized by the second electrode 112 and the third electrode 113.

The lid portion 12 shown in FIG. 1 is made using, for example, PDMS or Si. The lid part 12 has a side wall part 121. A lower end portion of the side wall portion 121 is joined to the well plate 11. The height from the bottom surface of the well plate 11 to the top surface of the lid part 12 is, for example, about 2 mm.

A first hole 122 is provided in the upper surface of one end of the lid portion 12, for example. Further, a second hole 123 is provided on the upper surface of the other end of the lid portion 12 . The first hole 122 is used, for example, as an inflow port through which a solution such as a buffer solution flows into the array device 10. Further, the second hole 123 is used, for example, as an outlet for discharging a solution such as a buffer solution from the array device 10. As the buffer solution, for example, PBS (Phosphate Buffered Salts) is used. The diameters of the first hole 122 and the second hole 123 are, for example, larger than the diameter of the iPS cell.

The culture well plate 13 has a plurality of culture wells formed on its upper surface, for example, in a grid pattern. The culture system well is formed, for example, in the shape of a substantially circular dish. The diameter of the culture system well is, for example, larger than the diameter of a well provided in the well plate 11. Note that the diameter of the culture system well may be approximately the same as that of the well provided in the well plate 11. The culture well plate 13 is arranged, for example, below the well plate 11 in the vertical direction.

The drive mechanism 131 supports the culture well plate 13 so as to be movable in the horizontal direction. The drive mechanism 131 is realized by, for example, a rail or the like. The drive mechanism 131 moves the culture well plate 13 according to instructions from the control device 20.

The control device 20 shown in FIG. 1 is a device that performs control for transferring at least one of the iPS cells accommodated in the well plate 11 to the culture well plate 13. The control device 20 has a processing circuit 21 , a memory 22 , an input interface 23 , a display 24 , and a connection interface 25 . The processing circuit 21, memory 22, input interface 23, display 24, and connection interface 25 are communicably connected to each other via a bus, for example.

The processing circuit 21 is a processor that functions as the core of the control device 20. The processing circuit 21 executes a program stored in the memory 22 or the like to realize a function corresponding to the program.

The memory 22 is a storage device such as a ROM (Read Only Memory), a RAM (Random Access Memory), an HDD (Hard Disk Drive), an SSD (Solid State Drive), and an integrated circuit storage device that stores various information. Furthermore, the memory 22 may be a drive device that reads and writes various information to and from a portable storage medium such as a CD-ROM drive, a DVD drive, and a flash memory. Note that the memory 22 does not necessarily need to be realized by a single storage device. For example, the memory 22 may be realized by a plurality of storage devices. Furthermore, the memory 22 may be located in another computer connected to the control device 20 via a network.

The memory 22 stores a transfer program and the like according to this embodiment. Note that these programs may be stored in the memory 22 in advance, for example. Further, for example, the information may be stored and distributed in a non-transitory storage medium, read from the non-transitory storage medium, and installed in the memory 22.

The input interface 23 receives various input operations from the user, converts the received input operations into electrical signals, and outputs the electrical signals to the processing circuit 21 . The input interface 23 is connected to input devices such as a mouse, a keyboard, a trackball, a switch, a button, a joystick, a touch pad, and a touch panel through which instructions are input by touching the operation surface. Furthermore, the input device connected to the input interface 23 may be an input device provided in another computer connected via a network or the like.

The display 24 displays various information according to instructions from the processing circuit 21. Any display can be appropriately used as the display, such as a liquid crystal display, an organic EL display, an LED display, a plasma display, and a CRT (Cathode Ray Tube) display.

The connection interface 25 is an interface between the control device 20 and other devices. Specifically, the connection interface 25 connects with, for example, the drive mechanism 131, the power supply 30, switches 31 and 32 for the power supply 30, the AC power supply 40, the switches 41 and 42 for the AC power supply 40, and a pump (not shown). . For example, the connection interface 25 connects the control signal generated by the processing circuit 21 to the drive mechanism 131, the power supply 30, switches 31 and 32 for the power supply 30, the AC power supply 40, the switches 41 and 42 for the AC power supply 40, or the pump. Output to.

The processing circuit 21 executes a transfer program or the like stored in the memory 22 to realize a function corresponding to the program. For example, the processing circuit 21 has a trap control function 211, a transfer control function 212, and a position control function 213 by executing a transfer program. In this embodiment, a case will be described in which the trap control function 211, transfer control function 212, and position control function 213 are realized by a single processor, but the present invention is not limited to this. For example, a processing circuit may be configured by combining a plurality of independent processors, and each processor may execute a program to realize the trap control function 211, the transfer control function 212, and the position control function 213.

The trap control function 211 is a function to control trapping of iPS cells by the well plate 11. For example, in the trap control function 211, the processing circuit 21 controls the application of an AC voltage to the second electrode 112 and the third electrode 113 of the well plate 11 to drive a trap mechanism provided for each well, and Trap iPS cells.

The transfer control function 212 is a function that controls the transfer of iPS cells accommodated in the well plate 11. For example, in the transfer control function 212, the processing circuit 21 drives the transfer mechanism provided for each well by controlling the application of DC voltage to the first electrode 111 and the second electrode 112 of the well plate 11. The iPS cells accommodated in the cell are transferred to the culture well plate 13.

The position control function 213 is a function to control the position of the culture well plate 13. For example, in the position control function 213, the processing circuit 21 controls the drive mechanism 131 to control the culture system so that any well of the culture system well plate 13 is located below a predetermined well of the well plate 11. Move the well plate 13.

Next, the iPS cell transfer process by the array device 10 configured as above will be described in detail.
First, for example, separated iPS cells are contained in a buffer solution and introduced into the array device 10 through the first hole 122 together with the buffer solution.

