JP2012003036A - Observation device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve sealability of the stage of an observation device.SOLUTION: An observation device includes: an image optical system; a specimen support 33 where a turret 12 is detachably attachable and an observation window 39 for transmitting illumination light is provided; a pinion gear 71 that makes the turret 12 rotate with a center 12A being an axis by rotating about a rotation axis 47A; an eccentric cam 73 that moves the turret 12 in the direction of an arrow A2 with the rotation axis 47A as a center by rotating about a rotation axis 48A; and a rotor 77 that is given a force that pushes the turret 12 in the horizontal direction and rotates about a rotation axis 76 that is supported to be movable in the direction for pushing the turret 12 and the reverse direction thereof. The present invention can be applied to the observation device of a cell, for example.

Description

  The present invention relates to an observation apparatus, and more particularly to an observation apparatus suitable for use in cell culture observation.

  In recent years, research and development for culturing cells in the field of regenerative medicine, drug discovery, etc. has been active. For example, a culture device (incubator) for culturing cells and an observation device such as a microscope for observing the state of cells In combination, the cell culture is observed.

  In order to culture cells, it is necessary to keep the room of the culture apparatus in an environment similar to that of a living body, for example, a temperature of about 37 ° C., a humidity of about 95 to 100%, and a carbon dioxide gas concentration of about 5%. As described above, since the inside of the culture apparatus is hot and humid, when an optical device such as a microscope or a driving component such as a motor for driving the stage is installed, the device or the component is damaged.

  Therefore, conventionally, a rotating base (stage) for placing a tray on which a sample container is placed is provided, and an incubator chamber for culturing cells in the sample container, and a motor chamber for storing a motor for driving the rotating base. It has been proposed that the atmosphere in the incubator chamber be sealed so as not to leak into the motor chamber (see, for example, Patent Document 1).

  In the culture microscope described in Patent Document 1, the rotation base is rotated by the θ stage motor in the motor chamber, and the rotation base is linearly moved by the R stage motor. Thereby, the position of the sample in the sample container can be moved in the Rθ polar coordinate system.

JP 2006-11415 A

  However, in the culture microscope described in Patent Document 1, it is necessary to provide a linear opening at the seal portion at the boundary between the incubator chamber and the motor chamber in order to move the rotation base linearly. Accordingly, the seal structure is complicated, and the durability of the seal portion is lowered, so that the sealability is lowered. Further, for example, when a liquid such as a culture solution is spilled on the rotating base, the spilled culture solution may leak from the linear opening to the motor chamber.

  The present invention has been made in view of such a situation, and is intended to improve the sealing performance of the stage of the observation apparatus.

  An observation apparatus according to one aspect of the present invention accommodates an imaging optical system that forms an image of an observation sample and the imaging optical system, and can transmit a light beam condensed by the imaging optical system on an upper surface. A housing having a window, a table provided on the upper surface of the housing so as to cover the position where the window is provided, at least a part of the outer periphery being an arc, and a table on which the observation sample is placed; and the housing A circular rotating member which is provided on the upper surface of the table and is rotatable about a first rotation axis which is set in a direction perpendicular to a surface on which the observation sample of the table is placed, which is in contact with the arc of the table And an eccentric cam that is provided on the upper surface of the housing and is in contact with the arc of the table at a position different from the rotating member and is rotatable around a second rotating shaft parallel to the first rotating shaft Different from the rotating member and the eccentric cam. Position and a biasing member to the table in contact with the circular arc of said table so as to push towards the rotary member or the eccentric cam that.

  In one aspect of the present invention, when the rotating member rotates around the first rotation axis, the table rotates around the center of the arc of the table, and the eccentric cam rotates around the second rotation axis. As a result, the table moves in the circumferential direction around the first rotation axis.

  According to one aspect of the present invention, the sealing performance of the stage of the observation apparatus can be improved.

