Picking device

Abstract

To enable accurate detection of height relative to the biological sample and to pick up the biological sample with high precision. [Solution] The picking device 1 comprises a storage tray 2 with a storage recess formed on the tray surface 10 that can accommodate a first liquid containing a biological sample; a hollow picking unit 3 positioned above the storage tray and acquiring the biological sample through an opening at its tip; a first illumination optical system 4 that irradiates a first observation light OL1 from above towards the storage tray through the opening from inside the picking unit; an observation optical system 6 positioned below the storage tray and observing the first observation light that has passed through the storage tray; and a control unit 7 that controls the relative positional relationship between at least the picking unit and the storage tray, wherein the control unit controls the positional relationship of the picking unit with respect to the storage recess based on the convergence state of the first observation light observed by the observation optical system.

Description

Technical Field

[0005] , , , , , , , ,

[0001] The present invention relates to a picking device.

Background Art

[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 functioning as a grip and is internally connected to a vacuum pump. The light source is a light emitting element such as a light emitting diode, and emits guide light to a minute article as a 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.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] In recent years, for example, when performing genetic tests or analyzing the structure and function of target biomolecules such as proteins, it is required to acquire biological samples of extremely minute sizes (sizes of several μm to several tens of μm, or sizes less than that) such as cells and genes. However, the conventional method described above relies on the external visibility of the guide light. Therefore, when the target object is a biological sample, it is practically difficult to visually determine from the outside whether or not the guide light is hitting the biological sample. In particular, in order to pick up a biological sample, it is necessary to properly approach the picking part, such as a vacuum suction tube, to the biological sample. However, because biological samples are extremely small, it is difficult to detect the height difference between the biological sample and the picking part. These factors make it difficult to pick up biological samples using conventional methods.

[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. [Means for solving the problem]

[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, 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.

[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 picking section opening 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 refracted by the tray surface or the surface of the first liquid and transmitted through the storage tray. As a result, a small portion of the first observation light passes from the picking section opening through the storage recess and through the storage tray. Subsequently, when the storage recess and the picking section opening approach each other in the height direction, the portion of the first observation light that passes from the picking section opening through the storage recess and through the storage tray gradually increases. When the picking section opening reaches (contacts) the surface of the first liquid contained in the storage recess, much of the first observation light passes from the picking section opening through the storage recess and through 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 liquid 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 has a plurality of storage recesses formed at intervals within the plane of the tray surface, and 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 is capable of directly observing the first observation light, and 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 a user-friendly picking device.

[0017] (5) A second illumination optical system is provided, which is positioned below the storage tray and irradiates 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 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, and 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 induce fluorescence emission from the biological sample. Therefore, fluorescence can be caused by 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 the ground state while emitting fluorescence. This allows the control unit to identify a specific storage recess containing a fluorescent biological sample 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 unit reaches the first liquid in the accommodation recess, while suppressing the tip of the picking unit from contacting the accommodation recess, the biological sample can be appropriately acquired inside the picking unit.

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

[0024] In this case, the first illumination optical system can irradiate the first observation light in a coaxial epi-illumination method so that the optical axis is coaxial with the central axis of the picking unit. Then, the first observation light transmitted through the accommodation tray can be reflected by a reflection mirror arranged coaxially with the optical axis and then imaged by the imaging unit. Therefore, the height of the picking unit can be detected more accurately based on the convergence state of the first observation light. Therefore, it is easier to position the opening of the picking unit closer to the liquid surface of the first liquid. Furthermore, since a reflection mirror is arranged below the accommodation tray, for example, it is possible to arrange the imaging unit horizontally outside the accommodation tray. Therefore, there is no need to secure a large space for setting the observation optical system below the accommodation tray. Therefore, the entire picking device can be designed compactly.

[0025] (9) A liquid layer made of a second liquid having hydrophobicity with respect to the first liquid may be provided on the tray surface of the accommodation tray so as to cover the accommodation recess.

[0026] In this case, since the liquid layer made of the second liquid covers the accommodation recess in which the first liquid is accommodated, the first liquid can be sealed and evaporation of the first liquid can be suppressed. Thereby, the biological sample can be maintained in a good state. Note that since the second liquid has hydrophobicity with respect to the first liquid, it is possible to suppress the first liquid and the second liquid from mixing together.

