Dispensing device
The dispensing device uses cameras and image recognition to align pipette tips with reservoirs and well plates, addressing misalignment issues and ensuring accurate liquid transfer.
Patent Information
- Application Number
- JP2024018367
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-02-09
- Publication Date
- 2025-08-22
AI Technical Summary
Existing dispensing devices face issues with unstable positioning of reservoirs and well plates, leading to misalignment of pipette tips, which can hinder smooth transfer of liquid samples.
The dispensing device employs multiple cameras and image recognition units to accurately align pipette tips with desired positions on reservoirs and well plates, using a path determination unit to correct misalignments and ensure precise movement paths based on recognized positions and angles.
This solution enables precise alignment of pipette tips with reservoirs and well plates, ensuring smooth and accurate transfer of liquid samples.
Smart Images

Figure 2025122751000001_ABST
Abstract
Description
[Technical Field]
[0001] The present invention relates to a dispensing device for dispensing a liquid. [Background technology]
[0002] Liquid samples such as specimens and reagents are analyzed in fields such as biochemistry, biology, and chemistry. To analyze liquid samples, a dispensing device is used to transfer the liquid sample from a reservoir to a well of a well plate.
[0003] The dispensing device disclosed in Patent Document 1 has multiple tips attached to multiple nozzles provided on a dispensing head, and uses the multiple tips to move liquid samples from a storage position to wells on a microplate. In a dispensing device in which multiple tips are detachably attached to a dispensing head, the position of the tips can become unstable. To address this issue, the dispensing device is equipped with a camera that photographs the tips from below, an image recognition unit that recognizes any misalignment of the tips based on the photographed results, and a control unit that corrects the misalignment of the tips. [Prior art documents] [Patent documents]
[0004] [Patent Document 1] Japanese Patent Application Publication No. 11-287812 Summary of the Invention [Problem to be solved by the invention]
[0005] In a dispensing device, a reservoir storing a liquid sample and a well plate into which the liquid sample is injected are arranged in fixed positions. However, if the position of the reservoir or well plate is unstable, the position of the moving pipette tip may not match the desired position in the reservoir or the desired well in the well plate, which may result in the liquid sample not being able to be moved smoothly.
[0006] SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a dispensing device that accurately aligns the position of a pipette tip with a desired position in a reservoir and with a desired well in a well plate. [Means for solving the problem]
[0007] One aspect of the dispensing device according to the present invention includes an aspirating and discharging device that aspirates and discharges liquid, a dispensing head on which the aspirating and discharging device is disposed, a plurality of pipette tips that are detachably attached to the dispensing head and that aspirate liquid from a reservoir using the aspirating and discharging device and discharge the liquid into a plurality of wells of a well plate, a horizontal movement mechanism that moves the dispensing head in a horizontal direction, a vertical movement mechanism that moves the dispensing head in a vertical direction, a downward photography device that is fixed in a fixed position and photographs the dispensing head and the plurality of pipette tips attached to the dispensing head from below, an upward photography device that is moved together with the dispensing head and photographs the reservoir and the well plate from above, and a photographing device for the downward photography device. an upper image recognition unit that recognizes the horizontal position of the reservoir and the horizontal position of the well plate from the image capture results of the upper image capture device; a path determination unit that determines a movement path of the dispensing head for each pipette tip used for dispensing, in accordance with the horizontal positions of the pipette tips relative to the dispensing head recognized by the lower image recognition unit and the horizontal position of the reservoir and the horizontal position of the well plate recognized by the upper image recognition unit; and a drive control unit that controls at least the horizontal movement mechanism in accordance with the movement path determined by the path determination unit.
[0008] With this dispensing device, the lower image recognition unit accurately recognizes the horizontal positions of multiple pipette tips, and the upper image recognition unit accurately recognizes the horizontal positions of the reservoirs and well plate, which can be unstable, so the path determination unit can determine a movement path for the dispensing head that suits the situation. Therefore, the horizontal positions of the moving pipette tips can be accurately aligned with the desired positions of the reservoirs and the desired wells of the well plate.
[0009] The reservoir may have a plurality of wells. The upper image recognition unit may recognize positions of the plurality of wells in the reservoir and the plurality of wells in the well plate from the image capture results of the upper image capture device, and the path determination unit may determine the movement path according to the positions of the plurality of wells in the reservoir and the plurality of wells in the well plate recognized by the upper image recognition unit. In this case, the positions of the reservoir and the wells of the well plate, which may be unstable in orientation in the horizontal plane, are accurately recognized, and the path determination unit can determine a movement path that is compatible with the positions of the wells of the reservoir and the well plate. Therefore, the horizontal position of the pipette tip can be accurately aligned with the desired well of the reservoir and the desired well of the well plate. Therefore, whether the reservoir has many wells in a small area or the well plate has many wells in a small area, the horizontal position of the pipette tip can be accurately aligned with the positions of these wells.
[0010] The dispensing device may further comprise a reference member that is fixed in a fixed position, is photographed from above by at least the upper photographing device, and has a mark that is used as a horizontal reference position for at least the upper photographing device. In this case, the dispensing head, which is moved together with the upward imaging device, can be accurately positioned in the horizontal direction relative to the reference position, and therefore the horizontal position of the pipette tip, which moves together with the dispensing head, can be accurately aligned with the desired position of the reservoir and the desired well of the well plate.
[0011] The dispensing device may further include a height recognition unit that recognizes a height of the reservoir from a distance between the upper image capture device and the reservoir measured by the upper image capture device using a distance measurement function, and recognizes a height of the well plate from a distance between the upper image capture device and the well plate measured by the upper image capture device using a distance measurement function. The path determination unit may determine the movement path according to the height of the reservoir and the height of the well plate recognized by the height recognition unit. In this case, the actual heights of the reservoirs and well plate, i.e., their vertical positions, can be easily recognized using the distance measurement function of the upward imaging device. Since the movement path is based on the recognized actual heights of the reservoirs and well plate, the height of the bottom end of each pipette tip used to dispense liquid samples can be appropriately controlled relative to the reservoirs and well plate.
[0012] The height recognition unit may recognize an inclination angle of the reservoir with respect to a horizontal plane from distances between the upper camera and multiple locations on the reservoir, measured by the upper camera using a distance measurement function, and may recognize an inclination angle of the well plate with respect to a horizontal plane from distances between the upper camera and multiple locations on the well plate, measured by the upper camera using a distance measurement function. The path determination unit may determine the movement path according to the inclination angles of the reservoir and the well plate recognized by the height recognition unit. In this case, the tilt angle between the reservoir and the well plate can be easily recognized using the distance measurement function of the upward imaging device. Since the movement path is based on the recognized tilt angle between the reservoir and the well plate, the height of the bottom end of each pipette tip used to dispense the liquid sample can be appropriately controlled relative to the reservoir and the well plate.
[0013] In the dispensing device, when the dispensing head is lowered by the vertical movement mechanism, the multiple pipette tips stored in the pipette tip storage unit may be attached to the dispensing head. The upward image capture device may capture an image of the multiple pipette tips stored in the pipette tip storage unit from above. The upward image recognition unit may recognize the horizontal positions of the multiple pipette tips stored in the pipette tip storage unit from the image capture results of the upward image capture device. The path determination unit may determine a movement path of the dispensing head when the multiple pipette tips stored in the pipette tip storage unit are attached to the dispensing head, depending on the horizontal positions of the multiple pipette tips stored in the pipette tip storage unit recognized by the upward image recognition unit. The drive control unit may control at least the horizontal movement mechanism in accordance with the movement path of the dispensing head determined by the path determination unit. In this case, since the upper image recognition unit accurately recognizes the horizontal positions of the multiple pipette tips stored in the pipette tip storage unit, the path determination unit can determine the movement path of the dispensing head when the multiple pipette tips stored in the pipette tip storage unit are attached to the dispensing head so as to match the horizontal positions of the multiple pipette tips stored in the pipette tip storage unit. Therefore, these pipette tips can be attached to the dispensing head accurately and reliably.