When iPS cells are introduced into the array device 10, for example, an instruction to trap the iPS cells is input from an operator. When an instruction to trap iPS cells is input, the processing circuit 21 executes the trap control function 211. In the trap control function 211 , the processing circuit 21 controls the opening and closing of the switches 31 , 32 , 41 , and 42 and drives the AC power supply 40 to apply an AC voltage to the second electrode 112 and the third electrode 113 of the well plate 11 . Apply.

FIG. 7 is a diagram showing a connection example of the switches 31, 32, 41, and 42 when iPS cells are trapped in the wells of the well plate 11. In order to apply an AC voltage between the second electrode 112 and the third electrode 113, the processing circuit 21 opens the switches 31 and 32 and closes the switches 41 and 42.

The buffer containing iPS cells is introduced through the first hole 122 of the lid 12, passes between the well plate 11 in the array device 10 and the lid 12, and then is discharged from the second hole 123. . The iPS cells contained in the buffer solution are subjected to dielectrophoretic force generated by the second electrode 112 and the third electrode 113, as shown in FIG. 8, as the buffer solution flows over the wells. This traps the iPS cells in the well. When the iPS cell trapping is completed, the processing circuit 21 opens the switches 41 and 42 and stops the AC power supply 40.

After the iPS cells are trapped in the wells of the well plate 11, for example, the operator specifies the well containing the iPS cells to be transferred. Once a well is designated, processing circuit 21 executes position control function 213. In the position control function 213, the processing circuit 21 controls the drive mechanism 131 to move the culture well plate 13.

Specifically, for example, when a well containing iPS cells to be transferred is designated, the processing circuit 21 identifies the culture well set for the designated well from the culture well plate 13. do. The culture system well set for the designated well may be set in advance or may be designated by the operator. The processing circuit 21 controls the drive mechanism 131 so that the specified culture well is located vertically below the specified well.

After the culture well plate 13 is moved, for example, an instruction to transfer iPS cells is input from an operator. When the instruction to transfer is input, the processing circuit 21 executes the transfer control function 212. In the transfer control function 212, the processing circuit 21 controls the opening and closing of the switches 31, 32, 41, and 42, and drives the power supply 30 to apply a DC voltage to the first electrode 111 and the second electrode 112 of the well plate 11. do.

FIG. 9 is a diagram showing an example of connections of the switches 31, 32, 41, and 42 when transferring iPS cells trapped in a well. FIG. 9 shows an example in which the well w11 is specified by the operator. When the culture system well corresponding to the well w11 is moved below the well w11 and a transfer instruction is input, the processing circuit 21 closes the switches 31-1 and 32-1 and closes the switches 31-2 to 31-6. , 32-2 to 32-6, 41, and 42 are opened, and the power supply 30 is driven. As a result, a DC voltage is applied between the first electrode 111-1 and the second electrode 112-1.

FIG. 10 is a schematic diagram showing an example of the operation of the movable electrode plate 1121 when a DC voltage is applied between the first electrode 111-1 and the second electrode 112-1. When a DC voltage is applied between the first electrode 111-1 and the second electrode 112-1, the drive electrode portion 1111 formed on the first electrode 111-1 and the drive electrode portion 1111 formed on the second electrode 112-1 are Electrostatic attraction is generated between the movable electrode plate 1121 and the movable electrode plate 1121, and the movable electrode plate 1121 rotates around the torsion rod 1122. As the movable electrode plate 1121 rotates, the portion functioning as the bottom of the well w11 is tilted vertically downward. As a result, the iPS cells placed on the movable electrode plate 1121 fall vertically downward.

Note that the buffer solution filled on the well plate 11 and the buffer solution filled on the culture system well plate 13 may be different. In such a case, surface tension is generated at the interface between different buffer solutions at the bottom of the well plate 11, so there is a possibility that the iPS cells will not fall just by rotating the movable electrode. Therefore, by flowing a large amount of buffer solution on the well plate 11 at the timing of rotating the movable electrode and increasing the internal pressure in the closed space on the upper side of the well plate 11, it is possible to encourage iPS cells to fall vertically downward. good. Further, at the timing of rotating the movable electrode, a dielectrophoretic force may be applied in addition to the gravitational force to encourage the iPS cells to fall vertically downward.

The space between the well plate 11 and the culture system well plate 13 is filled with a buffer solution. As shown in FIG. 10, the iPS cells that have fallen from the well w11 of the well plate 11 fall downward in the buffer solution according to gravity, and land in the culture system well that has been moved below the well w11. This completes the iPS cell transfer.

If there are multiple iPS cells to be transferred, the operator specifies, for example, the well containing the next target iPS cell. When the next well is designated by the operator, the processing circuit 21 identifies, for example, the culture system well set for the designated well. At this time, the identified culture well may be the previously identified culture well, or may be a different culture well. The processing circuit 21 moves the specified culture system well vertically below the specified well. Next, the operator inputs an instruction to transfer the iPS cells housed in the designated well. The processing circuit 21 controls the switches 31, 32, 41, and 42 and the power supply 30, and causes the iPS cells accommodated in the designated well to fall into the culture system well. For example, the processing circuit 21 repeats the above process as many times as the number of iPS cells to be transferred.

As described above, in the first embodiment, the cell transfer system uses the well plate 11 provided with a plurality of wells capable of accommodating iPS cells and selectively transfers the iPS cells accommodated in the wells using an electric field. It includes transport mechanisms 111 and 112 that can be transported, and a control device 20. The control device 20 transfers the iPS cells accommodated in the wells to the culture well plate 13 by driving the transfer mechanisms 111 and 112 using an electric field. This makes it possible to move the iPS cells to the next stage without human intervention during iPS cell creation and differentiation stage.

(Other examples)
The electrostatic actuator implemented in the first embodiment is not limited to those shown in FIGS. 3 to 5. The electrostatic actuator may have the configuration shown in FIGS. 11 to 13, for example. At this time, power supplies 30-1 and 30-2 and an AC power supply 40 are connected to the electrostatic actuator as shown in FIG. 14, for example. The power supply 30-1 has one end connected to the switch 31 and the other end grounded. The power supply 30-2 has one end connected to the switch 32 and the other end grounded. The power supplies 30-1 and 30-2 can be arbitrarily switched between an anode and a cathode.