It is a figure which shows typically one Embodiment of the observation system to which this invention is applied. It is a figure which shows the example of arrangement | positioning of the member for driving a turret. It is the top view which looked at the sample stand in which the turret was installed from the top. It is the perspective view which looked at the sample stand in which the turret was installed from diagonally upward. It is the side view which looked at the sample stand in which the turret was installed from the side. It is the reverse view which looked at the sample stand from the back. It is a figure which shows the example of the movement range of a turret. It is a figure which shows typically one Embodiment of the culture observation system to which this invention is applied. It is a figure which shows the example which installed the flask in the sample stand.

Hereinafter, modes for carrying out the present invention (hereinafter referred to as embodiments) will be described. The description will be given in the following order.
1. Embodiment 2. FIG. Modified example

<1. Embodiment>
[Configuration example of observation system]
FIG. 1 is a diagram schematically showing an embodiment of an observation system to which the present invention is applied.

  The observation system 1 is a system for observing a sample (for example, a cell or the like) in a transparent plastic dish 2 placed on a turret 12 which is a table for placing the sample, for example.

  The observation system 1 includes an observation device 11, a turret 12, and a personal computer (hereinafter referred to as PC) 13. The PC 13 is connected to a connection terminal 32 provided on the housing 31 of the observation apparatus 11 via the connection cable 14.

  The upper surface of the cylindrical casing 31 of the observation apparatus 11 is a sample stage 33 on a disc on which the turret 12 is installed. The casing 31 and the sample stage 33 are joined together via a ring-shaped seal 35 made of, for example, an O-ring, and an observation chamber 34 that is a space sealed by the casing 31 and the sample stage 33 is formed. .

  In FIG. 1, the inside of the observation chamber 34 is illustrated through the housing 31.

  On the sample stage 33, an illumination stand 36 having an illumination optical system 37 at the tip is installed. The illumination optical system 37 includes a light source and a lens (not shown) and irradiates the sample in the dish 2 with illumination light emitted from the light source. Further, the illumination stand 36 is joined to the mounting hole 33A (FIG. 3) of the sample stage 33 through a ring-shaped seal 38 formed of, for example, an O-ring in order to keep the observation chamber 34 hermetically sealed.

  A part of the sample stage 33 is provided with an observation window 39 made of a colorless and transparent material such as glass. Of the illumination light applied to the sample in the dish 2, light transmitted through the sample (hereinafter referred to as observation light) passes through the dish 2 and the observation window 39 and enters the observation chamber 34.

  An image of the sample by the observation light incident on the observation chamber 34 is imaged and photographed by an imaging optical system provided in the observation chamber 34. More specifically, the observation light incident on the observation chamber 34 is transmitted through the objective lens 40, reflected by the folding mirror 41, and image sensor (for example, CCD) provided in the camera 43 by the imaging lens 42. An image is formed on a light receiving surface of an image sensor, a CMOS image sensor, or the like. The camera 43 captures an image of the sample by the observation light and supplies the obtained image data to the PC 13 via the connection terminal 32 and the connection cable 14. The PC 13 displays a photographed sample image based on the acquired image data. In this way, the sample in the dish 2 can be observed from below through the bottom of the dish 2.

  Note that the focus of the objective lens 40 is automatically adjusted by an autofocus (AF) mechanism 44.

  In the observation chamber 34, in addition to the above-described imaging optical system, a drive system for a controller 45, a driver 46, a θ motor 47, and an R motor 48 is provided.

  The controller 45 controls the driver 46 according to a command input from the PC 13 via the connection cable 14 and the connection terminal 32 to drive the θ motor 47 and the R motor 48.

  The θ motor 47 is constituted by a stepping motor, for example, and drives the pinion gear 71 (FIG. 2).

  The R motor 48 is constituted by a stepping motor, for example, and drives an eccentric cam 73 (FIG. 2).

