Picking device

Abstract

Provided is a picking device (1) comprising: a housing tray (2) in which a housing recess capable of housing a first liquid containing a biological specimen is formed in a tray surface (10); a hollow picking section (3) which is disposed above the housing tray and which acquires the biological specimen through an opening that opens at a distal end part; a first illumination optical system (4) which irradiates the housing tray with a first observation light (OL1) from above through the opening from the inside of the picking section; an observation optical system (6) which is disposed below the housing tray and which observes the first observation light transmitted through the housing tray; and a control unit (7) which controls at least the relative positional relationship between the picking section and the housing tray. The control unit controls the positional relationship of the picking section with respect to the housing recess on the basis of the state of convergence of the first observation light observed by the observation optical system.

Description

Picking device

[0001] The present invention relates to a picking device. This application claims priority to Japanese Patent Application No. 2024-231244 filed in Japan on December 26, 2024, the content of which is incorporated herein by reference.

[0002] As one of the devices for picking (acquiring) a target object of a minute size, for example, a vacuum suction device including a vacuum suction tube having a suction port and a light source disposed in the vacuum suction tube and emitting guide light to the outside through the suction port is known (see, for example, Patent Document 1). The vacuum suction tube is fixed to one end of a main body that functions as a grip and is internally connected to a vacuum pump. The light source is, for example, a light-emitting element such as a light-emitting diode. The light source emits guide light to a minute article that is the target object through the suction port.

[0003] According to the vacuum suction device configured as described above, it is possible to grasp that the suction port has come into contact with a minute part by making the guide light invisible from the outside. Thereby, it becomes possible to adsorb minute parts and perform picking.

[0004] Japanese Patent Application Laid-Open No. 2007-21644

[0005] In recent years, for example, when performing gene testing or analyzing the structure and function of target biological substances such as proteins, it is required to obtain biological samples of extremely minute sizes (sizes of several μm to several tens of μm, or sizes smaller than that). However, in the above conventional method, since it is premised on visually recognizing the guide light from the outside, when the target object is a biological sample, it is practically difficult to visually recognize from the outside whether the guide light is hitting the biological sample. In particular, in order to pick up a biological sample, it is necessary to appropriately approach a picking part such as a vacuum suction tube to the biological sample. However, since the biological sample is of an extremely minute size, it is difficult to detect the height direction between the biological sample and the picking part. Due to these reasons, it is difficult to pick up a biological sample by the conventional method.

[0006] This invention has been made in consideration of these circumstances, and its objective is to provide a picking device that can appropriately detect the height difference between itself and a biological sample and can pick up the biological sample with high precision.

[0007] (1) The picking device according to the present invention comprises: an optically transparent storage tray having a storage recess formed on its surface that can accommodate a first liquid containing a biological sample; a hollow picking unit positioned above the storage tray and movable relative to the storage recess, which acquires the biological sample through an opening at its tip; a first illumination optical system that irradiates the storage tray from above with first observation light from inside the picking unit through the opening; an observation optical system positioned below the storage tray and observing the first observation light that has passed through the storage tray; and a control unit that controls the relative positional relationship between at least the picking unit and the storage tray. The control unit controls the positional relationship between the picking unit and the storage recess based on the convergence state of the first observation light observed by the observation optical system.

[0008] According to the picking device of the present invention, the control unit can control the relative positional relationship between the picking unit and the storage tray, so that the picking unit, which is positioned above the storage tray, can be controlled to gradually approach the storage recess formed in the storage tray in the height direction. At this time, the first illumination optical system can irradiate the storage tray with first observation light from inside the picking unit through the opening by the picking unit, bringing the storage recess of the storage tray and the opening of the picking unit closer together. The first observation light irradiated to the outside from the opening of the picking unit travels towards the storage tray while scattering into the surroundings.

[0009] Therefore, when the storage recess and the opening of the picking section are separated in the height direction, much of the first observation light is reflected by, for example, the tray surface of the storage tray, or refracts through the storage tray while passing through the tray surface or the surface of the first liquid. As a result, a small portion of the first observation light passes through the storage recess from the opening of the picking section to the storage tray. Subsequently, when the storage recess and the opening of the picking section approach each other in the height direction, the portion of the first observation light that passes through the storage recess from the opening of the picking section to the storage tray gradually increases. When the opening of the picking section reaches (contacts) the surface of the first liquid contained in the storage recess, much of the first observation light passes through the storage recess from the opening of the picking section to the storage tray.

[0010] Therefore, by observing the convergence state of the first observation light that has passed through the storage tray using the observation optical system, the height relationship between the storage recess and the picking unit can be determined. This allows the control unit to appropriately detect the height of the picking unit based on the convergence state of the first observation light observed by the observation optical system. As a result, it is possible to infer that the opening of the picking unit is located near the surface of the first liquid. Furthermore, the control unit can also control the speed of the picking unit relative to the storage recess based on changes in the convergence state of the first observation light. As a result, the biological sample contained in the storage recess together with the first liquid can be acquired inside the picking unit. This enables high-precision pickup of biological samples (including cells, proteins, genes, etc.).

[0011] (2) The storage tray may have multiple storage recesses formed at intervals within the plane of the tray surface. The control unit may move the picking unit and the storage tray relative to each other in the in-plane direction of the tray surface so that the picking unit is positioned above a specific storage recess in which the biological sample is stored.

[0012] In this case, the picking unit can be positioned above a specific storage recess in the storage tray where a biological sample is actually stored. Therefore, by controlling the positional relationship of the picking unit relative to the specific storage recess while performing height detection, the biological sample can be acquired. In particular, by selecting multiple specific storage recesses, biological samples can be acquired individually and continuously, enabling efficient biological sample pickup (acquisition) work. This can especially contribute to the automation of pickup work for individual sampling of biological samples.

[0013] (3) The observation optical system may be capable of directly observing the first observation light. The control unit may correct the in-plane positional displacement of the picking unit relative to the reference position based on the first observation light that has been directly observed.

[0014] In this case, the control unit can determine the actual in-plane position of the picking unit based on the observation results of the first observation light directly observed by the observation optical system. Therefore, the control unit can grasp the difference between the actual position of the picking unit and the reference position, and can correct the in-plane positional displacement to eliminate the difference. This allows for precise control of the relative positional relationship between the picking unit and the storage tray, leading to high-precision pickup of biological samples.

[0015] (4) The control unit may estimate the state of the tip of the picking unit based on the observation results of the observation optical system when the first observation light is directly observed.

[0016] In this case, the control unit can estimate the condition of the tip of the picking unit, such as whether the opening is blocked due to crushing or foreign matter entering, or whether the opening is deformed, based on the observation results of the first observation light (for example, the presence or absence of light and the light intensity of the first observation light) when directly observed by the observation optical system. This enables the detection of unintended abnormalities at the tip of the picking unit. Therefore, it is possible to quickly take measures such as replacing or repairing the picking unit, resulting in an easy-to-use picking device.

[0017] (5) The system may include a second illumination optical system positioned below the storage tray and irradiating the storage tray with a second observation light from below. The observation optical system may further observe the reflected light of the second observation light reflected by the storage tray including the storage recess. The control unit may determine the position of a specific storage recess based on the reflected light of the second observation light observed by the observation optical system.

[0018] In this case, the reflected light of the second observation light, which is irradiated from the second illumination optical system and reflected from the underside of the storage tray, can be observed by the observation optical system. Therefore, the control unit can accurately determine in advance the position of the characteristic storage recess where the biological sample is actually stored, based on the reflected light of the second observation light observed by the observation optical system. As a result, the control unit can distinguish between storage recesses that do not contain a biological sample and specific storage recesses that contain a biological sample. Consequently, the control unit can accurately position the picking unit above the specific storage recess where the biological sample is stored, and can efficiently perform the continuous picking operation of biological samples.

