JP7615799B2 - Cell Picking Device - Google Patents

Description

The present invention relates to a cell picking device.

When aspirating specific cells from a container such as a cell culture container, an operator manually aspirates the cells using an aspirating device such as a pipette while checking the position of the target cells using a microscope. However, this type of work requires skill, and aspirating cells is not easy for unskilled operators. The following Patent Document 1 proposes a cell aspirating system that assists in the aspirating of cells.

In the cell suction system described in Patent Document 1, a tubular tip that suctions cells stored in a container is attached to an aspiration unit. The position of the aspiration unit is adjusted three-dimensionally by a transport unit so that the tip of the tip approaches a specific cell.

JP 2016-112012 A

In a cell suction system such as that described in Patent Document 1, a motor is required as a drive unit for moving the suction unit to which the tip is attached. Since the cell suction system performs the suction operation of microscopic cells, high precision is required for the operation of the suction unit by the motor.

The object of the present invention is to provide a cell picking device that can confirm the accuracy of the motor's operation.

A cell picking device according to one aspect of the present invention is a cell picking device for aspirating cells from a sample in a sample container, and includes a motor that drives an aspiration arm to which a pipette tip can be attached, and a detection unit that detects the operation of the motor. The detection unit includes a rotating shaft that is driven to rotate by the motor, a rotating disk that is attached to the rotating shaft and rotates integrally with the rotating shaft, and a sensor provided near the rotating disk. The rotating disk has multiple slits that are provided at equal intervals in the circumferential direction of the rotating disk. The sensor detects the multiple slits to detect whether the motor has lost synchronization. One of the multiple slits is an initial position detection slit that has a different circumferential width from the other slits, and the sensor detects the initial position of the motor by detecting the initial position detection slit.

The present invention makes it possible to provide a cell picking device that can confirm the accuracy of the motor's operation.

FIG. 1 is a schematic diagram showing a configuration of a cell picking device according to an embodiment of the present invention. FIG. 2 is a side view showing a motor and a detector according to the embodiment. FIG. FIG. 13 is a flowchart showing a process of initial position detection. FIG. 11 is a plan view of a detection unit according to another embodiment.

Next, a cell picking device according to an embodiment of the present invention will be described with reference to the attached drawings.

(1) Configuration of the Cell Picking Apparatus Hereinafter, a cell picking apparatus 100 according to an embodiment of the present invention will be described with reference to the drawings. Fig. 1 is a schematic diagram showing the configuration of the cell picking apparatus 100 according to an embodiment of the present invention. As shown in Fig. 1, the cell picking apparatus 100 includes an aspiration unit 10, an observation unit 40, and a control unit 50. The aspiration unit 10 includes an aspiration arm 11, a drive unit 20, and a detection unit 30. In addition, a sample container 41 and a pipette tip rack 60 are provided in the cell picking apparatus 100.

The sample container 41 is, for example, a petri dish, and contains a sample including cells. When the suction arm 11 approaches the sample container 41, the cell is suctioned. The pipette tip rack 60 holds a number of replacement pipette tips 61. When the suction arm 11 approaches the pipette tip rack 60, the replacement pipette tips 61 are replaced.

The suction unit 10 includes a pipette-shaped suction arm 11. One of the replacement pipette tips 61 held in a pipette tip rack 60 is attached to the tip of the suction arm 11. Hereinafter, the replacement pipette tip 61 attached to the suction arm 11 will be simply referred to as tip 12. The suction unit 10 aspirates cells in a sample container 41 through tip 12, and ejects the aspirated cells into a well or the like of a culture plate (not shown). The same operation is then repeated using a new replacement pipette tip 61 and a new well.

The driving unit 20 includes a motor 21 for moving the suction arm 11 in three-dimensional directions. In FIG. 1, arrows are provided indicating the mutually orthogonal X, Y, and Z directions to clarify the positional relationship. The X and Y directions are orthogonal in a horizontal plane, and the Z direction corresponds to the up-down direction. The motor 21 includes, for example, a motor for rotating the suction arm 11 around a predetermined axis in a horizontal plane (in the XY plane). The motor 21 also includes, for example, a motor for rotating the suction arm 11 around a predetermined axis in a vertical plane (in the XZ plane). The motor 21 also includes, for example, a motor for moving the suction arm 11 forward and backward in the vertical direction (Z direction). For example, a stepping motor is used as the motor 21. The detection unit 30 is a functional unit for detecting the loss of synchronism and the initial position of the motor 21.