[Turret driving method]
Next, a method for driving the turret 12 will be described with reference to FIGS. FIG. 2 shows an arrangement example of members for driving the turret 12. More specifically, the upper right diagram in FIG. 2 shows an example of the arrangement of each member when the turret 12 is viewed from above, and the left diagram shows a left side view of the turret 12 in the upper right diagram. The lower view shows a lower side view of the turret 12 in the upper right view. In the upper right diagram of FIG. 2, members such as the turret 12 are simplified.

  3 is a top view of the sample table 33 on which the turret 12 is installed as viewed from above, FIG. 4 is a perspective view of the sample table 33 on which the turret 12 is installed as viewed from obliquely above, and FIG. 6 is a side view of the sample stage 33 viewed from the side, and FIG. 6 is a back view of the sample stage 33 viewed from the back. 3 to 6, illustration of the casing 31, the illumination stand 36, and the illumination optical system 37 is omitted.

  As shown in FIG. 2, the outer peripheral side surface of the turret 12 has a two-layer structure of a cylindrical portion 61 and a gear portion 62 having a smooth surface. The turret 12 is formed with circular openings 63 a to 63 e for placing the dish 2. The number of openings formed in the turret 12 can be set to an arbitrary number.

  The θ motor 47 is installed on the back surface of the sample stage 33 so that the rotation shaft 47A is perpendicular to the sample stage 33. The rotation shaft 47A penetrates the sample stage 33, and a pinion gear 71 is attached on the sample stage 33 side. Further, a ring-shaped seal 72 made of, for example, an O-ring is provided around the rotation shaft 47A in order to keep the observation chamber 34 hermetically sealed at the portion where the rotation shaft 47A penetrates the sample stage 33.

  The pinion gear 71 meshes with the gear portion 62 of the turret 12 at a predetermined position, and supports the turret 12 in the horizontal direction. Then, the pinion gear 71 is driven by the θ motor 47 and rotates around the rotation shaft 47A, whereby the turret 12 rotates in the direction of the arrow A1 (FIG. 2) about the center 12A. Thereby, the position of the sample in the dish 2 on the turret 12 can be moved in the θ direction of the Rθ polar coordinate system.

  The R motor 48 is installed on the back surface of the sample stage 33 so that the rotation shaft 48 </ b> A is perpendicular to the sample stage 33. The rotating shaft 48A penetrates the sample stage 33, and an eccentric cam 73 is attached on the sample stage 33 side. Further, a ring-shaped seal 74 made of, for example, an O-ring is provided around the rotation shaft 48A in order to keep the observation chamber 34 hermetically sealed at a portion where the rotation shaft 48A penetrates the sample stage 33.

  The eccentric cam 73 is formed with an outer peripheral shape such that the outer peripheral portion thereof is not equidistant from the rotation axis. The eccentric cam 73 is installed at a position about 90 degrees away from the portion where the turret 12 and the pinion gear 71 are in contact with each other in the outer circumferential direction of the turret 12. The outer periphery of the eccentric cam 73 is in contact with the cylindrical portion 61 of the turret 12 and supports the turret 12 in the horizontal direction. The eccentric cam 73 is driven by the R motor 48 and rotates around the rotation shaft 48A, so that the turret 12 is circumferentially centered on the rotation shaft 47A (the direction of the arrow A2 (FIG. 2)). Moving. Thereby, the position of the sample in the dish 2 on the turret 12 can be moved approximately in the R direction of the Rθ polar coordinate system.

  Although not shown in FIG. 1, as shown in FIGS. 2 to 6, the biasing lever mechanism 75 is arranged so that the shaft 75 </ b> A is perpendicular to the sample stage 33. It is installed on the back side. The shaft 75A penetrates the sample stage 33, and an urging lever 75B is attached on the sample stage 33 side. Although illustration is omitted, in order to maintain the sealing property of the observation chamber 34 in a portion where the shaft 75A penetrates the sample stage 33, a seal constituted by, for example, an O-ring is provided around the shaft 75A. Yes. The rotation shaft 76 perpendicular to the sample stage 33 can rotate around the axis and move in the direction of the arrow A3 (FIG. 2) with the shaft 75A as an axis and in the opposite direction. Supported at the tip. The rotating shaft 76 passes through the rotating body 77 on the disk, and the rotating body 77 rotates around the rotating shaft 76.