[0019] (6) The second illumination optical system may irradiate the biological sample with light in the wavelength range in which the biological sample emits fluorescence as the second observation light. The control unit may determine whether or not the selected biological sample has been acquired by the picking unit from a specific storage recess based on the reflected light of the second observation light observed by the observation optical system.

[0020] In this case, the second observation light emitted from the second illumination optical system can be used as excitation light to cause the biological sample to emit fluorescence. Therefore, fluorescence can be caused to emit from the biological sample due to irradiation with the second observation light. Specifically, the biological sample absorbs the light energy of the second observation light, which is the excitation light, and transitions to an excited state, then transitions to a ground state while emitting fluorescence. As a result, the control unit can identify the containment recess containing the biological sample emitting fluorescence as a specific containment recess based on the reflected light of the second observation light observed by the observation optical system. Furthermore, the control unit can accurately determine whether or not the selected biological sample has been acquired by the picking unit.

[0021] (7) The picking portion may be formed such that the outer diameter of the tip portion is smaller than the opening diameter of the receiving recess, and the inner diameter of the opening is smaller than the outer diameter of the tip portion.

[0022] In this case, when the opening of the picking section reaches the first liquid in the receiving recess, the tip of the picking section can be prevented from coming into contact with the receiving recess, while the biological sample can be properly acquired inside the picking section.

[0023] (8) The first illumination optical system may irradiate the first observation light such that the optical axis is coaxial with the central axis of the picking unit. The observation optical system may include a reflective mirror arranged coaxially with the optical axis and an imaging unit that images the reflected light of the first observation light reflected by the reflective mirror.

[0024] In this case, the first illumination optical system can irradiate the first observation light using a coaxial incident illumination method so that the optical axis is coaxial with the central axis of the picking section. The first observation light that has passed through the storage tray is then reflected by a reflective mirror positioned coaxially with the optical axis and then imaged by the imaging unit. Therefore, the height of the picking section can be detected with greater accuracy based on the convergence state of the first observation light. As a result, the opening of the picking section can be positioned even closer to the surface of the first liquid. Furthermore, since the reflective mirror is positioned below the storage tray, it is possible to position the imaging unit laterally outside the storage tray, for example. Therefore, it is not necessary to secure a large space below the storage tray to set up the observation optical system. Consequently, the entire picking device can be designed to be compact.

[0025] (9) The tray surface of the storage tray may be provided with a liquid layer consisting of a second liquid that is hydrophobic to the first liquid, so as to cover the storage recess.

[0026] In this case, the liquid layer consisting of the second liquid covers the receiving recess containing the first liquid, thus sealing the first liquid and suppressing its evaporation. This allows the biological sample to be maintained in good condition. Furthermore, since the second liquid is hydrophobic to the first liquid, mixing of the first and second liquids can be suppressed.

[0027] (10) The picking unit may have the first liquid inside the tip, and the biological sample may be acquired by the movement of the biological sample into the picking unit by capillary action.

[0028] In this case, the contact between the first liquids allows the biological sample to move (flow) into the picking section through capillary action. This enables the rapid acquisition of the biological sample while suppressing the load on the sample.

[0029] (11) The picking unit may have the first liquid inside the tip, and the biological sample may be acquired by the biological sample moving into the picking unit by diffusion.

[0030] In this case, contact between the first liquids can induce random movement between them. This allows the biological sample to be moved (flowed) into the picking section by diffusion, a physical phenomenon between the first liquids. This enables the rapid acquisition of the biological sample while suppressing the load on the biological sample.

[0031] (12) The picking unit may acquire the biological sample together with the first liquid.

[0032] In this case, the biological sample, along with the first liquid, can be moved into the picking section by, for example, creating negative pressure inside the picking section. This allows for the rapid acquisition of the biological sample while suppressing the load on the biological sample.

[0033] According to the picking device of the present invention, it is possible to appropriately detect the height difference between the device and the biological sample, and to pick up the biological sample from the receiving recess with high precision.

[0034] This is a perspective view showing an embodiment of the picking device according to the present invention. This is a perspective view of the picking device shown in Figure 1. This is a perspective view of the picking device shown in Figure 1, viewed from below. This is a perspective view of the storage tray shown in Figure 1. This is an enlarged longitudinal cross-sectional view of the area between the storage recess formed in the storage tray shown in Figure 1 and the tip of the picking device. This is an enlarged perspective view of the area around the observation hole in the tray stage shown in Figure 1. This is a longitudinal cross-sectional view of the picking unit and the first illumination optical system shown in Figure 1. This is an example of an observation image captured of the second observation light reflected from the lower surface of the storage tray. This is a schematic diagram showing a plurality of storage recesses included in the observation image shown in Figure 8. This is a longitudinal cross-sectional view showing the state in which the picking unit is moved downward toward a specific storage recess formed in the storage tray while irradiating with the first observation light. This is an example of an observation image captured of the first observation light in the state shown in Figure 10. This is a schematic diagram showing the relationship between a plurality of storage recesses included in the observation image shown in Figure 11 and the first observation light. This is a longitudinal cross-sectional view showing the state in which the opening of the picking unit reaches the liquid surface of the second liquid by moving the picking unit downward from the state shown in Figure 10. This is an example of an observation image captured of the first observation light in the state shown in Figure 13. This figure schematically shows the relationship between the multiple storage recesses and the first observation light included in the observation image shown in Figure 14. This is a longitudinal cross-sectional view showing the state in which the opening of the picking unit reaches the liquid surface of the first liquid by moving the picking unit downward from the state shown in Figure 13. This is an example of an observation image captured with the first observation light in the state shown in Figure 16. This figure schematically shows the relationship between the multiple storage recesses and the first observation light included in the observation image shown in Figure 17. This is an example of an observation image captured with the second observation light after the first liquid and biological sample in a specific storage recess have been acquired by the picking unit from the state shown in Figure 16. This figure schematically shows the multiple storage recesses included in the observation image shown in Figure 19. This is an enlarged longitudinal cross-sectional view of the area around the storage recess formed in the storage tray and the tip of the diagonally inclined picking device. This figure schematically shows the relationship between the multiple storage recesses and the first observation light included in the image of the first observation light in the state shown in Figure 21. This figure schematically shows the relationship between the multiple storage recesses and the first observation light included in the image of the first observation light in the state in which the picking unit shown in Figure 21 has moved downward.

[0035] The picking device according to the present invention will now be described with reference to the drawings. As shown in Figures 1 to 3, the picking device 1 of this embodiment comprises a storage tray 2, a hollow picking section 3, a first illumination optical system 4, a second illumination optical system 5, and a control unit 7. The storage tray 2 contains biological samples S (see Figure 5). The picking section 3 is positioned above the storage tray 2. The first illumination optical system 4 irradiates the storage tray 2 with a first observation light OL1 from inside the picking section 3. The second illumination optical system 5 is positioned below the storage tray 2 and irradiates the storage tray 2 with a second observation light OL2. The observation optical system 6 is positioned below the storage tray 2. The control unit 7 comprehensively controls each of these components.

[0036] The biological sample S is a sample collected from a living organism for purposes such as diagnosis, treatment, or research, and includes, for example, cells, biomolecules such as proteins, and genes. In this embodiment, the biological sample S is assumed to emit fluorescence upon irradiation with excitation light.

[0037] (Storage Tray) As shown in Figure 4, the storage tray 2 is formed in a circular shape in plan view from an optically transparent material. The top surface of the storage tray 2 is the tray surface 10. A set hole 11 is formed in the center of the storage tray 2, penetrating it vertically.

