Shaking device and incubation system

Abstract

Shaking conditions can be easily adjusted and changed. [Solution] A shaking device 10 is provided, which comprises a shaking table 11 having a mounting surface 11a on which a culture vessel containing a culture solution containing a culture object is placed, and a shaking mechanism 30 which shakes the shaking table in a plane parallel to the mounting surface, the shaking mechanism comprising a guide member 31 which supports the shaking table movably along a first axis (X-axis) and a second axis (Y-axis) which intersect each other in the plane parallel to the mounting surface, a drive belt 32 which moves the shaking table along the first axis and the second axis, and a drive unit 33 which drives the drive belt, and the drive unit drives the drive belt while independently controlling the movement of the shaking table along the first axis and the movement of the shaking table along the second axis.

Description

[Technical field]

[0001] The present invention relates to a shaking device and a culture system. [Background technology]

[0002] As one method for culturing a culture target such as a microorganism such as bacteria or a cell, a method of culturing while shaking (shaking) a culture solution containing the culture target is known. Specifically, a shaking device is used that shakes a culture vessel such as a flask containing a culture solution containing the culture target under certain culture conditions using a shaking table. By shaking the culture vessel, for example, oxygen, enzymes, etc. can be introduced into the culture solution and the culture solution can be effectively stirred, so that it is possible to promote the proliferation (growth) of the culture target.

[0003] As this type of shaking device, for example, Patent Document 1 listed below discloses a shaking device capable of smoothly rotating a shaking table at high speed (see Patent Document 1). This shaking device comprises a main housing including a fixed shaft body that is driven to rotate by a motor, an eccentric housing including an eccentric shaft body that is arranged eccentrically with respect to the fixed shaft body and connected to the main housing, a shaking table connected to the eccentric shaft body, and a rotation restriction mechanism that restricts the rotation of the shaking table. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2004-290084 A Summary of the Invention [Problem to be solved by the invention]

[0005] According to the conventional shaking device, the shaking table can be rotated (revolved) via the eccentric shaft by rotating the main housing including the fixed shaft, while the rotation of the shaking table is restricted by the rotation restricting mechanism. Therefore, the culture vessel set on the shaking table can be stably rotated and shaken. However, conventional shaking devices can only periodically perform the same operation of rotating the shaking table using the eccentric rotation mechanism (main housing and eccentric housing).When culturing a culture object, there is a need to appropriately adjust or change the shaking conditions, taking into consideration various conditions such as the type of culture object and culture solution, the purpose of culture, use, and progress of culture. In this regard, the above-mentioned conventional shaking device is limited to a specific movement of rotating the shaking table, and therefore cannot fully meet such needs, and there is room for improvement.

[0006] The present invention has been made in consideration of the above circumstances, and an object of the present invention is to provide a shaking device that allows shaking conditions to be easily adjusted and changed, and a culture system equipped with the shaking device. [Means for solving the problem]

[0007] (1) A shaking device according to the present invention includes a shaking table having a support surface on which a culture vessel containing a culture solution containing a culture target is placed, and a shaking mechanism for shaking the shaking table in a plane parallel to the support surface, the shaking mechanism including: a guide member for supporting the shaking table movably along a first axis and a second axis intersecting each other in a plane parallel to the support surface; a drive belt for moving the shaking table along the first axis and the second axis; and a drive unit for driving the drive belt, the drive unit driving the drive belt while independently controlling the movement of the shaking table along the first axis and the movement of the shaking table along the second axis. The guide member includes a fixed base, a movable base disposed above the fixed base and below the shaking base, a first guide member disposed between the fixed base and the movable base and supporting the movable base movably along the first axis relative to the fixed base, and a second guide member disposed between the movable base and the shaking base and supporting the shaking base movably along the second axis relative to the movable base, and the drive belt is continuously stretched across each of the fixed base, the movable base, and the shaking base. It is characterized by:

[0008] According to the shaking device of the present invention, the shaking table is supported by the guide member so as to be movable along a first axis and a second axis that intersect each other in a plane (horizontal plane) parallel to the mounting surface. As a result, by driving the drive belt by the drive unit, the shaking table can be moved along the first axis and the second axis while being guided by the guide member. Therefore, the shaking table can be periodically moved and shaken using the drive belt. Therefore, the culture solution contained in the culture vessel can be stirred, and the culture can be promoted.

[0009] In particular, the drive unit drives the drive belt while independently controlling the movement of the shaking table on the first and second axes, so that the shaking table can be shaken in various shaking patterns. For example, it is possible to shake the shaking table in a shaking pattern in which the shaking table is moved linearly along the first or second axis, or in a shaking pattern in which the shaking table is moved in a circular or elliptical motion by combining movements along the first and second axes. It is also possible to shake the shaking table in a shaking pattern in which a semicircular motion is repeated back and forth, or in a shaking pattern in which a figure of eight is drawn. In particular, a motion that purposely shifts the natural frequency of the culture vessel can be generated by continuous motion with a complex orbit. This makes it possible to make the liquid surface more disturbed, and it is expected that air and the like can be efficiently taken into the culture liquid. Furthermore, since adjustment is possible on two axes (X axis, Y axis), even when a different culture vessel is used, it is possible to change the shaking conditions to match the culture vessel to be used.

[0010] Therefore, the shaking table can be shaken in a fine and diverse shaking pattern, instead of the conventional shaking pattern limited to a specific movement. Therefore, the shaking conditions can be easily adjusted and changed according to the situation, etc., and the culture solution in the culture vessel can be stirred in the optimal state each time. In particular, shaking can be performed that gives the culture solution a stimulus with varying intensity, rather than a constant stimulus. Therefore, optimal culture can be performed according to the culture object and culture solution, etc.

[0012] moreover Since the drive belt is continuously stretched over each of the fixed table, the movable table, and the shaking table, by driving the drive belt, for example, the movable table supported by the first guide member can be moved relative to the fixed table, and the entire movable table and the shaking table can be moved along the first axis. Furthermore, by driving the drive belt, for example, the shaking table supported by the second guide member can be moved relative to the movable table, and the shaking table can be moved along the second axis. Furthermore, by driving the drive belt, for example, the shaking table can be moved relative to the movable table while moving the movable table relative to the fixed table, and the shaking table can be moved along the first axis and the second axis. In this way, the shaking table can be shaken in a fine and diverse shaking pattern using one drive belt (endless belt).

[0013] ( 2 ) The drive unit may include a first drive motor having a first drive pulley around which the drive belt is wound and provided on the fixed base, a second drive motor having a second drive pulley around which the drive belt is wound and provided on the fixed base, and a motor control unit that controls the drive of the first drive motor and the second drive motor, and rotates the first drive pulley and the second drive pulley in forward and reverse directions, respectively.

[0014] In this case, the motor control unit is used to control the rotation of the two drive motors, the first drive motor and the second drive motor, so that the drive pattern of the drive belt can be freely adjusted via the first drive pulley and the second drive pulley. Specifically, the drive pattern of the drive belt can be freely adjusted by controlling the rotation direction, rotation speed, rotation timing, etc. of the first drive motor and the second drive motor, so that the shaking table can be shaken in various shaking patterns in a plane parallel to the mounting surface. In particular, since the rotation of the first drive motor and the second drive motor is only controlled, it is easy to appropriately shake the shaking table in a desired shaking pattern.

[0015] ( 3) The culture system of the present invention comprises the shaking device, a first measuring device that measures the turbidity of the culture solution, and a control unit that controls the driving unit, and is characterized in that the control unit feedback-controls the driving unit so as to change the shaking conditions of the shaking table based on a first measurement result from the first measuring device.

[0016] According to the culture system of the present invention, in the process of culturing the culture solution while shaking the culture vessel using the shaking device, the turbidity of the culture solution can be measured using the first measurement device. This allows the control unit to grasp the culture state of the culture solution containing the culture subject based on the first measurement result (turbidity of the culture solution). Therefore, the control unit can grasp whether the culture has been properly completed by the shaking device or whether the culture is insufficient. Then, when the control unit determines that the culture is insufficient, for example, it feedback controls the drive unit to change the shaking conditions of the shaking table. This allows the culture to be promoted while shaking the culture vessel with different shaking patterns, and reliable culture can be efficiently performed.

[0017] ( 4 ) A second measuring device that measures a culture state of a culture object contained in the culture solution, and the control unit may feedback-control the drive unit so as to change the shaking conditions of the shaking table based on a second measurement result from the second measuring device.

[0018] In this case, the culture state of the culture object can be measured using the second measurement device, so the control unit can grasp the culture state of, for example, proteins or bacteria based on the second measurement result, and can grasp whether the desired number or amount has been obtained. If the control unit determines that the production of the culture object is insufficient, for example, it feedback controls the drive unit to change the shaking conditions of the shaking table. This makes it possible to promote culture by shaking the culture vessel with different shaking patterns, and to obtain the culture object efficiently and appropriately.

[0019] ( 5) The second measurement device may measure the fluorescence intensity of the fluorescence emitted by the culture object.

[0020] In this case, the second measuring device measures the fluorescence intensity from the culture object, and the control unit can grasp that a certain amount of the culture object has been produced by culture and expressed by various expression systems, etc. This is particularly effective when the culture object is a protein that emits fluorescence.

[0021] ( 6 ) The culture vessel is placed on the placement surface and includes a container holding section that holds the culture vessel, a thermoelectric element that is provided on the container holding section and that heats and cools the culture vessel, and a temperature control section that controls the thermoelectric element, and the control section may feedback control the temperature control section so as to change the temperature conditions for heating and cooling by the thermoelectric element based on a first measurement result from the first measurement device.