  The rotating body 77 is a cylinder of the turret 12 at a position about 135 degrees away from the portion where the turret 12 and the pinion gear 71 are in contact and the portion where the turret 12 and the eccentric cam 73 are in contact with each other in the outer circumferential direction of the turret 12. It is in contact with the part 61.

  The biasing lever mechanism 75 applies a force that rotates the shaft 75A in the direction of the arrow A3 about the shaft 75A to the biasing lever 75B. Thereby, a force that pushes the turret 12 in the direction of the horizontal arrow A3 with respect to the sample stage 33 about the shaft 75A is applied to the rotating body 77 connected to the biasing lever 75B via the rotating shaft 76. The As a result, the horizontal position of the turret 12 is stabilized.

  3 to 5, a lock mechanism 64 for the dish 2 may be provided at the center of the turret 12 in order to further stabilize the horizontal position of the dish 2 while the turret 12 is rotating. Good.

  Here, the moving range of the turret 12 will be described with reference to FIG. 7 indicates an example of the moving direction of the center of the opening 63a when the turret opening 63a is positioned on the observation window 39 of the sample stage 33.

  For example, the center of the opening 63 a of the turret 12 moves in the direction of the arrow A 11 about the rotation shaft 47 A of the θ motor 47 as the eccentric cam 73 rotates. That is, the center of the opening 63a moves in a direction away from the outer periphery of the sample stage 33 (upward direction of the arrow A11) or a direction approaching the outer periphery of the sample stage 33 (downward direction of the arrow A11). Further, the center of the opening 63a moves in the direction of arrow A12 about the center 12A of the turret 12 as the pinion gear 71 rotates in the state farthest from the outer periphery of the sample stage 33. Further, the center of the opening 63a moves in the direction of arrow A13 around the center 12A of the turret 12 as the pinion gear 71 rotates in the state closest to the outer periphery of the sample stage 33. Therefore, the sample placed on the center of the opening 63a can be moved to an arbitrary position within the range B indicated by the oblique lines on the observation window 39.

  The interval x between the arrow A12 and the arrow A13 coincides with the eccentric range of the eccentric cam 73, and the width of the range B in the direction of the arrow A11 can be changed by changing the eccentric range. . The range B is set so as to include the field of view of the objective lens 40 near the center of the observation window 39.

  As described above, in the observation apparatus 11, the position of the sample in the dish 2 placed on the turret 12 is adjusted by the pinion gear 71, the eccentric cam 73, and the rotating body 77 without moving the sample stage 33. can do. Therefore, it is not necessary to provide an opening for moving the turret 12 or the sample stage 33 in the sample stage 33, and the seal structure between the casing 31 and the sample stage 33 is a simple structure using only a ring-shaped seal. It can be realized with a configuration.

  As a result, the sealing property of the sample table 33 and the sealing property of the observation chamber 34 are improved. For example, a liquid such as a culture solution is spilled on the sample table 33 or the sample table 33 is charged with hydrogen peroxide gas or the like. Even if sterilization or sterilization is performed, the liquid or gas is prevented from leaking into the observation chamber 34. Further, since the seal structure is simplified, the durability of the seal portion is improved.

  Furthermore, in the observation apparatus 11, the turret 12 can be easily attached to and detached from the sample stage 33, and the portion of the sample stage 33 where the turret 12 is installed does not have an opening or an uneven part, so that maintenance properties such as cleaning are improved.