[0014] The dispensing device may further include a height recognition unit that recognizes the height of the bottom end of each pipette tip from the distance between the lower image capture device and the bottom end of each pipette tip, measured by the lower image capture device using a distance measurement function. The path determination unit may determine the movement path according to the height of the bottom end of each pipette tip recognized by the height recognition unit. In this case, the actual height of the bottom end of each pipette tip, i.e., the vertical position, can be easily recognized using the distance measurement function of the downward image capture device. Since the movement path is based on the recognized actual height of the bottom end of each pipette tip, the height of the bottom end of each pipette tip used to dispense a liquid sample can be appropriately controlled relative to the reservoir and well plate.
[0015] The dispensing device may further include at least one horizontal camera that is fixed in a fixed position and that takes images of the dispensing head and the plurality of pipette tips attached to the dispensing head from a horizontal direction. In this case, it becomes possible to determine whether the pipette tip is securely attached to the dispensing head, as well as the tilt angle of the pipette tip relative to the dispensing head and the amount of liquid drawn into the pipette tip.
[0016] The dispensing device may further include an inclination angle recognition unit that recognizes inclination angles of the plurality of pipette tips relative to the dispensing head from the image capture results of the horizontal image capture device. The path determination unit may determine the movement path according to the inclination angles of the plurality of pipette tips relative to the dispensing head recognized by the inclination angle recognition unit. The drive control unit may control the horizontal movement mechanism and the vertical movement mechanism according to the movement path determined by the path determination unit. In this case, the tilt angle recognition unit recognizes the tilt angle of the pipette tip relative to the dispensing head, and the path determination unit can determine a movement path that is compatible with the tilt angles of the multiple pipette tips relative to the dispensing head. Therefore, even if the tilt angle of any of the pipette tips is large, the pipette tip can be appropriately moved to the desired position in the reservoir and to the desired well in the well plate. [Effects of the Invention]
[0017] Aspects of the present invention allow for precise alignment of pipette tips to desired locations in reservoirs and thus to desired wells in well plates. [Brief explanation of the drawings]
[0018] [Figure 1] FIG. 1 is a front view of a dispensing device according to an embodiment of the present invention. [Figure 2] FIG. 2 is a right side view of the dispensing device of FIG. [Figure 3] FIG. 3 is a plan view of a first well plate used in a dispensing device according to an embodiment of the present invention. [Figure 4] FIG. 4 is a plan view of a second well plate used in a dispensing device according to an embodiment of the present invention. [Figure 5] FIG. 5 is a plan view of a reference member of a dispensing device according to an embodiment of the present invention. [Figure 6] FIG. 6 is a block diagram showing a control system of a dispensing device according to an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION
[0019] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. The drawings are not necessarily drawn to scale, and some features may be exaggerated or omitted.
[0020] Configuration of the dispensing device As shown in FIGS. 1 and 2, a dispensing device 1 according to an embodiment of the present invention includes a plate stage 2, a storage stage 4, a moving device 10, four cameras 30 to 33, and a reference member .
[0021] A first well plate (reservoir) 20 and a second well plate 22 are placed on the upper surface of the plate stage 2. The first well plate 20 is the source (dispensing source) of liquid samples such as specimens and reagents, and has a plurality of small holes, or wells 21, on its upper surface for storing the liquid samples. The second well plate 22 is the destination (dispensing destination) of the liquid samples, and has a plurality of small holes, or wells 23, on its upper surface for receiving the liquid samples. The liquid samples received in the wells 23 are then analyzed, for example, biochemically.
[0022] A stocker (pipette tip storage unit) 40 is placed on the upper surface of the storage stage 4. The stocker 40 stores multiple pipette tips 16 of the same shape and size. In this embodiment, the stocker 40 is a box with multiple small holes 41 into which the pipette tips 16 are inserted from above. The pipette tips 16 are circular tubes with a tapered shape, with the diameter decreasing toward the bottom. The small holes 41 in the stocker 40 have a shape that matches the outer shape of the pipette tips 16, i.e., a shape that allows the pipette tips 16 to fit snugly into them. In this way, the longitudinal directions of the multiple pipette tips 16 inserted into the multiple small holes 41 are oriented approximately vertically.
[0023] The transfer device 10 receives the pipette tips 16 from the stocker 40. The transfer device 10 also transfers the pipette tips 16 from the first well plate 20 to the second well plate 22 in order to transfer (dispense) the liquid sample from the first well plate 20 to the second well plate 22.
[0024] The movement device 10 has an X-direction beam 11, a Y-direction beam 12, a movable column 13, and a dispensing head 14. The X-direction beam 11 is supported by a column (not shown) and extends along the horizontal direction (X direction) AX. The Y-direction beam 12 is supported by the X-direction beam 11 and extends along the horizontal direction (Y direction) AY perpendicular to the X direction AX. The movable column 13 is supported by the Y-direction beam 12 and extends along the vertical direction (Z direction) AZ. The dispensing head 14 is fixed to the lower end of the movable column 13.
[0025] The Y-direction beam 12 supported by the X-direction beam 11 is moved along the X-direction AX by an X-direction drive mechanism 11A (see FIG. 6). The movable column 13 supported by the Y-direction beam 12 is moved along the Y-direction AY by a Y-direction drive mechanism 12A (see FIG. 6). The movable column 13 is also moved (raised and lowered) along the Z-direction AZ by a Z-direction drive mechanism 13A (see FIG. 6). In this way, the dispensing head 14 fixed to the movable column 13 can move in any of the X-direction AX, Y-direction AY, and Z-direction AZ. The structure of the movement device 10 is not limited to that of the illustrated embodiment; for example, the X-direction beam 11 may be supported so as to be able to rise and fall, and the movable column 13 may not be able to rise and fall relative to the X-direction beam 11 and the Y-direction beam 12.
[0026] Dispensing head 14 is equipped with an aspirating / discharging device 14A having a pump for aspirating and discharging liquid. A plurality of nozzles 15 of the same shape and size protrude from the bottom surface of dispensing head 14. The internal spaces of nozzles 15 communicate with aspirating / discharging device 14A. Pipette tips 16 are removably attached to each of these nozzles 15. Specifically, when the bottom end of nozzle 15 is inserted to a certain depth into the top end of the central hole of pipette tip 16, pipette tip 16 is attached to nozzle 15. Pipette tip 16 can be removed from nozzle 15 by pulling pipette tip 16 against nozzle 15 with a strong force.
[0027] The suction action of the pump of the suction / discharge device 14A causes the liquid sample to be sucked into the pipette tip 16. The discharge action of the suction / discharge device 14A causes the liquid sample to be discharged from the pipette tip 16. The suction / discharge device 14A can apply a suction force to all nozzles 15 at once, allowing the pipette tips 16 attached to all nozzles 15 to aspirate the liquid sample, or it can apply a suction force individually to specific nozzles 15, allowing the pipette tips 16 attached to the nozzles 15 to which the suction force has been applied to aspirate the liquid sample. The pump of the suction / discharge device 14A can apply a discharge force to all nozzles 15 at once, allowing the pipette tips 16 attached to all nozzles 15 to discharge the liquid sample, or it can apply a discharge force individually to specific nozzles 15, allowing the pipette tips 16 attached to the nozzles 15 to which the discharge force has been applied to discharge the liquid sample.
[0028] The moving device 10 moves the dispensing head 14 in the X direction AX and the Y direction AY, stops it above the stocker 40, and lowers the dispensing head 14. As the dispensing head 14 lowers, the lower ends of the multiple nozzles 15 are inserted into the upper ends of the central holes of the pipette tips 16 held in the stocker 40, and the pipette tips 16 are attached to the nozzles 15. After the dispensing head 14 has lowered to a certain extent so that the pipette tips 16 do not easily come off the nozzles 15, the moving device 10 raises the dispensing head 14. As the dispensing head 14 rises, the pipette tips 16 move away from the stocker 40 together with the nozzles 15. In this way, the moving device 10 removes the pipette tips 16 from the stocker 40.