[0038] As shown in Figures 1 and 2, the storage tray 2 is removably set on a flat tray stage 30. When the storage tray 2 is set on the tray stage 30, two directions that intersect each other perpendicularly in a plane parallel to the tray surface 10 (horizontal plane) are defined as the front-rear direction L1 and the left-right direction L2. Furthermore, the axis that passes vertically through the center of the setting hole 11 of the storage tray 2 is defined as the central axis O1. Furthermore, in a plan view from above, the direction that intersects the central axis O1 is defined as the radial direction.

[0039] The storage tray 2 is set on the upper surface of the tray stage 30 so as to be rotatable around a central axis O1, and is also assembled to the tray stage 30 by a holding jig 31. Below the tray stage 30, a rotation mechanism (not shown) for rotating the storage tray 2 is positioned. The holding jig 31 is assembled to the rotation mechanism through a through hole 32 (see Figure 3) formed in the tray stage 30, while pressing down on the storage tray 2 from above using the setting hole 11. As a result, the storage tray 2 can be rotated on the tray stage 30 at any rotation angle around the central axis O1 by the rotation mechanism. The operation of the rotation mechanism is controlled by the control unit 7.

[0040] As shown in Figure 4, a plurality of microchips 20 are provided on the tray surface 10 of the storage tray 2. The plurality of microchips 20 are arranged at regular intervals along two directions: the front-to-back direction L1 and the left-to-right direction L2. Each of the plurality of microchips 20 has a ring portion 21 that bulges upward from the tray surface 10, and a plurality of storage recesses 22 provided inside the ring portion 21. The plurality of storage recesses 22 are formed to be recessed to a certain depth from the tray surface 10, and open upward. The storage recesses 22 are, for example, circular recesses in plan view with a diameter in the range of several hundred nm to several tens of μm. The depth of the storage recesses 22 is, for example, in the range of several hundred nm to several tens of μm, similar to the diameter.

[0041] However, the diameter and depth of the receiving recess 22 are not limited to this case and may be changed as appropriate. Furthermore, the shape of the receiving recess 22 is not limited to a circular shape in plan view, but may be changed as appropriate, for example, to a polygonal shape in plan view. Furthermore, in the illustrated example, the bottom surface of the receiving recess 22 is formed as a flat surface. However, this is not limited to this case, and for example, the receiving recess 22 may be formed so that the bottom surface bulges downward in a hemispherical shape.

[0042] The plurality of accommodation recesses 22 are formed to be regularly arranged inside the ring portion 21. Specifically, the plurality of accommodation recesses 22 may be arranged at regular intervals along two directions, the front-rear direction L1 and the left-right direction L2, in a plan view, or may be arranged in a staggered pattern. In the present embodiment, the case where the plurality of accommodation recesses 22 are arranged in a staggered pattern shifted alternately along the front-rear direction L1 and the left-right direction L2 is taken as an example.

[0043] As shown in FIG. 5, the accommodation tray 2 configured as described above can accommodate the first liquid W1 containing the biological sample S. The first liquid W1 is not particularly limited, and examples thereof include a biological sample solution such as a buffer solution, a culture solution, and the like. Further, a liquid layer made of a second liquid W2 having hydrophobicity with respect to the first liquid W1 is provided on the tray surface 10 of the accommodation tray 2 so as to cover the accommodation recesses 22. The second liquid W2 is injected into the inside of the ring portion 21 in each microchip 20 so as to accumulate. The second liquid W2 is not particularly limited, and examples thereof include an oil or the like that is unlikely to affect the biological sample S.

[0044] As shown in FIGS. 1 to 3, the tray stage 30 is formed in a rectangular shape in a plan view, in which the length along the left-right direction L2 is longer than the length along the front-rear direction L1. The length of the tray stage 30 along the front-rear direction L1 is formed to be larger than the overall diameter of the accommodation tray 2. The accommodation tray 2 is combined such that the central axis O1 is shifted in the left-right direction L2 from the center of the tray stage 30.

[0045] As shown in Figures 3 and 6, the tray stage 30 has an observation hole 33 that penetrates the tray stage 30 in the vertical direction. The observation hole 33 is formed, for example, in a square shape in plan view, and is located at a position shifted in the left-right direction L2 from the central axis O1 of the storage tray 2, and is also located so as to be hidden from the lower surface of the storage tray 2. As a result, a part of the storage tray 2 is exposed below the tray stage 30 through the observation hole 33. Therefore, it is possible to view the storage tray 2 from below the tray stage 30 through the observation hole 33.

[0046] The observation hole 33 is sized to allow at least one of the multiple microchips 20 formed on the storage tray 2 to be placed inside, when viewed from above. In the illustrated example, the observation hole 33 is sized to allow 12 microchips 20 to be placed inside the observation hole 33. Furthermore, by rotating the storage tray 2 around the central axis O1 at predetermined rotation angles using a rotation mechanism, it is possible to place all of the multiple microchips 20 inside the observation hole 33.

[0047] The tray stage 30 is further formed with a positioning hole 34 that penetrates the tray stage 30 vertically. The positioning hole 34 is formed in a circular shape in plan view, smaller than the diameter of the microchip 20. However, the shape of the positioning hole 34 is not limited to this case, and may be, for example, a polygonal shape in plan view. The size of the positioning hole 34 is such that the tip 40a of the picking unit 3 (see Figure 5) can be seen from below through the positioning hole 34.

[0048] As configured above, the trace stage 30 is relatively movable with respect to the picking unit 3 by the stage moving mechanism 8 as shown in FIG. 1. In each drawing other than FIG. 1, the illustration of the stage moving mechanism 8 is omitted. The stage moving mechanism 8 is, for example, an XY moving mechanism capable of moving the trace stage 30 in two directions, the front-rear direction L1 and the left-right direction L2. The stage moving mechanism 8 includes, for example, a linear guide or the like, and is capable of moving the trace stage 30 along the front-rear direction L1 and the left-right direction L2 with high straightness and high precision. In addition to moving the trace stage 30 in the two directions of the front-rear direction L1 and the left-right direction L2, the stage moving mechanism 8 may be configured to move in the vertical direction. The operation of the stage moving mechanism 8 is controlled by the control unit 7.

[0049] (Picking Unit) As shown in FIGS. 1 to 3, the picking unit 3 is disposed above the storage tray 2 and is disposed so as to be relatively movable with respect to the storage tray 2. In the present embodiment, the trace stage 30 is movable in the front-rear direction L1 and the left-right direction L2 by the stage moving mechanism 8. Therefore, when the storage tray 2 side moves, the picking unit 3 is relatively movable in the front-rear direction L1 and the left-right direction L2 with respect to the storage tray 2. Further, the picking unit 3 is movable in the vertical direction by the picking moving mechanism 9. In each drawing other than FIG. 1, the illustration of the picking moving mechanism 9 is omitted.

[0050] The picking moving mechanism 9 includes, for example, a linear guide or the like, and is capable of moving the picking unit 3 along the vertical direction with high straightness and high precision. In addition to moving the picking unit 3 in the vertical direction, the picking moving mechanism 9 may be configured to move in the front-rear direction L1 and the left-right direction L2. Further, the operation of the picking moving mechanism 9 is controlled by the control unit 7. Therefore, the picking unit 3 of the present embodiment is fixed in position in the front-rear direction L1 and the left-right direction L2 and is movable in the vertical direction by the picking moving mechanism 9.