[0022] In this case, the culture vessel can be held against the mounting surface of the shaking table by using the vessel holder, and the culture can be performed stably. In particular, since the vessel holder is provided with a thermoelectric element, the culture liquid can be heated, cooled, etc. by controlling the thermoelectric element with the temperature control unit. Therefore, for example, the culture can be performed under a constant temperature condition, or the culture liquid can be rapidly cooled after reaching a certain turbidity to promote the expression of the culture target (e.g., protein). Furthermore, when the control unit determines that the culture is insufficient based on the first measurement result (turbidity of the culture solution) from the first measurement device, the control unit can feedback control the temperature control unit so that the culture is performed under different temperature conditions, which can lead to the promotion of the culture. Effect of the Invention

[0023] According to the present invention, the shaking conditions can be easily adjusted and changed. [Brief description of the drawings]

[0024] [Figure 1]FIG. 1 is a perspective view showing an embodiment of a culture system according to the present invention. [Diagram 2] FIG. 2 is a front view of the culture system shown in FIG. 1. [Diagram 3] FIG. 2 is a perspective view of the shaking device shown in FIG. [Figure 4] FIG. 4 is a top view of the shaking device shown in FIG. [Diagram 5] FIG. 5 is a perspective view of the shaking device shown in FIG. [Figure 6] 4 is a cross-sectional view of the shaking device taken along the line AA of FIG. 3. [Figure 7] FIG. 2 is a perspective view of the shaking table, the heat sink, and the surrounding area shown in FIG. [Figure 8] 8 is a perspective view showing a state in which the heat transfer member is removed from the state shown in FIG. 7. FIG. [Figure 9] 2 is a perspective view of the periphery of a heat sink, a container holding portion, and a measurement unit shown in FIG. 1. [Figure 10] 10 is a perspective view of the heat sink and the periphery of the container holding portion shown in FIG. 9. [Figure 11] 11 is a perspective view showing a state in which the culture vessel and the pressing member are removed from the state shown in FIG. 10. FIG. [Figure 12] 12 is a perspective view showing a state in which a thermally conductive sheet is removed from the state shown in FIG. 11. FIG. [Figure 13] FIG. 2 is a perspective view of the measurement unit shown in FIG. [Figure 14] 14 is a cross-sectional view showing the relationship between the measurement unit and the culture vessel shown in FIG. 13. [Figure 15] 4 is an example of an image (scattered light image, fluorescent image) captured by a dual-purpose image capturing section. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Hereinafter, embodiments of a shaking device and a culture system according to the present invention will be described with reference to the drawings. In the culture system of this embodiment, a target production substance (hereinafter simply referred to as the target substance) will be used as an example of the culture object, and the turbidity of the culture medium in which the target substance is expressed and the fluorescence intensity of the target substance will be measured simultaneously.

[0026] As shown in Figures 1 and 2, the culture system 1 of this embodiment has a shaking table 11 on which a culture vessel 2 containing a culture solution W containing a target substance is placed, and is equipped with a shaking device 10 that shakes (shakes) the culture vessel 2, a container holding unit 12 that holds the culture vessel 2 against the shaking table 11, a first measuring device 13 that measures the turbidity of the culture solution W, a second measuring device 14 that measures the culture state of the target substance contained in the culture solution W, and a control unit 15 that comprehensively controls each of these devices.

[0027] The target production substance means a substance produced by a microorganism through a process such as fermentation or metabolism, and includes, for example, proteins, organic compounds produced by fermentation of lactic acid bacteria, peptides, etc. In this embodiment, a protein is assumed as the target production substance. Therefore, the culture system 1 is assumed to be a protein culture system capable of simultaneously measuring the turbidity of the culture solution W in which the protein is expressed and the fluorescence intensity of the protein.

[0028] The culture solution W in which the target substance is expressed is contained in the culture vessel 2. The culture vessel 2 is shaken under predetermined culture conditions by a shaking device 10 constituting the culture system 1. As a result, the culture solution W increases in turbidity as the culture progresses within the culture vessel 2. The culture system 1 measures the turbidity of the culture solution W to grasp the progress of the culture (culture state), and also measures the fluorescence intensity of the target substance to grasp that a certain amount of the target substance has been obtained.

[0029] In this embodiment, a glass Erlenmeyer flask is used as the culture vessel 2. Therefore, the culture vessel 2 has a flat bottom 3 and a conical side wall 4. The connection portion between the bottom 3 and the side wall 4 is an annular curved surface portion 5 that extends continuously around the entire circumference of the bottom 3. However, the culture vessel 2 is not limited to an Erlenmeyer flask, and various flasks such as an eggplant-shaped flask, a round-bottom flask, a shake flask, etc. may be used as the culture vessel 2. Furthermore, a test tube, a petri dish, etc., or a cylindrical vessel such as a beaker may be used as the culture vessel 2.

[0030] Depending on the shape of the culture vessel used, the state of splashing and stirring of the culture solution W during shaking differs. Therefore, the shaking conditions may be changed for each type of culture vessel so as to provide optimal shaking conditions suitable for the culture vessel used. Specifically, this can be realized by controlling the first drive motor 80 and the second drive motor 82 by the motor control unit 84 described later so as to shake the shaking table 11 under shaking conditions corresponding to the culture vessel used. In this way, it is possible to perform shaking under shaking conditions corresponding to the culture vessel, rather than simply transferring the culture vessel to the shaking table 11.

[0031] Furthermore, in this embodiment, an example will be described in which Escherichia coli is used as a host cell, an expression vector whose expression is induced depending on temperature is used, and the target substance is expressed by the technique of the Escherichia coli cold shock expression system. Therefore, the culture solution W contains E. coli transformed with an expression vector (an expression vector containing a target gene that encodes a target substance).

[0032] Furthermore, the expression vector contains a specific promoter including the E. coli cold shock gene, the expression of which is induced when the culture temperature of E. coli is low (e.g., 15°C). Specifically, the lactose operon (lac I, Lac operator) is contained as a specific promoter. The lactose operon controls the expression of the promoter of the E. coli cold shock gene. It is possible to express the promoter of the E. coli cold shock gene by deregulating the lactose operon with a reagent (expression inducer) such as IPTG (Isopropyl-β-D-thiogalactopyranoside). However, a specific promoter such as the lactose operon is not essential and does not have to be included in the expression vector.

[0033] <Shaking device> As shown in FIGS. 1 to 5, the shaking device 10 includes a shaking table 11 having a mounting surface 11a on which the culture vessel 2 is mounted, and a shaking mechanism 30 for shaking the shaking table 11. The culture vessel 2 may be placed directly on the support surface 11a of the shaking table 11, but in this embodiment, the culture vessel 2 is indirectly placed on the support surface 11a via the heat sink 16 and the vessel holding portion 12.

[0034] 1, two directions that intersect perpendicularly to each other in a plane (horizontal plane) parallel to the mounting surface 11a of the shaking table 11 are defined as the X-axis (first axis) and the Y-axis (second axis). Furthermore, the direction along the X-axis is defined as the front-rear direction L1, and the direction along the Y-axis is defined as the left-right direction L2. Furthermore, an axis passing through the center of the shaking table 11 from top to bottom is defined as a central axis O. Furthermore, in a plan view seen from the top to bottom direction, a direction intersecting the central axis O is defined as a radial direction, and a direction rotating around the central axis O is defined as a circumferential direction. Furthermore, in the front-rear direction L1, the direction from the central axis O toward a first drive motor 80 and a second drive motor 82 (described later) is defined as the forward direction FW, and the opposite direction is defined as the rearward direction BK.

[0035] (Shaking table) 3 to 5, the shaking table 11 is formed in a plate shape having a certain thickness in the up-down direction, and is formed in a rectangular shape in a plan view that is longer in the front-rear direction L1 than in the left-right direction L2. However, the shape of the shaking table 11 is not limited to this case, and may be formed in a rectangular shape in a plan view that is longer in the left-right direction L2 than in the front-rear direction L1, or may be formed in a square shape in a plan view.

[0036] A connecting piece 20 to which a drive belt 32 (described later) is connected is fixed integrally to the shaking table 11. The connecting piece 20 is formed in an L-shape when viewed from the side, that is, a so-called L-angle. The connecting piece 20 is fixed to the shaking table 11 so as to contact the mounting surface 11a of the shaking table 11 from above, and to contact the front side surface of the shaking table 11 facing the forward FW from the forward FW. 5, a grooved plate 21 having a plurality of grooves formed therein is fixed to the front surface of the connecting piece 20 facing the forward direction FW. The grooved plate 21 has a plurality of grooves formed therein that are elongated in the up-down direction and spaced apart in the left-right direction L2. These grooves correspond to a plurality of grooves and protrusions (not shown) formed in the drive belt 32.

[0037] (Shaking mechanism) As shown in FIGS. 3 to 5, the shaking mechanism 30 shakes the shaking table 11 configured as described above in a plane parallel to the placement surface 11a. The shaking mechanism 30 includes a guide member 31 that supports the shaking table 11 movably along the X-axis and the Y-axis, a drive belt 32 that moves the shaking table 11 along the X-axis and the Y-axis, and a drive unit 33 that drives the drive belt 32. Note that the drive belt 32 is not shown in FIG. 5.

[0038] (Guide member) The guide member 31 comprises a fixed base 40, a movable base 50 arranged above the fixed base 40 and below the shaking base 11, a first guide member 60 arranged between the fixed base 40 and the movable base 50 and supporting the movable base 50 so as to be movable along the X-axis relative to the fixed base 40, and a second guide member 70 arranged between the movable base 50 and the shaking base 11 and supporting the shaking base 11 so as to be movable along the Y-axis relative to the movable base 50.

[0039] The fixed base 40 includes a first fixed plate 41 having a constant thickness in the vertical direction, and a pair of second fixed plates 42 fixed to the first fixed plate 41 while overlapping the first fixed plate 41. The fixed base 40 functions as a base base for each component that constitutes the shaking device 10.

[0040] The first fixing plate 41 is formed in a square shape in a plan view, and is formed to have a sufficient length along the front-rear direction L1 and the left-right direction L2. The shape of the first fixing plate 41 is not limited to a square shape in a plan view, and may be changed as appropriate. The first fixing plate 41 may be formed in the shape of a single plate, or may be formed by combining multiple divided plates.

[0041] Support columns 43 extending downward are fixed to the four corners of the first fixing plate 41. This allows the entire shaking device 10 to be stably installed on the installation surface using the support columns 43. As shown in Fig. 1, the shaking device 10 has an exterior cover 17 that surrounds each component, including the fixed base 40, the support 43, and the shaking table 11, from the outside. As a result, each component, including the fixed base 40, the support 43, and the shaking table 11, is concealed from the outside by being covered by the exterior cover 17. Note that the exterior cover 17 is not shown in Fig. 2.

