JP2006064850A - Microscopic inspection apparatus, microscopic inspection system and microwell plate transfer device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microscopic inspection apparatus capable of successively and efficiently inspecting a number of samples. <P>SOLUTION: The microscopic inspection apparatus 100 is equipped with a cassette 102 which can house a plurality of sheets of samples 101, an elevator to vertically move the cassette 102, a microscope 132 to enlarge and observe a sample 101, an XY stage 105 to appropriately place the sample 101 in an observation position, and a carrying device 104 to carry the sample 101 between the cassette 102 and the XY stage 105. The carrying device 104 is equipped with a holding part to hold a sample 101, a horizontal moving mechanism to horizontally move the holding part, and a lifting mechanism to move up and down the holding part, and a rotating mechanism to rotate the holding part. The XY stage 105 has an upper table 119 which can move in the X direction, and a sample 101 is mounted on the upper table 119. The upper table 119 has an opening 128 where a fork portion 117 of the carrying device 104 passes up and down. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a microscope inspection apparatus or microscope inspection system that sequentially inspects a large number of specimens.

  In the medical field, pathological examinations are performed for diagnosing diseases. Among them, microscopic examination is an important tool in histological examination, cell examination, blood examination and the like.

  Conventionally, a specimen (specimen) placed on a slide glass, a microwell plate, or the like is observed by an examiner set on a microscope stage by hand. However, large hospitals, inspection contracting organizations, etc. have to perform a large amount of inspections, and the efficiency is required. Therefore, techniques for automatically transporting specimens have been proposed so far.

  Japanese Patent Application Laid-Open No. 2003-139784 discloses a technique for extruding a specimen from a sample rack.

  Japanese translation of PCT publication No. 2000-501844 discloses a technique in which a specimen is pushed out from a cassette disposed above and slid down on a stage.

  Japanese Patent Application Laid-Open No. 11-83687 discloses a technique in which a specimen stored in a cassette is gripped and transported one by one by a transport device / stage.

Japanese Patent Laying-Open No. 2003-215459 discloses a conveying means for conveying a sample from a cassette to a stage of a microscope.
JP 2003-139784 A Special Table 2000-501844 Japanese Patent Laid-Open No. 11-83687 JP 2003-215559 A

  In Japanese Patent Application Laid-Open No. 2003-139784, a dedicated sample carrier is required, and the specimen can be moved only in one axis for changing the observation position, and the other axis is a method for moving the observation optical axis. Not suitable for observation.

  In Japanese translation of PCT publication No. 2000-501844, it is necessary to store the specimens one by one in the carrier in order to protect the specimens.

  In Japanese Patent Application Laid-Open No. 11-83687, since the specimen is received at both ends in the longitudinal direction in the cassette, the transport apparatus / stage must grasp the specimen inside so that it can be observed in that state. Therefore, the observation area of the specimen is restricted to be narrow. For this reason, it is good if the sample is present only at the center of the specimen as in a normal slide glass specimen, but it is not suitable when the sample is present in a wide area of the specimen such as a microarray.

  In Japanese Patent Application Laid-Open No. 2003-215559, two rotation / up / down mechanisms and two translation / up / down mechanisms are involved, and the apparatus becomes complicated and large. In addition, the number of times the specimen is delivered increases the risk of breakage and contamination.

  The present invention has been made in consideration of such a situation, and an object of the present invention is to provide a microscope inspection apparatus or a microscope inspection system capable of efficiently and sequentially inspecting a large number of specimens.

  One aspect of the present invention is directed to a microscope inspection apparatus for sequentially inspecting a plurality of specimens. The microscope inspection apparatus of the present invention includes a cassette capable of storing a plurality of specimens arranged vertically, an elevator for raising and lowering the cassette in the vertical direction, a microscope for enlarging the specimen, and an observation position of the specimen by the microscope. And a transport device for transporting the sample between the cassette and the stage. The transport device includes a holding unit for holding the sample, and a holding unit in the horizontal direction. It is equipped with a horizontal movement mechanism for linear movement and an elevating mechanism for raising and lowering the holding part in the vertical direction. The specimen is taken out from the cassette and carried to the stage, and the cassette is picked up from the stage and taken up. The stage has a table on which the specimen is placed, and the table has an opening through which the holding unit of the transport device passes vertically. Over di is a table, together with the can horizontally reciprocate between the observation position by the specimen transfer position and the microscope to pass the conveying device and the specimen may move X-Y horizontal to change the observation region of the specimen.

  One aspect of the present invention is a microscopic inspection system in which a microwell plate is transported by a transport robot that runs along a single guide rail, and a microwell plate for delivering the microwell plate between the transport robot and the microscope. It is directed to a well plate transfer device. The microscope includes a stage for appropriately moving the placed microwell plate while the microwell plate is placed at a predetermined receiving position. A microwell plate transfer apparatus according to the present invention includes a plate pedestal capable of rotating 90 degrees to receive a microwell plate from a transport robot, a microwell plate on the plate pedestal, and a microwell plate on a stage at the receiving position. 180 degree reversal transfer machine for exchanging at the same time, 180 degree reversal transfer machine is a reversing arm for holding the microwell plate at both ends, and a rotation for rotating the reversing arm 180 degrees A mechanism and a lifting mechanism for lifting and lowering the reversing arm.

  The present invention is directed, in part, to a microscopy system for sequentially inspecting microwell plates. The microscope inspection system of the present invention includes a culture chamber for culturing a microwell plate, a microscope for inspecting the microwell plate, and a transport robot for transporting the microwell plate at least between the culture chamber and the microscope. It has. The transfer robot travels along one guide rail. The microscope includes a stage for appropriately moving the placed microwell plate while the microwell plate is placed at a predetermined receiving position. The microscopy system further includes a plate cradle that can be rotated 90 degrees to receive a microwell plate from a transfer robot, and a microwell plate on the plate cradle and a microwell plate on the stage at the receiving position at the same time. 180 degree reverse transfer machine. The 180-degree reversing transfer machine includes a reversing arm having a holding portion for holding the microwell plate at both ends, a rotating mechanism for rotating the reversing arm by 180 degrees, and a lifting mechanism for raising and lowering the reversing arm. .