The observation unit 40 has a stage on which the sample container 41 is placed. The observation unit 40 has a function of illuminating the sample container 41 on the stage. The observation unit 40 also has a function of observing the sample in the sample container 41 while magnifying it with a microscope, and a function of imaging the sample in the sample container 41 while magnifying it.

The control unit 50 includes a CPU (Central Processing Unit) and a memory. The control unit 50 controls the suction unit 10 and the observation unit 40. The control unit 50 controls the drive unit 20 of the suction unit 10 to move the suction arm 11 in three-dimensional directions. The control unit 50 controls the observation unit 40 to obtain an image of the sample magnified by the microscope provided in the observation unit 40. The control unit 50 also controls the observation unit 40 to obtain an image of the sample captured in the observation unit 40. The display unit 51 includes, for example, an LCD (liquid crystal display) panel, and displays images obtained by the observation unit 40. The operation unit 52 accepts user operations. The user can give the control unit 50 an instruction to operate the suction arm 11 by operating the operation unit 52.

(2) Configuration of the Detection Unit Next, the configuration of the detection unit 30 will be described with reference to Figs. 2 to 4. Fig. 2 is a side view showing the motor 21 and the detection unit 30 according to this embodiment. In Figs. 2 to 4, arrows are provided indicating the mutually orthogonal X1, Y1, and Z1 directions to clarify the positional relationship. The X1, Y1, and Z1 directions in Figs. 2 to 4 may or may not coincide with the X, Y, and Z directions in Fig. 1. The relationship between the directions is determined according to the mounting mode of the motor 21. For convenience, the Z1 direction will be described as the up-down direction of the detection unit 30.

The detection unit 30 includes a rotating shaft 31, a rotating disk 32, and a sensor 33. The rotating shaft 31 is a shaft driven by the rotation output of the motor 21. The rotating disk 32 is fixed to the rotating shaft 31. The rotating disk 32 is, for example, a metal disk. The rotating disk 32 rotates integrally with the rotating shaft 31 by the drive of the motor 21. The sensor 33 is arranged so as to sandwich the outer peripheral end of the rotating disk 32. The sensor 33 is fixed to a predetermined member 34 provided in the suction unit 10. The sensor 33 includes a first member 331 and a second member 332. The first member 331 and the second member 332 sandwich the outer peripheral end of the rotating disk 32 from above and below. One of the first member 331 and the second member 332 includes a light-emitting unit that emits light, and the other includes a light-receiving unit that receives the light emitted from the light-emitting unit. That is, the sensor 33 has a light-projecting section facing one side of the rotating disk 32 and a light-receiving section facing the other side of the rotating disk 32. The sensor 33 is capable of detecting an object between the first member 331 and the second member 332 by determining whether or not the light emitted from the light-projecting section is received by the light-receiving section. In this manner, in this embodiment, a photoelectric sensor is used as the sensor 33. For example, visible light, infrared light, etc. can be used as the light source of the photoelectric sensor.

Figure 3 is a plan view of the detection unit 30. As shown in Figure 3, a plurality of slits SL are provided on the outer peripheral end of the rotating disk 32. The plurality of slits SL include a plurality of slits SL1 for detecting out-of-step and one slit SL2 for detecting initial position. In the example shown in Figure 3, seven slits SL1 for detecting out-of-step are provided. Note that the slit SL2 for detecting initial position also functions as a slit for detecting out-of-step.

The multiple slits SL are arranged at equal intervals on the outer periphery of the rotating disk 32. Specifically, the center positions of the slits SL in the circumferential direction are equally spaced. The circumferential intervals between two adjacent out-of-step detection slits SL1 are also equal. As shown in FIG. 3, the slit width of the out-of-step detection slit is K1, and the slit width of the initial position detection slit SL2 is K2. The slit widths K1 and K2 are the circumferential widths of the rotating disk 32. Here, K1<K2, and the slit width K2 of the initial position detection slit SL2 is larger than the slit width K1 of the out-of-step detection slit SL1. As long as K1 and K2 are different widths, K1>K2 may be acceptable.