[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. [Effects of the Invention]

[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. [Brief explanation of the drawing]

[0034] [Figure 1]This is a perspective view showing an embodiment of the picking device according to the present invention. [Figure 2] Figure 1 is a perspective view of the picking device shown. [Figure 3] Figure 1 is a perspective view of the picking device shown in Figure 1, viewed from below. [Figure 4] Figure 1 is a perspective view of the storage tray. [Figure 5] Figure 1 is a magnified longitudinal cross-sectional view of the area between the storage recess formed in the storage tray and the tip of the picking device. [Figure 6] Figure 1 is a magnified perspective view of the area around the observation hole in the tray stage. [Figure 7] Figure 1 is a longitudinal cross-sectional view of the picking section and the first illumination optical system. [Figure 8] This is an example of an observation image captured from the second observation light reflected from the underside of the storage tray. [Figure 9] This figure schematically shows multiple recessed areas included in the observation image shown in Figure 8. [Figure 10] This is a longitudinal cross-sectional view showing the state in which the picking part is being moved downward toward a specific storage recess formed in the storage tray while the first observation light is being irradiated. [Figure 11] This is an example of an observation image captured using the first observation light in the state shown in Figure 10. [Figure 12] This figure schematically shows the relationship between the multiple recessed areas and the first observation light contained in the observation image shown in Figure 11. [Figure 13] This is a longitudinal cross-sectional view showing the state in which the opening of the picking part reaches the liquid surface of the second liquid, achieved by moving the picking part downward from the state shown in Figure 10. [Figure 14] This is an example of an observation image captured using the first observation light in the state shown in Figure 13. [Figure 15] This figure schematically shows the relationship between the multiple recessed areas and the first observation light contained in the observation image shown in Figure 14. [Figure 16]This is a longitudinal cross-sectional view showing the state in which the opening of the picking part reaches the liquid surface of the first liquid, achieved by moving the picking part downward from the state shown in Figure 13. [Figure 17] This is an example of an observation image captured using the first observation light in the state shown in Figure 16. [Figure 18] Figure 17 schematically shows the relationship between the multiple recessed areas and the first observation light contained in the observation image. [Figure 19] This is an example of an observation image captured using the second observation light after the first liquid and biological sample in a specific containment recess were acquired by the picking unit, starting from the state shown in Figure 16. [Figure 20] This figure schematically shows multiple recessed areas included in the observation image shown in Figure 19. [Figure 21] This is a magnified 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. [Figure 22] Figure 21 schematically shows the relationship between the multiple recessed areas included in the captured image of the first observation light and the first observation light itself, in the state shown in Figure 21. [Figure 23] This figure schematically shows the relationship between the multiple accommodating recesses included in the image captured by the first observation light and the first observation light when the picking section shown in Figure 21 is moved downward. [Modes for carrying out the invention]

[0035] The picking device according to the present invention will be described below with reference to the drawings. As shown in Figures 1 to 3, the picking device 1 of this embodiment includes a storage tray 2 for storing biological samples S (see Figure 5), a hollow picking section 3 positioned above the storage tray 2, a first illumination optical system 4 that irradiates a first observation light OL1 from inside the picking section 3 toward the storage tray 2, a second illumination optical system 5 positioned below the storage tray 2 and irradiating a second observation light OL2 toward the storage tray 2, an observation optical system 6 positioned below the storage tray 2, and a control unit 7 that 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] (Full 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 orthogonally within a plane parallel to the tray surface 10 (horizontal plane) are defined as the front-to-back direction L1 and the left-to-right direction L2. Furthermore, the axis that passes vertically through the center of the set hole 11 of the storage tray 2 is defined as the central axis O1. In addition, in a plan view from the vertical direction, 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 is a rotating mechanism (not shown) for rotating the storage tray 2. The holding jig 31 is assembled to the rotating 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, multiple microchips 20 are provided on the tray surface 10 of the storage tray 2. The multiple 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 multiple microchips 20 comprises a ring portion 21 that bulges upward from the tray surface 10, and a plurality of receiving recesses 22 provided inside the ring portion 21. The plurality of receiving recesses 22 are formed to be recessed to a certain depth from the tray surface 10, and open upward. The receiving recesses 22 are, for example, circular recesses in plan view, formed with a diameter in the range of several hundred nanometers to several tens of micrometers. The depth of the receiving recesses 22 is, for example, in the range of several hundred nanometers to several tens of micrometers, 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 the only case; for example, the receiving recess 22 may be formed so that the bottom surface bulges downwards in a hemispherical shape.