  ADVANTAGE OF THE INVENTION According to this invention, the microscope inspection apparatus or microscope inspection system which can test | inspect many samples efficiently sequentially is provided.

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

First Embodiment This embodiment is directed to a microscope inspection apparatus that sequentially inspects specimens stored in a cassette.

  1 to 3 are top views showing an operation state of the microscope inspection apparatus according to the first embodiment of the present invention. FIG. 1 shows a state in which the transport device takes out the sample from the cassette, FIG. 2 shows a state in which the transport device delivers the sample to the stage, and FIG. 3 shows a state in which the sample is at the observation position. 1 to 3 are drawn with the microscope omitted for ease of understanding. FIG. 4 is a perspective view of a cassette containing a specimen, and shows a state in which the transport apparatus takes out the specimen from the cassette. 5 and 6 are front views of the microscope of the microscope inspection apparatus according to the first embodiment of the present invention. FIG. 5 shows a state where the transport device delivers the sample to the stage, and FIG. 6 shows a state where the sample is at the observation position.

  In FIG. 1 to FIG. 3, the microscope inspection apparatus 100 is a cassette 102 that can store a plurality of specimens 101 side by side, an elevator 103 that moves the cassette 102 up and down, and a specimen 101 for magnifying observation. Microscope 132 (see FIGS. 5 and 6), an XY stage 105 for appropriately arranging the specimen 101 at an observation position by the microscope 132, and conveyance for conveying the specimen 101 between the cassette 102 and the XY stage 105. Device 104.

  The specimen 101 is a biochemical sample such as a slide glass or a microwell plate.

  The elevator 103 includes a table 106 on which the cassette 102 is placed, a guide 110 that supports the table 106 so as to be movable up and down, a ball screw 109 that moves the table 106 up and down, and a motor 107 that rotates the ball screw 109. The belt 108 rotates the motor 107 by transmitting the driving force of the motor 107 to the ball screw 109.

  The transport device 104 includes a holding unit for holding the specimen 101, a horizontal movement mechanism for linearly moving the holding unit in the horizontal direction, an elevating mechanism for moving the holding unit up and down, and a holding unit in a horizontal plane. And a rotation mechanism for rotating the inside. The holding part includes an arm 116 and a U-shaped fork part 117. The fork part 117 includes an adsorption part 118 for adsorbing and holding the specimen 101. The rotation mechanism includes a shaft 115 that rotatably holds the arm 116, and a motor (not shown) for rotating the shaft 115. The elevating mechanism includes a guide 114 that holds the arm 116 so that it can be raised and lowered, and a motor (not shown) for raising and lowering the arm 116. The horizontal movement mechanism includes a guide 113 that holds the arm 116 so as to be horizontally movable, a motor 111 that horizontally moves the arm 116, and a belt 112 that transmits the driving force of the motor 111. .

  The XY stage 105 includes a lower table 121, a middle table 120 that can move in the Y direction with respect to the lower table 121, and an upper table 119 that can move in the X direction with respect to the middle table 120. A specimen 101 is placed on the surface. The upper table 119 has an opening 128 through which the fork portion 117 of the transport device 104 passes vertically. Further, the upper table 119 has a suction part 131 for holding the specimen 101. The XY stage 105 has an X guide 124 that supports the upper table 119 to move in the X direction with respect to the middle table 120, a ball screw 123 for moving the upper table 119 in the X direction, and a ball screw 123 for rotating. A Y guide (not shown) that supports the middle table 120 to move in the Y direction relative to the lower table 121, a ball screw 126 for moving the middle table 120 in the Y direction, and a ball screw. And a motor 125 for rotating 126.

  Further, in order to position the specimen 101 placed on the upper table 119 of the XY stage 105, the upper table 119 has a positioning pin 129, and the arm 116 of the transport device 104 and the lower table 121 of the XY stage 105 are biased. A pin 130 is provided.

  As shown in FIG. 4, the cassette 102 has a plurality of slots 137 arranged one above the other, and each slot 137 holds the end of the specimen 101 so that the plurality of specimens 101 are arranged one above the other. Can be accommodated. As shown in FIGS. 1 to 3, the cassette 102 is placed on the table 106 of the elevator 103.

  The table 106 of the elevator 103 is configured such that the driving force of the motor 107 is transmitted to the ball screw 109 by the belt 108 and can be moved up and down along the guide 110.

  The arm 116 of the conveying device 104 can be moved linearly by a belt 112 and a guide 113 driven by a motor 111, can be moved up and down by a guide 114 and a motor (not shown), and is rotated around a shaft 115 by another motor (not shown). It is configured to be possible.

  1 and 4 show a state in which the transport apparatus 104 takes out the specimen 101 from the cassette 102. FIG. The table 106 of the elevator 103 is raised or lowered to the height at which the specimen 101 to be inspected in the cassette 102 is taken out by the conveying device 104. The arm 116 of the transfer device 104 moves to the left side of the figure, and a U-shaped fork portion 117 enters the cassette 102 and moves up by raising the specimen 101 by a slight amount below the backlash amount with the slot 137. The fork part 117 is provided with an adsorption part 118, which adsorbs and holds the lifted specimen 101.

  FIG. 2 shows a state in which the transport apparatus 104 delivers the sample 101 to the XY stage 105. In the XY stage 105, the upper table 119 is located at the left end of the figure. The arm 116 holding the sample 101 moves to the right side of the drawing by driving the belt 112 (two-dot chain line state), and then rotates 90 degrees counterclockwise around the shaft 115. At that time, the height of the arm 116 is located above the upper surface of the upper table 119, and the arm 116 passes over the upper table 119.