[0042] 3 to 5, the pair of second fixing plates 42 are thicker than the first fixing plate 41 and are formed into a rectangular shape in a plan view that is longer in the front-rear direction L1 than in the left-right direction L2. Specifically, each of the pair of second fixing plates 42 has a constant width along the left-right direction L2 and is formed long along the front-rear direction L1 so as to cover the first fixing plate 41 from above over its entire length. The pair of second fixing plates 42 are disposed on both the left and right sides of the first fixing plate 41. As a result, the pair of second fixing plates 42 are disposed so as to be parallel to each other with a gap therebetween in the left-right direction L2.

[0043] Support plates 44 that support a first drive motor 80 and a second drive motor 82, which will be described later, are fixed to the front ends of the pair of second fixed plates 42. The support plates 44 have the same thickness as the second fixed plate 42, and are disposed so as to overlap the upper surfaces of the second fixed plates 42. Furthermore, the support plates 44 are formed so as to protrude forward FW beyond the second fixed plate 42. The support plate 44 has a through hole 45 that is circular in plan view and penetrates the support plate 44 from top to bottom. The support plate 44 also has a guide groove 46 that opens toward the rear BK and upward.

[0044] Furthermore, a front connecting plate 47 and a rear connecting plate 48 that connect the second fixed plates 42 to each other in the left-right direction L2 are fixed to the pair of second fixed plates 42. Each of the front connecting plate 47 and the rear connecting plate 48 has a thickness equivalent to that of the second fixed plate 42, and is formed into a rectangular shape in a plan view that is longer in the left-right direction L2 than in the front-rear direction L1. The front connecting plate 47 is disposed so as to overlap the upper surfaces of the front ends of the pair of second fixed plates 42, and connects the second fixed plates 42 to each other in the left-right direction L2. The front connecting plate 47 is disposed so as to be located rearward BK of the support plate 44. The rear connecting plate 48 is disposed so as to overlap the upper surfaces of the rear ends of the pair of second fixed plates 42, and connects the second fixed plates 42 to each other in the left-right direction L2.

[0045] The movable base 50 includes a pair of first movable plates 51 arranged to overlap the pair of second fixed plates 42 from above, and a second movable plate 52 connecting the pair of first movable plates 51 in the left-right direction L2. In the illustrated example, the movable base 50 is formed as a single plate in which a pair of a first movable plate 51 and a second movable plate 52 are integrated together. However, this is not limited to this case, and the pair of the first movable plate 51 and the second movable plate 52 may be formed separately and then combined together to form the movable base 50.

[0046] Each of the pair of first movable plates 51 has a thickness equivalent to that of the second fixed plate 42, and is formed into a rectangular shape in a plan view that is longer in the front-rear direction L1 than in the left-right direction L2. The first movable plate 51 is formed so that the width along the left-right direction L2 is smaller than the width of the second fixed plate 42, and the length along the front-rear direction L1 is smaller than the length of the second fixed plate 42. The pair of first movable plates 51 are disposed above the pair of second fixed plates 42, and are disposed parallel to each other with a gap therebetween in the left-right direction L2. The pair of first movable plates 51 are disposed outboard of the front connecting plate 47 in the left-right direction L2, and disposed rearward BK of the support plate 44. Furthermore, the pair of first movable plates 51 are disposed inside the guide groove 46 formed in the support plate 44 so as to be able to enter from the rear BK.

[0047] The second movable plate 52 has a thickness equivalent to that of the pair of first movable plates 51, and is formed in a rectangular shape in a plan view that is longer in the left-right direction L2 than in the front-rear direction L1. The second movable plate 52 is formed so that the length in the front-rear direction L1 is smaller than the length of the first movable plate 51, and is formed so as to be shifted rearward BK side from the front end of the first movable plate 51. A through hole 53 is formed in the center of the second movable plate 52, penetrating the second movable plate 52 in the up-down direction. The through hole 53 is formed in a rectangular shape in a plan view that is longer in the left-right direction L2 than in the front-rear direction L1 in accordance with the shape of the second movable plate 52, and mainly functions as a lightening hole. Therefore, the through hole 53 is not essential and may not be provided.

[0048] A first guide member 60 is provided between the fixed base 40 and the movable base 50 configured as described above. The first guide member 60 comprises a pair of first guide rails 61 fixed respectively to the upper surfaces of the pair of second fixed plates 42, and a first movable block 62 fixed respectively to the lower surfaces of the pair of first movable plates 51.

[0049] The pair of first guide rails 61 are fixed to the upper surface of the second fixed plate 42 so as to be located below the pair of first movable plates 51, respectively. The pair of first guide rails 61 are formed to extend along the front-rear direction L1, and are formed to be longer in the front-rear direction L1 than the first movable plates 51. The pair of first guide rails 61 are arranged at an interval in the left-right direction L2 and arranged parallel to each other. Furthermore, a guide groove that is recessed inward and extends along the front-rear direction L1 is formed on the side surface of the first guide rail 61 facing the left-right direction L2.

[0050] The first movable block 62 is assembled from above to the first guide rail 61 so as to be relatively movable in the front-rear direction L1 along the guide groove. The first movable block 62 is assembled to the first guide rail 61 in a state in which it is prevented from coming off upward, and is assembled in a state in which it has high slidability. A plurality of (two) first movable blocks 62 are attached to each of the pair of first movable plates 51 at intervals in the front-rear direction L1.

[0051] The first guide member 60 having the first guide rail 61 and the first movable block 62 is provided between the second fixed plate 42 and the first movable plate 51, so that the movable base 50 can be moved smoothly along the front-rear direction L1 (X-axis) relative to the fixed base 40. Therefore, the first guide member 60 functions as a linear guide mechanism that realizes smooth linear movement of the movable base 50 along the front-rear direction L1. Note that the first movable block 62 may be configured so that a plurality of balls (rolling bodies) are circulated and the balls circulate along the guide groove of the first guide rail 61. In this case, the first guide member 60 can function as a so-called linear guide, and the movable base 50 can be moved more smoothly with less resistance relative to the fixed base 40.

[0052] As shown in FIGS. 3 to 6, a second guide member 70 is provided between the movable table 50 and the shaking table 11. The second guide member 70 includes a pair of second guide rails 71 fixed to the upper surface of the second movable plate 52, and a pair of second movable blocks 72 fixed to the lower surface of the shaking table 11.

[0053] The pair of second guide rails 71 are formed to extend along the left-right direction L2, and are formed to be longer in the left-right direction L2 than the shaking table 11. The pair of second guide rails 71 are arranged at an interval in the front-rear direction L1 and are arranged parallel to each other so as to sandwich the through hole 53 therebetween. Furthermore, a guide groove that is recessed inward and extends along the left-right direction L2 is formed on the side surface of the second guide rail 71 facing the front-rear direction L1.

[0054] The second movable block 72 is assembled from above to the second guide rail 71 so as to be relatively movable in the left-right direction L2 along the guide groove. The second movable block 72 is assembled to the second guide rail 71 in a state in which it is prevented from coming off upward, and is assembled in a state in which it has high slidability. The second movable blocks 72 are attached to the underside of the shaking table 11 on the front FW side and the underside of the rear BK side, and a plurality of (two) second movable blocks 72 are attached at intervals in the left-right direction L2.

[0055] A second guide member 70 having a second guide rail 71 and a second movable block 72 is provided between the second movable plate 52 and the shaking table 11, so that the shaking table 11 can be moved smoothly along the left-right direction L2 (Y-axis) relative to the movable table 50. Therefore, the second guide member 70 functions as a linear guide mechanism that realizes smooth linear movement of the shaking table 11 along the left-right direction L2. The second movable block 72 may also be configured so that a plurality of balls (rolling bodies) are circulated along the guide groove 46 of the second guide rail 71. In this case, the second guide member 70 can function as a so-called linear guide, and the shaking table 11 can be moved more smoothly with less resistance relative to the movable table 50.

[0056] (Drive belt, drive unit) 3 to 5, the drive belt 32 is continuously stretched across the fixed table 40, the movable table 50, and the shaking table 11 configured as described above. The drive unit 33 drives the drive belt 32 while independently controlling the movement of the shaking table 11 in the front-rear direction L1 along the X axis and the movement of the shaking table 11 in the left-right direction L2 along the Y axis.

[0057] The drive unit 33 includes a first drive motor 80 having a first drive pulley 81 around which the drive belt 32 is wound and is mounted on the fixed base 40, a second drive motor 82 having a second drive pulley 83 around which the drive belt 32 is wound and is mounted on the fixed base 40, and a motor control unit 84 that controls the drive of the first drive motor 80 and the second drive motor 82, respectively, and controls the rotation of the first drive pulley 81 and the second drive pulley 83, respectively.

[0058] The first drive motor 80 and the second drive motor 82 are fixed to the lower surface of the support plate 44 that constitutes the fixed base 40. Specifically, the first drive motor 80 and the second drive motor 82 are fixed to the lower surface of the support plate 44 with their output shafts (not shown) facing upward. The output shafts pass through insertion holes 45 formed in the support plate 44, and protrude upward from the support plate 44. The first drive pulley 81 and the second drive pulley 83 are connected to the output shaft of the first drive motor 80 and the output shaft of the second drive motor 82. This allows the first drive pulley 81 and the second drive pulley 83 to rotate in accordance with the drive of the first drive motor 80 and the second drive motor 82.

[0059] The first drive motor 80 and the second drive motor 82 are not limited to specific motors, but are, for example, stepping motors whose rotation angle, rotation speed, rotation direction, etc. can be controlled by pulse signals.

[0060] The motor control unit 84 outputs pulse signals, which are electrical signals, to each of the first drive motor 80 and the second drive motor 82, thereby digitally controlling the output shafts to rotate at a predetermined rotation angle, rotation speed, and rotation direction. The motor control unit 84 is mounted on, for example, the control board 18 shown in Fig. 1. The control board 18 is supported by a support member (not shown) while being disposed below the fixed base 40. Furthermore, the control board 18 also has a control unit 15 mounted thereon, which performs overall control of the entire culture system 1 including the shaking device 10. The operation of the motor control unit 84 is controlled by the control unit 15. The control board 18 is not shown in Fig. 2.

[0061] The drive belt 32 is a band-shaped endless belt that is continuously wound around a plurality of pulleys including a first drive pulley 81 and a second drive pulley 83. The material, type, etc. of the drive belt 32 are not particularly limited, but it is preferable that the drive belt 32 is a belt that has excellent resistance to lateral pressure, flexibility, and a high coefficient of friction. Furthermore, in this embodiment, the drive belt 32 is a grooved belt having grooves and protrusions (not shown) formed continuously and alternately over the entire length on the main surface that contacts the multiple pulleys. However, this is not limited to this case, and the drive belt 32 may be, for example, a flat belt without grooves.