[0029] The moving device 10 then moves the dispensing head 14 in the X direction AX and the Y direction AY, stops it above the first well plate 20, and lowers the dispensing head 14. As the dispensing head 14 lowers, the lower ends of the pipette tips 16 are inserted into the wells 21 of the first well plate 20. The aspirating / discharging device 14A applies a suction force to the desired pipette tip 16, and the pipette tip 16 aspirates the liquid sample from the desired well 21. The moving device 10 then raises the dispensing head 14.
[0030] Furthermore, the moving device 10 moves the dispensing head 14 in the X direction AX and the Y direction AY, stops it above the second well plate 22, and lowers the dispensing head 14. As the dispensing head 14 lowers, the lower ends of the pipette tips 16 are inserted into the wells 23 of the second well plate 22. The suction and discharge device 14A applies a discharge force to the desired pipette tip 16, and the pipette tip 16 discharges the liquid sample into the desired well 23.
[0031] Each pipette tip 16 is transparent or semi-transparent, allowing the liquid sample aspirated into the pipette tip 16 to be observed from the outside.
[0032] An upper camera (upper photographing device) 30 is attached to the side of the dispensing head 14, and the upper camera 30 moves together with the dispensing head 14. The upper camera 30 photographs objects in its lower field of view from above. The upper camera 30 is capable of capturing moving images. Preferably, the upper camera 30 is capable of color photography. When the dispensing head 14 is above the first well plate 20, the upper camera 30 photographs the first well plate 20 from above. When the dispensing head 14 is above the second well plate 22, the upper camera 30 photographs the second well plate 22 from above. When the dispensing head 14 is above a stocker 40, the upper camera 30 photographs the multiple pipette tips 16 stored in the stocker 40 from above. In the illustrated embodiment, the upper camera 30 is fixed to the left side of the dispensing head 14 in Figure 1, but the position of the upper camera 30 is not limited to the position in the illustrated embodiment and may, for example, be on the right side of the dispensing head 14 in Figure 1.
[0033] The dispensing device 1 is also provided with a lower camera (lower photographing device) 31. The lower camera 31 is fixed in a fixed position and photographs objects in its upper field of view from below. The lower camera 31 is capable of capturing moving images. Preferably, the lower camera 31 is capable of color photography. When the dispensing head 14 is located above the lower camera 31, the lower camera 31 photographs the dispensing head 14 and the pipette tips 16 attached to the dispensing head 14 from below. In the illustrated embodiment, the lower camera 31 is fixed to a position on the right side of the plate stage 2 in FIG. 1, but the position of the lower camera 31 is not limited to the position in the illustrated embodiment and may be, for example, on the left side of the plate stage 2 in FIG. 1.
[0034] Preferably, each of the upper and lower cameras 30 and 31 has an autofocus function and a distance measurement function. In this embodiment, the distance measurement function is a function that measures the distance between the camera and a subject when the camera is focused by the autofocus function.
[0035] When the dispensing head 14 is above the first well plate 20, the upper camera 30 can use the autofocus function and distance measurement function to measure the distance between the upper camera 30 and the first well plate 20. When the dispensing head 14 is above the second well plate 22, the upper camera 30 can use the autofocus function and distance measurement function to measure the distance between the upper camera 30 and the second well plate 22.
[0036] In addition, when the dispensing head 14 is located above the lower camera 31, the lower camera 31 can use its autofocus and distance measurement functions to measure the distance between each pipette tip 16 attached to the dispensing head 14 and the lower camera 31.
[0037] The dispensing device 1 is also provided with an X-direction camera (horizontal direction image capture device) 32 and a Y-direction camera (horizontal direction image capture device) 33. The cameras 32 and 33 are fixed in fixed positions and capture images of objects in their lateral fields of view from the horizontal direction. The cameras 32 and 33 are capable of capturing moving images. Preferably, the cameras 32 and 33 are capable of capturing color images. The cameras 32 and 33 capture images of the dispensing head 14 and the pipette tips 16 attached to the dispensing head 14 from the horizontal direction.
[0038] In the illustrated embodiment, the X-direction camera 32 is fixed to the left side of the plate stage 2 in FIG. 1, but the position of the X-direction camera 32 is not limited to the position in the illustrated embodiment and may be, for example, the right side of the plate stage 2 in FIG. 1. In the illustrated embodiment, the Y-direction camera 33 is fixed to the left side of the plate stage 2 in FIG. 2, but the position of the Y-direction camera 33 is not limited to the position in the illustrated embodiment and may be, for example, the right side of the plate stage 2 in FIG. 2. The Y-direction camera 33 may be omitted. Furthermore, instead of cameras 32 and 33, a single camera may be provided that captures images of the dispensing head 14 and pipette tip 16 horizontally and from directions oblique to the X direction AX and the Y direction AY.
[0039] The dispensing device 1 is also provided with a reference member 35. The reference member 35 is fixed in a fixed position, photographed from above by at least the upper camera 30, and used as a reference position in at least the horizontal directions (X direction AX and Y direction AY) of the upper camera 30. Preferably, the reference member 35 is disposed above the lower camera 31 so that it can also be photographed from below by the lower camera 31, allowing accurate alignment of the upper camera 30 with respect to the lower camera 31.
[0040] 2, the dispensing device 1 further includes a stocker exchange device 42. The stocker exchange device 42 is movable along the Y direction AY. After the moving device 10 removes the pipette tips 16 from the stocker 40 as described above, the stocker exchange device 42 replaces the stocker 40 from which the pipette tips 16 have been removed with a new stocker 40A that holds a plurality of pipette tips 16.
[0041] As shown in FIG. 3, a plurality of wells 21 are formed on the top surface of a first well plate 20, which is the source of dispensing a liquid sample. A label 20a is attached to the top surface of the first well plate 20. A mark representing an identifier is printed on the label 20a. The identifier indicates, for example, the type of liquid sample stored in the first well plate 20 and the number of the first well plate 20. The illustrated mark representing the identifier is a barcode, but it may also be a two-dimensional code.
[0042] When the dispensing head 14 is positioned above the first well plate 20, the upper camera 30 photographs a mark representing the identifier of the label 20a on the first well plate 20. By identifying the identifier of the photographed label 20a, it is possible to determine whether the desired type of liquid sample is being dispensed. In addition, by saving the identifier of the photographed label 20a as data in a storage device, it is possible to determine the number of a used first well plate 20.
[0043] As shown in Fig. 4, a plurality of wells 23 are formed on the upper surface of second well plate 22, into which the liquid sample is dispensed. A label 22a is attached to the upper surface of second well plate 22. A mark representing an identifier is printed on label 22a. The identifier indicates, for example, the type of liquid sample to be stored in second well plate 22 and the number of second well plate 22. The illustrated mark representing the identifier is a barcode, but it may also be a two-dimensional code.
[0044] When the dispensing head 14 is located above the second well plate 22, the upper camera 30 photographs a mark representing the identifier of the label 22a on the second well plate 22. By identifying the identifier of the photographed label 22a, the number of the second well plate 22 in which the liquid sample is stored can be determined. By recording the association between the identifier of the first well plate 20, which is the source of the liquid sample, and the identifier of the second well plate 20, which is the destination of the liquid sample, it is possible to know the source and destination of the liquid sample.
[0045] 3 and 4, the size, number, and pitch of wells 21 may be different from those of wells 23. As will be described later, in dispensing device 1, a desired pipette tip 16 can aspirate a liquid sample from a desired well 21 in first well plate 20 and can dispense a liquid sample into a desired well 23 in second well plate 22.
[0046] As shown in Fig. 5, the reference member 35 has a mark 36. The mark 36 is photographed from above by at least the upper camera 30 and is used as a reference position in at least the horizontal direction (the X direction AX and the Y direction AY in Figs. 1 and 2) of the upper camera 30. The mark 36 is preferably a crosshair as shown in Fig. 5, but may be another pattern.
[0047] Preferably, the reference member 35 is a transparent plate made of, for example, glass or a plastic material, and the lower camera 31 can also photograph the mark 36. Therefore, the reference member 35 can be used to align the upper and lower cameras 30, 31. When the lower camera 31 is installed, it is preferable to align the lower camera 31 in the X direction AX and the Y direction AY using, for example, the intersection of the crosshairs of the mark 36 as a reference while photographing the mark 36 with the lower camera 31.