  The upper table 119 is provided with an opening 128, and the arm 116 descends through the opening 128 to the height of the upper surface of the upper table 119. Here, the arm 116 releases the sample 101 and releases it. The arm 116 continues to descend below the upper table 119, and the specimen 101 is placed on the upper table 119.

  The XY stage 105 moves the upper table 119 slightly to the upper left in the figure, and the positioning pin 129 provided on the upper table 119 presses the specimen 101 against the biasing pin 130 provided on the arm 116 and the lower table 121. . As a result, the specimen 101 is pressed by the biasing pin 130 and applied to the positioning pin 129 to be positioned. Here, the suction unit 131 provided on the upper table 119 sucks and holds the sample 101.

  FIG. 5 is a front view of the microscope 132 in this state. The revolver 134 holding the objective lens 133 is retracted upward. A tube 135 for dropping immersion oil is fixed to the microscope 132, the tip nozzle 136 is positioned above the specimen 101, and the other end is connected to an oil bottle via a pump (not shown). When the sample 101 is adsorbed on the upper table 119, the pump is driven and oil is dripped from the tip nozzle 136 onto the sample 101 by a pre-adjusted amount.

  3 and 6 show a state in which the specimen 101 is at the observation position. After the oil is dropped on the specimen 101, the upper table 119 moves the specimen 101 to the microscope optical axis 138, and the revolver 134 is lowered to a position where the tip of the objective lens 133 is in contact with the oil on the specimen 101. Next, with the tip of the objective lens 133 in contact with the oil, the XY stage 105 is driven XY to align the observation start position of the specimen 101 with the optical axis and start observation. The XY stage 105 is provided with a position sensor (not shown) that reads XY coordinates, and is configured to read the observation position coordinates of the specimen 101. The position sensor may be of any type, such as electrical, magnetic, or optical.

  When the inspection is completed, the revolver 134 is raised again and retracted, and then the XY stage 105 and the transport device 104 perform the reverse operation to store the specimen 101 in the original position of the cassette 102.

  When performing transmitted light observation, a condenser lens (not shown) is disposed below the upper table 119 of the XY stage 105, illuminates through the opening 128, and lowers when the upper table 119 moves when the specimen 101 is delivered. Are configured to evacuate. Thereafter, when the inspection is continued, the elevator 103 is raised or lowered, and the same operation as described above is repeated according to the carry-out height of the next specimen 101.

  According to the present embodiment, a large number of specimens 101 can be automatically set on the microscope 132 sequentially, and the microscopic inspection can be performed efficiently.

  In this embodiment, the transport device 104 is configured to unload the specimen 101 from the cassette 102 and deliver and place it on the XY stage 105, so that both ends of the specimen 101 can be received and observed, and a wide range of the specimen 101 is detected. I can mirror it.

  In this embodiment, the specimen 101 can be rotated 90 degrees so that the longitudinal direction of the specimen 101 can be directed in the X (left and right) direction of the microscope 132. Therefore, the stage can shorten the stroke in the Y (front and back) direction. The frame can be made shorter. The fact that the frame can be shortened not only simply can be reduced back and forth, but also because it is advantageous in terms of rigidity, the width and thickness can be reduced, and the entire microscope can be configured compactly.

  The holding unit of the transfer device 104 does not have to be in the fork shape, but when performing transmitted light observation, the bottom surface of the observation unit is not as dirty as possible. Therefore, in this embodiment, the observation unit near the center of the sample is avoided by using a fork shape. Thus, the specimen 101 can be held and contamination of the observation part can be avoided.

  In this embodiment, since the specimen 101 can be positioned with respect to the stage, a reproducible position coordinate is given to the specimen 101. When reexamination is necessary, the same part can be observed again using this coordinate. it can.

  Further, in the present embodiment, oil immersion oil is automatically dropped onto the specimen 101, and the objective lens 133 is once brought into contact with the oil and then moved to the observation start position, so that bubbles in the oil can be removed. Therefore, at the time of high-magnification observation using an oil immersion objective lens, the inspector only has to observe the specimen 101 that has been automatically set, or can simply shoot and record an image, Labor saving can be achieved.

(Modification)
In this embodiment, there is only one cassette 102 on which the specimen 101 is set. However, if the table 106 of the elevator 103 has a rack shape and can be set with a plurality of cassettes, more specimens can be set. 101 can be continuously inspected.

  The holding means for the specimen 101 is not limited to the adsorption method described in the present embodiment, and other methods such as a mechanical method may be used.

  Further, in this embodiment, belt drive and linear guide movement are used as the moving mechanism of the elevator and the conveying device, but the moving mechanism is not limited to this, and other mechanisms may be used.

  The positioning mechanism for the specimen 101 on the stage is not limited to the method described in this embodiment, and any other method may be used as long as the relative position with respect to the stage is similarly regulated.

Second Embodiment The present embodiment is directed to a microscope inspection system. More specifically, a microwell plate is transported at least between a culture chamber and a microscope by a transport robot that travels along a single guide rail. Directed to microscopy systems.

<System configuration>
FIG. 7 is a plan view of a microscope inspection system according to the second embodiment of the present invention. As shown in FIG. 7, the microscopy system 200 includes an empty plate mounting shelf 201 for storing an empty microwell plate 208, and a treatment liquid or a cell turbid liquid is dispensed to the microwell plate 208. A dispenser 202, a culture chamber 203 for culturing the turbid liquid dispensed in the microwell plate 208, a microscope 204 for inspecting the microwell plate 208, and the microwell plate 208 And a transfer robot 220.

  The microwell plate 208 generally has a transparent rectangle made of polystyrene or the like, and has a large number of recesses into which a turbid liquid such as cells called wells can be placed. And chamfering for fixing. Various types such as color, size, number of wells, and shape are commercially available depending on the application. For example, the most standard microwell plate 208 is 86 × 128 × 12 mm and has 96 wells.