FIG. 11 is an enlarged view of the structure of the well plate 11a shown in FIG. 14 near the wells. Further, FIG. 12 shows an example of a cross-sectional view taken along line AA of the well plate 11a shown in FIG. Further, FIG. 13 shows an example of a cross-sectional view taken along the line BB of the well plate 11a shown in FIG.

In FIG. 11, the first electrode 111a is represented by a broken line and is formed near one side of the well along the y-axis direction. The second electrode 112a and the third electrode 113 are represented by dashed lines and are formed along the x-axis direction so as to sandwich the well. The first electrode 111a is disposed above the second electrode 112a and the third electrode 113. The first electrode 111a has a drive electrode portion 1111a at a position intersecting a region sandwiched between the second electrode 112a and the third electrode 113. For example, a portion of the drive electrode portion 1111a protrudes into a space provided within the well plate 11. The portion of the drive electrode portion 1111a that protrudes into the internal space has, for example, a columnar shape with a quadrangular cross section. An insulating layer 11111a is provided on the side surface of the drive electrode portion 1111a on the side surface portion 11212a side. By protruding a portion of the drive electrode portion 1111, it becomes possible to effectively apply electrostatic force.

The second electrode 112a has a movable electrode plate 1121a, support rods 1124a-1, 1124a-2, and a contact portion 1125a. The movable electrode plate 1121a has a flat part 11211a and a side part 11212a. The plane portion 11211a is formed for each well substantially parallel to the xy plane so as to serve as a cylindrical partition plate within the well. The side surface portion 11212a is formed substantially perpendicular to the plane portion 11211a.

The movable electrode plate 1121a is in contact with the contact portion 1125a via conductive support rods 1124a-1 and 1124a-2. When a DC voltage is applied between the first electrode 111a and the second electrode 112a, the side surface portion 11212a is attracted to the drive electrode portion 1111a due to electrostatic attraction generated between the side surface portion 11212a and the drive electrode portion 1111a. In a state where the side surface portion 11212a is attracted to the drive electrode portion 1111a and is in contact with the surface of the insulating layer 11111a, the flat portion 11211a functions as the bottom of each well. A space is formed around the movable electrode plate 1121a in the well plate 11a so that the movable electrode plate 1121a can be translated in translation by the support rods 1124a-1 and 1124a-2. The movable electrode plate 1121a, the support rods 1124a-1, 1124a-2, and the contact portion 1125a form an electrostatic movement actuator as a transfer mechanism for each well.

The distance between the second electrode 112a and the third electrode 113, which are formed across the well, is shorter than the diameter of the well, and parts of the second electrode 112a and the third electrode 113 are exposed inside the well. . When a voltage is applied between the second electrode 112a and the third electrode 113 while the array device 10a is filled with a buffer solution, a dielectrophoretic force is generated in the direction toward the inside of the well, as shown in FIG. do. A trap mechanism is realized by the second electrode 112a and the third electrode 113.

Next, the transfer process of iPS cells using the well plate 11a configured as above will be explained in detail.
First, for example, the processing circuit 21 executes the transfer control function 212. In the transfer control function 212, the processing circuit 21 closes the switches 31, 32 and opens the switches 41, 42. Then, the processing circuit 21 controls the power supplies 30-1 and 30-2, and applies voltages of different polarities to the first electrode 111a and the second electrode 112a. As a result, electrostatic attraction is generated between the side surface portion 11212a and the drive electrode portion 1111a, and the side surface portion 11212a is attracted to the drive electrode portion 1111a. In a state where the side surface portion 11212a is attracted to the drive electrode portion 1111a, the flat portion 11211a functions as the bottom of the well.

Next, an instruction to trap iPS cells is input from the operator. When an instruction to trap iPS cells is input, the processing circuit 21 executes the trap control function 211. In the trap control function 211, the processing circuit 21 opens the switches 31 and 32 and closes the switches 41 and 42. The processing circuit 21 applies an AC voltage to the second electrode 112a and the third electrode 113 of the well plate 11a by driving the AC power supply 40.

The buffer containing iPS cells is introduced through the first hole 122 of the lid 12, passes between the well plate 11a in the array device 10a and the lid 12, and then is discharged from the second hole 123. . The iPS cells contained in the buffer are subjected to dielectrophoretic force generated between the second electrode 112a and the third electrode 113 when the buffer flows over the well. This traps the iPS cells in the well. When the iPS cell trapping is completed, the processing circuit 21 opens the switches 41 and 42 and stops the AC power supply 40.

After the iPS cells are trapped in the wells of the well plate 11a, for example, the operator specifies the well containing the iPS cells to be transferred. Once a well is designated, processing circuit 21 executes position control function 213. In the position control function 213, the processing circuit 21 controls the drive mechanism 131 to move the culture well plate 13.

After the culture well plate 13 is moved, for example, an instruction to transfer iPS cells is input from an operator. When the instruction to transfer is input, the processing circuit 21 executes the transfer control function 212. In the transfer control function 212, the processing circuit 21 closes the switches 31 and 32 and applies voltages of the same polarity to the first electrode 111a and the second electrode 112a. As a result, electrostatic repulsion is generated between the side surface portion 11212a and the drive electrode portion 1111a, and the side surface portion 11212a is separated from the drive electrode portion 1111a. When the side surface portion 11212a separates from the drive electrode portion 1111a, the iPS cells placed on the flat surface portion 11211a functioning as the bottom of the well fall vertically downward, as shown in FIG. 15. Note that the processing circuit 21 can control the bottom of any well by selecting the switches 31 and 32 to close.