[0051] As shown in Figures 5 and 7, the picking unit 3 is capable of acquiring a biological sample S contained in the receiving recess 22 through an opening 40b that opens at the tip 40a. The picking unit 3 mainly comprises a hollow capillary tube 40 for acquiring the biological sample S, a cylindrical adapter 41 for holding the base end (upper end) of the capillary tube 40, and a holder 42 for holding the capillary tube 40 via the adapter 41.

[0052] The capillary tube 40 is, for example, a glass capillary tube or pipette with an outer diameter of several micrometers to several millimeters and a length of several tens of millimeters, and extends in a straight shape along the vertical direction. As shown in Figure 5, the tip portion 40a (lower end) of the capillary tube 40 is formed to become sharper as it goes downwards. An opening 40b for acquiring a biological sample S is formed at the tip portion 40a of the capillary tube 40. The tip portion 40a of the capillary tube 40 functions as the tip portion of the picking section 3. Furthermore, the capillary tube 40 is formed such that the outer diameter of the tip portion 40a is smaller than the opening diameter of the receiving recess 22, and the inner diameter of the opening 40b is smaller than the outer diameter of the tip portion 40a. In this embodiment, the axis that passes through the center of the capillary tube 40 in the vertical direction is defined as the central axis O2 of the picking section 3.

[0053] As shown in Figure 7, an adapter 41 is positioned above the capillary tube 40. A holder 42 is positioned above the adapter 41. The capillary tube 40 is integrally assembled with the adapter 41 by, for example, inserting it from below. The holder 42 has a hollow portion 42a that penetrates the holder 42 vertically and is formed coaxially with the central axis O2. The adapter 41 is integrally assembled with the holder 42 by, for example, fitting or screwing the adapter 41 into the hollow portion 42a of the holder 42 from below. In this way, the holder 42 holds the capillary tube 40 via the adapter 41 with its tip portion 40a facing downwards.

[0054] Furthermore, a tube 44 is attached to the holder 42 via a joint member 43. In the illustrated example, the joint member 43 is assembled to the holder 42 from the side. The tube 44 is, for example, a capillary tube with an outer diameter of several millimeters, and communicates with the inside of the capillary tube 40 through the hollow portion 42a of the holder 42. This makes it possible to remove the biological sample S acquired in the picking section 3 (acquired inside the capillary tube 40) to the outside of the picking section 3, for example, through the tube 44.

[0055] In the picking section 3 configured as described above, as shown in Figure 5, a small amount of the first liquid W1, which is contained in the receiving recess 22, is pre-filled inside the tip portion 40a of the capillary tube 40. This first liquid W1 is stably held inside the capillary tube 40 by surface tension or the like.

[0056] (First Illumination Optical System) As shown in Figure 7, the first illumination optical system 4 is positioned above the picking section 3 and includes a first light irradiation section 50 that is integrally combined with the holder 42. The first light irradiation section 50 irradiates the first observation light OL1 so that its optical axis is coaxial with the central axis O2 of the picking section 3. As a result, the first light irradiation section 50 irradiates the first observation light OL1 from above towards the storage tray 2 through the opening 40b of the capillary tube 40 from inside the picking section 3. Therefore, the first illumination optical system 4 irradiates the first observation light OL1 by coaxial incident illumination. The operation of the first illumination optical system 4 is controlled by the control unit 7.

[0057] For example, an LED light source can be used as the first light irradiation unit 50. However, the first light irradiation unit 50 is not limited to an LED light source, and other light sources may be used. In this embodiment, the first light irradiation unit 50 irradiates with a first observation light OL1, which is white scattered light.

[0058] (Second Illumination Optical System) As shown in Figures 2 and 3, the second illumination optical system 5 is positioned below the tray stage 30 on which the storage tray 2 is set. The second illumination optical system 5 irradiates the storage tray 2, which is exposed downwards through the observation hole 33, with second observation light OL2 from below. The second illumination optical system 5 includes a second light irradiation unit 55 that irradiates the second observation light OL2. The second light irradiation unit 55 is positioned offset from directly below the observation hole 33 in at least one of the front-to-back direction L1 and left-to-right direction L2, and irradiates the storage tray 2 with second observation light OL2 at an angle. The operation of the second illumination optical system 5 is controlled by the control unit 7.

[0059] However, the positional relationship of the second light irradiation unit 55 with respect to the storage tray 2 is not limited to this case. For example, the second light irradiation unit 55 may be positioned radially away from below the tray stage 30, and the irradiated second observation light OL2 may be guided to the storage tray 2 via optical means such as a reflective mirror.

[0060] For example, an LED light source can be used as the second light irradiation unit 55. However, the second light irradiation unit 55 is not limited to an LED light source, and other light sources may be used. In this embodiment, the second light irradiation unit 55 irradiates with a blue second observation light OL2. In particular, the second light irradiation unit 55 irradiates with excitation light, which is light in the wavelength range in which the biological sample S emits fluorescence, as the second observation light OL2.

[0061] Furthermore, the second illumination optical system 5 is not limited to a configuration comprising one second light irradiation unit 55, but may also be configured to comprise, for example, two or more second light irradiation units 55. In this case, for example, light of different wavelengths may be irradiated as the second observation light OL2 from each of the multiple second light irradiation units 55.

[0062] Furthermore, in this embodiment, an excitation filter (not shown) may be placed between the second light irradiation unit 55 and the observation hole 33. The excitation filter allows transmission of light in a specific wavelength range used as excitation light. As the excitation filter, for example, a known optical filter (bandpass filter) having a dielectric multilayer film and capable of wavelength separation can be suitably employed. Therefore, by placing an excitation filter, it becomes possible to more reliably irradiate the storage tray 2 with excitation light in a specific wavelength range as the second observation light OL2.

[0063] (Observation Optical System) As shown in Figures 1 to 3, the observation optical system 6 observes the first observation light OL1 that has passed through the storage tray 2 including the storage recess 22, and also observes the reflected light of the second observation light OL2 that has been reflected by the storage tray 2 including the storage recess 22. The observation optical system 6 comprises a reflective mirror 60 and an imaging unit 61. The reflective mirror 60 is positioned below the tray stage 30 on which the storage tray 2 is set. The imaging unit 61 captures the reflected light reflected by the reflective mirror 60.

[0064] The reflective mirror 60 is, for example, a total reflection mirror, positioned directly below the center of the observation hole 33 so as to be coaxial with the optical axis of the first illumination optical system 4. This allows the reflective mirror 60 to reflect the first observation light OL1 that has passed through the storage tray 2. The reflective mirror 60 is positioned to reflect the first observation light OL1 that has passed through the storage tray 2 towards the imaging unit 61 at a reflection angle of approximately 45 degrees. Furthermore, the reflective mirror 60 is also capable of reflecting the second observation light OL2 that has been reflected from the lower surface of the storage tray 2 towards the imaging unit 61.

[0065] The imaging unit 61 is located below the tray stage 30 and is positioned laterally along the front-to-back direction L1. The imaging unit 61 comprises, for example, a cylindrical imaging case 62 and an imaging unit 63 provided at the rear end of the imaging case 62. An objective lens 64 is provided at the front end of the imaging case 62. Inside the imaging case 62 is an imaging optical system (not shown) including an imaging lens. Inside the imaging unit 63 is at least an image sensor (not shown) that captures the reflected light of the first observation light OL1 and the reflected light of the second observation light OL2 that have entered through the objective lens 64 and the imaging optical system. As the image sensor, for example, a CMOS sensor or a CCD sensor can be used.

[0066] As a result, the imaging unit 61 is able to acquire observation images of the first observation light OL1 and observation images of the second observation light OL2, respectively. Inside the imaging case 62, wiring cables (power lines, signal lines) (not shown) are arranged to be electrically connected to the image sensor, and the captured images (observation images of the first observation light OL1 and observation images of the second observation light OL2) are output to the control unit 7.