As shown in FIG. 3, the sensor 33 is located at the outer circumferential end of the rotating disk 32. Since FIG. 3 is a plan view of the rotating disk 32, the first member 331 of the sensor 33 is depicted as being located above the rotating disk 32. The second member 332 of the sensor 33 is located on the rear side of the rotating disk 32. FIG. 3 shows the sensor 33 overlapping one of the out-of-step detection slits SL1. With the above configuration, the detection unit 30 performs out-of-step detection and initial position detection, which will be described next.

(3) Step-out detection A method of step-out detection of the motor 21 by the detection unit 30 will be described. The control unit 50 drives the motor 21 by providing a pulse signal to the motor 21. When the motor 21 is driven, the rotating disk 32 rotates with the rotating shaft 31 as the center of rotation. When the rotating disk 32 rotates, the outer periphery of the rotating disk 32 passes between the first member 331 and the second member 332 of the sensor 33, as shown in FIG. 3. The sensor 33 detects the slit SL passing between the first member 331 and the second member 332. That is, the sensor 33 detects the step-out detection slit SL1 and the initial position detection slit SL2 passing between the first member 331 and the second member 332.

The control unit 50 acquires detection information of the slit SL from the sensor 33. The control unit 50 counts the number of slit SL detected while a pulse signal is being given to the motor 21. The control unit 50 determines whether the motor 21 has stepped out based on the number of pulses given to the motor 21 and the number of detected slit SL. In other words, when the motor 21 is operating correctly, the relationship between the number of pulses given and the rotation angle of the motor is determined. The control unit 50 can determine whether the motor 21 has stepped out based on whether the rotation angle of the motor calculated from the number of detected slit SL matches the rotation angle corresponding to the number of pulses.

Note that the slit width K2 of the initial position detection slit SL2 is different from the slit width K1 of the out-of-step detection slit SL1, but the control unit 50 counts only the number of detections of the slit SL. Therefore, the initial position detection slit SL2 is also used as a slit for out-of-step detection.

(4) Initial Position Detection Next, a method of detecting the initial position of the motor 21 by the detection unit 30 will be described. FIG. 4 is a partially enlarged plan view of the detection unit 30. FIG. 4 is a plan view of the rotating disk 32, and an enlarged view of the slit SL2 for detecting the initial position. FIG. 5 is a flow chart showing a method of detecting the initial position. First, in step S1 shown in FIG. 5, the control unit 50 rotates the rotating disk 32 in the R1 direction shown in FIG. 4, and acquires the number of pulses between P1 and P2. Specifically, the control unit 50 rotates the rotating disk 32 in the R1 direction and determines whether the sensor 33 detects the slit SL. In the example of FIG. 4, the sensor 33 detects the slit SL immediately after passing the position P1. Thereafter, the control unit 50 determines whether the sensor 33 detects the rotating disk 32. In the example of FIG. 4, the sensor 33 detects the rotating disk 32 immediately after reaching the position P2. Then, the control unit 50 acquires the number of pulses of the pulse signal output while the detection position of the sensor 33 moves from the position P1 to the position P2.

Next, in step S2, the control unit 50 determines whether the slit SL detected in step S1 is the initial position detection slit SL2. The control unit 50 obtains the slit width of the slit SL from the number of pulses acquired in step S1, and determines whether the slit width matches the slit width K2 of the initial position detection slit SL2. If it is determined that the detected slit SL is the initial position detection slit SL2, the process proceeds to step S3. If the detected slit SL is not the initial position detection slit SL2, the process returns to step S1 and detects the next slit SL.

In step S3, the control unit 50 rotates the rotating disk 32 in the R2 direction while the sensor 33 detects position P2. Then, the control unit 50 stops the rotating disk 32 when the sensor 33 detects position P3. The number of pulses for rotating the rotating disk 32 at this time is preset. In step S4, the control unit 50 determines whether the slit SL2 or the rotating disk 32 is detected at the stop position. If the rotating disk 32 is detected at the stop position, in step S5, the control unit 50 rotates the rotating disk 32 in the R1 direction and stops the rotating disk 32 when the sensor 33 detects position P1. In other words, since it is determined that the motor 21 is not out of step, the motor 21 is put on standby at the initial position. As a result, the rotation direction of the motor 21 is adjusted to the direction from P1 to P2 (the direction in which the motor 21 will be rotated next) and then the motor 21 is stopped. If it is determined in step S4 that the slit SL2 has been detected at the stop position, in step S6, the control unit 50 determines that the motor 21 has lost synchronism, and ends the process. For example, the control unit 50 displays a message on the display unit 51 indicating that the motor 21 has lost synchronism.