Note that the buffer solution filled on the well plate 11a and the buffer solution filled on the culture system well plate 13 may be different. In such a case, since surface tension is generated at the interface between different buffer solutions in the lower part of the well plate 11a, there is a possibility that the iPS cells will not fall just by shifting the movable electrode. Therefore, by flowing a large amount of buffer solution over the well plate 11a at the timing of shifting the movable electrode and increasing the internal pressure in the closed space on the upper side of the well plate 11a, it is possible to encourage iPS cells to fall vertically downward. good. Furthermore, at the timing of shifting the movable electrode, dielectrophoretic force may be applied in addition to the gravitational force to encourage the iPS cells to fall vertically downward.

Furthermore, the structure of the electrostatic movement actuator is not limited to the structures shown in FIGS. 11 to 13, for example. The electrostatic movement actuator may be configured as shown in FIGS. 16 and 17, for example. That is, the drive electrode portion 1111a is provided on the side wall side of the internal space with respect to the side surface portion 11212a. When the plane part 11211a functions as the bottom of the well, electrostatic repulsion is generated between the drive electrode part 1111a and the side part 11212a, and the drive electrode part 1111a and the side part 11212a are separated. put. When the iPS cells placed on the flat part 11211a are dropped downward, electrostatic attraction is generated between the drive electrode part 1111a and the side part 11212a to attract the side part 11212a to the drive electrode part 1111a.

(Second embodiment)
FIG. 18 is a diagram showing an example of the configuration of a cell transfer system according to the second embodiment. The cell transfer system shown in FIG. 18 includes an array device 10b and a control device 20b. FIG. 18 shows a schematic cross-sectional view of the array device 10b and a block diagram of the control device 20b. The control device 20b is connected to a power source 30, an AC power source 40, switches 31, 32, 41, and 42 that open and close these connections, and a pump 50.

The array device 10b is a device that accommodates iPS cells and can transfer the accommodated iPS cells to subsequent cell culture system wells. The array device 10b has a well plate 11b for accommodating iPS cells, and a lid part 12 that tightly covers the well plate 11b.

The well plate 11b has a plurality of recesses called wells formed in the upper surface thereof, for example, in a grid shape. This can be said to mean that a well array is formed in the well plate 11b. The opening of the well is formed to be approximately circular. The diameter of the opening of the well is about 15 μm to 20 μm, which is larger than the diameter of the iPS cells.

The well plate 11b is made of, for example, PDMS or Si. Inside the well plate 11b, a trap mechanism for trapping iPS cells in the wells and a first transport mechanism for selectively transporting the iPS cells trapped in the wells using an electric field are formed. The trap mechanism and the first transfer mechanism are realized by, for example, a first electrode 111, a second electrode 112b, and a third electrode 113 formed inside the well plate 11b.

FIG. 19 is an enlarged top view of the well structure of the well plate 11b shown in FIG. 18. Further, FIG. 20 shows an example of a cross-sectional view taken along line AA of the well plate 11b shown in FIG. Further, FIG. 21 shows an example of a cross-sectional view taken along line BB of the well plate 11b shown in FIG.

In FIG. 19, the first electrode 111 is represented by a broken line and is formed near one side of the well along the y-axis direction. The second electrode 112b and the third electrode 113 are represented by dashed lines and are formed along the x-axis direction so as to sandwich the well. The first electrode 111 is disposed above the second electrode 112b and the third electrode 113. The first electrode 111 has a drive electrode portion 1111 similarly to the well plate 11 shown in the first embodiment. The drive electrode section 1111 has triangular prism sections 1112 and 1113 exposed to a space provided within the well plate 11b.

The second electrode 112b includes a movable electrode plate 1121b, a torsion rod 1122b, and a fixed part 1123. An internal space is formed around the movable electrode plate 1121b in the well plate 11 so that the movable electrode plate 1121b can rotate around the torsion rod 1122b. The movable electrode plate 1121b has a first plane part 11211b located on the well side and a second plane part 11212b located on the side surface of the internal space. The angle between the first plane part 11211b and the second plane part 11212b is, for example, a predetermined angle so that the cross section of the movable electrode plate 1121b has a substantially dogleg shape as shown in FIG. .

The first plane part 11211b is formed so that its width is narrower than the width of the second plane part 11212b, and its thickness is thicker than the thickness of the second plane part 11212b. By forming in this way, the first plane part 11211b becomes heavier than the second plane part 11212b. Therefore, when no voltage is applied to the first electrode 111 and the second electrode 112b, the first flat part 11211b falls into the well, and the first flat part 11211b functions as the bottom of the well.

The torsion rod 1122b is made of a conductive member. The torsion rod 1122b is provided near the region where the movable electrode plate 1121b is bent. The movable electrode plate 1121b is connected to the fixed part 1123 via a torsion rod 1122b. The movable electrode plate 1121b, the torsion rod 1122b, and the fixed part 1123 form an electrostatic rotary actuator as a first transfer mechanism for each well.

Culture system wells 114 are formed in the well plate 11b. The culture system well 114 is a well provided on the downstream side of the well plate 11b, and collects iPS cells flushed with the buffer solution.

The control device 20b shown in FIG. 18 is a device that performs control for transferring at least one of the iPS cells accommodated in the wells of the well plate 11b to the culture system well 114 of the well plate 11b. The control device 20b includes a processing circuit 21b, a memory 22, an input interface 23, a display 24, and a connection interface 25. The processing circuit 21b, memory 22, input interface 23, display 24, and connection interface 25 are communicably connected to each other via a bus, for example.

The processing circuit 21b is a processor that functions as the core of the control device 20b. The processing circuit 21b implements a function corresponding to the program by executing a transfer program or the like stored in the memory 22 or the like. For example, the processing circuit 21b has a trap control function 211 and a transfer control function 212b by executing a transfer program. In this embodiment, a case will be described in which the trap control function 211 and the transfer control function 212b are realized by a single processor, but the present invention is not limited to this. For example, a processing circuit may be configured by combining a plurality of independent processors, and each processor may execute a program to realize the trap control function 211 and the transfer control function 212b.