[0067] (Control Unit) The control unit 7 shown in Figure 1 comprehensively controls each component that makes up the picking device 1. Specifically, the control unit 7 comprehensively controls each component by having the CPU execute various programs as appropriate, thereby enabling the picking device 1 to perform the acquisition work (pickup work) of biological samples S. The various programs are recorded on a computer-readable recording medium (not shown).

[0068] "Computer-readable recording media" refers to portable media such as flexible disks, magneto-optical disks, CD-ROMs, and semiconductor memory, which are read via a drive device (e.g., a CD-ROM drive) or interface (e.g., a USB interface). Furthermore, "computer-readable recording media" is not limited to the above-mentioned portable media, but may also include storage units such as hard disks built into computer systems (which include hardware such as operating systems and peripheral devices). Moreover, "computer-readable recording media" may also include those that dynamically hold programs for a short period of time, such as communication lines used when transmitting programs over networks such as the Internet or communication lines such as telephone lines, and those that hold programs for a fixed period of time, such as volatile memory inside computer systems that act as servers or clients in such cases.

[0069] The control unit 7 controls at least the relative positional relationship between the picking unit 3 and the storage tray 2. Specifically, the control unit 7 controls the tray stage 30 by the stage movement mechanism 8, thereby controlling the relative positional relationship between the storage tray 2 and the picking unit 3 in the front-to-back direction L1 and the left-to-right direction L2 (in-plane control). Furthermore, the control unit 7 controls the picking unit 3 by the picking movement mechanism 9, thereby controlling the relative positional relationship between the storage tray 2 and the picking unit 3 in the up-to-down direction (height control).

[0070] In particular, the control unit 7 controls the positional relationship of the picking unit 3 with respect to the storage recess 22 based on the convergence state of the first observation light OL1 observed by the observation optical system 6. This allows for height control of the picking unit 3 with respect to the storage recess 22. This will be explained in detail later. Furthermore, the control unit 7 is capable of determining the position of a specific storage recess 22 in which a biological sample S is actually stored, based on the reflected light of the second observation light OL2 observed by the observation optical system 6. The position of the storage recess 22 refers to the XY coordinates (position in the front-to-back direction L1 and left-to-right direction L2) with respect to the reference position of the storage tray 2.

[0071] (Operation of the picking device) Next, we will explain the sequence of steps involved in picking up (acquiring) a biological sample S (a biological sample S emitting fluorescence) using the picking device 1 configured as described above.

[0072] As shown in Figure 4, the first liquid W1 is contained in the multiple storage recesses 22 of each microchip 20 in the storage tray 2, as shown in Figure 5. Furthermore, the biological sample S is contained together with the first liquid W1 in multiple locations among the multiple storage recesses 22. Accordingly, the multiple storage recesses 22 include storage recesses 22 that do not contain the biological sample S and storage recesses 22 that actually contain the biological sample S. In this embodiment, the storage recess 22 that actually contains the biological sample S is described as a specific storage recess 22A. In Figure 5, the case in which three storage recesses 22 are specific storage recesses 22A is shown as an example.

[0073] Furthermore, as shown in Figure 5, consider the case where the microchip 20 is injected with the second liquid W2, and the liquid layer of the second liquid W2 covers a plurality of receiving recesses 22. This allows the liquid layer of the second liquid W2 to seal the first liquid W1 and suppress the evaporation of the first liquid W1. Therefore, the biological sample S contained in a specific receiving recess 22A can be maintained in good condition. In addition, since the second liquid W2 is hydrophobic with respect to the first liquid W1, mixing of the first liquid W1 and the second liquid W2 can be suppressed.

[0074] First, the control unit 7 controls the relative positional relationship between the storage tray 2 and the picking unit 3 in the front-to-back direction L1 and the left-to-right direction L2, and works in cooperation with the rotation of the storage tray 2 around the central axis O1 by the rotation mechanism to position one of the multiple microchips 20 formed on the storage tray 2 directly below the picking unit 3, as shown in Figure 6. This ensures that at least one microchip 20 located directly below the picking unit 3 is positioned inside the observation hole 33 of the storage tray 2.

[0075] Next, as shown in Figures 2 and 3, the second observation light OL2 is irradiated from the second light irradiation unit 55 of the second illumination optical system 5 toward the storage tray 2. The observation optical system 6 then observes the reflected light of the second observation light OL2 reflected from the lower surface of the storage tray 2. Specifically, the reflected light of the second observation light OL2 is captured by the imaging unit 61 via the reflection mirror 60. As a result, an observation image P2 of the second observation light OL2 can be obtained, as shown in Figure 8. The reflected light of the second observation light OL2 includes changes in light intensity, including brightness and luminance, caused by the storage recesses 22 in which the first liquid W1 is stored. Therefore, as shown in Figure 8, the positions of multiple storage recesses 22 can be determined based on the observation image P2. In the observation image P2 shown in Figure 8, the staggered arrangement of parts indicates multiple storage recesses 22.

[0076] In particular, the second observation light OL2 is excitation light for causing the biological sample S to emit fluorescence, so it is possible to identify the biological sample S contained in a specific containment recess 22A. Specifically, when the second observation light OL2, which is excitation light, is irradiated, the expressed biological sample S emits fluorescence due to the irradiation of the excitation light. The biological sample S absorbs the light energy of the excitation light and transitions to an excited state, and then transitions to a ground state while emitting fluorescence. As a result, the control unit 7 can accurately determine in advance the position of a specific containment recess 22A in which the biological sample S is actually contained, among the multiple containment recesses 22, based on the observation image P2 of the second observation light OL2 shown in Figure 8. Note that Figure 8 shows an example in which all of the containment recesses 22 contain biological samples S. Therefore, the observation image P2 shown in Figure 8 shows the case in which all of the multiple containment recesses 22 are the specific containment recess 22A.

[0077] Therefore, among the multiple containment recesses 22, the specific containment recess 22A in which the fluorescent biological sample S is actually contained can be identified by the change in light intensity. Thus, as shown in Figure 9, for example, it is possible to distinguish between the specific containment recess 22A in which the fluorescent biological sample S is actually contained and the containment recess 22 in which the biological sample S is not contained. Figure 9 is a schematic diagram showing multiple containment recesses 22 (including the specific containment recess 22A). In Figure 9, the specific containment recess 22A in which the fluorescent biological sample S is actually contained and the containment recess 22 in which the biological sample S is not contained are indicated by the difference in dot density. In Figure 9, the dot density is shown to be higher in the specific containment recess 22A than in the containment recess 22 in which the biological sample S is not contained. This point is also the same in Figures 12, 15, 18, 20, 22, and 23.

[0078] Therefore, the control unit 7 can identify specific housing recesses 22A in which the fluorescent biological sample S is actually contained, based on the observation image P2 of the second observation light OL2. Figure 9 illustrates four specific housing recesses 22A.

[0079] Next, the control unit 7 moves the storage tray 2 and the picking unit 3 relative to each other in the in-plane direction (front-to-back direction L1 and left-to-right direction L2) of the tray surface 10 so that the picking unit 3 is positioned above one of the specific storage recesses 22A containing the fluorescent biological sample S (target for pickup).

[0080] Specifically, the control unit 7 recognizes the XY coordinates (positions in the front-to-back direction L1 and left-to-right direction L2) of a specific storage recess 22A relative to the reference position of the storage tray 2 from the observation image P2 of the second observation light OL2. The picking unit 3 is positioned at a preset XY coordinate relative to the reference position of the storage tray 2. Therefore, the control unit 7 controls the tray stage 30 by the stage movement mechanism 8 so that the XY coordinates of the specific storage recess 22A and the XY coordinates of the picking unit 3 coincide, thereby controlling the relative positional relationship between the storage tray 2 and the picking unit 3 in the front-to-back direction L1 and left-to-right direction L2. As a result, the picking unit 3 can be positioned above the specific storage recess 22A.