[0062] The pulleys other than the first driving pulley 81 and the second driving pulley 83 will be described. In this embodiment, the plurality of pulleys include a first driven pulley 90, a second driven pulley 91, a first intermediate pulley 92, a second intermediate pulley 93, a third intermediate pulley 94, and a fourth intermediate pulley 95.

[0063] The first driven pulley 90 and the second driven pulley 91 are rotatably provided on the upper surface of the rear end portion of a pair of second fixed plates 42 constituting the fixed base 40. As a result, the first driven pulley 90 is disposed at a distance from the first driving pulley 81 in the front-rear direction L1, and is disposed so as to be aligned in a straight line along the front-rear direction L1. Similarly, the second driven pulley 91 is disposed at a distance from the second driving pulley 83 in the front-rear direction L1, and is disposed so as to be aligned in a straight line along the front-rear direction L1.

[0064] The first driven pulley 90 and the second driven pulley 91 are mounted on the pair of second fixed plates 42 and are therefore immovable in the front-rear direction L1 and the left-right direction L2. The first driving pulley 81, the second driving pulley 83, the first driven pulley 90 and the second driven pulley 91 are disposed so as to be positioned outside the movable base 50 in the left-right direction L2.

[0065] The first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 are rotatably provided on the upper surface of the movable base 50. The first intermediate pulley 92 and the second intermediate pulley 93 are provided on the upper surface of the front end portion of a pair of first movable plates 51 constituting the movable base 50. In this case, the first intermediate pulley 92 and the second intermediate pulley 93 are arranged so as to be aligned in a straight line along the left-right direction L2. The first intermediate pulley 92 is arranged closer to the first driving pulley 81, and the second intermediate pulley 93 is arranged closer to the second driving pulley 83.

[0066] The third intermediate pulley 94 and the fourth intermediate pulley 95 are provided on the upper surface of the pair of first movable plates 51. In this case, the third intermediate pulley 94 and the fourth intermediate pulley 95 are arranged so as to be aligned in a straight line along the left-right direction L2, and are arranged so as to be located rearward BK of the first intermediate pulley 92 and the second intermediate pulley 93. Furthermore, the third intermediate pulley 94 and the fourth intermediate pulley 95 are arranged so that their peripheral surfaces are at the same position in the front-rear direction L1 with respect to the front surface of the grooved plate 21 fixed to the shaking table 11.

[0067] Furthermore, the third intermediate pulley 94 is disposed at a distance from the second intermediate pulley 93 in the front-rear direction L1 and is arranged in a straight line along the front-rear direction L1. Similarly, the fourth intermediate pulley 95 is disposed at a distance from the first intermediate pulley 92 in the front-rear direction L1 and is arranged in a straight line along the front-rear direction L1.

[0068] The first driving pulley 81, the second driving pulley 83, the first driven pulley 90, the second driven pulley 91, the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94 and the fourth intermediate pulley 95 configured as described above are each arranged to maintain the same height. The drive belt 32 is continuously stretched, for example, from the first drive pulley 81 through the first intermediate pulley 92, the second intermediate pulley 93, the second drive pulley 83, the second driven pulley 91, the third intermediate pulley 94, the fourth intermediate pulley 95 and the first driven pulley 90, and then back to the first drive pulley 81. In particular, the drive belt 32 is stretched over a plurality of pulleys while maintaining a constant tension and preventing slack. Furthermore, the drive belt 32 is stretched over a plurality of pulleys while preventing vertical positional deviation and slippage.

[0069] Furthermore, a plurality of elongated grooves corresponding to the grooves and protrusions of the drive belt 32 are formed around the entire circumference of the peripheral surfaces of the first drive pulley 81, the second drive pulley 83, the first driven pulley 90, and the second driven pulley 91. As a result, the drive belt 32 is stretched around the plurality of pulleys in a state where slippage is suppressed by meshing with the grooves.

[0070] Furthermore, the drive belt 32 is connected in a state where slippage is suppressed by meshing with a groove formed on the front surface of the grooved plate 21 fixed to the shaking table 11. This makes it possible to move the shaking table 11 by driving the drive belt 32.

[0071] In the shaking device 10 configured as described above, by controlling the rotation of the two drive motors, the first drive motor 80 and the second drive motor 82, the drive pattern of the drive belt 32 can be freely adjusted via the first drive pulley 81 and the second drive pulley 83. Specifically, the motor control unit 84 outputs drive pulses to the first drive motor 80 and the second drive motor 82 to control the rotation direction, rotation speed, rotation timing, etc. of the first drive motor 80 and the second drive motor 82, thereby making it possible to freely adjust the drive pattern of the drive belt 32. This makes it possible to move the entire movable table 50 and the shaking table 11 in the front-rear direction L1 along the X-axis relative to the fixed table 40, to move the shaking table 11 in the left-right direction L2 along the Y-axis relative to the movable table 50, and to move the shaking table 11 in a complex two-dimensional manner in the front-rear direction L1 and the left-right direction L2 along the X-axis and Y-axis. This will be explained in more detail later.

[0072] Furthermore, the shaking mechanism 30 of this embodiment is provided with a first position detection switch 100 and a second position detection switch 101 for detecting excessive movement of the shaking table 11. The first position detection switch 100 is provided on the front connecting plate 47 that constitutes the fixed base 40. The first position detection switch 100 is arranged with the switch portion 100a facing the rear BK, and switches from an OFF state to an ON state when the movable base 50 comes into contact with the switch portion 100a from the rear BK. As a result, the first position detection switch 100 outputs a first detection signal to the motor control unit 84.

[0073] The second position detection switch 101 is provided on the first movable plate 51 constituting the movable base 50. The second position detection switch 101 is arranged with the switch part 101a facing inward in the left-right direction L2 (facing the shaking base 11), and switches from an OFF state to an ON state when the shaking base 11 comes into contact with the switch part 101a from the left-right direction L2. As a result, the second position detection switch 101 outputs a second detection signal to the motor control unit 84.

[0074] Therefore, the motor control unit 84 can detect that the shaking table 11 has moved excessively in the front-back direction L1 and the left-right direction L2 based on the first detection signal and the second detection signal while shaking the shaking table 11. This enables the motor control unit 84 to stop the pulse signals output to the first drive motor 80 and the second drive motor 82. Therefore, appropriate shaking can be performed.

[0075] As shown in FIGS. 1 and 2, the culture system 1 includes a heat sink 16 and a container holder 12 combined with the shaking table 11 of the shaking device 10 configured as described above. The heat sink 16 is assembled in a state in which it is placed on the mounting surface 11a of the shaking table 11 via a relay member 110. The container holding part 12 is assembled to the heat sink 16 in a state in which it is disposed above the heat sink 16. As a result, the culture vessel 2 is held by the container holding part 12 in a state in which it is indirectly placed on the mounting surface 11a of the shaking table 11 via the container holding part 12 and the heat sink 16.

[0076] 7, the relay member 110 is formed in a cylindrical shape having an upper flange portion 111 and a lower flange portion 112, and is disposed coaxially with the central axis O. The lower flange portion 112 is fixed to the shaking table 11 in a state in which it is placed on the mounting surface 11a of the shaking table 11. In this way, the relay member 110 is integrally combined with the shaking table 11.

[0077] (heat sink) As shown in Figures 1, 2 and 7, the heat sink 16 comprises a lower connecting portion 120 which is placed on the lower flange portion 112 by being overlapped from above on the lower flange portion 112, an upper connecting portion 121 which is arranged above the lower connecting portion 120 with a fixed gap between it and the lower connecting portion 120, and a plurality of heat dissipation fins 122 which are arranged between the lower connecting portion 120 and the upper connecting portion 121, and are arranged coaxially with the central axis O.

[0078] Lower connecting portion 120 is formed in a circular shape in a plan view with an outer diameter larger than that of lower flange portion 112, and is integrally combined with lower flange portion 112 in a state in which lower connecting portion 120 is overlapped with lower flange portion 112 from above. The upper connecting portion 121 includes an upper connecting plate 125 that is circular in plan view and has the same outer diameter as the lower connecting portion 120, and a bulging portion 126 that protrudes upward from the center of the upper connecting plate 125. The bulging portion 126 is square in plan view. Furthermore, a through hole (not shown) is formed in the center of the upper connecting portion 121, which penetrates the bulging portion 126 and the entire upper connecting portion 121 in the vertical direction.

[0079] 7 and 8, a heat transfer member 130 is combined from above with the upper connecting portion 121. The heat transfer member 130 includes a cylindrical first heat transfer member 131 disposed inside the through hole, and a second heat transfer member 132 having a square shape in a plan view and overlapping with the bulging portion 126 from above. The first heat transfer member 131 is fitted, for example, inside the through hole, and the lower surface thereof protrudes downward beyond the lower surface of the upper connecting plate 125. The second heat transfer member 132 is formed to have an outer size smaller than the outer shape of the bulging portion 126, and protrudes upward beyond the bulging portion 126. The upper surface of the second heat transfer member 132 is a flat heat transfer surface 132a.

[0080] The heat dissipation fins 122 are formed in a circular plate shape with an outer diameter larger than the outer size of the shaking table 11, and are arranged coaxially with the central axis O, with multiple fins arranged at intervals in the vertical direction between the lower connecting portion 120 and the upper connecting portion 121. Specifically, a vertically long heat transfer rod (not shown) extending in the up-down direction is disposed between the lower connecting part 120 and the heat transfer member 130 combined with the upper connecting part 121. A plurality of heat transfer rods are disposed at intervals in the circumferential direction around the central axis O, and are disposed in a state in which they penetrate the plurality of heat dissipation fins 122 in the up-down direction. The upper end of the heat transfer rod is in contact with the lower surface of the second heat transfer member 132. This thermally connects the heat transfer member 130 and the heat transfer rod. Furthermore, spacers 135 (see FIG. 2) inserted into the heat transfer rod are disposed between adjacent heat dissipation fins 122 in the vertical direction. As a result, the multiple fins are disposed so as to be overlapped with each other at regular intervals in the vertical direction via the spacers 135, and are supported by the heat transfer rod.