  The dispenser 202 is a device for instilling a reagent or the like into a well provided on the microwell plate 208, and various models are commercially available. The dispensing machine 202 basically includes a dispensing head, an arm that supports the head, a base portion, and a microwell plate mounting table. In general, many dispensing heads move.

  The culture chamber 203 is a room that can maintain a constant temperature, humidity, and sterility, and a plurality of hook-shaped protrusions (in other words, slots) for supporting the microwell plate 208 are provided at regular intervals on both sides of the inner wall. A large number of microwell plates 208 are inserted and stored in the slots. In general, the culture chamber 203 is provided with several to ten slots, and each slot is assigned a column number and a slot number (address) for management.

  The microscope 204 is the most representative inspection apparatus, and includes an objective lens that is an inspection head, an arm that holds the objective lens, a base portion, and an electric XY stage 240. The delivery position of the microwell plate 208 is set on the XY stage 240, and the transfer robot 220 places or picks up the microwell plate 208 at this delivery position. At this time, in order to avoid interference with the arm of the microscope 204, the stroke of the XY stage is the observation range of the microwell plate 208 plus the length to the delivery position. Further, a positioning device and a fixing mechanism are provided so that the placed microwell plate 208 is fixed at a fixed position.

  The transfer robot 220 includes a carriage that runs on one guide rail 221 laid along the arrangement of the culture chamber 203 and the microscope 204, a three-axis + rotation-driven linear movement type and an articulated type drive unit, And an arm 222 operated by a driving unit. The arm 222 is provided with a pinch chuck or a vacuum chuck for gripping the microwell plate 208 at the tip. In response to an instruction from the controller, the transfer robot 220 takes out the microwell plate 208 at the designated address of the culture chamber 203 and transfers it to the microscope 204 or the dispenser 202, or transfers the microwell plate 208 after the inspection to the original culture chamber 203. Or return to the address.

  The microscope inspection system 200 further receives a microwell plate 208 from the transfer robot 220 and rotates it by 90 degrees, and a microwell plate 208 and an XY stage 240 in the 90-degree rotation plate holder 270. A 180-degree reversing transfer machine 260 for simultaneously exchanging the microwell plate 208 in FIG.

  Next, a microwell plate transport sequence in the microscope inspection system 200 will be described.

  First, the transfer robot 220 pulls out an empty microwell plate 208 from the empty plate mounting shelf 201 and carries it to a predetermined position of the dispenser 202. In the dispenser 202, a dispensing pipette (not shown) takes out the processing solution and the cell turbid solution, moves on the microwell plate 208 in parallel with the guide rail 221, and puts an appropriate amount on the well portion of the microwell plate 208. Instill. The dispenser 202 is configured so that two microwell plates 208 can be placed in order to shorten the tact time. Thereby, during the dispensing operation to one microwell plate 208, the transport robot 220 transports another dispensed microwell plate 208 to the culture chamber 203, and dispenses a new empty microwell plate 208. Can be carried into machine 202. Thereafter, the microwell plate 208 stored in the culture chamber 203 for an appropriate time is transported to the XY stage 240 of the microscope 204 by the transport robot 220.

  In the culture chamber 203, the slots hold both ends of the long side of the microwell plate 208. This is because the length of the culture chamber 203 in the opening direction is shortened, the size of the entire system can be reduced, and stability when the microwell plate itself is placed is also good. From this point, it is preferable that the longitudinal direction of the microwell plate 208 is perpendicular to the guide rail 221 of the transport robot 220.

  In the microscope 204, since the objective lens is supported by the arm, the stroke of the XY stage that moves under the objective lens should be small in the arm direction, that is, in the front-rear direction with respect to the observer. The microscope 204 is often placed vertically on the guide rail 221 of the transfer robot 220 so that the observer can work away from the transfer robot 220 for the safety of the observer. From this point, it is preferable that the longitudinal direction of the microwell plate 208 is parallel to the guide rail 221 of the transport robot 220.

  Since the dispenser 202 does not need to have an operator, the delivery robot 220 may be installed in a direction in which the microwell plate 208 can be easily placed. That is, with respect to the dispenser 202, the longitudinal direction of the microwell plate 208 may be perpendicular or parallel to the guide rail 221.

  About the empty plate mounting shelf 201, the same thing as the culture room 203 can be said.

  After all, in order to make the entire microscope inspection system compact, the longitudinal direction of the microwell plate 208 should be perpendicular to the guide rail 221 with respect to the empty plate mounting shelf 201, the dispenser 202, and the culture chamber 203. In order to improve safety and inspection accuracy, the longitudinal direction of the microwell plate 208 may be parallel to the guide rail 221 with respect to the microscope 204. However, in this arrangement, it is necessary to rotate the microwell plate 208 by 90 degrees prior to the inspection by the microscope 204.

  As a method of rotating the microwell plate by 90 degrees, a method of adding a rotation mechanism for rotating the microwell plate held by the arm of the transfer robot around an axis perpendicular to the upper surface thereof, and rotating the microwell plate on the stage of the microscope A method of providing a rotation mechanism, a method of installing a turntable for rotating the microwell plate by 90 degrees near the guide rail of the transfer robot, and the like can be considered. The method of adding the rotation mechanism to the arm of the transfer robot is to add a rotation axis to the three-axis + rotation transfer robot, resulting in an expensive transfer robot. In the method of providing a rotation mechanism on the stage, since transmission observation is performed with a microscope, the stage must have a large aperture for light passage, which is difficult in terms of design. In the method of installing the turntable, after the transfer robot places the microwell plate on the turntable, the turntable rotates and the transfer robot grips the microwell plate again, but because the chuck width is different, It is necessary to devise measures such as increasing the stroke of the chuck, and since this work is performed on the way back and forth, time loss is inevitable.