The transfer control function 212b is a function that controls the transfer of iPS cells accommodated in the well plate 11b. For example, in the transfer control function 212b, the processing circuit 21b drives the first transfer mechanism and the second transfer mechanism to transfer the iPS cells accommodated in the wells of the well plate 11b to the culture system wells 114. More specifically, the processing circuit 21b includes, for example, an electrostatic rotary actuator as a first transfer mechanism formed by a movable electrode plate 1121b, a torsion rod 1122b, and a fixed part 1123, and an array of solutions such as buffer solutions. A pump 50 as a second transfer mechanism that supplies the device 10b is driven. The processing circuit 21b controls the application of a DC voltage to the first electrode 111 and the second electrode 112b of the well plate 11b, and controls the pump 50 to transfer the iPS cells accommodated in the well to the culture system well 114. do.

Next, the iPS cell transfer process using the cell transfer system configured as above will be described in detail. In addition, in this description, for example, the power supplies 30-1, 30-2 and the AC power supply 40 are connected to the first electrode 111, the second electrode 112b, and the third electrode 113 formed inside the well plate 11b. They are connected as shown in FIG.

First, in an initial state in which no voltage is applied to the first electrode 111 and the second electrode 112b, the first flat portion 11211b falls into the well due to its own weight and functions as the bottom of the well.

Next, an instruction to trap iPS cells is input from the operator. When an instruction to trap iPS cells is input, the processing circuit 21b executes the trap control function 211 to generate iPS cells contained in the buffer between the second electrode 112b and the third electrode 113. It is trapped in the well by dielectrophoretic force.

After the iPS cells are trapped in the wells of the well plate 11b, for example, the operator specifies the well containing the iPS cells to be transferred. When a well is specified, the processing circuit 21b executes the transfer control function 212b. In the transfer control function 212b, the processing circuit 21b closes the switches 31 and 32 so as to apply voltages of the same polarity to the first electrode 111 and the second electrode 112b in the designated well. As a result, electrostatic repulsion is generated between the second plane part 11212b in the designated well and the drive electrode part 1111, and the second plane part 11212b is separated from the drive electrode part 1111. When the second plane part 11212b separates from the drive electrode part 1111, the iPS cells placed on the first plane part 11211b, which was functioning as the bottom of the designated well, are removed as shown in FIGS. 23 and 24. , lifted upwards. By being lifted by the first flat portion 11211b, the iPS cells are exposed from within the well to the surface of the well plate 11b. At this time, the AC voltage may be applied by changing the frequency of the applied AC power so that dielectrophoretic force is applied upward to the second electrode 112b and the third electrode 113 of the designated well.

While the movable electrode plate 1121b is rotating and the iPS cells are being lifted, for example, an instruction to transfer the iPS cells is input from the operator. When the instruction to transfer is input, the processing circuit 21b executes the transfer control function 212b and drives the pump 50. By driving the pump 50, a solution such as a buffer solution is supplied into the array device 10b, and the iPS cells exposed on the surface of the well plate 11b are washed away by the solution. The flushed iPS cells are collected in the culture system well 114.

As described above, in the second embodiment, the cell transfer system includes the array device 10b and the control device 20b. The array device 10b includes a well plate 11b provided with a plurality of wells that can accommodate iPS cells, and first transfer mechanisms 111 and 112b that can selectively transfer iPS cells accommodated in the wells using an electric field. 2 transfer mechanism 50 is provided. The array device 10b drives the first transfer mechanisms 111, 112 and the second transfer mechanism 50 to transfer the iPS cells accommodated in the wells to the culture wells 114. This makes it possible to move the iPS cells to the next stage without human intervention during iPS cell creation and differentiation stage.

Note that the processing performed by the processing circuit 21b when transferring iPS cells to the culture well 114 is not limited to the above. For example, the processing circuit 21b may execute the trap control function 211 when the pump 50 supplies the solution into the array device 10b. Specifically, in the trap control function 211, the processing circuit 21b generates a dielectrophoretic force between the second electrode 112b and the third electrode 113 of the well not designated by the operator. By doing so, it is possible to prevent iPS cells that are not desired to be transferred to the culture well 114 from being erroneously swept away.

Furthermore, the structure of the electrostatic rotary actuator is not limited to, for example, the structures shown in FIGS. 19 to 21. The electrostatic rotary actuator may be configured as shown in FIG. 25, for example. That is, the drive electrode part 1111 is provided on the bottom surface of the internal space that the second plane part 11212b comes into contact with when the movable electrode plate 1121b rotates. At this time, for example, a power source 30 and an AC power source 40 are connected to the actuator as shown in FIG. 2.

When the first plane part 11211b is to function as the bottom of the well, no voltage is applied to the first electrode 111 and the second electrode 112b, and the first plane part 11211b is allowed to fall into the well by its own weight. When lifting the iPS cells placed on the first plane part 11211b upward, electrostatic attraction is generated between the drive electrode part 1111 and the second plane part 11212b, and the drive electrode part 1111 is moved to the second plane part. Attracts 11212b.

(Other examples)
In the second embodiment, the iPS cells accommodated in the wells of the well plate 11b are lifted by the movable electrode plate 1121b, and the lifted iPS cells are swept away and recovered in the culture system well 114. . However, the means for transferring lifted iPS cells is not limited to this. The lifted iPS cells may, for example, be trapped in an upper trap well plate and transferred to a culture well.

FIG. 26 is a diagram showing another example of the configuration of the cell transfer system according to the second embodiment. The cell transfer system shown in FIG. 26 includes a well plate 11c as an array device, a control device 20c, and an upper trap well plate 60. FIG. 26 shows a schematic cross-sectional view of the well plate 11c and the upper trap well plate 60, and a block diagram of the control device 20c. The control device 20c is connected to a power source 30, an AC power source 40, switches 31, 32, 41, and 42 for opening and closing these connections, and a drive mechanism 70 for driving the upper trap well plate 60 in the vertical direction.