[0081] The heat transfer member 130, the heat dissipation fins 122, the heat transfer rods, and the spacers 135 are formed from a material having excellent thermal conductivity (heat dissipation properties), and may be made of either metal or non-metal.

[0082] (Container holding part) As shown in Figures 9 to 11, the container holding part 12 is equipped with a container support part 140 that is combined with the upper connecting part 121 from above and supports the culture container 2 from below, and a ring-shaped pressing member 150 that surrounds the culture container 2 from the radial outside and is engaged with the container support part 140 from above.

[0083] As shown in FIG. 12, the container support part 140 includes a first support part 141 having a support body having a circular shape in a planar view and a flat upper surface serving as a support surface 142a, and a ring-shaped second support part 145 surrounding the support body 142 from the radially outer side. The first support portion 141 is combined with the upper connecting portion 121 in a state where it overlaps the upper connecting plate 125 from above. A fitting hole 143 that penetrates the support body 142 in the vertical direction is formed in the center of the support body 142. The fitting hole 143 is formed in a rectangular shape in a plan view corresponding to the outer shape of the second heat transfer member 132 of the heat transfer member 130. The first support portion 141 is combined with the upper connecting portion 121 in a state where the second heat transfer member 132 is fitted inside the fitting hole 143.

[0084] As shown in Fig. 12, the second support part 145 is assembled to the first support part 141 from above in a state in which the second support part 145 surrounds the support body 142 from the outside in the radial direction. The second support part 145 is formed with a locking piece 146 that protrudes upward and has an arc shape in a plan view that extends along the circumferential direction. Two locking pieces 146 are provided at intervals in the circumferential direction. In the illustrated example, the two locking pieces 146 are arranged to face each other in the radial direction with the central axis O in between. However, this is not limited to this case, and for example, three or more locking pieces 146 may be provided at intervals in the circumferential direction.

[0085] 10 and 12, when the culture vessel 2 is set, the locking piece 146 is disposed radially outward of the curved surface portion 5 and the side wall portion 4 of the culture vessel 2. Furthermore, the locking piece 146 is formed so as to have a smaller diameter from the bottom to the top in accordance with the inclination of the side wall portion 4 of the culture vessel 2.

[0086] 9 and 10, the pressing member 150 is formed in a ring shape surrounding the curved surface portion 5 and the side wall portion 4 of the culture vessel 2 from the outside in the radial direction, and is combined with the second support portion 145 from above. The pressing member 150 is formed so as to have a smaller diameter from the bottom to the top in accordance with the inclination of the side wall portion 4 of the culture vessel 2. The lower surface of the pressing member 150 is formed with a pair of locking holes (not shown) into which the pair of locking pieces 146 can be inserted from below and into which the locking pieces 146 are respectively locked. Therefore, after the culture vessel 2 is set on the support surface 142a, the pressing member 150 can be set from above and the locking pieces 146 can be locked in the locking holes, thereby making it possible to integrally combine the pressing member 150 with the vessel support part 140.

[0087] Therefore, the pressing member 150 can be assembled with one touch without using fastening members such as bolts. In particular, the pressing member 150 has a diameter that decreases from bottom to top in accordance with the shape of the culture vessel 2, so that the culture vessel 2 can be held in a state in which the culture vessel 2 is prevented from slipping out upward.

[0088] In this embodiment, the case where the container support part 140 is combined with the pressing member 150 by using the locking piece 146 has been described as an example, but the present invention is not limited to this case. For example, the container support part 140 and the pressing member 150 may be provided with magnets or the like without providing the locking piece 146, and the pressing member 150 may be combined by using magnetic force.

[0089] The second support portion 145 including the pair of locking pieces 146 is formed of a material with excellent thermal conductivity (heat dissipation), and is thermally connected to a thermally conductive sheet 165 described later. As a result, the pair of locking pieces 146 are thermally connected to a Peltier element 160 described later via the thermally conductive sheet 165. Therefore, by utilizing the pair of locking pieces 146, the culture vessel 2 can be efficiently heated and cooled from the side wall portion 4 side and the curved surface portion 5 side.

[0090] (Thermoelectric element) As shown in FIG. 12, the container holder 12 configured as described above is provided with a Peltier element 160 as a thermoelectric element for heating and cooling the culture container 2 set therein. 7 and 8, the Peltier element 160 is formed in a square shape in a plan view corresponding to the outer shape of the heat transfer surface 132a of the heat transfer member 130, and is placed on the heat transfer surface 132a. As a result, the second main surface 162 of the Peltier element 160 is in surface contact with the heat transfer surface 132a with the first main surface 161 facing upward. The first main surface 161 and the second main surface 162 of the Peltier element 160 switch between heating (heat dissipation) and cooling (heat absorption) depending on the direction of the supplied current based on the inverse principle of the Seebeck effect.

[0091] 12, the Peltier element 160 is disposed inside the fitting hole 143 formed in the support body 142 of the container support part 140, with the first main surface 161 being flush with the support surface 142a. This enables the Peltier element 160 to heat and cool the culture container 2 placed therein from the bottom part 3. 11, a heat conductive sheet 165 that covers the entire first main surface 161 and the support surface 142a from above is provided on the inside of the second support part 145. Therefore, it is possible to efficiently and uniformly heat and cool the entire bottom part 3 of the culture vessel 2 via the heat conductive sheet 165.

[0092] 8, the second main surface 162 of the Peltier element 160 is in surface contact with the heat transfer surface 132a of the heat transfer member 130, and is therefore thermally connected to the plurality of heat dissipation fins 122 via the heat transfer member 130 and the heat transfer rod. Therefore, the Peltier element 160 can improve the heating efficiency and cooling efficiency by utilizing heat exchange with the outside air by the heat dissipation fins 122, and it is possible to efficiently and quickly heat and cool the culture vessel 2.

[0093] 1, the multiple heat dissipation fins 122 are covered from the outside in the radial direction by the upper cover 19, and are therefore hidden from the outside. The upper cover 19 is combined with, for example, the exterior cover 17. Furthermore, a fan (not shown) or the like may be provided on the upper cover 19. By providing a fan, for example, it is possible to supply outside air to the inside of the upper cover 19 or to exhaust outside air from the inside of the upper cover 19, thereby making it possible to increase the heat exchange rate of the heat dissipation fins 122.

[0094] As shown in Fig. 12, the culture system 1 includes a temperature control unit 170 that controls the Peltier element 160. The temperature control unit 170 is mounted on, for example, the control board 18 shown in Fig. 1, and its operation is controlled by the control unit 15. Therefore, the temperature control unit 170 controls the timing of the current supplied to the Peltier element 160, the current flow time, the direction of the current, and the like, by signals from the control unit 15. This makes it possible to control the heating and cooling of the culture vessel 2 by utilizing the Peltier element 160. The container holder 12 incorporating the Peltier element 160, the heat dissipation fins 122, the temperature control unit 170, and the like function as a temperature control device for heating and cooling the culture container 2.

[0095] In this embodiment, a temperature sensor may be provided to measure the temperature of the culture vessel 2 that changes due to the Peltier element 160. In this case, the temperature control unit 170 may control the Peltier element 160 based on the measurement result of the temperature sensor. This makes it easier to control the temperature of the culture vessel 2 more appropriately. Furthermore, in this embodiment, a thermally conductive sheet thermally connected to the Peltier element 160 may be further provided on, for example, the inner peripheral surface of the pressing member 150. In this case, it becomes possible to heat and cool the culture vessel 2 not only from the bottom 3 side, but also from the curved surface portion 5 and the side wall portion 4 side. In particular, due to a synergistic effect with the pair of locking pieces 146 thermally connected to the Peltier element 160, it becomes possible to heat and cool the culture vessel 2 even more effectively.

[0096] <1st measuring device, 2nd measuring device> As shown in Figures 1 and 2, the culture system 1 is equipped with a measurement unit 180 including a first measurement device 13 that measures the turbidity of the culture solution W, and a second measurement device 14 that measures the culture state of a target substance contained in the culture solution W. The measurement unit 180 is disposed so as to be located above the shaking device 10 and to be located outside the culture vessel 2 held by the vessel holding part 12. Specifically, the measurement unit 180 is disposed outside in the left-right direction L2 with a gap between the culture vessel 2 and the pressing member 150. The measurement unit 180 is held by a support member or the like (not shown).

[0097] The support member may be integrally combined with the fixed base 40 of the shaking device 10, or may be provided separately from the shaking device 10. The measurement unit 180 may be disposed so as to be located in front of the culture container 2 (FW) or behind the culture container 2 (BK).

[0098] As shown in FIG. 9, the measurement unit 180 measures the turbidity of the culture solution W and the culture state of the target substance through a measurement hole 151 formed in the pressing member 150. As shown in Figures 9, 13 and 14, the measurement unit 180 includes a light irradiation section 181 that irradiates excitation light EL toward the culture vessel 2, an excitation filter 182 arranged between the light irradiation section 181 and the culture vessel 2, a dual-purpose imaging section 183 that respectively acquires a scattered light image 191 (see Figure 15) and a fluorescent image 192 (see Figure 15), a fluorescent filter 184 arranged between the dual-purpose imaging section 183 and the culture vessel 2, and a holding case 185 that holds each of these components.

[0099] (Light irradiation part) As shown in Fig. 14, the light irradiating unit 181 irradiates the excitation light EL toward the interface between the inner surface of the culture vessel 2 and the culture solution W through the measurement hole 151 (see Fig. 9) of the pressing member 150. The light irradiating unit 181 is disposed so as to irradiate the excitation light EL diagonally downward. For example, an LED light source can be used as the light irradiating unit 181. However, the light irradiating unit 181 is not limited to an LED light source, and other light sources may be used as long as they can irradiate light including the wavelength range of the excitation light EL.

[0100] The light emitting portion 181 is combined with a heat dissipation member 187 including a plurality of heat dissipation fins 186. This allows the heat generated by the light emitting portion 181 to be dissipated via the heat dissipation member 187.

[0101] (Excitation filter) As shown in FIGS. 13 and 14, the excitation filter 182 is held by a holding case 185 so as to be located between the light irradiation unit 181 and the culture container 2. The excitation filter 182 allows the transmission of light in a specific wavelength range used as the excitation light EL from the light irradiated by the light irradiating unit 181. As the excitation filter 182, for example, a known optical filter (bandpass filter) having a dielectric multilayer film and capable of wavelength separation can be suitably used. In particular, the excitation filter 182 allows the transmission of light in a wavelength range different from the wavelength range that the fluorescence filter 184 allows to pass.