  In the microscopic inspection system 200 of this embodiment, the microwell plate 208 is rotated 90 degrees and passed from the transfer robot 220 to the microscope 204. For this reason, the microscope inspection system 200 includes a 90-degree rotating plate pedestal 270 and a 180-degree inversion transfer machine 260. The 90-degree rotation plate support 270 rotates the microwell plate 208 received from the transfer robot 220 by 90 degrees. The 180-degree reversing transfer machine 260 is disposed between the rotation center of the 90-degree rotation plate support 270 and the microwell plate transfer position of the XY stage 240, and the micro-well plate 208 of the 90-degree rotation plate support 270 By simultaneously grasping and lifting the microwell plate 208 of the XY stage 240, rotating 180 degrees and lowering, the two microwell plates 208 are exchanged in one operation.

  It is very effective in terms of tact to exchange the two microwell plates 208 in one operation. This is because if this 180-degree reversal transfer machine 260 is not present, after the inspection of the microwell plate 208 with the microscope 204 is completed, the transfer robot 220 grips the microwell plate 208 and carries it to the culture chamber 203 for the next micro-transfer. The microscope 204 is forced to rest until the well plate 208 comes. If there is a 180-degree reversal transfer machine 260, the transport robot 220 may carry the next microwell plate 208 to the 90-degree rotating plate pedestal 270 during the microscopic examination, and the microscope 204 will move to the next microwell plate 208. You can start testing immediately. In general, in such a microscope inspection system, it is not uncommon for the culture chamber 203 and the microscope 204 to be separated by about 3 m, and the effect is great in terms of shortening tact.

  In addition to this, a method of installing a temporary mounting table on which two microwell plates can be placed near the microscope is also conceivable. In this case, the conveyance robot carries out the next microwell plate from the culture chamber during the microwell plate inspection with the microscope, places it on the temporary mounting table, and waits until the inspection with the microscope is completed. When the inspection is finished and the stage is in the delivery position, the stage microwell plate is picked up, placed in an empty space on the temporary mounting table, and the next microwell plate already placed is gripped and placed on the stage. . Thereafter, the stage enters an inspection operation, and the transfer robot again grips the inspected microwell plate on the temporary mounting table, returns it to the culture chamber, and carries out the next microwell plate.

  The method of the present embodiment in which two microwell plates 208 are exchanged in one operation is extremely superior in terms of tact, compared to the method of installing a temporary mounting table on which two microwell plates can be placed.

<Structure of 90-degree rotating plate base>
FIG. 8 is a plan view showing the relationship among the XY stage 240, the 180-degree reversing transfer machine 260, the 90-degree rotating plate base 270, and the arm 222 of the transfer robot 220. FIG. 9 is a side view of the 90-degree rotating plate pedestal 270. The structure of the 90-degree rotating plate pedestal 270 will be described with reference to two drawings.

  As shown in FIG. 8, the 90-degree rotating plate support 270 has a plate mounting table 271, and the plate mounting table 271 is provided with four pins 275 for positioning the microwell plate. The plate mounting table 271 is provided with a lever 272 that presses the placed microwell plate 208 against the positioning pin 275, and the lever 272 is moved by the cylinder 273. Further, the plate mounting table 271 is provided with a spring 274. The spring 274 moves the lever 272 to the open position when the cylinder 273 is OFF.

  The plate mounting table 271 has a U-shape in which an opening for the reversing arm 261 of the 180-degree reversing transfer machine 260 that moves up and down is provided. Further, as shown in FIG. 8, the plate mounting table 271 is fixed to a plate 277 attached to the rotating shaft 278 via a spacer member 276 for creating a space. Thus, a space is secured below the mounting surface of the plate mounting table 271 so as not to interfere with the reversing arm 261 when the 90-degree rotating plate receiving table 270 rotates. The rotating shaft 278 is connected to the motor 280 via a transmission mechanism 279 including a pulley and a timing belt. The plate mounting table 271 is rotated 90 degrees forward and backward by the rotation of the motor 280.

  The 90-degree rotating plate receiving base 270 performs 90-degree reversal of the plate mounting base 271 repeatedly according to an instruction from a controller (not shown).

<Structure of 180-degree reverse transfer machine>
FIG. 10 is a side view of the 180-degree reversal transfer machine 260 and shows the relationship with the upper table of the XY stage 240. FIG. 11 is a front view of the 180-degree reversal transfer machine 260 and shows the relationship between the plate mounting table 271 of the 90-degree rotating plate receiving table 270 and the upper table 241 of the XY stage 240.

  The 180-degree reversing transfer machine 260 has a reversing arm 261, and the reversing arm 261 has a plurality of suction portions 267 at both ends. The reversing arm 261 is fixed to the rotating shaft 262 and is rotatable. The rotating shaft 262 is connected to the motor 264 via a transmission mechanism 263 including a pulley and a timing belt. The reversing arm 261 performs a reversing operation repeatedly by 180 degrees as the motor 264 rotates. These members are supported by a guide set 266 so as to be movable up and down, and are moved up and down by a motor 265.

  The 180-degree reversing transfer machine 260 performs the vertical movement of the reversing arm 261 between the positions A and B shown in FIG. 10 and the 180-degree repetitive reversing movement of the reversing arm 261 according to an instruction from a controller (not shown). .

<Structure of XY stage>
The structure of the XY stage 240 will be described with reference to FIGS.

  As shown in FIG. 8, the upper table 241 of the XY stage 240 is also an X-direction moving table of a three-layer XY stage. The upper table 241 has a U-shape with an opening in consideration of vertical movement of the 180-degree reversing arm 261 and transmitted illumination. The upper table 241 includes a positioning pin 243 of the microwell plate 208, a lever 244 that fixes and positions the microwell plate 208, a cylinder 246 that presses the lever 244, and a spring that returns the lever 244 to the open position when the cylinder 246 is OFF. H.245.