[0048] Control system of the dispensing device As shown in FIG. 6, the dispensing device 1 includes a processor 50, a storage device 51, an input device 52, a display device 53, and a speaker .
[0049] The processor 50 is a CPU (Central Processing Unit) or an MPU (Micro-Processing Unit). The processor 50 operates according to a computer program stored in a storage device 51, and controls the X-direction drive mechanism 11A, the Y-direction drive mechanism 12A, the Z-direction drive mechanism 13A, the stocker exchange device 42, the display device 53, and the speaker 54. The processor 50 may be composed of a single processing unit or multiple processing units.
[0050] The processor 50 has an upper image recognition unit 50a, an X-direction image recognition unit 50b, a Y-direction image recognition unit 50c, a lower image recognition unit 50d, a suction / discharge control unit 50e, a height recognition unit 50f, a drive control unit 50g, a path determination unit 50h, and a stocker exchange control unit 50i. These are control functions that are executed by the processor 50 operating in accordance with a computer program.
[0051] The upper image recognition unit 50a receives a video image capture signal from the upper camera 30 and recognizes an upper image based on the video image capture signal. The upper image is a video image captured by the upper camera 30 and may include images of the reference member 35, the stocker 40, the first well plate 20, or the second well plate 22, depending on the position of the upper camera 30. The upper image recognition unit 50a recognizes the horizontal position of the first well plate 20 (the X direction AX and the Y direction AY in FIGS. 1 and 2 ) and the horizontal position of the second well plate 22 from the capture results of the upper camera 30. For example, the upper image recognition unit 50a may recognize the positions of the four corners of the first well plate 20 and the four corners of the second well plate 22 and store the coordinates of these positions in the storage device 51. Alternatively, the upper image recognition unit 50a may recognize the positions of the center points of the well plates 20 and 22 and store the coordinates of these positions in the storage device 51. Alternatively, marks may be attached to predetermined positions on the well plates 20 and 22, and the upper image recognition unit 50a may recognize the positions of the marks on the well plates 20 and 22 and store the coordinates of these positions in the storage device 51.
[0052] The upper image recognition unit 50a also recognizes the orientation of the first well plate 20 in the horizontal plane (the XY plane in FIGS. 1 and 2) and the orientation of the second well plate 22 in the horizontal plane from the image capture results of the upper camera 30. The upper image recognition unit 50a also recognizes the positions of the multiple wells 21 in the first well plate 20 from the horizontal position of the first well plate 20 and the orientation of the first well plate 20 in the horizontal plane. The upper image recognition unit 50a also recognizes the positions of the multiple wells 23 in the second well plate 22 from the horizontal position of the second well plate 22 and the orientation of the second well plate 22 in the horizontal plane.
[0053] Furthermore, the upper image recognition unit 50a recognizes the horizontal positions of the multiple pipette tips 16 stored in the stocker 40 from the photographing results of the upper camera 30. If at least one of the pipette tips 16 is displaced from a predetermined position, the upper image recognition unit 50a can also determine the positional displacement of that pipette tip.
[0054] Furthermore, the upper image recognition unit 50a recognizes the horizontal position of the intersection of the crosshairs of the mark 36 on the reference member 35 from the image capture results of the upper camera 30. When the center of the upper image coincides with the intersection of the crosshairs of the mark 36 on the reference member 35, the upper image recognition unit 50a records the coordinate command value in the X direction AX and the coordinate command value in the Y direction AY of the dispensing head 14, for example, in the storage device 51. As will be described later, the coordinate command value in the X direction AX of the dispensing head 14 is a command value supplied from the drive control unit 50g to the X-direction drive mechanism 11A to control the position of the dispensing head 14 in the X direction AX. The coordinate command value in the Y direction AY of the dispensing head 14 is a command value supplied from the drive control unit 50g to the Y-direction drive mechanism 12A to control the position of the dispensing head 14 in the Y direction AY. The coordinate command values in the X direction AX and the Y direction AY of the dispensing head 14 recorded when the center of the upper image coincides with the intersection of the crosshairs of the mark 36 are used as coordinate values indicating the horizontal reference position of the dispensing head 14 (for example, the origin of the X direction AX and the Y direction AY) when moving the dispensing head 14 horizontally.
[0055] The X-direction image recognition unit 50b receives a moving image capture signal from the X-direction camera 32 and recognizes an X-direction image based on the moving image capture signal. The X-direction image is a moving image captured by the X-direction camera 32 and includes images of the dispensing head 14 and the pipette tip 16. The X-direction image recognition unit 50b functions as an inclination angle recognition unit that recognizes the inclination angle of the pipette tip 16 relative to the dispensing head 14 in the YZ plane from the image capture results of the X-direction camera 32.
[0056] The Y-direction image recognition unit 50c receives a moving image capture signal from the Y-direction camera 33 and recognizes a Y-direction image based on the moving image capture signal. The Y-direction image is a moving image captured by the Y-direction camera 33 and includes images of the dispensing head 14 and the pipette tip 16. The Y-direction image recognition unit 50c functions as an inclination angle recognition unit that recognizes the inclination angle of the pipette tip 16 relative to the dispensing head 14 in the XZ plane from the image capture results of the Y-direction camera 33.
[0057] The lower image recognition unit 50d receives a moving image capture signal from the lower camera 31 and recognizes a lower image based on the moving image capture signal. The lower image is a moving image captured by the lower camera 31 and includes an image of the reference member 35. When the dispensing head 14 is located above the lower camera 31, the lower image includes images of the dispensing head 14 and pipette tips 16. The lower image recognition unit 50d recognizes the horizontal positions of the multiple pipette tips 16 relative to the dispensing head 14 from the image capture results of the lower camera 31.
[0058] The suction / discharge control unit 50e controls the suction / discharge device 14A to cause the desired pipette tip 16 to aspirate a liquid sample at a desired timing, and to cause the desired pipette tip 16 to discharge a liquid sample at a desired timing. Therefore, the desired pipette tip 16 can aspirate a liquid sample from a desired well 21 of the first well plate 20, and can discharge a liquid sample into a desired well 23 of the second well plate 22.
[0059] The height recognition unit 50f recognizes the height (position in the Z direction AZ) of the first well plate 20 from the distance between the upper camera 30 and the first well plate 20 measured by the upper camera 30 using the distance measurement function and the coordinate command value in the Z direction AZ of the dispensing head 14 when that distance was measured. The height recognition unit 50f also recognizes the height of the second well plate 22 from the distance between the upper camera 30 and the second well plate 22 measured by the upper camera 30 using the distance measurement function and the coordinate command value in the Z direction AZ of the dispensing head 14 when that distance was measured. As will be described later, the coordinate command value in the Z direction AZ of the dispensing head 14 is a command value supplied from the drive control unit 50g to the Z-direction drive mechanism 13A to control the height of the dispensing head 14. Because the upper camera 30 is fixed to the dispensing head 14, the height of the subject can be recognized from the distance between the upper camera 30 and the subject and the coordinate command value in the Z direction AZ of the dispensing head 14 when that distance was measured.
[0060] Furthermore, the height recognition unit 50f can recognize the tilt angle of the first well plate 20 with respect to the horizontal plane (the XY plane in FIGS. 1 and 2) from the distances between the upper camera 30 and multiple locations on the first well plate 20 measured by the upper camera 30 using its distance measurement function, and the coordinate command values in the Z direction AZ of the dispensing head 14 when these distances were measured. Furthermore, the height recognition unit 50f can recognize the tilt angle of the second well plate 22 with respect to the horizontal plane from the distances between the upper camera 30 and multiple locations on the second well plate 22 measured by the upper camera 30 using its distance measurement function, and the coordinate command values in the Z direction AZ of the dispensing head 14 when these distances were measured.
[0061] Furthermore, the height recognition unit 50f recognizes the height of the bottom end of each pipette tip 16 from the distance between the lower camera 31 and the bottom end of each pipette tip 16 measured by the lower camera 31 using the distance measurement function, and the height of the lower camera 31.