[0102] In the illustrated example, the excitation filter 182 is a framed filter having an excitation filter body 182a having a dielectric multilayer film or the like, and a ring-shaped frame portion 182b surrounding the entire circumference of the excitation filter body 182a. The excitation filter body 182a is formed to have a diameter larger than at least the light irradiation portion 181. The excitation filter 182 is held in a holding case 185 so as to be replaceable.

[0103] (Combined imaging unit) The dual-purpose imaging unit 183 has the function of capturing an image of scattered light that is generated when excitation light EL irradiated from the light irradiation unit 181 is reflected at the interface between the inner surface of the culture vessel 2 and the culture solution W, and acquiring it as a scattered light image 191 (see Figure 15), and the function of capturing an image of the fluorescence emitted by the expressed target substance due to irradiation with excitation light EL, and acquiring it as a fluorescence image 192 (see Figure 15). Therefore, the dual-purpose imaging section 183 serves as both a first imaging section for acquiring a scattered light image 191 and a second imaging section for acquiring a fluorescent image 192, and is capable of acquiring both the scattered light image 191 and the fluorescent image 192.

[0104] The dual-purpose imaging section 183 includes, for example, a soft (flexible) or hard tubular imaging guide 200 and an imaging unit 201 provided at the tip of the imaging guide 200. At least an objective lens (not shown) and an imaging element (not shown) that captures an image through the objective lens are included inside the imaging unit 201. As the imaging element, for example, a CMOS sensor or a CCD sensor can be adopted.

[0105] Dual-purpose imaging section 183 is inserted into holding hole 185a formed in holding case 185, and is thereby held in holding case 185. Dual-purpose imaging section 183 is arranged with imaging unit 201 facing the culture vessel 2. The base end of imaging guide 200 is drawn out to the outside of holding case 185. Inside the imaging guide 200, a wiring cable (power line, signal line) not shown is arranged which is electrically connected to the imaging element, and outputs the two captured images (scattered light image 191 and fluorescent image 192) to the control unit 15.

[0106] (fluorescence filter) The fluorescent filter 184 is held by a holding case 185 so as to be located between the combined image capturing section 183 and the culture vessel 2 . The fluorescence filter 184 transmits light in a wavelength range including the wavelength of the fluorescence emitted by the target substance, and restricts the transmission of light in at least the wavelength range of the excitation light EL. As the fluorescence filter 184, for example, a known optical filter (bandpass filter) having a dielectric multilayer film and capable of wavelength separation can be suitably used. In the illustrated example, the fluorescent filter 184 is a framed filter having a fluorescent filter body 184a having a dielectric multilayer film or the like, and a ring-shaped frame portion 184b surrounding the entire periphery of the fluorescent filter body 184a.

[0107] A filter plate 210 is provided in the holding case 185 so as to be located closer to the culture vessel 2 side than the fluorescent filter 184. A first imaging hole 211 and a second imaging hole 212 are formed in the filter plate 210, penetrating the filter plate 210 in the thickness direction. The dual-purpose imaging section 183 is disposed so that the imaging axis IA passes through the central portion between the first imaging hole 211 and the second imaging hole 212 in the left-right direction L2. As a result, when viewed from the incubation vessel 2 side, the imaging units 201 of the dual-purpose imaging section 183 are disposed so as to be inserted inside the first imaging hole 211 and the second imaging hole 212, respectively. The imaging axis IA is disposed so as to intersect with the interface irradiated with the excitation light EL. In particular, the dual-purpose imaging section 183 is disposed so that the imaging axis IA is non-coaxial with the optical axis of the excitation light EL reflected on the inner surface.

[0108] 15, the dual-purpose imaging section 183 is capable of acquiring a fluorescent image 192 through the fluorescent filter 184 and the first imaging hole 211, and is also capable of acquiring a scattered light image 191 through the second imaging hole 212. Therefore, it is possible to acquire both the scattered light image 191 and the fluorescent image 192 using one dual-purpose imaging section 183. Furthermore, the fluorescent image 192 and the scattered light image 191 can be included in one captured image 190 captured by the dual-purpose imaging section 183.

[0109] As shown in FIG. 13, the dual-purpose imaging section 183 is positioned so that the imaging axis IA intersects with the interface where the excitation light EL is irradiated, so that the optical center LO of the excitation light EL irradiated to the interface can be positioned at the center of the captured image 190 as shown in FIG. 15. 15, a part of frame 184b is intentionally reflected in captured image 190. In this way, fluorescence filter 184 uses frame 184b to block strong reflected light from optical center LO from entering captured image 190.

[0110] (Control unit) 1, the control unit 15 mounted on the control board 18 shown in Fig. 1 is also connected to the light irradiation unit 181 and the dual-purpose imaging unit 183 and controls their operations as shown in Fig. 14. For example, the control unit 15 controls the irradiation timing, irradiation time, etc. of the light irradiation unit 181, and also controls the imaging timing, etc. of the dual-purpose imaging unit 183. Furthermore, the control unit 15 includes at least a memory unit 220 that stores the scattered light image 191 and the fluorescent image 192 captured by the dual-purpose imaging unit 183, and a measurement unit 221 that measures the turbidity of the culture solution W and the fluorescent intensity of the target substance based on the scattered light image 191 and the fluorescent image 192.

[0111] In this embodiment, one captured image 190 includes a scattered light image 191 and a fluorescent light image 192, and therefore the memory section 220 stores the scattered light image 191 and the fluorescent light image 192 in association with each other. As shown in FIG. 15, the measurement unit 221 determines the area of ​​the scattered light image 191 and the fluorescent image 192 contained in the captured image 190 that is located at the same distance from the optical center LO as the data acquisition area R, extracts a partial image of the scattered light image 191 and a partial image of the fluorescent image 192 within the data acquisition area R, and measures the turbidity of the culture solution W and the fluorescence intensity of the target substance from each of these partial images.

[0112] The light irradiating unit 181, the excitation filter 182, the combined image capturing unit 183, and the measurement unit 221 function as a first measurement device 13 that measures the turbidity of the culture solution W. Furthermore, the light irradiating unit 181, the excitation filter 182, the fluorescent filter 184, the combined image capturing unit 183, and the measurement unit 221 function as a second measurement device 14 that measures the culture state of the target substance contained in the culture solution W. Thus, the scattered light image 191 functions as a first measurement result, and the fluorescent light image 192 functions as a second measurement result.

[0113] Furthermore, the control unit 15 controls various components of the culture system 1 in an overall manner by appropriately executing various programs using the CPU, thereby causing the culture system 1 to perform the culture work. The various programs are recorded in a computer-readable recording medium (not shown).

[0114] A "computer-readable recording medium" is a portable medium such as a flexible disk, a magneto-optical disk, a CD-ROM, or a semiconductor memory, which is read via a drive device (e.g., a CD-ROM drive device) or an interface (e.g., a USB interface). Furthermore, the "computer-readable recording medium" is not limited to the portable medium described above, but may be a storage unit such as a hard disk built into a computer system (including hardware such as an OS and peripheral devices). Furthermore, the term "computer-readable recording medium" may also include something that dynamically holds a program for a short period of time, such as a communication line when transmitting a program via a network such as the Internet or a communication line such as a telephone line, or something that holds a program for a fixed period of time, such as volatile memory inside a computer system that serves as the server or client in that case.

[0115] Furthermore, the control unit 15 feedback-controls the motor control unit 84 constituting the drive unit 33 so as to change the shaking conditions of the shaking table 11 based on the result of the turbidity measured by the measurement unit 221 (measurement result from the first measurement device 13). Furthermore, the control unit 15 feedback-controls the motor control unit 84 so as to change the shaking conditions of the shaking table 11 based on the result of the fluorescence intensity of the target substance measured by the measurement unit 221 (measurement result from the second measurement device 14). Furthermore, the control unit 15 performs feedback control of the temperature control unit 170 so as to change the temperature conditions for heating and cooling by the Peltier element 160 based on the turbidity result.

[0116] (Effects of culture system) Next, a series of steps for culturing the culture solution W, measuring the turbidity of the culture solution W, and measuring the fluorescence intensity of the expressed target substance using the culture system 1 configured as described above will be described. The explanation will include the culturing of E. coli and the expression of the target substance.

[0117] First, E. coli containing an expression vector is placed in the culture solution W contained in the culture vessel 2. Next, the culture vessel 2 is held using a vessel holder 12 combined with a shaking table 11 shown in Figures 1 and 2, and then the culture vessel 2 is shaken using a shaking device 10 while maintaining a predetermined culture temperature (e.g., 37°C). This allows E. coli to be cultured. Furthermore, the turbidity of the culture solution W tends to increase as the culture of E. coli progresses.

[0118] After the culture vessel 2 is held by the vessel holding part 12, the temperature control part 170, which has received an instruction from the control part 15, controls the Peltier element 160 to heat the culture vessel 2 via the first main surface 161. This makes it possible to efficiently and uniformly heat the bottom part 3 of the culture vessel 2 by using the thermally conductive sheet 165, and to heat and maintain the culture solution W at a predetermined culture temperature.

[0119] At this time, the second main surface 162 of the Peltier element 160 functions as a heat absorbing surface. Since the second main surface 162 is thermally connected to the plurality of heat dissipation fins 122, the heat absorbing efficiency can be improved. Therefore, a temperature difference can be easily generated between the first main surface 161 and the second main surface 162, and the heat dissipation performance (heating performance) of the first main surface 161 can be improved. Therefore, the culture solution W can be easily heated efficiently.

[0120] Also, before, after, or in parallel with the heating of the culture vessel 2 described above, the motor control unit 84, which has received an instruction from the control unit 15, controls the first drive motor 80 and the second drive motor 82 shown in FIG. 3 to drive the drive belt 32. This allows the shaking table 11 to be moved in the front-back direction L1 along the X-axis and in the left-right direction L2 along the Y-axis while being guided by the guide member 31. This allows the shaking table 11 to be periodically moved using the drive belt 32, and the shaking table 11 to be shaken. Therefore, the culture solution W contained in the culture vessel 2 can be agitated, and the culture can be promoted.