[0042] The multiple receiving recesses 22 are formed to be regularly arranged inside the ring portion 21. Specifically, the multiple receiving recesses 22 may be arranged at regular intervals along two directions, the front-to-back direction L1 and the left-to-right direction L2, in a plan view, or they may be arranged in a staggered pattern. In this embodiment, an example is given in which the multiple receiving recesses 22 are arranged in a staggered pattern, alternately offset along the front-to-back direction L1 and the left-to-right direction L2.

[0043] As shown in Figure 5, the storage tray 2 configured as described above is capable of containing a first liquid W1 containing a biological sample S. The first liquid W1 is not particularly limited, but examples include biological sample solutions such as buffer solutions and culture media. Furthermore, a liquid layer consisting of a second liquid W2, which is hydrophobic to the first liquid W1, is provided on the tray surface 10 of the storage tray 2 so as to cover the storage recess 22. The second liquid W2 is injected into each microchip 20 so as to accumulate inside the ring portion 21. The second liquid W2 is not particularly limited, but examples include oils that are less likely to affect the biological sample S.

[0044] (Tray Stage) As shown in Figures 1 to 3, the tray stage 30 is formed in a rectangular shape in plan view, with a length in the left-right direction L2 being longer than the length in the front-back direction L1. The tray stage 30 is formed such that the length in the front-back direction L1 is greater than the overall diameter of the storage tray 2. The storage tray 2 is assembled such that its 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 positioned at a location shifted L2 in the left-right direction from the central axis O1 of the storage tray 2, and is positioned so as to be hidden on the lower surface of the storage tray 2. As a result, a portion 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 it. 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 positioning holes 34 that penetrate vertically through the tray stage 30. The positioning holes 34 are formed in a circular shape in plan view, smaller than the diameter of the microchip 20, for example. However, the shape of the positioning holes 34 is not limited to this case, and may be, for example, a polygonal shape in plan view. The positioning hole 34 is sized such that the tip 40a of the picking section 3 can be seen from below through the positioning hole 34.

[0048] As described above, the tray stage 30 is movable relative to the picking section 3 by a stage movement mechanism 8, as shown in Figure 1. Note that the stage movement mechanism 8 is not shown in the drawings other than Figure 1. The stage movement mechanism 8 is, for example, an XY movement mechanism capable of moving the tray stage 30 in two directions: the front-rear direction L1 and the left-right direction L2. The stage movement mechanism 8 is equipped with, for example, a linear guide, and is capable of moving the tray stage 30 along the front-rear direction L1 and the left-right direction L2 with high linearity and high precision. Furthermore, the stage movement mechanism 8 may be configured to move the tray stage 30 not only in the forward / backward direction L1 and the left / right direction L2, but also in the up / down direction. The operation of the stage movement mechanism 8 is controlled by the control unit 7.

[0049] (Picking section) As shown in Figures 1 to 3, the picking unit 3 is positioned above the storage tray 2 and is also positioned to be movable relative to the storage tray 2. In this embodiment, the tray stage 30 is movable in the front-rear direction L1 and the left-right direction L2 by the stage movement mechanism 8. As the storage tray 2 moves, the picking unit 3 is able to move relative to the storage tray 2 in the front-rear direction L1 and the left-right direction L2. Furthermore, the picking unit 3 is movable vertically by the picking movement mechanism 9. Note that the picking movement mechanism 9 is not shown in any of the drawings other than Figure 1.

[0050] The picking movement mechanism 9 is equipped with, for example, a linear guide, and is capable of moving the picking unit 3 along the vertical direction with high linearity and high precision. In addition to moving the picking unit 3 in the vertical direction, the picking movement mechanism 9 may also be configured to move it in the front-to-back direction L1 and the left-to-right direction L2. Furthermore, the operation of the picking movement mechanism 9 is controlled by the control unit 7. Therefore, the picking unit 3 in this 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 movement mechanism 9.

[0051] As shown in Figures 5 and 7, the picking unit 3 is capable of acquiring the biological sample S contained in the storage recess 22 through the opening 40b that is opened at the tip 40a. The picking unit 3 mainly comprises a hollow capillary tube 40 for acquiring a 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 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 40a of the capillary tube 40. The tip 40a of the capillary tube 40 functions as the tip 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 passing through the center of the capillary tube 40 in the vertical direction is defined as the central axis O2 of the picking portion 3.