  FIG. 8 shows a state in which the upper table 241 of the XY stage 240 has come to the delivery position of the microwell plate 208. The delivery position is set to a position shifted by about 2 mm in order to avoid interference between the microwell plate 208 and the positioning pins 243 on the upper table 241 during delivery.

  The upper table 241 is driven by a ball screw 248 and a motor 249 along one X guide 247. The ball screw 248 and the motor 249 are fixed to the middle table 242 of the XY stage having a three-sheet structure. The middle table 242 is provided with an opening 253 for transmitted illumination. The middle table 242 is moved in the Y direction by the motor 250 and the ball screw 252 along the two Y guides 251.

  The member 254 is a condenser lens in an upright microscope and an objective lens in an inverted microscope. Since the condenser lens of the upright microscope and the objective lens of the inverted microscope have to be arranged close to the bottom surface of the microwell plate 208, the XY stage 240 is used as a microwell plate in order to avoid interference with the lower surface of the upper table 241. When the receiving operation is started, it moves downward. An objective lens (not shown), a revolver, and an eyepiece tube are placed on the arm 255 of the microscope.

<Transfer and inspection sequence of microwell plate>
In FIG. 8, the transfer robot 220 grips the microwell plate 208 by the arm 222, moves on the guide rail 221, and stops at the position shown in the figure. Thereafter, the microwell plate 208 is mounted on the plate mounting table 271 of the 90-degree rotating plate receiving table 270. At this time, the positioning lever 272 of the microwell plate 208 is opened because the cylinder 273 is OFF. After confirming that the microwell plate 208 is placed on the plate mounting table 271 by a signal from the transfer robot 220, the cylinder 273 is turned on and the positioning lever 272 is pushed. At this time, the other end of the lever 272 pushes the chamfered portion of the microwell plate 208, presses the microwell plate 208 against the pin 275 provided on the plate mounting table 271, and the microwell plate 208 is positioned.

  Thereafter, the plate mounting table 271 of the 90-degree rotating plate receiving base 270 rotates 90 degrees in the direction of the arrow in the drawing, and rotates 90 degrees with the opening of the upper table 241 of the XY stage 240 in preparation for the rising of the 180-degree reversing arm 261. It stops so that the opening of the plate mounting table 271 of the plate receiving table 270 faces each other. Next, the 180-degree reversing arm 261 rises, receives the microwell plate 208, is fixed by vacuum suction, stops at a specified height, rotates 180 degrees, and then descends again. At this time, by turning off vacuum suction, the microwell plate 208 is transferred to the upper table 241 of the XY stage 240 and stopped at the designated lower end position.

  Next, when the microwell plate 208 is placed on the upper table 241 of the XY stage 240, the cylinder 246 is turned on, the lever 244 is pressed, and the microwell plate 208 is positioned and fixed between the pin 243.

  Thereafter, the XY stage 240 moves to the left in the drawing, and the entire microwell plate is inspected with an objective lens (not shown). At the same time as the XY stage 240 moves to the left, the plate mounting table 271 of the 90-degree rotating plate receiving table 270 rotates to the original position and stops.

  On the other hand, while the inspection by the microscope 204 is being performed, the transport robot 220 transports the next microwell plate 208 from the culture chamber 203 and stops at the original position. The microwell plate 208 is mounted on the mounting table 271. When the microwell plate 208 is mounted, the microwell plate 208 is positioned, and the plate mounting table 271 of the 90-degree rotating plate receiving base 270 is rotated again, and the opening is stopped according to the opening of the XY stage 240. Then, the end of the inspection of the XY stage 240 is awaited.

  When the inspection with the microscope 204 is completed, the XY stage 240 moves to the delivery position of the microwell plate 208. After that, the 180-degree reversing arm 261 starts to rise, receives the microwell plate 208 of the XY stage 240 and the microwell plate 208 of the 90-degree rotating plate pedestal 270, is fixed by vacuum suction, and rises to the upper end. Rotate 180 degrees.

  When the rotation is completed, the 180-degree reversing arm 261 turns off the vacuum suction and starts to descend, and moves the microwell plate 208 to the XY stage 240 and the 90-degree rotating plate base 270. The two microwell plates 208 are respectively placed on the upper table 241 and the plate mounting table 271 and repositioned, and the microwell plate 208 of the XY stage 240 is subjected to inspection, and the microwell plate of the 90-degree rotating plate receiving table 270 is used. 208 is transferred to the culture chamber 203 by the transfer robot 220.

  Thereafter, the designated microwell plate 208 is inspected in the same procedure, and the inspected microwell plate 208 is returned to the culture chamber 203.

  As can be seen from the above description, the microscopic inspection system 200 according to the present embodiment includes the empty plate mounting shelf 201, the dispenser 202, the culture chamber 203, and the microscope 204 all with respect to the guide rail 221 of the transport robot 220. The entire system is compact because it is arranged in a direction suitable for compactness.

  In addition, the microwell plate 208 received from the transfer robot 220 by the 90-degree rotating plate pedestal 270 and the 180-degree reversing transfer machine 260 can be placed on the XY stage 240 of the microscope 204 in an appropriate direction in a short time. Therefore, the tact time is favorably shortened.

  The embodiments of the present invention have been described above with reference to the drawings. However, the present invention is not limited to these embodiments, and various modifications and changes can be made without departing from the scope of the present invention. Also good.

  One aspect of the present invention is directed to a microscope inspection apparatus for sequentially inspecting a plurality of specimens, and includes a microscope inspection apparatus listed in the following items.