[0121] In particular, the drive unit 33 drives the drive belt 32 while independently controlling the movement of the shaking table 11 on the X-axis and Y-axis, so that the shaking table 11 can be shaken in various shaking patterns. Specifically, the motor control unit 84 is used to control the rotation of two drive motors, the first drive motor 80 and the second drive motor 82, so that the drive pattern of the drive belt 32 can be adjusted via the first drive pulley 81 and the second drive pulley 83. More specifically, the motor control unit 84 can be used to adjust the rotation direction, rotation speed, rotation timing, etc. of the first drive motor 80 and the second drive motor 82, thereby freely adjusting the drive pattern of the drive belt 32. As a result, it is possible to shake the shaking table 11 in a shaking pattern in which the shaking table 11 is moved linearly in the front-back direction L1 along the X axis or the left-right direction L2 along the Y axis, or in a shaking pattern in which the shaking table 11 is moved in a circular or elliptical motion by combining movements along the X and Y axes. Furthermore, it is also possible to shake the shaking table 11 in a shaking pattern in which a semicircular motion is repeated back and forth, or in a shaking pattern that draws a figure of eight, by combining movements along the X and Y axes.

[0122] For example, as shown in FIG. 4, the culture vessel 2 can be shaken in the front-rear direction L1 by rotating a first drive motor 80 and a second drive motor 82 in mutually opposite rotation directions at the same rotation speed. Specifically, the first drive motor 80 is rotated in the direction indicated by the arrow M1, and the second drive motor 82 is rotated in the direction indicated by the arrow M2. As a result, the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 can all be moved toward the forward direction FW via the drive belt 32. Furthermore, the first drive motor 80 is rotated in the direction indicated by the arrow M3, and the second drive motor 82 is rotated in the direction indicated by the arrow M4. As a result, the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 can all be moved toward the backward direction BK via the drive belt 32. Therefore, by alternately performing the above-mentioned operations, the movable table 50 and the shaking table 11 as a whole can be moved linearly back and forth along the X-axis (front-back direction L1) along the first guide rail 61 of the first guide member 60. This allows the culture vessel 2 to be shaken along the front-back direction L1.

[0123] Furthermore, by rotating the first drive motor 80 and the second drive motor 82 in the same rotation direction and at the same rotation speed, the culture vessel 2 can be shaken in the left-right direction L2. Specifically, the first drive motor 80 is rotated in the direction indicated by the arrow M1, and the second drive motor 82 is rotated in the direction indicated by the arrow M4. As a result, the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 can all be moved in one direction in the left-right direction L2 via the drive belt 32. Furthermore, the first drive motor 80 is rotated in the direction indicated by the arrow M3, and the second drive motor 82 is rotated in the direction indicated by the arrow M2. As a result, the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 can all be moved in the other direction in the left-right direction L2 via the drive belt 32. Therefore, by alternately performing the above-mentioned operations, the shaking table 11 can be moved linearly back and forth along the Y-axis (left-right direction L2) along the second guide rail 71 of the second guide member 70 without moving the movable table 50. This allows the culture vessel 2 to be shaken along the left-right direction L2.

[0124] Furthermore, for example, by rotating the first drive motor 80 and the second drive motor 82 at different rotational speeds and in the same or opposite rotational directions, the above-mentioned operations can be combined, and the culture vessel 2 can be shaken in a shaking pattern such as moving it back and forth in an oblique direction, a shaking pattern such as a circular motion or an elliptical motion as described above, a shaking pattern in which semicircular motion is repeated back and forth, or a shaking pattern that draws a figure eight.

[0125] Therefore, according to the shaking device 10 of this embodiment, it is possible to shake the shaking table 11 and the culture vessel 2 in various fine shaking patterns, rather than the conventional shaking patterns limited to specific movements. Therefore, the shaking conditions can be easily adjusted and changed according to the situation, etc., and the culture solution W in the culture vessel 2 can be agitated in an optimal state each time. In particular, shaking can be performed to give a stimulus of varying intensity to the culture solution W, rather than a constant stimulus, so that optimal culture can be performed according to the target substance, culture solution W, etc.

[0126] For example, when the culture is performed by the shaking device 10 until certain conditions (for example, the time for shaking the culture vessel 2, the number of shakings, etc.) are satisfied, the shaking of the shaking table 11 and the culture vessel 2 is temporarily stopped. Furthermore, as shown in Fig. 9, the culture vessel 2 is moved close to the measurement unit 180 so that the measurement unit 180 can perform measurement through the observation hole. This allows the relative positional relationship between the culture vessel 2, the light irradiation unit 181, and the combined image capture unit 183 to be set to an appropriate positional relationship, as shown in Fig. 13.

[0127] Next, the turbidity of the culture solution W is measured. Specifically, light is emitted from the light irradiating unit 181. This allows the excitation light EL to be irradiated toward the culture vessel 2 through the excitation filter 182, and also allows the excitation light EL to be irradiated toward the interface between the inner surface of the culture vessel 2 and the culture solution W. As a result, a portion of the excitation light EL is reflected at the interface and becomes scattered light.

[0128] Therefore, using the dual-purpose image capturing section 183, an image of the scattered light reflected at the interface can be captured and acquired as the scattered light image 191 shown in Fig. 15. At this time, a fluorescent image 192 is also captured by the dual-purpose image capturing section 183, but since the target substance has not yet been expressed at this stage, this differs from the fluorescent image 192 that should be acquired. The captured image 190 acquired by the dual-purpose image capturing section 183 is output to the control section 15 and stored in the memory section 220. Furthermore, the measurement section 221 measures the turbidity of the culture solution W based on the acquired scattered light image 191. Specifically, the measurement section 221 measures the turbidity based on the light intensity including the brightness and luminance of the scattered light image 191, or on changes in the color information of the RGB colors of the scattered light image 191, or the like.

[0129] As a result, the culture state of E. coli can be grasped based on the measured turbidity, and it can be determined (estimated) whether or not a certain amount of E. coli has been cultured. When it is confirmed that E. coli has been cultured appropriately, it is possible to cause expression of the target substance by cold shock expression or the like.

[0130] On the other hand, when it is determined from the turbidity measurement results that the E. coli culture is insufficient, the control unit 15 performs feedback control to continue the E. coli culture. In this case, the control unit 15 performs feedback control of the motor control unit 84 so as to change the shaking conditions of the shaking table 11. This allows the motor control unit 84 to drive the first drive motor 80 and the second drive motor 82 under different shaking conditions from the previous shaking conditions, and the shaking of the culture vessel 2 can be resumed. In particular, since different shaking conditions are used, it is possible to promote culture while providing a different stimulus to the culture solution W.

[0131] Furthermore, in addition to changing the shaking conditions, the control unit 15 feedback-controls the temperature control unit 170 so as to change the temperature conditions for the Peltier element 160 to heat and cool the culture vessel 2. This makes it possible to resume shaking of the culture vessel 2 while maintaining the temperature of the culture solution W at a temperature higher than 37° C., for example. This can therefore lead to the promotion of culture.

[0132] After shaking is performed again, the turbidity of the culture solution W is measured again by the measurement unit 180. In this manner, the cultivation and the measurement of the turbidity are repeated until the E. coli is cultivated appropriately. Therefore, the cultivation can be performed efficiently.

[0133] As a result of these, if it is determined that the culture of E. coli is sufficient, a step of expressing the target substance by cold shock expression is carried out. In this case, the culture vessel 2 is first cooled and maintained under a constant low temperature condition (about 15°C). Specifically, the temperature control unit 170 controls the Peltier element 160 to cool the culture vessel 2 via the first main surface 161 based on an instruction from the control unit 15. This makes it possible to efficiently and uniformly cool the bottom 3 of the culture vessel 2 using the thermally conductive sheet 165. Therefore, the culture solution W can be quickly cooled and maintained at a low temperature of about 15°C. At this time, since the second main surface 162 is thermally connected to the plurality of heat dissipation fins 122, it is possible to improve the heat dissipation efficiency. Therefore, it is possible to improve the heat absorption performance (cooling performance) of the first main surface 161.

[0134] Next, a reagent such as IPTG is added to the culture vessel 2. By adding this reagent, the control of the lactose operon contained in the expression vector can be released, and a specific promoter whose expression is induced under low temperature conditions can be expressed. On the other hand, the expression of proteins contained in the E. coli itself can be suppressed. As a result, the target substance can be expressed efficiently and with high purity.

[0135] Next, after the target substance is expressed, excitation light EL is irradiated from the light irradiation unit 181 toward the interface between the inner surface of the culture vessel 2 and the culture solution W. This causes the expressed target substance to emit fluorescence due to the irradiation of the excitation light EL. Specifically, the target substance absorbs the light energy of the excitation light EL and transitions to an excited state, and then transitions to a ground state while emitting fluorescence.

[0136] Therefore, the dual-purpose image capturing section 183 can be used to capture an image of the fluorescence emitted by the target substance, and acquired as a fluorescence image 192 shown in Fig. 15. The fluorescence image 192 acquired by the dual-purpose image capturing section 183 is output to the control section 15 and stored in the memory section 220. Furthermore, the measurement section 221 measures the fluorescence intensity of the target substance based on the acquired fluorescence image 192. Specifically, the measurement section 221 measures the fluorescence intensity based on the light intensity including the brightness and luminance of the fluorescence image 192, or on changes in the color information of the RGB colors of the fluorescence image 192, or the like.

[0137] In particular, since the fluorescence filter 184 is disposed between the dual-purpose image capture unit 183 and the culture vessel 2, it is possible to block at least the light in the wavelength range of the excitation light EL reflected by the culture vessel 2, and to prevent the excitation light EL from reaching the dual-purpose image capture unit 183. Therefore, it is possible to remove noise and the like caused by the excitation light EL from the acquired fluorescence image 192, and it is possible to acquire a highly accurate fluorescence image 192. Therefore, the measurement unit 221 can measure the fluorescence intensity of the target substance based on the fluorescence image 192, and it is possible to know whether or not a certain amount of the target substance has been obtained.

[0138] 15, when the fluorescent image 192 is captured by the dual-purpose image capturing section 183, the scattered light image 191 can also be captured, so that the scattered light image 191 and the fluorescent image 192 can be included in one captured image 190. Therefore, the memory section 220 can store the scattered light image 191 and the fluorescent image 192 in association with each other.