[0062] The drive control unit 50g controls the X-direction drive mechanism (horizontal direction movement mechanism) 11A by timely supplying coordinate command values in the X direction AX of the dispensing head 14 to the X-direction drive mechanism 11A, and moves the Y-direction beam 12 along the X direction AX relative to the X-direction beam 11. In this way, the drive control unit 50g controls the position of the dispensing head 14 in the X direction AX.
[0063] The drive control unit 50g also controls the Y-direction drive mechanism (horizontal movement mechanism) 12A by timely supplying coordinate command values in the Y direction AY of the dispensing head 14 to the Y-direction drive mechanism 12A, thereby moving the movable column 13 along the Y direction AY relative to the Y-direction beam 12. In this way, the drive control unit 50g controls the position of the dispensing head 14 in the Y direction AY.
[0064] Furthermore, the drive control unit 50g controls the Z-direction drive mechanism (vertical direction movement mechanism) 13A by timely supplying coordinate command values in the Z direction AZ of the dispensing head 14 to the Z-direction drive mechanism 13A, and moves the movable column 13 along the Z direction AZ relative to the Y-direction beam 12. In this way, the drive control unit 50g controls the position (height) of the dispensing head 14 in the Z direction AZ.
[0065] The path determination unit 50h determines a movement path of the dispensing head 14 and transfers the movement path of the dispensing head 14 to the drive control unit 50g. The movement path is determined as a change over time in coordinate command values in the X, Y, and Z directions of the dispensing head 14, which are supplied to the drive mechanisms 11A, 12A, and 13A. The movement path may be determined by correcting movement path data (data on the change over time in coordinate command values in the X, Y, and Z directions of the dispensing head 14) previously stored in the storage device 51, or by creating new movement path data. In other words, the path determination unit 50h may determine a new movement path of the dispensing head 14, or may correct a previously determined movement path.
[0066] The movement path of the dispensing head 14 is determined for each pipette tip 16 used to dispense a liquid sample. A movement path suitable for one pipette tip 16 may not necessarily be suitable for another pipette tip 16, and so the movement path determined by the path determination unit 50h may include multiple movement paths for multiple pipette tips 16. However, if the movement path for one pipette tip 16 is within a predetermined range from the movement paths for other pipette tips 16, the movement path for one pipette tip 16 may be shared with the other pipette tips 16. In this way, the path determination unit 50h determines the movement path of the dispensing head 14 for each pipette tip 16 used for dispensing.
[0067] When the center of the upper image captured by the upper camera 30 coincides with the intersection of the crosshairs of the mark 36 on the reference member 35, the path determination unit 50h uses the coordinate command values in the X direction AX and the Y direction AY of the dispensing head 14 recorded in the storage device 51 by the upper image recognition unit 50a as coordinate values indicating the reference position (e.g., the origin) of the movement path in the X direction AX and the Y direction AY. Therefore, the movement path determined by the path determination unit 50h is based on the intersection of the crosshairs of the mark 36.
[0068] The path determination unit 50h determines a movement path of the dispensing head 14 when the multiple pipette tips 16 stored in the stocker 40 are attached to the dispensing head 14, in accordance with the horizontal positions of the multiple pipette tips 16 stored in the stocker 40 recognized by the upper image recognition unit 50a. The drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A in accordance with the movement path of the dispensing head 14 determined by the path determination unit 50h, to align the multiple nozzles 15 with the horizontal positions of the multiple pipette tips 16 stored in the stocker 40. The drive control unit 50g also controls the Z-direction drive mechanism 13A in accordance with the movement path of the dispensing head 14 determined by the path determination unit 50h, to insert the lower end of the nozzle 15 into the upper end of the central hole of the pipette tip 16 held in the stocker 40.
[0069] Furthermore, the path determination unit 50h determines the movement path of the dispensing head 14 for each pipette tip 16 used to dispense a liquid sample, based on the horizontal position of the pipette tip 16 relative to the dispensing head 14 recognized by the lower image recognition unit 50d and the horizontal positions of the first well plate 20 and the second well plate 22 recognized by the upper image recognition unit 50a. That is, the path determination unit 50h automatically determines the X and Y coordinates of the destination position of the dispensing head 14. By determining the destination coordinates, the path determination unit 50h can automatically calculate the movement amounts in the X and Y directions. Particularly in this embodiment, the path determination unit 50h determines the movement path of the dispensing head 14 based on the horizontal positions of the multiple wells 21 in the first well plate 20 and the horizontal positions of the multiple wells 23 in the second well plate 22 recognized by the upper image recognition unit 50a.
[0070] In this embodiment, the path determination unit 50h determines the movement path of the dispensing head 14 for each pipette tip 16 used to dispense a liquid sample in accordance with the height of the first well plate 20, the tilt angle of the first well plate 20 with respect to the horizontal plane, the height of the second well plate 22, and the tilt angle of the second well plate 22 with respect to the horizontal plane, all of which are recognized by the height recognition unit 50f. Furthermore, in this embodiment, the path determination unit 50h determines the movement path of the dispensing head 14 for each pipette tip 16 used to dispense a liquid sample in accordance with the height of the bottom end of each pipette tip 16 recognized by the height recognition unit 50f. Furthermore, in this embodiment, the path determination unit 50h determines the movement path of the dispensing head 14 for each pipette tip 16 used to dispense a liquid sample, also in accordance with the tilt angles of the multiple pipette tips 16 relative to the dispensing head 14 recognized by the X-direction image recognition unit (tilt angle recognition unit) 50b and the Y-direction image recognition unit (tilt angle recognition unit) 50c.
[0071] The drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A according to the movement path determined by the path determination unit 50h to position each pipette tip 16 used to dispense a liquid sample with a desired well 21 in the first well plate 20. Then, the drive control unit 50g controls the Z-direction drive mechanism 13A according to the movement path determined by the path determination unit 50h to insert the lower end of the pipette tip 16 into the well 21. The drive control unit 50g also controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A according to the movement path of the dispensing head 14 determined by the path determination unit 50h to position each pipette tip 16 used to dispense a liquid sample with a desired well 23 in the second well plate 22. Then, the drive control unit 50g controls the Z-direction drive mechanism 13A according to the movement path of the dispensing head 14 determined by the path determination unit 50h to insert the lower end of the pipette tip 16 into the well 23.
[0072] The stocker exchange control unit 50i controls the stocker exchange device 42 to exchange the stocker 40 from which the pipette tips 16 have been removed with a new stocker 40A that holds a plurality of pipette tips 16.
[0073] The input device 52 is operated by a user of the dispensing device 1, and supplies commands corresponding to the operation to the processor 50. For example, the user can operate the input device 52 to start the operation of the dispensing device 1 or to stop it in an emergency.
[0074] Display device 53 displays, for example, a moving image captured by one of cameras 30 to 33. Furthermore, if an abnormality is found in the state captured by one of cameras 30 to 33, display device 53 displays the abnormality. If an abnormality is found in the state captured by one of cameras 30 to 33, speaker 54 generates an alarm sound to notify the user of the abnormality.
[0075] How to use the dispensing device Next, how to use the dispensing device 1 will be described. First, the lower camera 31 is positioned with reference to the already fixed reference member 35. At this time, while the lower camera 31 is photographing the mark 36, the user operates the input device 52 to display the lower image photographed by the lower camera 31 on the display device 53. Then, the lower camera 31 is fixed with the center position of the lower image aligned with the intersection of the crosshairs of the mark 36. In this way, the position of the lower camera 31 in the X direction AX and the Y direction AY is aligned with the intersection of the crosshairs of the mark 36 as the reference.