The well plate 11c has a plurality of recesses called wells formed in the upper surface thereof, for example, in a grid pattern. This can be said to mean that a well array is formed in the well plate 11c. The opening of the well is formed to be approximately circular. The diameter of the opening of the well is about 15 μm to 20 μm, which is larger than the diameter of the iPS cells. Each well of the well plate 11c is provided with an actuator having the structure shown in FIGS. 19 to 21 or 25, for example.

The control device 20c is a device that performs control for transferring at least one of the iPS cells accommodated in the wells of the well plate 11c to a culture well plate 80 placed in place of the well plate 11c. The control device 20c includes a processing circuit 21c, a memory 22, an input interface 23, a display 24, and a connection interface 25. The processing circuit 21c, the memory 22, the input interface 23, the display 24, and the connection interface 25 are communicably connected to each other via a bus, for example.

The processing circuit 21c is a processor that functions as the core of the control device 20c. The processing circuit 21c executes a transfer program or the like stored in the memory 22 or the like to realize a function corresponding to the program. For example, the processing circuit 21c has a trap control function 211 and a transfer control function 212c by executing a transfer program. In this embodiment, a case will be described in which the trap control function 211 and the transfer control function 212c are realized by a single processor, but the present invention is not limited to this. For example, a processing circuit may be configured by combining a plurality of independent processors, and each processor may execute a program to realize the trap control function 211 and the transfer control function 212c.

The transfer control function 212c is a function to control the transfer of iPS cells accommodated in the well plate 11c. For example, in the transfer control function 212c, the processing circuit 21c drives the first transfer mechanism and the second transfer mechanism to transfer the iPS cells accommodated in the wells of the well plate 11c to the culture well plate 80. More specifically, the processing circuit 21c includes, for example, an electrostatic rotary actuator as a first transfer mechanism formed by a movable electrode plate 1121b, a torsion rod 1122b, and a fixed part 1123, an upper trap well plate 60, and a second transfer mechanism having a drive mechanism 70 that drives the upper trap well plate 60; The processing circuit 21c controls the application of a DC voltage to the first electrode 111 and the second electrode 112b of the well plate 11c, and controls the drive mechanism 70 to transfer iPS cells accommodated in the wells to the culture well plate 80. Transfer to.

The upper trap well plate 60 has a plurality of trap wells formed on the lower surface, for example, in a grid pattern. For example, a droplet having a diameter slightly larger than the diameter of a well provided in the well plate 11c is held in the trap well by surface tension. For example, the trap wells exist in the same number as the wells provided in the well plate 11c, and are provided in the upper trap well plate 60 in the same arrangement as the wells in the well plate 11c. The upper trap well plate 60 is arranged, for example, above the well plate 11c in the vertical direction.

The drive mechanism 70 supports the upper trap well plate 60 so as to be movable in the vertical direction. The drive mechanism 70 is realized using, for example, a stepping motor. The drive mechanism 70 moves the upper trap well plate 60 in the vertical direction according to instructions from the control device 20c.

Next, the iPS cell transfer process using the cell transfer system configured as above will be described in detail.
First, in an initial state in which no voltage is applied to the first electrode 111 and the second electrode 112b, the first flat portion 11211b falls into the well due to its own weight and functions as the bottom of the well.

Subsequently, an instruction to trap iPS cells is input by the operator to the control device 20c, and a solution containing iPS cells is supplied to the well plate 11c. When an instruction to trap iPS cells is input, the processing circuit 21c executes the trap control function 211 to generate iPS cells contained in the buffer between the second electrode 112b and the third electrode 113. It is trapped in the well by dielectrophoretic force.

After the iPS cells are trapped in the wells of the well plate 11c, for example, the operator specifies the well containing the iPS cells to be transferred. When a well is designated, the processing circuit 21c executes the transfer control function 212c. In the transfer control function 212c, the processing circuit 21c generates electrostatic repulsion between the second plane part 11212b and the drive electrode part 1111 in the designated well, and causes the second plane part 11212b and the drive electrode part 1111 to Pull apart. When the second plane part 11212b separates from the drive electrode part 1111, the iPS cells placed on the first plane part 11211b, which was functioning as the bottom of the designated well, are lifted upward.

While the movable electrode plate 1121b is rotating and the iPS cells are being lifted, an instruction to collect the iPS cells is input from the operator, for example. When an instruction to collect is input, the processing circuit 21c executes the transfer control function 212c and drives the drive mechanism 70. The drive mechanism 70 lowers the upper trap well plate 60 to a preset position under control from the processing circuit 21c.

When the upper trap well plate 60 is lowered to a preset position, for example, as shown in FIGS. 27 and 28, the droplets held in the trap wells are applied to the iPS cells lifted by the movable electrode plate 1121b. comes into contact. When the iPS cells come into contact with the droplet, they are taken into the droplet by the surface tension of the droplet. The processing circuit 21c lowers the upper trap well plate 60 and once stops the upper trap well plate 60, then raises the upper trap well plate 60 to a preset position.

When lowering the upper trap well plate 60, the processing circuit 21c may perform the trap control function 211, for example. Specifically, in the trap control function 211, the processing circuit 21c generates a dielectrophoretic force between the second electrode 112b and the third electrode 113 of the well not designated by the operator. By doing so, it is possible to prevent iPS cells that are not desired to be transferred to the upper trap well plate 60 from being erroneously taken into the droplets of the upper trap well plate 60.

When the upper trap well plate 60 is raised to a predetermined position, the well plate 11c is replaced with a culture system well plate 80 at the stage of the cell transfer system.

The culture well plate 80 has a plurality of culture wells formed on its upper surface, for example, in a grid pattern. The culture system well is formed, for example, in the shape of a substantially circular dish. The diameter of the culture system well is, for example, larger than the diameter of the trap well provided in the upper trap well plate 60. For example, the culture well holds a larger amount of solution than the droplets held in the trap well. Note that the diameter of the culture system well may be approximately the same as that of the trap well.