[0053] As shown in Figure 7, an adapter 41 is positioned above the capillary tube 40, and 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 unit 3 (acquired inside the capillary tube 40) to the outside of the picking unit 3, for example, through a 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 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] (1st 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, and 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 is positioned offset in at least one of the front-to-back direction L1 and left-to-right direction L2 from directly below the observation hole 33, and includes a second light irradiation unit 55 that 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 irradiator 55 with respect to the storage tray 2 is not limited to this case. For example, the second light irradiator 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 arranging 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 optics) 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 includes a reflective mirror 60 positioned below the tray stage 30 on which the storage tray 2 is set, and an imaging unit 61 that 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 bottom 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) electrically connected to the image sensor are arranged, and the acquired 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) As shown in Figure 1, the control unit 7 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 (pickup) 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 portable media mentioned above, but may also include storage units such as hard disks built into computer systems (including hardware such as operating systems and peripheral devices). Furthermore, "computer-readable recording media" may 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, as well as 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 to control 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), and controls the relative positional relationship between the storage tray 2 and the picking unit 3 in the up-to-down direction by controlling the picking unit 3 by the picking movement mechanism 9 (height control).

[0070] In particular, the control unit 7 controls the positional relationship of the picking unit 3 with respect to the receiving 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 receiving 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 the biological sample S is actually contained, 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 is the XY coordinate (position in the front-to-back direction L1 and left-to-right direction L2) relative 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 multiple storage recesses 22 in each microchip 20 of 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. Thus, 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 recesses 22 that actually contain the biological sample S are described as specific storage recesses 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, the microchip 20 is filled with the second liquid W2, and the liquid layer of the second liquid W2 is provided so as to cover the multiple receiving recesses 22. This allows the first liquid W1 to be sealed by the liquid layer of the second liquid W2, and the evaporation of the first liquid W1 can be suppressed. Therefore, the biological sample S contained in a specific containment recess 22A can be maintained in good condition. Furthermore, 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 housing recesses 22 in which the first liquid W1 is contained. Therefore, as shown in Figure 8, the positions of multiple housing recesses 22 can be determined based on the observation image P2.

[0076] In particular, the second observation light OL2 is excitation light used to induce fluorescence emission from the biological sample S, making it possible to identify the biological sample S contained in a specific containment recess 22A. Specifically, by irradiating with the second observation light OL2, which is excitation light, the expressed biological sample S emits fluorescence due to the irradiation of the excitation light. The biological sample S then transitions to an excited state by absorbing the light energy of the excitation light, and then transitions to a ground state while emitting fluorescence. As a result, the control unit 7 can accurately determine the location 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. Figure 8 shows an example where all of the containment recesses 22 are filled with biological samples S. Therefore, the observation image P2 shown in Figure 8 shows the case where all of the multiple containment recesses 22 are filled with a 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. 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 section will explain height control. 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 / 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, gradually bringing a specific storage recess 22A and the opening 40b of the capillary tube 40 closer together. Figure 10 illustrates, as an example, a specific storage recess 22A and two storage recesses 22 in which no biological sample S is stored.

[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 or refracted by the surface of the second liquid W2, for example, 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 using the first observation light OL1, it can be confirmed that the area around a specific accommodating recess 22A becomes faintly brighter. Note that the observation image P1 shown in Figure 11, similar to Figure 8, shows the case where all of the multiple accommodating recesses 22 are the specific accommodating recess 22A. The faint illumination around a specific recess 22A is related to the fact that, as shown in Figure 12, the first observation light OL1 spreads widely around the specific 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, and the component that passes from the picking unit 3 to the storage tray 2 gradually increases. Therefore, as shown in Figure 14, 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 accommodating recess 22A suddenly becomes brighter. Note that the observation image P1 shown in Figure 14, similar to Figure 11, shows the case where all of the multiple accommodating recesses 22 are the specific accommodating recess 22A. 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 using the first observation light OL1 that a spot of brightness is observed around the specific accommodating recess 22A. Note that the observation image P1 shown in Figure 17, similar to Figure 14, shows the case where all of the multiple accommodating recesses 22 are the specific accommodating recess 22A. The localized brightness centered around the specific recess 22A is related to the fact that, as shown in Figure 18, the first observation light OL1 converges around the specific recess 22A, transitioning 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 section 3 (inside the capillary tube 40). This allows for high-precision pickup of the biological sample S (expressed biological sample S). Furthermore, since the outer diameter of the tip 40a of the capillary tube 40 is smaller than the opening diameter of the receiving recess 22, it is possible to pick up the biological sample S while suppressing contact between the tip 40a of the capillary tube 40 and the receiving 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, and 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, concerns such as drawing in the second liquid W2 can be eliminated, and 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 within the specific accommodating 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 using 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, similar to Figure 17, shows the case where all of the multiple accommodating recesses 22 are the specific accommodating recess 22A. As shown in section A, the presence of spot-like black areas with lower brightness than other parts is related to the fact that, as shown in Figure 20, the first liquid W1 containing the biological sample S has been removed from a specific containment recess 22A and acquired into the picking section 3.