[0076] Next, the upper camera 30 is aligned with the lower camera 31. The alignment of the upper camera 30 may be performed by the processor 50 in response to a command from the input device 52 by the user, or may be performed autonomously by the processor 50. In either case, the drive control unit 50g of the processor 50 sequentially supplies coordinate command values to the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A to move the dispensing head 14 in the horizontal direction. Then, when the center of the upper image captured by the upper camera 30 coincides with the intersection of the crosshairs of the mark 36 on the reference member 35, the upper image recognition unit 50a records the coordinate command values in the X-direction AX and the Y-direction AY of the dispensing head 14 in, for example, the storage device 51 as coordinate values indicating the horizontal reference position of the dispensing head 14 (e.g., the origin of the X-direction AX and the Y-direction AY).
[0077] Thereafter, when the user operates the input device 52 to instruct the processor 50 to start the operation of the dispensing device 1, the dispensing device 1 operates autonomously in accordance with the computer program as described below.
[0078] First, at least one of the X-direction image recognition unit 50b and the Y-direction image recognition unit 50c checks whether or not a pipette tip 16 is attached to the dispensing head 14. It is abnormal for a pipette tip 16 to be attached to the dispensing head 14 in the initial state. Therefore, if a pipette tip 16 is attached to the dispensing head 14, the processor 50 displays on the display device 53 that a pipette tip 16 is attached to the dispensing head 14 and generates an alarm from the speaker 54. This allows the user to operate the input device 52 to bring the operation of the dispensing device 1 to an emergency stop. The user then removes the pipette tip 16 from the dispensing head 14 and discards it.
[0079] If no pipette tips 16 are attached to the dispensing head 14, the drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A to move the dispensing head 14 above the storage stage 4. Then, the upper image recognition unit 50a determines whether or not a stocker 40 is present on the storage stage 4, based on the information image captured by the upper camera 30. If a stocker 40 is present on the storage stage 4, the upper image recognition unit 50a determines whether or not a pipette tip 16 is stored in that stocker 40. Thereafter, the upper image recognition unit 50a reconfirms the position of the stocker 40.
[0080] If there is no stocker 40 on the storage stage 4, the stocker replacement control unit 50i controls the stocker replacement device 42 to place a new stocker 40 holding pipette tips 16 on the storage stage 4. If there is an empty stocker 40 on the storage stage 4, the stocker replacement control unit 50i controls the stocker replacement device 42 to replace the empty stocker 40 with a new stocker 40 holding pipette tips 16 and place the new stocker 40 on the storage stage 4.
[0081] When a stocker 40 storing pipette tips 16 is on the storage stage 4, the path determination unit 50h determines, for each pipette tip 16, a movement path of the dispensing head 14 when the multiple pipette tips 16 stored in the stocker 40 are attached to the dispensing head 14. That is, the movement path determined by the path determination unit 50h may include multiple movement paths for the multiple pipette tips 16 stored in the stocker 40. However, if the positional deviation of the multiple pipette tips 16 stored in the stocker 40 is within a predetermined range, the path determination unit 50h may determine only one movement path. As described above, the path determination unit 50h may determine a new movement path for the dispensing head 14 or may correct a previously determined movement path based on the positional deviation of the pipette tips 16 stored in the stocker 40. The drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A according to the movement path of the dispensing head 14 determined by the path determination unit 50h, to align at least one nozzle 15 with the horizontal position of a pipette tip 16 stored in the stocker 40. The drive control unit 50g also controls the Z-direction drive mechanism 13A according to the movement path of the dispensing head 14 determined by the path determination unit 50h, to insert the lower end of the nozzle 15 into the upper end of the central hole of the pipette tip 16 held in the stocker 40. In this way, at least one pipette tip 16 stored in the stocker 40 is attached to the dispensing head 14. Next, the drive control unit 50g controls the Z-direction drive mechanism 13A to raise the dispensing head 14 together with the pipette tip 16, and separate the pipette tip 16 from the stocker 40.
[0082] As described above, the movement path determined by the path determination unit 50h may include multiple movement paths for multiple pipette tips 16 stored in the stocker 40. Therefore, if a pipette tip 16 stored in the stocker 40 is not attached to any of the nozzles 15, the drive control unit 50g again controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A according to the movement path of the dispensing head 14 determined by the path determination unit 50h to align the nozzle 15 to which the pipette tip 16 is not attached with the horizontal position of the pipette tip 16 left behind in the stocker 40. In addition, the drive control unit 50g controls the Z-direction drive mechanism 13A according to the movement path of the dispensing head 14 determined by the path determination unit 50h to insert the lower end of the nozzle 15 into the upper end of the central hole of the pipette tip 16 left behind in the stocker 40. In this way, the pipette tip 16 left behind in the stocker 40 is attached to the dispensing head 14.
[0083] After all pipette tips 16 stored in the stocker 40 have been attached to the dispensing head 14 in this manner, the X-direction image recognition unit 50b recognizes the tilt angle of each pipette tip 16 in the YZ plane relative to the dispensing head 14 from the image capture results of the X-direction camera 32. Furthermore, the Y-direction image recognition unit 50c recognizes the tilt angle of each pipette tip 16 in the XZ plane relative to the dispensing head 14 from the image capture results of the Y-direction camera 33. The tilt angle of each pipette tip 16 is used to determine the movement path of the dispensing head 14 for that pipette tip 16.
[0084] If the tilt angle of any pipette tip 16 is greater than a predetermined threshold, the processor 50 displays on the display device 53 that the tilt angle of that pipette tip 16 is too large and generates an alarm sound from the speaker 54. This allows the user to operate the input device 52 to urgently stop the operation of the dispensing device 1.
[0085] Furthermore, the drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A to move the dispensing head 14 to a position above the lower camera 31. The lower image recognition unit 50d then recognizes the horizontal positions of the multiple pipette tips 16 relative to the dispensing head 14 from the image capture results of the lower camera 31. The horizontal position of each pipette tip 16 relative to the dispensing head 14 is used to determine the movement path of the dispensing head 14 for that pipette tip 16.
[0086] Furthermore, the height recognition unit 50f recognizes the height of the bottom end of each pipette tip 16 from the distance between the lower camera 31 and the bottom end of each pipette tip 16 measured by the lower camera 31 using its distance measurement function, and the height of the lower camera 31. The height of the bottom end of each pipette tip 16 is also used to determine the movement path of the dispensing head 14 for that pipette tip 16.
[0087] If the height of the bottom end of any of the pipette tips 16 is smaller than a predetermined threshold, the processor 50 displays on the display device 53 a message indicating that the pipette tip 16 may be detached from the dispensing head 14 and generates an alarm sound from the speaker 54. This allows the user to operate the input device 52 to bring the operation of the dispensing device 1 to an emergency stop.
[0088] Next, the drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A to move the dispensing head 14 to a position above a predetermined position where the second well plate 22 should be located. Then, the upper image recognition unit 50a determines whether or not the second well plate 22 is present based on the image captured by the upper camera 30.
[0089] If the second well plate 22 is not present, the processor 50 displays on the display device 53 that the second well plate 22 is not present and generates an alarm sound from the speaker 54. This allows the user to place the second well plate 22 in a predetermined position. If the second well plate 22 is present, the upper image recognition unit 50a determines whether or not the second well plate 22 is covered with a lid based on the image captured by the upper camera 30.
[0090] If the second well plate 22 is covered with a lid, the processor 50 displays on the display device 53 that the second well plate 22 is covered with a lid and generates an alarm from the speaker 54. This allows the user to remove the lid from the second well plate 22. If the second well plate 22 is not covered with a lid, the upper image recognition unit 50a recognizes the horizontal position and orientation in the horizontal plane of the second well plate 22 from the image capture results of the upper camera 30, and recognizes the positions of the multiple wells 23 in the second well plate 22 from the horizontal position and orientation in the horizontal plane of the second well plate 22. The positions of the multiple wells 23 are also used to determine the movement path of the dispensing head 14 for each pipette tip 16.
[0091] Next, the upper image recognition unit 50a identifies the identifier represented by the mark on the label 22a on the second well plate 22 from the image captured by the upper camera 30, and displays the identifier on the display device 53. This allows the user to determine whether the desired type of second well plate 22 is about to be used, and if the identifier does not correspond to the desired type of second well plate 22, the user can operate the input device 52 to urgently stop the operation of the dispensing device 1. If the operation is not stopped, the upper image recognition unit 50a records the identifier in, for example, the storage device 51.