  Moreover, in the observation apparatus 11, the structure of the drive system which drives the turret 12 can be simplified, and the freedom degree of arrangement | positioning of the optical system in the observation chamber 34 improves. Furthermore, the observation apparatus 11 can be reduced in size.

<2. Modification>
[Configuration example of culture observation system]
FIG. 8 is a diagram schematically showing a configuration example of a culture observation system 201 using the observation system 1 of FIG.

  The culture observation system 201 is configured by installing an incubator 211 in the observation system 1 of FIG.

  The casing 221 of the incubator 211 can be attached to and detached from the upper surface of the sample stage 33 of the observation apparatus 11, and is sealed by the sample stage 33 and the casing 221 with the casing 221 placed on the upper surface of the sample stage 33. A culture chamber 222 which is a space is formed.

  A mesh shelf 223 is provided at a position higher than the illumination optical system 37 in the housing 221. On the mesh shelf 223, a container 224 containing a carbon dioxide generating agent 225 for keeping the concentration of carbon dioxide in the culture chamber 222 at a predetermined concentration is installed. Further, a container 226 containing humidified water 227 for adjusting the humidity in the culture chamber 222 is installed on the mesh shelf 223.

  Further, a temperature / humidity sensor 228 is provided at a predetermined position higher than the mesh shelf 223 in the housing 221. The temperature / humidity sensor 228 measures the temperature and humidity in the culture chamber 222 and supplies a signal indicating the measurement result to the temperature / humidity control unit 229 provided outside the culture chamber 222.

  Further, a heater 230 is provided on the ceiling of the housing 221. The temperature / humidity control unit 229 turns on or off the heater 230 based on the temperature and humidity of the culture chamber 222 measured by the temperature / humidity sensor 228, and changes the atmosphere in the culture chamber 222 to a predetermined level suitable for cell culture. Control is performed so as to maintain the conditions (for example, the temperature is 37 ° C. and the humidity is 95 to 100%).

  As described above, since the sample table 33 has high sealing performance, the atmosphere in the culture chamber 222 is maintained at a predetermined condition, and the atmosphere in the culture chamber 222 leaks into the observation chamber 34, and the components in the observation chamber 34 Is prevented from being damaged.

  A carbon dioxide cylinder or the like can be used instead of the carbon dioxide generating agent 225.

[Other variations]
As described above, since the observation chamber 34 has excellent sealing properties, for example, the observation apparatus 11 can be installed in a commercially available incubator apparatus to perform cell culture observation.

  In the above description, the example in which the turret 12 is installed on the sample stage 33 has been shown. However, as described above, there is no opening or uneven portion at the position where the turret of the sample stage 33 is installed. Other containers can be installed freely. For example, as shown in FIG. 9, a flask 251 containing a sample can be installed. FIG. 9 shows an example in which carrying handles 252 a and 252 b are provided on the sample stage 33.

  Furthermore, the shape of the outer periphery of the turret 12 is not necessarily circular. For example, when the movement range (rotatable angle) of the rotation direction of the turret 12 is limited, a range in which the pinion gear 71, the eccentric cam 73, and the rotating body 77 may be in contact with each other on the outer periphery of the turret 12. Only a part including the arc may be an arc.

  In the above description, an example in which the mechanism for driving the turret 12 in the rotational direction is realized by the combination of the gear portion 62 (super gear) and the pinion gear 71 is described, but other mechanisms may be used.

  Furthermore, the shape of the sample stage 33 is not necessarily circular, and can be set to an arbitrary shape such as a rectangle. However, in the case of a circular shape, an O-ring or the like can be used for the seal 35 between the housing 31 and the sample stage 33, and the sealing performance of the observation chamber 34 can be easily improved.

  In the above description, an example in which the rotation shaft 47A for rotating the pinion gear 71 and the rotation shaft 48A for rotating the eccentric cam 73 are driven by the motor has been described. However, one or both of them may be driven manually. Is also possible. In other words, at least one of the pinion gear 71 and the eccentric cam 73 can be manually rotated.