[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 this is not the only 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 liquids W1 together. Furthermore, this method is not limited to utilizing capillary action; for example, random motion may be generated by contact between the first liquids W1, and the biological sample S may be moved into the picking unit 3 by diffusion, which is a physical phenomenon between the first liquids W1. Even in this case, the biological sample S can be obtained quickly while suppressing the burden on the biological sample S.

[0096] Furthermore, after acquiring the biological sample S in the picking unit 3, the biological sample S may be removed to the outside through a tube 44 that communicates 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 stored in other storage recesses 22. Specifically, after the control unit 7 moves the picking unit 3 upward, it 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 so that the XY coordinates of the picking unit 3 match those of the next target, a specific 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 obtained from another storage recess 22.

[0097] In this way, by selecting multiple specific containment recesses 22A, biological samples S expressed from each containment 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 tasks) Furthermore, during the process of performing the pickup operation described above, if necessary, a calibration operation may be performed to correct the position (XY coordinates) of the picking unit 3 relative to the reference position of the storage tray 2. 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, the relative positional relationship between the picking unit 3 and the storage tray 2 can be controlled with high precision, leading to highly accurate pickup of the biological sample 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 intrusion 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, the light intensity, etc.). This allows for the detection of unintended abnormalities in the tip 40a of the capillary tube 40. Therefore, replacement and repair of the capillary tube 40 can be carried out quickly, resulting in an easy-to-use picking device 1.

[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 injected 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 does not need to 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 receiving 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. Furthermore, when using the second liquid W2 to cover multiple accommodating recesses 22, it is preferable to pre-fill the inside of 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 upwards, and the first observation light OL1 and the second observation light OL2 may be imaged. However, by positioning the reflective mirror 60 below the storage tray 2, the imaging unit 61 can be positioned horizontally outside the storage tray 2, as shown in Figures 1 to 3. Therefore, it is not necessary to secure a large space below the storage tray 2 for setting the observation optical system 6. Consequently, 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 receiving 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 image of the first observation light OL1 captured by the imaging unit 61 has the center of brightness C 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 center of brightness C shifts as indicated by arrow B, 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 tilt 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 or tilt of the picking unit 3.

[0109] Furthermore, while the biological sample S is not limited to any specific material, it is preferable to use a material 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. Moreover, biomolecules such as nucleic acids, cations, chitin, cellulose, and AT regions that are subject to fluorescent staining may also be used as the biological sample S. Furthermore, various genes may also be used as the biological sample S.