[0092] Next, the height recognition unit 50f recognizes the height of the second well plate 22 from the distance between the upper camera 30 and the second well plate 22 measured by the upper camera 30 using its distance measurement function and the coordinate command values in the Z direction AZ of the dispensing head 14 when that distance was measured. The height recognition unit 50f also recognizes the tilt angle of the second well plate 22 with respect to the horizontal plane from the distances between the upper camera 30 and multiple locations on the second well plate 22 and the coordinate command values in the Z direction AZ of the dispensing head 14 when those distances were measured. The second well plate 22 and the tilt angle are also used to determine the movement path of the dispensing head 14 for each pipette tip 16.
[0093] When liquid is present in the wells 23 of the second well plate 22, which is the destination of the liquid sample, the upper image recognition unit 50a recognizes the color of the liquid in the wells 23 of the second well plate 22 from the image captured by the upper camera 30. For example, if the liquid sample to be dispensed is a culture medium containing cells and the culture medium for cultivating the cells is stored in the wells 23 of the second well plate 22, which is the destination of the liquid sample, phenol red may be included to check the hydrogen ion exponent (pH) of the culture medium. In this case, the color of the liquid indicates the pH of the culture medium. The color of the liquid may also indicate contamination or changes in the liquid over time. If the color of the liquid is not the desired color, the processor 50 displays on the display device 53 that the color of the liquid sample is abnormal and generates an alarm from the speaker 54. This allows the user to operate the input device 52 to emergency stop the operation of the dispensing device 1.
[0094] If the operation is not stopped, the drive control unit 50g then controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A to move the dispensing head 14 to a position above a predetermined position where the first well plate 20 should be. Then, the upper image recognition unit 50a determines whether or not the first well plate 20 is present based on the image captured by the upper camera 30.
[0095] If the first well plate 20 is not present, the processor 50 displays on the display device 53 that the first well plate 20 is not present and generates an alarm sound from the speaker 54. This allows the user to place the first well plate 20 in a predetermined position. If the first well plate 20 is present, the upper image recognition unit 50a determines whether or not a lid is placed on the first well plate 20 based on the image captured by the upper camera 30.
[0096] If the first well plate 20 is covered with a lid, the processor 50 displays on the display device 53 that the first well plate 20 is covered with a lid and generates an alarm from the speaker 54. This allows the user to remove the lid from the first well plate 20. If the first well plate 20 is not covered with a lid, the upper image recognition unit 50a recognizes the horizontal position and orientation in the horizontal plane of the first well plate 20 from the image capture results of the upper camera 30, and recognizes the positions of the multiple wells 21 in the first well plate 20 from the horizontal position and orientation in the horizontal plane of the first well plate 20. The positions of the multiple wells 21 are also used to determine the movement path of the dispensing head 14 for each pipette tip 16.
[0097] Next, the upper image recognition unit 50a identifies the identifier represented by the mark on the label 20a on the first well plate 20 from the image captured by the upper camera 30, and displays the identifier on the display device 53. This allows the user to determine whether the desired type of liquid sample is being dispensed, and if the identifier does not correspond to the desired type of liquid sample, the user can operate the input device 52 to urgently stop the operation of the dispensing device 1. If the operation is not stopped, the upper image recognition unit 50a records the identifier in, for example, the storage device 51.
[0098] Next, the height recognition unit 50f recognizes the height of the first well plate 20 from the distance between the upper camera 30 and the first well plate 20 measured by the upper camera 30 using its distance measurement function and the coordinate command values in the Z direction AZ of the dispensing head 14 when that distance was measured. The height recognition unit 50f also recognizes the tilt angle of the first well plate 20 with respect to the horizontal plane from the distances between the upper camera 30 and multiple locations on the first well plate 20 and the coordinate command values in the Z direction AZ of the dispensing head 14 when those distances were measured. The first well plate 20 and the tilt angle are also used to determine the movement path of the dispensing head 14 for each pipette tip 16.
[0099] Furthermore, the upper image recognition unit 50a recognizes the color of the liquid sample in the wells 21 of the first well plate 20 from the image capture results of the upper camera 30. If the liquid sample to be dispensed is a culture medium containing cells and contains phenol red to check the pH of the culture medium, the color of the liquid sample represents the pH of the culture medium. The color of the liquid sample may also represent contamination or changes in the liquid sample over time. If the color of the liquid sample is not the desired color, the processor 50 displays on the display device 53 that the color of the liquid sample is abnormal and generates an alarm sound from the speaker 54. This allows the user to operate the input device 52 to urgently stop the operation of the dispensing device 1.
[0100] If the operation is not stopped, the liquid sample is dispensed from the first well plate 20 to the second well plate 22. If the liquid sample is a culture medium containing cells, the upper image recognition unit 50a may recognize whether or not cells are present in the desired well 21 of the first well plate 20 from the image capture result of the upper camera 30. If no cells are present in the desired well 21, the processor 50 displays a message on the display device 53 indicating that no cells are present and generates an alarm sound from the speaker 54. This allows the user to operate the input device 52 to urgently stop the operation of the dispensing device 1.
[0101] The dispensing of a liquid sample involves aspirating and discharging the liquid sample. During the aspirating operation, the drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A to position at least one pipette tip 16 used for dispensing above a predetermined well 21 in the first well plate 20, according to the movement path of the dispensing head 14 determined by the path determination unit 50h. The drive control unit 50g then controls the Z-direction drive mechanism 13A to insert the lower end of at least one pipette tip 16 used for dispensing into a predetermined well 21 in the first well plate 20, according to the movement path determined by the path determination unit 50h. Furthermore, the aspirating / discharging control unit 50e controls the aspirating / discharging device 14A, causing the pipette tip 16 to aspirate the liquid sample from the predetermined well 21. The drive control unit 50g then controls the Z-direction drive mechanism 13A to raise the dispensing head 14 and move the pipette tip 16 away from the first well plate 20.
[0102] As described above, the movement path determined by the path determination unit 50h may include multiple movement paths for multiple pipette tips 16. Therefore, the above-described liquid sample aspirating operation may be repeatedly performed so that the multiple pipette tips 16 each aspirate the liquid sample from the target well 21. After all of the pipette tips 16 used for dispensing have aspirated the liquid sample from the first well plate 20, the liquid sample dispensing operation is performed.
[0103] In dispensing a liquid sample, the drive control unit 50g controls the X-direction drive mechanism 11A and the Y-direction drive mechanism 12A according to the movement path of the dispensing head 14 determined by the path determination unit 50h, to position at least one pipette tip 16 used for dispensing above a predetermined well 23 of the second well plate 22. The drive control unit 50g then controls the Z-direction drive mechanism 13A according to the movement path determined by the path determination unit 50h, to insert the lower end of at least one pipette tip 16 used for dispensing into a predetermined well 23 of the second well plate 22. The suction / discharge control unit 50e then controls the suction / discharge device 14A, causing the pipette tip 16 to dispense the liquid sample into the predetermined well 23. The drive control unit 50g then controls the Z-direction drive mechanism 13A to raise the dispensing head 14 and move the pipette tip 16 away from the second well plate 22.
[0104] As described above, the movement path determined by the path determination unit 50h may include multiple movement paths for multiple pipette tips 16. Therefore, the above-described liquid sample dispensing operation may be repeatedly performed so that the multiple pipette tips 16 each dispense liquid samples into their target wells 23. After all of the pipette tips 16 used for dispensing have dispensed liquid samples into the second well plate 22, the autonomous operation of the dispensing device 1 ends.
[0105] In this embodiment, the lower image recognition unit 50d accurately recognizes the horizontal positions of the multiple pipette tips 16 from the image capture results of the lower camera 31. Furthermore, the upper image recognition unit 50a accurately recognizes the horizontal positions of the first well plate 20 and the second well plate 22, which may be unstable, from the image capture results of the upper camera 30. The path determination unit 50h then determines the movement path of the dispensing head 14 for each pipette tip 16 used for dispensing, based on the horizontal positions of the multiple pipette tips 16, the horizontal positions of the first well plate 20, and the horizontal positions of the second well plate 22. Therefore, the horizontal position of the moving pipette tip 16 can be accurately aligned with the desired position of the first well plate 20 and the desired well 23 of the second well plate 22.