After the culture well plate 80 is installed, for example, an operator inputs an instruction to release the iPS cells. When the instruction to open is input, the processing circuit 21c executes the transfer control function 212c and drives the drive mechanism 70. The drive mechanism 70 lowers the upper trap well plate 60 to a preset position under control from the processing circuit 21c.

When the upper trap well plate 60 is lowered to a preset position, for example, as shown in FIG. The two liquids come into contact with the solution held in the liquid, resulting in a two-liquid mixed state. When the two liquids are in a mixed state, the surface tension is lost. As a result, the iPS cells taken into the droplet of the trap well move by gravity to the solution they come in contact with. Therefore, it is possible to move the iPS cells to the next stage without human intervention when creating the iPS cells and at the differentiation stage.

Note that the upper trap well plate 60 is not limited to trapping the iPS cells lifted by the movable electrode plate 1121b above. iPS cells may be trapped with an upper trap well roller.

FIG. 30 is a diagram showing another example of the configuration of the cell transfer system according to the second embodiment. The cell transfer system shown in FIG. 30 includes a well plate 11c, a controller 20d, and an upper trap well roller 60d. FIG. 30 shows a schematic cross-sectional view of the well plate 11c and the upper trap well roller 60d, and a block diagram of the control device 20d. The control device 20d is connected to a power source 30, an AC power source 40, switches 31, 32, 41, 42 for opening and closing these connections, and a drive mechanism 70d for driving the upper trap well roller 60d.

The control device 20d is a device that performs control for transferring at least one of the iPS cells accommodated in the wells of the well plate 11c to a culture well plate 80 placed in place of the well plate 11c. The control device 20d includes a processing circuit 21d, a memory 22, an input interface 23, a display 24, and a connection interface 25. The processing circuit 21d, the memory 22, the input interface 23, the display 24, and the connection interface 25 are communicably connected to each other via a bus, for example.

The processing circuit 21d is a processor that functions as the core of the control device 20d. The processing circuit 21d implements a function corresponding to the program by executing a transfer program or the like stored in the memory 22 or the like. For example, the processing circuit 21d has a trap control function 211 and a transfer control function 212d by executing a transfer program.

The transfer control function 212d is a function to control the transfer of iPS cells accommodated in the well plate 11c. For example, in the transfer control function 212d, the processing circuit 21d drives the first transfer mechanism and the second transfer mechanism to transfer the iPS cells accommodated in the wells of the well plate 11c to the culture well plate 80. More specifically, the processing circuit 21d includes, for example, an electrostatic rotary actuator as a first transfer mechanism formed by a movable electrode plate 1121b, a torsion rod 1122b, and a fixed part 1123, an upper trap well roller 60d, and and a second transfer mechanism having a drive mechanism 70d that drives the upper trapwell roller 60d. The processing circuit 21d controls the application of a DC voltage to the first electrode 111 and the second electrode 112b of the well plate 11c, and controls the drive mechanism 70d to transfer iPS cells accommodated in the wells to the culture well plate 80. Transfer to.

The upper trap well roller 60d is a cylindrical roller that rotates around an axis. A plurality of trap wells are formed, for example, in a grid pattern on the circumferential surface of the upper trap well roller 60d. For example, a droplet having a diameter slightly larger than the diameter of a well provided in the well plate 11c is held in the trap well by surface tension. For example, there are the same number of trap wells as the wells provided in the well plate 11c, and the trap wells are provided in the upper trap well roller 60d in the same arrangement as the wells in the well plate 11c. The upper trap well roller 60d is arranged, for example, above the well plate 11c in the vertical direction.

The drive mechanism 70d movably supports the upper trap well roller 60d. The drive mechanism 70d moves the upper trap well roller 60d in the vertical direction according to instructions from the control device 20c. Further, the drive mechanism 70d moves the upper trap well roller 60d in the planar direction while rotating the upper trap well roller 60d around the axis according to instructions from the control device 20c. At this time, the moving speed in the plane direction corresponds to the rotational speed of the upper trap well roller 60d.

Next, the iPS cell transfer process using the cell transfer system configured as above will be described in detail.
First, the processing circuit 21d uses the transfer control function 212d to rotate the movable electrode plate 1121b provided in a designated well and lift up the iPS cells accommodated in this well. Then, while the iPS cells are being lifted, for example, an instruction to collect the iPS cells is input from the operator. When an instruction to collect is input, the processing circuit 21d drives the drive mechanism 70d using the transfer control function 212d. The drive mechanism 70d lowers the upper trap well roller 60d to a preset position under control from the processing circuit 21d.

When the upper trap well roller 60d descends to a preset position, the droplets held in a predetermined trap well row formed in the axial direction on the surface of the upper trap well roller 60d are moved to the corresponding one on the well plate 11c. The iPS cells held up by the movable electrode plate 1121b in the well row are contacted. When the iPS cells come into contact with the droplet, they are taken into the droplet by the surface tension of the droplet.

After lowering and once stopping the upper trap well roller 60d, the processing circuit 21d rotates the upper trap well roller 60d at a predetermined rotational speed and moves it in the plane direction at a speed corresponding to this rotational speed. When the last trap well row of the upper trap well roller 60d reaches the last well row of the well plate 11c, the processing circuit 21d raises the upper trap well roller 60d to a preset position.

When the upper trap well roller 60d is lowered and moved in a plane over the well plate 11c, the processing circuit 21d may execute the trap control function 211, for example. Specifically, in the trap control function 211, the processing circuit 21d generates a dielectrophoretic force between the second electrode 112b and the third electrode 113 of the well not specified by the operator. By doing so, it is possible to prevent iPS cells that are not desired to be transferred to the upper trap well roller 60d from being erroneously taken into the droplets of the upper trap well roller 60d.

When the upper trap well roller 60d is raised to a predetermined position, the well plate 11c is replaced with a culture system well plate 80 at the stage of the cell transfer system. After the culture well plate 80 is installed, for example, an operator inputs an instruction to release the iPS cells. When the instruction to open is input, the processing circuit 21d executes the transfer control function 212d and drives the drive mechanism 70d. The drive mechanism 70d lowers the upper trap well roller 60d to a preset position under control from the processing circuit 21d.