[0110] Furthermore, the present invention includes the following embodiments. <1> 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 section is positioned above the storage tray and is movable relative to the storage recess, and through an opening at its tip, it acquires the biological sample. A first illumination optical system that irradiates a first observation light from above towards the storage tray through the opening from inside the picking section, An observation optical system is positioned below the storage tray and observes the first observation light that has passed through the storage tray, The system includes at least a control unit that controls the relative positional relationship between the picking unit and the storage tray, The picking device is characterized in that the control unit controls the positional relationship of the picking part with respect to the receiving recess based on the convergence state of the first observation light observed by the observation optical system. <2> <1> In the picking device described above, The storage tray has multiple storage recesses formed at intervals within the surface of the tray, 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 among a plurality of storage recesses in which the biological sample is stored. <3> <2> In the picking device described above, The observation optical system is configured to allow direct observation of the first observation light. The control unit corrects the in-plane positional deviation of the picking unit relative to a reference position based on the first observation light directly observed, in a picking device. <4> <3> In the picking device described above, The control unit estimates 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, in a picking device. <5> <2> from <4> In a picking device described in any one of the following, It is equipped with 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 further observes the reflected light of the second observation light reflected by the storage tray including the storage recess, The control unit is a picking device that determines the position of a specific recess based on the reflected light of the second observation light observed by the observation optical system. <6> <5> In the picking device described above, The second illumination optical system irradiates the biological sample with light in the wavelength range in which it emits fluorescence as the second observation light. The control unit determines, based on the reflected light of the second observation light observed by the observation optical system, whether or not the selected biological sample has been acquired by the picking unit from a specific storage recess. <7> <1> from <6> In a picking device described in any one of the following, The picking device 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> <1> from <7> In a picking device described in any one of the following, 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. The aforementioned observation optical system is A reflective mirror arranged coaxially with the optical axis, A picking device comprising: an imaging unit that images the reflected light of the first observation light reflected by the reflective mirror; <9> <1> from <8> In a picking device described in any one of the following, A picking device wherein a liquid layer consisting of a second liquid that is hydrophobic to the first liquid is provided on the tray surface of the storage tray so as to cover the storage recess. <10> <9> In the picking device described above, The picking device comprises a picking section having the first liquid inside the tip, and acquiring the biological sample by the movement of the biological sample into the picking section by capillary action. <11> <9> In the picking device described above, The picking device comprises a picking section having the first liquid inside the tip, and acquiring the biological sample by the movement of the biological sample into the picking section due to diffusion. <12> <1> from <9> In a picking device described in any one of the following, The picking unit is a picking device that acquires the biological sample along with the first liquid. [Explanation of Symbols]

[0111] S... Biological sample OL1...First observation light OL2...Second observation light W1…1st liquid W2...Second liquid 1… Picking device 2…Storage tray 3…Picking Department 4...First illumination optical system 5…Second illumination optical system 6… Observation Optical System 7…Control Unit 10...Tray surface 22…Accommodation recess 22A...Specific recessed area 40a... The tip of the capillary tube (the tip of the picking part) 40b...Opening of the capillary tube (opening of the picking section) 60…Reflective mirror 61…Imaging Department

Claims

1. 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 section is positioned above the storage tray and is movable relative to the storage recess, and through an opening at its tip, the biological sample is acquired. A first illumination optical system that irradiates a first observation light from above towards the storage tray through the opening from inside the picking section, An observation optical system is positioned below the storage tray and observes the first observation light that has passed through the storage tray, The system includes at least a control unit that controls the relative positional relationship between the picking unit and the storage tray, The picking device is characterized in that the control unit controls the positional relationship of the picking part with respect to the receiving recess based on the convergence state of the first observation light observed by the observation optical system.

2. In the picking device according to claim 1, The storage tray has multiple storage recesses formed at intervals within the surface of the tray, 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 among a plurality of storage recesses in which the biological sample is stored.

3. In the picking device according to claim 2, The observation optical system is configured to allow direct observation of the first observation light. The control unit corrects the in-plane positional deviation of the picking unit relative to the reference position based on the first observation light directly observed, in a picking device.

4. In the picking device according to claim 3, The control unit estimates 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, in a picking device.

5. In the picking device according to claim 2 or 3, It is equipped with 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 further observes the reflected light of the second observation light reflected by the storage tray including the storage recess, The control unit is a picking device that determines the position of a specific recess based on the reflected light of the second observation light observed by the observation optical system.

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

7. In the picking device according to claim 1, The picking device 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. In the picking device according to claim 1, 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. The aforementioned observation optical system is A reflective mirror arranged coaxially with the optical axis, A picking device comprising: an imaging unit that images the reflected light of the first observation light reflected by the reflective mirror;

9. In the picking device according to claim 1, A picking device wherein a liquid layer consisting of a second liquid that is hydrophobic to the first liquid is provided on the tray surface of the storage tray so as to cover the storage recess.

10. In the picking device according to claim 9, The picking device comprises a picking section having the first liquid inside the tip, and acquiring the biological sample by the movement of the biological sample into the picking section by capillary action.

11. In the picking device according to claim 9, The picking device comprises a picking section having the first liquid inside the tip, and acquiring the biological sample by the movement of the biological sample into the picking section due to diffusion.

12. In the picking device according to claim 1, The picking unit is a picking device that acquires the biological sample along with the first liquid.

Images