[0081] Next, the control unit 7 controls the vertical relative positional relationship between the storage tray 2 and the picking unit 3 so that the opening 40b of the capillary tube 40 in the picking unit 3 is located near the liquid surface of the first liquid W1 stored in a specific storage recess 22A, or reaches the liquid surface.

[0082] This height control will now be explained. First, the control unit 7 stops the irradiation of the second observation light OL2 from the second light irradiation unit 55 of the second illumination optical system 5, and then irradiates the first observation light OL1 from the first light irradiation unit 50 of the first illumination optical system 4, as shown in Figure 7. As a result, the first observation light OL1 passes through the hollow part 42a of the holder 42 and the inside of the capillary tube 40, and then proceeds toward the storage tray 2 while scattering outwards from the opening 40b of the capillary tube 40, as shown in Figure 10. Simultaneously with or before or after the irradiation of the first observation light OL1, the control unit 7 moves the picking unit 3 downward using the picking movement mechanism 9. As a result, the control unit 7 gradually brings the specific storage recess 22A and the opening 40b of the capillary tube 40 closer together. In Figure 10, the specific storage recess 22A and two storage recesses 22 that do not contain a biological sample S are shown as an example.

[0083] As shown in Figure 10, when a specific storage recess 22A and the opening 40b of the capillary tube 40 are spaced apart in the vertical direction (height direction), much of the first observation light OL1 is reflected by, for example, the surface of the second liquid W2, or refracted by the surface of the second liquid W2, and passes through the storage tray 2. As a result, only a small portion of the first observation light OL1 passes from the picking section 3 through the specific storage recess 22A and through the storage tray 2.

[0084] Therefore, as shown in Figure 11, from the observation image P1 captured by the imaging unit 61 of the observation optical system 6 with the first observation light OL1, it can be confirmed that the area around the specific housing recess 22A becomes faintly brighter. Note that the observation image P1 shown in Figure 11 shows the case where all of the multiple housing recesses 22 are the specific housing recess 22A, similar to Figure 8. The faint brightening around the specific housing recess 22A is related to the fact that, as shown in Figure 12, the first observation light OL1 spreads out widely around the specific housing recess 22A, resulting in a large diameter of light (unfocused state).

[0085] Subsequently, as the picking unit 3 moves further downward, when the opening 40b of the capillary tube 40 reaches the liquid surface of the second liquid W2, as shown in Figure 13, at least the component of the first observation light OL1 that is reflected by the liquid surface of the second liquid W2 disappears. Therefore, the component of the first observation light OL1 that transmits from the picking unit 3 to the storage tray 2 gradually increases. As a result, as shown in Figure 14, it can be confirmed that the observation image P1 captured by the imaging unit 61 of the observation optical system 6 of the first observation light OL1 changes so that the area around the specific storage recess 22A suddenly becomes brighter. Note that the observation image P1 shown in Figure 14 shows the case where all of the multiple storage recesses 22 are the specific storage recess 22A, similar to Figure 11. The sudden increase in brightness around a specific recess 22A is related to the fact that, as shown in Figure 15, the first observation light OL1 begins to converge around the specific recess 22A and transitions to a state where the diameter of the light begins to decrease (intermediate convergence state).

[0086] Furthermore, as the picking unit 3 moves further downward through the second liquid W2, as shown in Figure 16, when the opening 40b of the capillary tube 40 reaches (or is near) the liquid surface of the first liquid W1 contained in a specific containment recess 22A, a large portion of the first observation light OL1 passes through the specific containment recess 22A from the opening 40b of the capillary tube 40 and through the containment tray 2.

[0087] Therefore, as shown in Figure 17, it can be confirmed from the observation image P1 captured by the imaging unit 61 of the observation optical system 6 that the first observation light OL1 is brightened in a spot-like manner around the specific housing recess 22A. Note that the observation image P1 shown in Figure 17 shows the case where all of the multiple housing recesses 22 are the specific housing recess 22A, similar to Figure 14. The spot-like brightness around the specific housing recess 22A is related to the fact that, as shown in Figure 18, the first observation light OL1 converges around the specific housing recess 22A and transitions to a state where the diameter of the light is small (converged state).

[0088] From the above, by observing the convergence state of the first observation light OL1 that has passed through the storage tray 2 using the observation optical system 6, the height relationship between a specific storage recess 22A and the picking unit 3 can be determined. Accordingly, the control unit 7 can detect the height of the picking unit 3 based on the convergence state of the first observation light OL1 from the observation image P1 of the first observation light OL1 observed by the observation optical system 6. This makes it possible to infer that the opening 40b of the capillary tube 40 has reached the liquid surface of the first liquid W1 stored in the specific storage recess 22A, or is located near the liquid surface.

[0089] As a result, the biological sample S contained in the first liquid W1, which is contained in a specific containment recess 22A, can be acquired into the picking unit 3 (inside the capillary tube 40). This allows for high-precision pickup of the biological sample S (expressed biological sample S). The tip 40a of the capillary tube 40 has an outer diameter smaller than the opening diameter of the containment recess 22. Therefore, the biological sample S can be picked up while suppressing contact between the tip 40a of the capillary tube 40 and the containment recess 22.

[0090] In this embodiment in particular, as shown in Figure 6, the capillary tube 40 already contains the first liquid W1. Therefore, when the opening 40b of the capillary tube 40 reaches or is near the liquid surface of the first liquid W1 in a specific receiving recess 22A, the first liquids W1 come into contact with each other. As a result, the biological sample S, along with the first liquid W1, can be moved (flowed) into the capillary tube 40 by capillary action. This allows for the rapid acquisition of the biological sample S while suppressing the burden on the biological sample S. In particular, since the biological sample S is moved using capillary action, there is no need to create negative pressure inside the capillary tube 40 to draw the first liquid W1 in the receiving recess 22A into the capillary tube 40. If negative pressure is created inside the capillary tube 40, there is a possibility that the second liquid W2 will also be drawn into the capillary tube 40. In this respect, since capillary action is used, the concern of drawing in the second liquid W2 can be eliminated. Therefore, only the biological sample S to be picked up can be acquired.

[0091] Furthermore, when acquiring a biological sample S, for example, when it is estimated that the opening 40b of the capillary tube 40 is located near the liquid surface of the first liquid W1 in a specific containment recess 22A, the irradiation of the first observation light OL1 by the first light irradiation unit 50 may be stopped, and the irradiation of the second observation light OL2 from the second light irradiation unit 55 may be started. In this case, the picking unit 3 is moved further downward while observing the observation image P2 captured by the second observation light OL2. This makes it possible to recognize, based on the observation image P2, that the opening 40b of the capillary tube 40 has reached the liquid surface of the first liquid W1 in the specific containment recess 22A, and that the biological sample S has been acquired by the picking unit 3.

[0092] Specifically, in the case described above, the change in light intensity caused by the disappearance or reduction of the first liquid W1 and biological sample S from the specific containment recess 22 is included in the reflected light of the second observation light OL2. Therefore, as shown in Figure 19, the observation image P2 captured by the imaging unit 61 of the observation optical system 6 of the second observation light OL2 includes a spot-like black area with lower brightness than other parts, as shown in section A. Note that the observation image P2 shown in Figure 19 shows the case where all of the multiple containment recesses 22 are the specific containment recess 22A, similar to Figure 17. The inclusion of a spot-like black area with lower brightness than other parts, as shown in section A, is related to the state in which the first liquid W1 containing the biological sample S has disappeared from the specific containment recess 22A and been acquired into the picking unit 3, as shown in Figure 20.