  1. The microscope inspection apparatus of the present invention includes a cassette capable of storing a plurality of specimens arranged vertically, an elevator for raising and lowering the cassette in the vertical direction, a microscope for enlarging the specimen, and an observation position of the specimen by the microscope. And a transport device for transporting the sample between the cassette and the stage. The transport device includes a holding unit for holding the sample, and a holding unit in the horizontal direction. It is equipped with a horizontal movement mechanism for linear movement and an elevating mechanism for raising and lowering the holding part in the vertical direction. The specimen is taken out from the cassette and carried to the stage, and the cassette is picked up from the stage and taken up. The stage has a table on which the specimen is placed, and the table has an opening through which the holding unit of the transport device passes vertically. Over di is a table, together with the can horizontally reciprocate between the observation position by the specimen transfer position and the microscope to pass the conveying device and the specimen may move X-Y horizontal to change the observation region of the specimen.

  2. In another microscope inspection apparatus according to the first aspect of the present invention, in the first aspect, the transport device further includes a rotation mechanism that rotates the holding unit in a horizontal plane, and rotates the sample by 90 degrees and places the sample on the stage.

  3. Another microscope inspection apparatus of the present invention further includes positioning means for positioning the specimen placed on the stage in the first or second term, and the stage holds the positioned specimen. The holding means is further provided.

  4). In another one of the first to third aspects of the present invention, the microscope inspection apparatus according to the present invention further includes a dropping mechanism for the immersion observation liquid at the sample delivery position between the transport device and the stage.

  One aspect of the present invention is a microscopic inspection system in which a microwell plate is transported by a transport robot that runs along a single guide rail, and a microwell plate for delivering the microwell plate between the transport robot and the microscope. It is directed to a well plate transfer device, and includes a micro well plate transfer device listed in the following sections. Note that the microscope of the microscope inspection system includes a stage for moving the mounted microwell plate as appropriate while the microwell plate is mounted at a predetermined receiving position.

  5. The microwell plate transfer apparatus of the present invention is for simultaneously exchanging a plate receiving base for receiving a microwell plate from a transport robot, a microwell plate on the plate receiving base and a microwell plate on a stage at the receiving position. 180-degree reversal transfer machine, the 180-degree reversal transfer machine, a reversing arm for holding the microwell plate at both ends, a rotating mechanism for rotating the reversing arm 180 degrees, and a reversing arm And an elevating mechanism for elevating and lowering.

  6). In another microwell plate transfer device of the present invention, in the fifth aspect, the plate support includes a plate mounting table on which the microwell plate is mounted, and a rotation mechanism that rotates the plate mounting table by 90 degrees. Yes.

  7). Another microwell plate transfer apparatus according to the present invention is the micro-plate transfer apparatus according to the fifth aspect, wherein the 180-degree inversion transfer machine has an adsorption unit for vacuum-adsorbing the microwell plates held at both ends of the inversion arm, The plate cradle is configured to avoid interference with the vertical movement and rotation of the reversing arm of the 180-degree reversing transfer machine.

  The present invention is directed, in part, to a microscopy system for sequentially inspecting microwell plates and includes a microscopy system listed in the following sections.

  8). The microscope inspection system of the present invention includes a culture chamber for culturing a microwell plate, a microscope for inspecting the microwell plate, and a transport robot for transporting the microwell plate at least between the culture chamber and the microscope. And a transport robot that travels along one guide rail, and the microscope has a microwell plate placed at a predetermined receiving position and moves the placed microwell plate appropriately. In addition, the microscope inspection system further exchanges a plate cradle for receiving a microwell plate from the transfer robot, a microwell plate on the plate cradle, and a microwell plate on the stage at the receiving position at the same time. 180 degree reversal transfer machine for The 180-degree reversing transfer machine further includes a reversing arm having a holding portion for holding the microwell plate at both ends, a rotating mechanism for rotating the reversing arm by 180 degrees, and a lifting mechanism for moving the reversing arm up and down. And.

  9. Another microscope inspection system according to the present invention is the microscope support system according to item 8, wherein the plate receiving table includes a plate mounting table on which the microwell plate is mounted and a rotation mechanism that rotates the plate mounting table by 90 degrees.

  One aspect of the present invention is a microscopic inspection system in which a microwell plate is transported by a transport robot that runs along a single guide rail, and a microwell plate for delivering the microwell plate between the transport robot and the microscope. It is directed to a well plate transfer method, and includes a micro well plate transfer method listed in the following sections.

  10. In the microwell plate transfer method of the present invention, a microwell plate carried by a transport robot is placed on a plate support, and a microwell plate on a plate support and a microwell plate on a stage of a microscope are combined. Replace at the same time.

  11. Another microwell plate transfer method of the present invention is the same as that described in item 10, in which the microwell plate on the plate cradle is rotated by 90 degrees before the microwell plate is replaced, and the microcradle plate is replaced on the plate cradle after the microwell plate is replaced. A microwell plate is rotated 90 degrees.

It is a top view which shows the operation state of the microscope inspection apparatus by 1st embodiment of this invention, and the conveyance apparatus has shown the state which takes out the sample from a cassette. It is a top view which shows the operation state of the microscope inspection apparatus by 1st embodiment of this invention, and has shown the state which the conveyance apparatus delivers the sample to a stage. It is a top view which shows the operation state of the microscope inspection apparatus by 1st embodiment of this invention, and has shown the state which has a sample in an observation position. It is a perspective view of the cassette which accommodates the sample, and has shown the state from which a conveying apparatus takes out a sample from a cassette. It is a front view of the microscope of the microscope inspection apparatus by 1st embodiment of this invention, and the conveyance apparatus has shown the state which delivers a sample to a stage. It is a front view of the microscope of the microscope inspection apparatus by 1st embodiment of this invention, and has shown the state which has a sample in an observation position. It is a top view of the microscope inspection system by 2nd embodiment of this invention. It is a top view which shows the relationship between the XY stage shown by FIG. 7, the 180 degree inversion transfer machine, a 90 degree rotation plate base, and the arm of a conveyance robot. FIG. 9 is a side view of the 90-degree rotating plate support shown in FIG. 8. It is a side view of the 180 degree inversion transfer machine shown by FIG. 8, and has shown the relationship with the upper table of XY stage. It is a front view of the 180 degree inversion transfer machine shown by FIG. 8, and has shown the relationship between the plate mounting base of a 90 degree rotation plate stand, and the upper table of an XY stage.