[0106] In particular, the upper image recognition unit 50a individually recognizes the positions of the multiple wells 21 in the first well plate 20 and the positions of the multiple wells 23 in the second well plate 22 from the image capture results of the upper camera 30, so even if the orientations of the first well plate 20 and the second well plate 23 in the horizontal plane are unstable, the path determination unit 50h can determine a movement path that is compatible with the positions of the wells 21 in the first well plate 20 and the wells 23 in the second well plate 22. Therefore, whether the first well plate 20 has a large number of wells 21 in a small area or the second well plate 22 has a large number of wells 23 in a small area, the horizontal position of the pipette tip 16 can be accurately aligned with the positions of these wells 23.
[0107] Variations Although the present invention has been shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that changes may be made in form and detail without departing from the scope of the invention as set forth in the appended claims. Such changes, modifications and alterations are intended to be within the scope of the invention.
[0108] For example, in the above embodiment, the reservoir from which the liquid sample is transferred is a first well plate 20 having a plurality of wells 21. However, the reservoir may also be a container having a single space for storing the liquid sample.
[0109] In the above embodiment, four pipette tips 16 are arranged in a row in the X direction AX. However, the number of pipette tips 16 may be two or more and is not limited to four. The pipette tips 16 may also be arranged in multiple rows.
[0110] In the above embodiment, the upper image recognition unit 50a recognizes the positions of the multiple wells 21 in the first well plate 20 from the horizontal position of the first well plate 20 and the orientation of the first well plate 20 in the horizontal plane. The upper image recognition unit 50a also recognizes the positions of the multiple wells 23 in the second well plate 22 from the horizontal position of the second well plate 22 and the orientation of the second well plate 22 in the horizontal plane. However, the upper image recognition unit 50a may also recognize the positions of the multiple wells 21 in the first well plate 20 and the positions of the multiple wells 23 in the second well plate 22 from the upper image. [Explanation of symbols]
[0111] 1...dispensing device, 10...moving device, 11A...X-direction driving mechanism (horizontal direction moving mechanism), 12A...Y-direction driving mechanism (horizontal direction moving mechanism), 13A...Z-direction driving mechanism (vertical direction moving mechanism), 14...dispensing head, 14A...suction and discharge device, 16...pipette tip, 20...first well plate (reservoir), 21...well, 22...second well plate, 23...well, 30...upper camera (upper photographing device), 31...lower camera ( downward image capturing device), 32...X-direction camera (horizontal image capturing device), 33...Y-direction camera (horizontal image capturing device), 35...reference member, 36...mark, 40...stocker (pipette tip storage section), 50...processor, 50a...upper image recognition section, 50b...X-direction image recognition section (tilt angle recognition section), 50c...Y-direction image recognition section (tilt angle recognition section), 50d...lower image recognition section, 50f...height recognition section, 50g...drive control section, 50h...path determination section
Claims
1. a suction and discharge device for suctioning and discharging a liquid; a dispensing head in which the suction and discharge device is disposed; a plurality of pipette tips detachably attached to the dispensing head, the pipette tips aspirating liquid from a reservoir using the aspirating and dispensing device and dispensing the liquid into a plurality of wells of a well plate; a horizontal movement mechanism that moves the dispensing head in a horizontal direction; a vertical movement mechanism that moves the dispensing head in a vertical direction; a bottom image capturing device that is fixed in a fixed position and captures images of the dispensing head and the plurality of pipette tips attached to the dispensing head from below; an upper photographing device that is moved together with the dispensing head and photographs the reservoir and the well plate from above; a lower image recognition unit that recognizes the horizontal positions of the plurality of pipette tips relative to the dispensing head from the photographing results of the lower photographing device; an upper image recognition unit that recognizes the horizontal positions of the reservoir and the well plate from the photographing results of the upper photographing device; a path determination unit that determines a movement path of the dispensing head for each pipette tip used for dispensing, in accordance with the horizontal positions of the plurality of pipette tips relative to the dispensing head recognized by the lower image recognition unit, and the horizontal positions of the reservoir and the well plate recognized by the upper image recognition unit; a drive control unit that controls at least the horizontal direction movement mechanism in accordance with the movement path determined by the path determination unit; A dispensing device comprising:
2. the reservoir has a plurality of wells; the upper image recognition unit recognizes the positions of the plurality of wells in the reservoir and the positions of the plurality of wells in the well plate from the photographing results of the upper photographing device; The path determination unit determines the movement path according to the positions of the plurality of wells in the reservoir and the positions of the plurality of wells in the well plate recognized by the upper image recognition unit.
2. The dispensing device according to claim 1.
3. The camera further includes a reference member that is fixed at a fixed position, is photographed from above by at least the upper image capturing device, and has a mark that is used as a reference position in the horizontal direction of at least the upper image capturing device.
2. The dispensing device according to claim 1.
4. The apparatus further includes a height recognition unit that recognizes the height of the reservoir from the distance between the upper image capture device and the reservoir measured by the upper image capture device using a distance measurement function, and recognizes the height of the well plate from the distance between the upper image capture device and the well plate measured by the upper image capture device using a distance measurement function, The path determination unit determines the movement path according to the height of the reservoir and the height of the well plate recognized by the height recognition unit.
2. The dispensing device according to claim 1.
5. the height recognition unit recognizes an inclination angle of the reservoir with respect to a horizontal plane from the distance between the upper photographing device and a plurality of points on the reservoir, which is measured by the upper photographing device using a distance measurement function, and recognizes an inclination angle of the well plate with respect to a horizontal plane from the distance between the upper photographing device and a plurality of points on the well plate, which is measured by the upper photographing device using a distance measurement function; The path determination unit determines the movement path according to the tilt angle of the reservoir and the tilt angle of the well plate recognized by the height recognition unit.
2. The dispensing device according to claim 1.
6. When the dispensing head is lowered by the vertical movement mechanism, the plurality of pipette tips stored in the pipette tip storage unit are attached to the dispensing head, the upward photographing device photographs the plurality of pipette tips stored in the pipette tip storage unit from above, the upper image recognition unit recognizes the horizontal positions of the plurality of pipette tips stored in the pipette tip storage unit from the photographing results of the upper photographing device; the path determination unit determines a movement path of the dispensing head when the plurality of pipette tips stored in the pipette tip storage unit are attached to the dispensing head, according to the horizontal positions of the plurality of pipette tips stored in the pipette tip storage unit recognized by the upper image recognition unit; The drive control unit controls at least the horizontal direction movement mechanism in accordance with the movement path of the dispensing head determined by the path determination unit.
2. The dispensing device according to claim 1.
7. a height recognition unit that recognizes the height of the bottom end of each pipette tip from the distance between the lower image capture device and the bottom end of each pipette tip, the distance being measured by the lower image capture device using a distance measurement function; The path determination unit determines the movement path in accordance with the height of the bottom end of each pipette tip recognized by the height recognition unit.
2. The dispensing device according to claim 1.
8. The apparatus further includes at least one horizontal direction image capture device that is fixed in a fixed position and captures images of the dispensing head and the plurality of pipette tips attached to the dispensing head from a horizontal direction.
2. The dispensing device according to claim 1.
9. a tilt angle recognition unit that recognizes tilt angles of the plurality of pipette tips with respect to the dispensing head from the photographing result of the horizontal direction photographing device, the path determination unit determines the movement path in accordance with the tilt angles of the plurality of pipette tips relative to the dispensing head, which are recognized by the tilt angle recognition unit; The drive control unit controls the horizontal movement mechanism and the vertical movement mechanism according to the movement path determined by the path determination unit.
9. The dispensing device according to claim 8.
Citation Information
Patent Citations
Automatic dispensing apparatus and dispense method
JP1999287812A
Cited By
Liquid adding method, control device, equipment, system and storage medium
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