[0093] Therefore, the control unit 7 can accurately determine from the observation image P2 captured by the second observation light OL2 whether or not a biological sample S has been acquired by the picking unit 3 from within a specific storage recess 22A, based on the reflected light of the second observation light OL2.

[0094] As described above, the picking device 1 of this embodiment can appropriately detect the height difference between itself and the biological sample S, and can pick up the biological sample S (expressed biological sample S) with high accuracy.

[0095] In the above embodiment, when acquiring the biological sample S, the biological sample S was acquired together with the first liquid W1 contained in a specific receiving recess 22A, but the method is not limited to this case. It is sufficient to acquire at least a portion of the expressed biological sample S into the picking unit 3 by utilizing the capillary action caused by the contact of the first liquid W1s. Furthermore, the method is not limited to utilizing the capillary action; for example, random movement may be generated by the contact of the first liquid W1s, and the biological sample S may be moved into the picking unit 3 by the diffusion phenomenon, which is a physical phenomenon between the first liquid W1s. Even in this case, the biological sample S can be acquired quickly while suppressing the burden on the biological sample S.

[0096] Furthermore, after acquiring a biological sample S in the picking unit 3, the biological sample S may be removed to the outside through a tube 44 communicating with the hollow portion 42a of the holder 42 of the first illumination optical system 4, as shown in Figure 7. This allows for the efficient and continuous pickup of biological samples S contained in other storage recesses 22. Specifically, after the control unit 7 moves the picking unit 3 upward, the relative positional relationship between the storage tray 2 and the picking unit 3 in the front-to-back direction L1 and the left-to-right direction L2 is controlled so that the XY coordinates of the picking unit 3 coincide with the XY coordinates of the next target storage recess 22A. This allows the picking unit 3 to be positioned above another storage recess 22. Subsequently, by repeating the same steps as in the above embodiment, a biological sample S can be acquired from another storage recess 22.

[0097] In this way, by selecting multiple specific receiving recesses 22A, biological samples S expressed from each receiving recess 22A can be acquired individually and continuously. Therefore, efficient biological sample S pickup (acquisition) can be performed. In particular, it is possible to automate the pickup process for individually sampling biological samples S.

[0098] (Other optional operations) During the pickup operation described above, if necessary, the position (XY coordinates) of the picking unit 3 relative to the reference position of the storage tray 2 may be corrected (calibrated). In this case, for example, the control unit 7 controls the tray stage 30 to position the positioning hole 34 shown in Figure 6, which is formed in the tray stage 30, directly below the picking unit 3. Next, the first observation light OL1 is irradiated from the first light irradiation unit 50. As a result, the first observation light OL1 passes through the positioning hole 34 and then enters the reflection mirror 60. Therefore, it is possible to directly observe the first observation light OL1 with the observation optical system 6.

[0099] Therefore, the control unit 7 can determine the actual XY coordinates of the picking unit 3 based on the observation results of the first observation light OL1 directly observed by the observation optical system 6. This allows the control unit 7 to grasp the difference between the actual position of the picking unit 3 and the reference position, and to correct the positional deviation of the XY coordinates of the picking unit 3 to eliminate the difference. As a result, it is possible to accurately control the relative positional relationship between the picking unit 3 and the storage tray 2, which leads to high-precision pickup of biological samples S.

[0100] The calibration process described above can be carried out using known calibration methods, such as using a known calibration plate. Furthermore, the calibration process may be performed, for example, before setting the storage tray 2 on the tray stage 30, or after removing the storage tray 2. In this case, the positioning holes 34 may be used, but the first observation light OL1 may also be directly observed through the observation holes 33 formed in the tray stage 30.

[0101] Furthermore, the control unit 7 may also estimate the state of the tip 40a of the capillary tube 40 based on the observation results of the observation optical system 6 when it directly observes the first observation light OL1. Specifically, the control unit 7 estimates the state of the tip 40a of the capillary tube 40, such as whether the opening 40b of the capillary tube 40 is blocked due to crushing or the entry of foreign matter, or whether the opening 40b is deformed, based on the observation results of the first observation light OL1 (for example, the presence or absence of light from the first observation light OL1, light intensity, etc.). This makes it possible to detect unintended abnormalities in the tip 40a of the capillary tube 40. As a result, it is possible to quickly take action such as replacing or repairing the capillary tube 40, making the picking device 1 easy to use.

[0102] Although embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. Embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. Embodiments and their modifications include, for example, those that can be easily imagined by those skilled in the art, those that are substantially the same, and those that are equivalent.

[0103] For example, in the above embodiment, the case in which the second liquid W2 is poured so as to cover the multiple receiving recesses 22 was described as an example, but the second liquid W2 is not essential and may not be provided. Even in this case, the same effects can be achieved. However, it is preferable to provide the second liquid W2 because it can suppress evaporation of the first liquid W1, etc.

[0104] Furthermore, although the above embodiment was described using the example of a case where the first liquid W1 is pre-filled inside the capillary tube 40, this first liquid W1 is not essential and may not be provided. Even in this case, it is possible to obtain the biological sample S inside the capillary tube 40 by, for example, using capillary action. Moreover, in this case, it is possible to move the biological sample S, along with the first liquid W1, from the containment recess 22 into the capillary tube 40 by, for example, creating negative pressure inside the picking section 3 using the tube 44. Even in this case, the biological sample S can be obtained quickly while suppressing the load on the biological sample S. When using the second liquid W2 to cover multiple containment recesses 22, it is preferable to pre-fill the capillary tube 40 with the first liquid W1.

[0105] Furthermore, although the above embodiment was described using a configuration in which the observation optical system 6 is equipped with a reflective mirror 60 as an example, the invention is not limited to this case. For example, the imaging unit 61 may be placed below the observation hole 33 without providing a reflective mirror 60. In this case, for example, the imaging unit 61 may be placed vertically so as to face upward, and the first observation light OL1 and the second observation light OL2 may be imaged. However, by placing the reflective mirror 60 below the storage tray 2, the imaging unit 61 can be placed horizontally outside the storage tray 2 as shown in Figures 1 to 3, so there is no need to secure a large space below the storage tray 2 for setting the observation optical system 6. Therefore, the entire picking device 1 can be designed to be compact.

[0106] Furthermore, in the above embodiment, the height of the picking unit 3 was detected based on the convergence state of the first observation light OL1. In addition to this, it is also possible to control the speed of the picking unit 3 based on changes in the diameter of the light, changes in light intensity, etc., caused by refraction of the first observation light OL1.

[0107] Furthermore, in the above embodiment, for example, as shown in Figure 21, if the picking unit 3 is positioned in an inclined position in the vertical direction, the optical axis of the first observation light OL1 is positioned at a location offset from the specific housing recess 22A. Note that in Figure 21, the inclination of the picking unit 3 is exaggerated in the illustration. Therefore, in this case, as shown in Figure 22, the brightness center C in the image of the first observation light OL1 captured by the imaging unit 61 is located at a position offset from the specific housing recess 22A. Then, when the picking unit 3 moves downward from this state, as shown in Figure 23, the brightness center C shifts as indicated by arrow B as it moves downward, and the diameter of the light decreases.

[0108] Therefore, based on the observation results of the first observation light OL1, it is possible to determine that the picking unit 3 is tilted based on the change in the center C of the light and the change in the diameter of the light. In particular, the tilt angle and direction of the picking unit 3 can be determined based on the amount of change (shift amount) and the direction of change of the center C of the light. In such cases, the tilt of the picking unit 3 may be controlled using the control unit 7. This allows for accurate height detection of the picking unit 3. In this way, the control unit 7 controls the positional relationship of the picking unit 3 with respect to the receiving recess 22, including controlling the height position of the picking unit 3 or controlling its tilt.