Explanation of symbols

DESCRIPTION OF SYMBOLS 100 ... Microscope inspection apparatus, 101 ... Sample, 102 ... Cassette, 103 ... Elevator, 104 ... Transport device, 105 ... XY stage, 106 ... Table, 107 ... Motor, 108 ... Belt, 109 ... Ball screw, 110 ... Guide, 111 ... Motor, 112 ... Belt, 113 ... Guide, 114 ... Guide, 115 ... Shaft, 116 ... Arm, 117 ... Fork part, 118 ... Suction part, 119 ... Upper table, 120 ... Middle table, 121 ... Lower table, 122 ... Motor , 123 ... Ball screw, 124 ... X guide, 125 ... Motor, 126 ... Ball screw, 128 ... Opening, 129 ... Pin, 130 ... Energizing pin, 131 ... Suction part, 132 ... Microscope, 133 ... Objective lens, 134 ... Revolver 135, tube, 136, tip nozzle, 137, slot, DESCRIPTION OF SYMBOLS 38 ... Microscope optical axis, 200 ... Microscope inspection system, 201 ... Empty plate mounting shelf, 202 ... Dispenser, 203 ... Culture chamber, 204 ... Microscope, 208 ... Microwell plate, 220 ... Transfer robot, 221 ... Guide rail , 222 ... arm, 240 ... XY stage, 241 ... upper table, 242 ... middle table, 243 ... pin, 244 ... lever, 245 ... spring, 246 ... cylinder, 247 ... X guide, 248 ... ball screw, 249 ... motor, 250 ... motor, 251 ... Y guide, 252 ... ball screw, 253 ... opening, 254 ... member, 255 ... arm, 260 ... 180 degree reversing transfer machine, 261 ... reversing arm, 262 ... rotating shaft, 263 ... transmission mechanism, 264 ... Motor, 265 ... Motor, 266 ... Guide set, 267 ... Suction part, 270 ... 90 degrees Rolling plate cradle, 271 ... plate mounting base, 272 ... lever, 273 ... cylinder, 274 ... spring 275 ... pin, 276 ... spacer member, 277 ... plate, 278 ... rotary shaft, 279 ... transmission mechanism, 280 ... motor.

Claims (7)

It is a microscope inspection device for sequentially inspecting multiple specimens,
A cassette that can store a plurality of specimens side by side;
An elevator for moving the cassette up and down,
A microscope for magnifying the specimen,
A stage for appropriately arranging the specimen at an observation position by a microscope;
A transport device for transporting the specimen between the cassette and the stage,
The transport device includes a holding unit for holding the specimen, a horizontal moving mechanism for linearly moving the holding unit in the horizontal direction, and an elevating mechanism for moving the holding unit up and down. Take out the specimen and bring it to the stage to place it, take the specimen from the stage and carry it to the cassette for storage.
The stage has a table on which a sample is placed, the table has an opening through which the holding unit of the transfer device passes vertically, and the stage passes the table to and from the transfer device. A microscope inspection apparatus that can horizontally reciprocate between a position and an observation position by a microscope, and can move in the XY direction to change the observation site of the specimen.   2. The microscope inspection apparatus according to claim 1, wherein the transport device further includes a rotation mechanism that rotates the holding unit in a horizontal plane, and the sample is rotated by 90 degrees and placed on the stage.   In Claim 1 or Claim 2, while further comprising positioning means for positioning the specimen placed on the stage, the stage further comprises holding means for holding the positioned specimen. Microscope inspection equipment.   4. The microscope inspection apparatus according to claim 1, further comprising a liquid immersion observation liquid dropping mechanism at a sample delivery position between the transport device and the stage. In a microscopic inspection system in which a microwell plate is transported by a transport robot that travels along one guide rail, a microwell plate transfer device for delivering the microwell plate between the transport robot and the microscope,
The microscope is equipped with a stage for appropriately moving the placed microwell plate while the microwell plate is placed at a predetermined receiving position,
A plate cradle capable of rotating 90 degrees to receive the microwell plate from the transfer robot;
A 180-degree inversion transfer machine for simultaneously exchanging the microwell plate on the plate cradle and the microwell plate on the stage at the receiving position;
The 180-degree reversing transfer machine includes a reversing arm for holding the microwell plate at both ends, a rotating mechanism for rotating the reversing arm by 180 degrees, and a lifting mechanism for moving the reversing arm up and down. Well plate transfer device. In claim 5, the 180-degree reversal transfer machine has a suction part for vacuum-sucking the microwell plate held at both ends of the reversing arm,
A microwell plate transfer device in which the plate support is configured to avoid interference with the vertical movement and rotation of the reversing arm of the 180 ° reversing transfer device. A microscopic inspection system for sequentially inspecting microwell plates,
A culture chamber for culturing microwell plates;
A microscope for inspecting the microwell plate;
It is a transfer robot for transferring the microwell plate between at least the culture chamber and the microscope, and includes a transfer robot that travels along one guide rail,
The microscope is equipped with a stage for appropriately moving the placed microwell plate while the microwell plate is placed at a predetermined receiving position,
The microscope inspection system
A plate cradle capable of rotating 90 degrees to receive the microwell plate from the transfer robot;
A 180-degree reversal transfer machine for simultaneously exchanging the microwell plate on the plate cradle and the microwell plate on the stage at the receiving position;
The 180-degree reversing transfer machine includes a reversing arm having a holding portion for holding the microwell plate at both ends, a rotating mechanism for rotating the reversing arm by 180 degrees, and a lifting mechanism for raising and lowering the reversing arm. , Microscopy system.

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