When the upper trap well roller 60d descends to a preset position, the droplets held in the predetermined trap well row formed on the surface of the upper trap well roller 60d and the culture wells of the culture well plate 80 are separated. The retained solution comes into contact with the liquid, resulting in a two-liquid mixed state. This causes the surface tension to lapse, and the iPS cells that have been taken up in the droplet in the trap well move by gravity to the solution they come in contact with.

After lowering and once stopping the upper trap well roller 60d, the processing circuit 21d rotates the upper trap well roller 60d at a predetermined rotational speed and moves it in the plane direction at a speed corresponding to this rotational speed. Due to the rotational movement of the upper trap well roller 60d, for example, as shown in FIG. Each column is contacted with the solution sequentially. As a result, the iPS cells taken into the droplet of the trap well move by gravity to the solution they come into contact with. Therefore, it is possible to move the iPS cells to the next stage without human intervention when creating the iPS cells and at the differentiation stage.

In another example of the second embodiment, the iPS cells housed in the wells of the well plate 11c are held in the trap wells of the upper trap well plate 60 and the upper trap well roller 60d due to surface tension. The following example explains the case where the data is imported using . However, the force that entraps iPS cells into the trap well droplet is not limited to surface tension. An electrode layer may be provided inside the upper trap well plate 60 and the upper trap well roller 60d to generate dielectrophoretic force between the electrodes.

According to at least one embodiment described above, the cell transfer system can transfer iPS cells in units of cells.

The term "processor" used in the description of the embodiments refers to, for example, a CPU (central processing unit), a GPU (Graphics Processing Unit), an application specific integrated circuit (ASIC), or a programmable logic device. (For example, it refers to circuits such as Simple Programmable Logic Device (SPLD), Complex Programmable Logic Device (CPLD), and Field Programmable Gate Array (FPGA)). A processor realizes its functions by reading and executing a program stored in a memory circuit. Note that instead of storing the program in the memory circuit, the program may be directly incorporated into the processor circuit. In this case, the processor realizes its functions by reading and executing a program built into the circuit. Note that each processor in each of the above embodiments is not limited to being configured as a single circuit for each processor, but may be configured as a single processor by combining multiple independent circuits to realize its functions. Good too. Furthermore, a plurality of components in each of the above embodiments may be integrated into one processor to realize its functions.

Although several embodiments of the invention have been described, these embodiments are presented by way of example and are not intended to limit the scope of the invention. These embodiments can be implemented in various other forms, and various omissions, substitutions, and changes can be made without departing from the gist of the invention. These embodiments and their modifications are included within the scope and gist of the invention as well as within the scope of the invention described in the claims and its equivalents.

10, 10a, 10b...Array device 11, 11a to 11c...Well plate 111, 111-1, 111a...First electrode 1111, 1111a...Drive electrode part 11111a...Insulating layer 1112, 1113...Triangular prism part 112, 112-1, 112a, 112b...Second electrode 1121, 1121a, 1121b...Movable electrode plate 1122, 1122b...Torsion rod 1123...Fixed part 1124a-1, 1124a-2...Support rod 1125a...Contact part 11211a...Plane part 11211b...First plane part 11212a... Side part 11212b... Second plane part 113... Third electrode 114... Culture system well 12... Lid part 121... Side wall part 122... First hole 123... Second hole 13... Culture system well plate 131... Drive mechanism 20, 20b to 20d...Control device 21, 21b to 21d...Processing circuit 211...Trap control function 212, 212b to 212d...Transfer control function 213...Position control function 22...Memory 23...Input interface 24...Display 25...Connection interface 30, 30 -1, 30-2...Power supply 31, 31-1 to 31-6, 32, 32-1 to 32-6...Switch 40...AC power supply 41, 42...Switch 50...Pump 60...Upper trap well plate 60d...Upper Trap well rollers 70, 70d...drive mechanism 80...culture system well plate

Claims (9)

a well plate provided with each well capable of accommodating iPS cells;
an electrostatic actuator that is provided in each well and functions as a bottom of each well or forms a state where the bottom is removed depending on the applied voltage;
a transfer control unit that causes the iPS cells placed on the electrostatic actuator to fall into a culture well by controlling a voltage applied to the electrostatic actuator;
A cell transfer system comprising: The electrostatic actuator is an electrostatic rotary actuator .
The cell transfer system according to claim 1 . The electrostatic actuator is an electrostatic movement actuator ,
The cell transfer system according to claim 1 . a well plate provided with each well capable of accommodating iPS cells;
an electrostatic actuator provided in each of the wells, which functions as a bottom of each well, and whose bottom rises in response to an applied voltage;
a transfer mechanism that transfers the iPS cells placed on the raised bottom to a culture system well;
By controlling the voltage applied to the electrostatic actuator, the iPS cells placed on the electrostatic actuator are lifted, and by controlling the transfer mechanism, the lifted iPS cells are transferred to the culture system. a transfer control unit for transferring to the well;
A cell transfer system comprising: The transfer mechanism has a pump that supplies the solution,
The transfer control unit controls the pump to supply the solution, thereby pushing the lifted iPS cells into the culture well .
The cell transfer system according to claim 4 . The transfer mechanism has a trap well that captures the lifted iPS cells using a droplet,
The transfer control unit brings the lifted iPS cells into contact with a droplet in the trap well and takes them into the droplet, and brings the droplet containing the iPS cells into contact with a solution in the culture well. , transferring the iPS cells taken into the droplet to the culture system well ;
The cell transfer system according to claim 4 . A plurality of trap wells are provided in a trap well plate ,
The cell transfer system according to claim 6 . A plurality of the trap wells are provided on the circumferential surface of the trap well roller .
The cell transfer system according to claim 6 . Each well of the well plate is provided with a trap mechanism for attracting the iPS cells ;
The cell transfer system according to any one of claims 1 to 8 .