As described above, the turntable 32 of this embodiment is provided with a plurality of slits SL at equal intervals in the circumferential direction of the turntable 32. One of the plurality of slits SL provided on the turntable 32 is an initial position detection slit SL2, which has a different circumferential width from the other slits SL. The sensor 33 can detect the initial position of the motor 21 by detecting the initial position detection slit SL2. In addition, by counting the number of slits SL detected by the sensor 33, it can detect whether the motor 21 has stepped out.

The cell picking device 100 of this embodiment is capable of detecting out-of-step and initial position of the motor 21 using one turntable 32 and one sensor 33. Compared to a case where separate turntables and sensors are provided for out-of-step detection and initial position detection, the device configuration can be made smaller and the device costs can be reduced. If separate turntables and sensors are provided for out-of-step detection and initial position detection, it is necessary to adjust the positions of these components so that they do not interfere with each other, which results in a larger device configuration, but the detection unit 30 of this embodiment can be made compact. Also, in this embodiment, out-of-step detection and initial position detection can be performed by changing the width of the slit SL, and the device mechanism does not become complicated in order to perform both detections.

(5) Other embodiments FIG. 6 is a plan view showing a turntable 32A according to another embodiment. The turntable 32A has a plurality of slits SL at equal intervals in the circumferential direction, as in the above embodiment. Also, as in the above embodiment, one of the plurality of slits SL is an initial position detection slit SL2 having a slit width K2. Unlike the turntable 32 in FIG. 3, the turntable 32A has an auxiliary slit SL3 on the opposite side (180-degree inverted side) of the initial position detection slit SL2. The slit width K3 of the auxiliary slit SL3 is larger than K1 and smaller than K2. The configuration other than the turntable 32A is the same as that of the cell picking device 100 of the above embodiment described with reference to FIGS. 1 to 5. By utilizing the detection unit 30 having the turntable 32A, the detection unit 30 can detect a position other than the initial position using the auxiliary slit SL3. In the example of FIG. 6, a position inverted by 180 degrees from the initial position can be detected. In other words, two rotation positions of the motor 21, including the initial position, can be detected. Furthermore, by including slits SL with different slit widths among the slits SL, it is possible to detect three or more rotation positions of the motor 21.

In the above embodiment, a photoelectric sensor was used as an example of the sensor 33 that detects each slit of the rotating disk 32, but the type of sensor is not particularly limited. Other sensors such as laser sensors and proximity sensors can also be used. In addition, in the above embodiment, a transmissive photoelectric sensor was used as the sensor 33, but a reflective photoelectric sensor may also be used.

In the above embodiment, the motor 21 is described as being either a motor that rotates the suction arm 11 in the XY plane, a motor that rotates the suction arm 11 in the XZ plane, or a motor that moves the suction arm 11 forward and backward in the Z direction. The detection unit 30 of this embodiment may be applied to any of the motors for moving the suction arm 11, or may be applied to multiple motors.

(6) Correspondence between each component of the claims and each element of the embodiment Below, examples of correspondence between each component of the claims and each element of the embodiment will be described, but the present invention is not limited to the following examples. In the above embodiment, the R1 direction is an example of the first direction, and the R2 direction is an example of the second direction. Also, in the above embodiment, the rotational position of the motor 21 detected by the auxiliary slit SL3 is an example of the auxiliary position.

Various elements having the configuration or function described in the claim may be used as each component of the claim.

(7) Aspects It will be understood by those skilled in the art that the exemplary embodiments described above are specific examples of the following aspects.

(Section 1)
1. A cell picking device for aspirating cells from a sample in a sample container, comprising:
a motor for driving an aspiration arm to which a pipette tip can be attached;
A detection unit that detects the operation of the motor;
Equipped with
The detection unit is
A rotating shaft that is rotated by the motor;
a rotating disk attached to the rotating shaft and rotating integrally with the rotating shaft;
A sensor provided near the rotating disk;
Including,
The rotating disk has a plurality of slits provided at equal intervals in a circumferential direction of the rotating disk,
having
The sensor detects the presence or absence of step-out of the motor by detecting the plurality of slits,
One of the multiple slits is an initial position detection slit having a circumferential width different from the other slits, and the sensor detects the initial position of the motor by detecting the initial position detection slit.