[0109] Furthermore, while the biological sample S is not limited to any particular type, it is preferable to use, for example, a substance that has the function of emitting fluorescence and is subject to fluorescent staining. In this case, for example, a typical protein that is subject to fluorescent staining can be used as the biological sample S. Furthermore, for example, biomolecules such as nucleic acids, cations, chitin, cellulose, and A-T regions that are subject to fluorescent staining may be used as the biological sample S. Furthermore, various genes may be used as the biological sample S.

[0110] Furthermore, the present invention includes the following embodiments: <1> A picking device comprising: an optically transparent storage tray having a storage recess formed on its surface that can accommodate a first liquid containing a biological sample; a hollow picking unit disposed above the storage tray and movable relative to the storage recess, and for acquiring the biological sample through an opening at its tip; a first illumination optical system that irradiates a first observation light from above toward the storage tray through the opening from inside the picking unit; an observation optical system disposed below the storage tray and for observing the first observation light that has passed through the storage tray; and a control unit that controls the relative positional relationship between at least the picking unit and the storage tray, wherein the control unit controls the positional relationship between the picking unit and the storage recess based on the convergence state of the first observation light observed by the observation optical system. <2> The picking device according to <1>, wherein the storage tray has a plurality of storage recesses formed at intervals within the plane of the tray surface, and the control unit moves the picking unit and the storage tray relative to each other in the in-plane direction of the tray surface so that the picking unit is positioned above a specific storage recess in which a biological sample is stored among the plurality of storage recesses. <3> The picking device according to <2>, wherein the observation optical system is capable of directly observing the first observation light, and the control unit corrects the in-plane positional deviation of the picking unit relative to the reference position based on the first observation light that has been directly observed. <4> The picking device according to <3>, wherein the control unit estimates the state of the tip of the picking unit based on the observation result of the observation optical system when the first observation light is directly observed.<5> A picking device according to any one of <2> to <4>, comprising a second illumination optical system positioned below the storage tray and irradiating the storage tray with a second observation light from below, wherein the observation optical system further observes the reflected light of the second observation light reflected by the storage tray including the storage recess, and the control unit determines the position of a specific storage recess based on the reflected light of the second observation light observed by the observation optical system. <6> A picking device according to <5>, wherein the second illumination optical system irradiates light in the wavelength range in which the biological sample emits fluorescence as the second observation light, and the control unit determines whether or not the selected biological sample has been acquired by the picking unit from a specific storage recess based on the reflected light of the second observation light observed by the observation optical system. <7> A picking device according to any one of <1> to <6>, wherein the picking unit is formed such that the outer diameter of the tip is smaller than the opening diameter of the storage recess, and the inner diameter of the opening is smaller than the outer diameter of the tip. <8> A picking device according to any one of <1> to <7>, wherein the first illumination optical system irradiates the first observation light such that the optical axis is coaxial with the central axis of the picking section, and the observation optical system comprises a reflective mirror arranged coaxially with the optical axis, and an imaging unit that images the reflected light of the first observation light reflected by the reflective mirror. <9> A picking device according to any one of <1> to <8>, wherein a liquid layer consisting of a second liquid having hydrophobicity with respect to the first liquid is provided on the tray surface of the storage tray so as to cover the storage recess. <10> A picking device according to <9>, wherein the picking section has the first liquid inside the tip, and the biological sample is acquired by the biological sample moving inside the picking section by capillary action.<11> A picking device according to <9>, wherein the picking section has the first liquid inside the tip, and the biological sample is acquired by the biological sample moving inside the picking section due to diffusion. <12> A picking device according to any one of <1> to <9>, wherein the picking section acquires the biological sample together with the first liquid.

[0111] According to the present invention, it is possible to appropriately detect the height difference between the biological sample and the device, and to pick up the biological sample from the receiving recess with high precision.

[0112] S...Biological sample OL1...First observation light OL2...Second observation light W1...First liquid W2...Second liquid 1...Picking device 2...Storage tray 3...Picking unit 4...First illumination optical system 5...Second illumination optical system 6...Observation optical system 7...Control unit 10...Tray surface 22...Storage recess 22A...Specific storage recess 40a...Tip of capillary tube (tip of picking unit) 40b...Opening of capillary tube (opening of picking unit) 60...Reflection mirror 61...Imaging unit

Claims

1. A picking device comprising: an optically transparent storage tray having a storage recess formed on its surface that can accommodate a first liquid containing a biological sample; a hollow picking unit positioned above the storage tray and movable relative to the storage recess, and for acquiring the biological sample through an opening at its tip; a first illumination optical system that irradiates a first observation light from above toward the storage tray through the opening from inside the picking unit; an observation optical system positioned below the storage tray and observing the first observation light that has passed through the storage tray; and a control unit that controls the relative positional relationship between at least the picking unit and the storage tray, wherein the control unit controls the positional relationship between the picking unit and the storage recess based on the convergence state of the first observation light observed by the observation optical system.

2. A picking device according to claim 1, wherein the storage tray has a plurality of storage recesses formed at intervals within the plane of the tray surface, and the control unit moves the picking unit and the storage tray relative to each other in the in-plane direction of the tray surface so that the picking unit is positioned above a specific storage recess in which a biological sample is stored.

3. A picking device according to claim 2, wherein the observation optical system is capable of directly observing the first observation light, and the control unit corrects the in-plane positional displacement of the picking part with respect to the reference position based on the directly observed first observation light.

4. A picking device according to claim 3, wherein the control unit estimates the state of the tip of the picking unit based on the observation result of the observation optical system when the first observation light is directly observed.

5. A picking device according to any one of claims 2 to 4, comprising a second illumination optical system disposed below the storage tray and irradiating the storage tray with a second observation light from below, wherein the observation optical system further observes the reflected light of the second observation light reflected by the storage tray including the storage recess, and the control unit determines the position of a specific storage recess based on the reflected light of the second observation light observed by the observation optical system.

6. A picking device according to claim 5, wherein the second illumination optical system irradiates light in the wavelength range in which the biological sample emits fluorescence as the second observation light, and the control unit determines whether or not the selected biological sample has been acquired by the picking unit from a specific storage recess based on the reflected light of the second observation light observed by the observation optical system.

7. A picking device according to any one of claims 1 to 6, wherein the picking portion is formed such that the outer diameter of the tip portion is smaller than the opening diameter of the receiving recess, and the inner diameter of the opening is smaller than the outer diameter of the tip portion.

8. A picking device according to any one of claims 1 to 7, wherein the first illumination optical system irradiates the first observation light such that its optical axis is coaxial with the central axis of the picking section, and the observation optical system comprises a reflective mirror arranged coaxially with the optical axis, and an imaging unit that images the reflected light of the first observation light reflected by the reflective mirror.

9. A picking device according to any one of claims 1 to 8, wherein a liquid layer consisting of a second liquid having hydrophobicity with respect to the first liquid is provided on the tray surface of the storage tray so as to cover the storage recess.

10. A picking device according to claim 9, wherein the picking section has the first liquid inside the tip portion, and the biological sample is acquired by the movement of the biological sample into the picking section by capillary action.

11. A picking device according to claim 9, wherein the picking section has the first liquid inside the tip portion, and the biological sample is acquired by the biological sample moving inside the picking section due to diffusion.

12. A picking device according to any one of claims 1 to 9, wherein the picking unit acquires the biological sample together with the first liquid.

Images