  Further, the arrangement of the pinion gear 71, the eccentric cam 73, and the rotating body 77 is ideal in the example shown in FIG. 2, but is not necessarily limited to this example. What is necessary is just to arrange | position so that the center 12A of the turret 12 may be located inside the cam 73 and the triangle which connects each contact point of the rotary body 77 and the turret 12. In consideration of the arrangement of the optical system, it is desirable to dispose the pinion gear 71 (θ motor 47) and the eccentric cam 73 (R motor 48) away from the observation window 39.

  In the above description, the illumination optical system 37 is provided on the sample stage 33 and the imaging optical system is provided below the sample stage 33 (inside the observation chamber 34). It is also possible to reverse the arrangement of the image optical system.

  Further, the light source may be provided in the observation chamber 34 without being provided in the illumination optical system 37, and the sample may be irradiated with illumination light via the illumination stand 36 and the illumination optical system 37.

  In this specification, the term “system” refers to an overall apparatus composed of a plurality of apparatuses and means.

  The embodiments of the present invention are not limited to the above-described embodiments, and various modifications can be made without departing from the scope of the present invention.

  DESCRIPTION OF SYMBOLS 1 Observation system, 2 Dish, 11 Observation apparatus, 12 Turret, 13 Personal computer, 31 Case, 33 Sample stand, 34 Observation room, 35 Seal, 36 Illumination stand, 37 Illumination optical system, 38 Seal, 39 Observation window, 40 Objective lens, 42 imaging lens, 43 camera, 47 θ motor, 47A rotating shaft, 48R motor, 48A rotating shaft, 61 cylindrical section, 62 gear section, 63 opening section, 71 pinion gear, 72 seal, 73 eccentric cam , 74 seal, 75 bias lever mechanism, 75A shaft, 75B bias lever, 76 rotating shaft, 77 rotating body, 201 observation culture system, 211 incubator, 221 housing, 222 culture chamber, 228 temperature / humidity sensor, 229 temperature / humidity control , 230 heater

Claims (6)

An imaging optical system that forms an image of the observation sample;
A housing containing the imaging optical system and having a window on the upper surface through which a light beam condensed by the imaging optical system can pass;
A table provided on the upper surface of the housing so as to cover a position where the window is provided, and at least a part of the outer periphery is an arc, and a table on which the observation sample is placed;
A circular shape that is provided on the upper surface of the housing and is in contact with the arc of the table and is rotatable about a first rotation axis that is set in a direction perpendicular to the surface of the table on which the observation sample is placed. A rotating member of
An eccentric cam provided on the upper surface of the housing, in contact with the arc of the table at a position different from the rotating member, and rotatable about a second rotation axis parallel to the first rotation axis;
An urging member provided on an upper surface of the housing and in contact with the arc of the table so as to push the table toward the rotating member or the eccentric cam at a position different from the rotating member and the eccentric cam; An observation apparatus comprising: At least one of the first rotating shaft and the second rotating shaft is driven by a motor,
The observation apparatus according to claim 1, wherein the motor is provided in a space sealed by the housing. The observation apparatus according to claim 2, wherein an upper surface of the housing and a side surface of the housing are joined via a ring-shaped seal. The rotating member is constituted by a gear,
The observation apparatus according to claim 1, wherein a portion of the outer peripheral side surface of the table that is in contact with the rotating member is configured by a gear corresponding to the rotating member. The rotating member, the eccentric cam, and the rotating member, the eccentric so that the center of the arc of the table is positioned inside a triangle connecting each contact point between the biasing member and the arc of the table. An observation device in which the lead cam and the biasing member are arranged. The observation apparatus according to claim 1, further comprising an incubator that is detachable from an upper surface of the casing and maintains an atmosphere in a space above the casing under a predetermined condition.

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