It is possible to provide a cell picking device that can confirm the accuracy of the motor's operation.

(Section 2)
2. The cell picking device according to claim 1,
The detection unit may detect whether or not the motor has lost synchronism based on the number of the plurality of slits including the initial position detection slit detected by the sensor.

The initial position detection slit can also be used to detect out-of-step.

(Section 3)
3. The cell picking device according to claim 1 or 2,
The detection section may detect an initial position of the motor based on a circumferential width of the initial position detection slit detected by the sensor.

The initial position of the motor can be detected by using the difference in the width of the slits.

(Section 4)
The cell picking device according to any one of claims 1 to 3,
The plurality of slits may be provided at an outer circumferential edge of the rotating disk.

Sensors can be placed on the outer periphery of the turntable.

(Section 5)
A cell picking device according to any one of claims 1 to 4,
The sensor may include a light-projecting portion facing one surface of the rotating disk, and a light-receiving portion facing the other surface of the rotating disk.

It is possible to detect the rotating disk and the slits in the rotating disk located between the light-emitting unit and the light-receiving unit.

(Section 6)
6. The cell picking device according to any one of claims 1 to 5,
The detection unit may calculate the circumferential width of the detected slit by rotating the turntable in a first direction, and when the circumferential width of the detected slit matches the width of the initial position detection slit, determine that the detected slit is the initial position detection slit.

Step-out can also be detected during the initial position detection process.

(Section 7)
A cell picking device according to any one of claims 1 to 6,
One of the multiple slits may be an auxiliary slit having a circumferential width different from the initial position detection slit and the other slits, and the sensor may detect the auxiliary position of the motor by detecting the auxiliary slit.

By utilizing the difference in the width of the slits, it is possible to detect multiple rotational positions of the motor.

10...Aspiration unit, 11...Aspiration arm, 12...Pipette tip, 20...Drive unit, 21...Motor, 30...Detection unit, 31...Rotary shaft, 32...Turntable, 33...Sensor, 331...First member, 332...Second member, 40...Observation unit, 50...Control unit, 100...Cell picking device

Claims (7)

1. A cell picking device for aspirating cells from a sample in a sample container, comprising:
a motor for driving an aspiration arm to which a pipette tip can be attached;
A detection unit that detects the operation of the motor;
Equipped with
The detection unit is
A rotating shaft that is rotated by the motor;
a rotating disk attached to the rotating shaft and rotating integrally with the rotating shaft;
A sensor provided near the rotating disk;
Including,
The rotating disk has a plurality of slits provided at equal intervals in a circumferential direction of the rotating disk,
having
The sensor detects the presence or absence of step-out of the motor by detecting the plurality of slits,
A cell picking device, wherein one of the multiple slits is an initial position detection slit having a circumferential width different from the other slits, and the sensor detects the initial position of the motor by detecting the initial position detection slit. The cell picking device according to claim 1, wherein the detection unit detects whether the motor is out of step based on the number of the plurality of slits, including the initial position detection slit, detected by the sensor. The cell picking device according to claim 1 or 2, wherein the detection unit detects the initial position of the motor based on the circumferential width of the initial position detection slit detected by the sensor. The cell picking device according to any one of claims 1 to 3, wherein the plurality of slits are provided at the outer peripheral end of the rotating disk. The cell picking device according to any one of claims 1 to 4, wherein the sensor comprises a light-emitting unit facing one surface of the turntable and a light-receiving unit facing the other surface of the turntable. The cell picking device according to any one of claims 1 to 5, wherein the detection unit calculates the circumferential width of the detected slit by rotation of the turntable in a first direction, and when the circumferential width of the detected slit matches the width of the initial position detection slit, determines that the detected slit is the initial position detection slit. The cell picking device according to any one of claims 1 to 6, wherein one of the plurality of slits is an auxiliary slit having a circumferential width different from the initial position detection slit and the other slits, and the sensor detects the auxiliary slit to detect the auxiliary position of the motor.

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