[0139] In addition, when it is determined from the measurement results of the fluorescence intensity that the expression of the target substance is insufficient, the control unit 15 feedback controls the motor control unit 84 to resume shaking of the culture vessel 2 in order to further promote the expression. In this case, the control unit 15 performs feedback control of the motor control unit 84 so as to change the shaking conditions of the shaking table 11. This allows the motor control unit 84 to drive the first drive motor 80 and the second drive motor 82 under different shaking conditions from the previous shaking conditions, and the shaking of the culture vessel 2 can be resumed. In particular, since different shaking conditions are used, a different stimulus can be applied to the culture solution W. This can promote the expression of the target substance.

[0140] After shaking is performed again, the fluorescence intensity of the target substance is measured again by the measurement unit 180. In this manner, shaking of the culture solution W and measurement of the fluorescence intensity are repeated until the expressed target substance is appropriately obtained. Therefore, a constant amount of the target substance can be obtained efficiently.

[0141] As described above, according to the culture system 1 of this embodiment, it is possible to measure the turbidity of the culture solution W at the required timing, and further to continuously measure the fluorescence intensity of the target substance in a series of steps. In particular, the control unit 15 feedback-controls the motor control unit 84 and the temperature control unit 170 based on the measurement results of the turbidity of the culture solution W and the measurement results of the fluorescence intensity of the expressed target substance, so that it is possible to efficiently culture E. coli and obtain a constant amount of the expressed target substance.

[0142] Furthermore, since the turbidity of the culture solution W can be measured based on the scattered light reflected at the interface between the inner surface of the culture vessel 2 and the culture solution W, it is less susceptible to the influence of, for example, the concentration of the culture solution W or bubbling on the liquid surface of the culture solution W. Therefore, the turbidity of the culture solution W can be measured stably and accurately, and it is easy to accurately grasp the culture state of the culture solution W containing the target substance. Furthermore, since the fluorescence intensity of the target substance can be measured without removing the culture solution W from the culture container 2, contamination of the culture solution W can be prevented, and the fluorescence intensity can be measured with high accuracy.

[0143] Furthermore, according to the culture system 1 of this embodiment, the scattered light image 191 and the fluorescent image 192 are each captured using one combined image capturing section 183, so there is no need to use two image capturing sections. This makes it possible to simplify the configuration and reduce the cost of components. Furthermore, since the scattered light image 191 and the fluorescent image 192 can be simultaneously included in one captured image 190 captured by the combined image capturing section 183, it is possible to grasp, for example, the relationship (correlation) between turbidity and fluorescent intensity.

[0144] Furthermore, as shown in Figure 15, since the optical center LO of the excitation light EL is located at the center of the captured image 190, a scattered light image 191 and a fluorescent image 192 can be included evenly and in a balanced manner in a single captured image 190 captured by the dual-purpose imaging unit 183. Moreover, frame portion 184b of fluorescence filter 184 can be used to block the reflected light (excitation light EL) itself from the optical center LO from directly penetrating into captured image 190. Therefore, strong light can be prevented from penetrating into captured image 190, and problems such as whiteout can be prevented from occurring in scattered light image 191 and fluorescent image 192. This makes it possible to acquire scattered light image 191 and fluorescent image 192 in which, for example, changes in RGB color information, changes in brightness such as gradation, changes in luminance, etc. are clearly shown, allowing turbidity measurement and fluorescence intensity measurement to be performed with high accuracy.

[0145] Furthermore, since the measurement unit 221 extracts partial images within the data acquisition region R that are located the same distance from the optical center LO to acquire them as the scattered light image 191 and the fluorescent image 192, both images can be acquired under conditions of equivalent light intensity. Therefore, it is possible to perform measurements of turbidity and fluorescent intensity based on the scattered light image 191 and the fluorescent image 192 acquired under equivalent conditions.

[0146] Furthermore, since the scattered light image 191 and the fluorescent image 192 can be stored in association with each other in the memory unit 220, it is possible to grasp information such as the correlation between the state of turbidity and the state of expression of a target substance. Therefore, by accumulating this information, it is possible to estimate, for example, the degree of turbidity at which a target substance will be expressed. As a result, the operations from culture to expression of a target substance can be carried out efficiently.

[0147] Furthermore, since the excitation filter 182 is provided, excitation light EL in a wavelength range suitable for emission of fluorescence can be appropriately irradiated toward the culture vessel 2. In particular, since the wavelength range of the excitation filter 182 and the wavelength range of the fluorescence filter 184 can be made different, overlapping of the excitation spectrum and the fluorescence spectrum can be prevented, and a decrease in the contrast of the fluorescence image 192, etc. can be suppressed.

[0148] Furthermore, since the culture system 1 of this embodiment is equipped with the shaking device 10, the shaking conditions can be easily adjusted and changed, as described above. In particular, since the drive belt 32 is continuously stretched over each of the fixed table 40, the movable table 50, and the shaking table 11, the shaking table 11 can be shaken in various fine shaking patterns using one drive belt (endless belt) 32. Furthermore, since the motor control unit 84 is used to simply control the rotation of the first drive motor 80 and the second drive motor 82, it is easy to appropriately shake the shaking table 11 in a desired shaking pattern.

[0149] Although the 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. The embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the gist of the invention. The embodiments and their modifications include, for example, those that can be easily imagined by a person skilled in the art, those that are substantially the same, those that are within the scope of the equivalents, and the like.

[0150] For example, in the above embodiment, the expression vector does not need to contain a specific promoter such as the lactose operon. In this case, when the culture temperature of E. coli is lowered (about 15°C), the target substance can be expressed without adding any reagent. Furthermore, in the above embodiment, an example has been described in which an expression vector whose expression is induced depending on temperature is used to express a target substance by the method of E. coli cold shock expression system, but the present invention is not limited to this case. Any other expression vector can be used as long as it can express the target substance.

[0151] Furthermore, the target substance is not limited to a specific one as long as it has at least the function of emitting fluorescence and is a target of fluorescent staining. For example, a protein, which is a typical target of fluorescent staining, can be used as the target substance. Furthermore, as a target substance other than a protein, for example, a biomolecule, such as a nucleic acid, a cation, chitin, cellulose, or an AT region, which is a target of fluorescent staining, can be used.

[0152] Furthermore, in the above embodiment, an example was described in which an Erlenmeyer flask was used as the culture vessel 2, but as described above, other shapes of flasks, test tubes, petri dishes, beakers, etc. may be used as the culture vessel 2. When the culture vessel 2 is changed, the relative positional relationship of the light irradiation unit 181 and the combined image pickup unit 183 (first image pickup unit, second image pickup unit) with respect to the culture vessel 2 may be appropriately changed in accordance with the shape of the culture vessel 2. For example, when a cylindrical beaker is used as the culture vessel 2, the light irradiation unit and the combined image pickup unit 183 may be arranged so as to be horizontal to the peripheral wall surface of the beaker. In this way, the relative positions of the light emitting section and the combined imaging section 183 (first imaging section, second imaging section) may be changed as appropriate depending on the type, shape, application, and the like of the culture vessel 2.

[0153] Furthermore, in the above embodiment, the turbidity of the culture solution W was measured by the first measuring device 13 (light irradiating section 181, excitation filter 182, dual-purpose image capturing section 183, and measuring section 221) based on the scattered light of the excitation light reflected at the interface between the inner surface of the culture vessel 2 and the culture solution W, but this is not limited to this case. For example, the first measuring device may be configured to irradiate detection light from the light irradiating section so as to pass through the culture solution W, and receive the detection light that has passed through the culture solution W at the light receiving section. Even in this case, it is possible to measure the turbidity from the optical density that changes as the culture progresses, for example, based on the difference between the amount of irradiated light and the amount of received light (amount of transmitted light). In any case, as long as the turbidity of the culture solution W can be measured, the first measurement device may be configured in any way.

[0154] Furthermore, when the culture vessel 2 is shaken by the shaking device 10 to culture the culture solution W, the culture object is not limited to E. coli as in the above embodiment, but a wide variety of culture objects can be selected. The culture subject may be, for example, a microorganism such as yeast or bacteria. In particular, when bacteremia (infectious disease) occurs, which is a state in which bacteria have invaded the blood, it is known that blood culture is performed to identify the bacteria that cause it. Therefore, even in this case, it is possible to culture bacteria by using the shaking device 10 of this embodiment to shake the culture vessel 2 while maintaining it at a predetermined temperature (e.g., 35°C). Therefore, even in this case, the culture system 1 including the shaking device 10 of this embodiment can be suitably used.

[0155] Furthermore, in the above embodiment, an example was given in which the culture state of a target substance was measured by measuring the fluorescence intensity of the fluorescence emitted by the target substance (protein) using the second measuring device 14 (light irradiation unit 181, excitation filter 182, fluorescence filter 184, dual-purpose imaging unit 183 and measurement unit 221), but the present invention is not limited to this case. The second measuring device may be configured appropriately according to the culture object, etc., as long as it can measure the culture state of the culture object contained in the culture solution W. For example, when performing the above-mentioned blood culture, it is known that the amount of carbon dioxide emitted by the bacteria as they breathe increases as the bacteria culture progresses. In this case, the acidity of the culture solution W increases due to the increase in carbon dioxide, so that, for example, the color of the indicator provided in the culture container 2 changes. Therefore, it is possible to measure the culture state of the bacteria by measuring the change in the absorbance of the indicator. Therefore, the second measuring device may be configured to measure the change in the absorbance of the indicator. In this way, the second measurement device may be configured appropriately depending on the culture object, the purpose of the culture, and the like.

[0156] The present invention further includes the following aspects. <1> A shaking table having a mounting surface on which a culture vessel containing a culture solution containing a culture object is mounted; A shaking mechanism for shaking the shaking table in a plane parallel to the mounting surface, The shaking mechanism includes: A guide member that supports the shaking table movably along a first axis and a second axis that intersect with each other in a plane parallel to the mounting surface; A drive belt that moves the shaking table along the first axis and the second axis; A drive unit that drives the drive belt, The shaking device is characterized in that the drive unit drives the drive belt while independently controlling the movement of the shaking table along the first axis and the movement of the shaking table along the second axis. <2> <1> In the shaking device according to the present invention, The guide member is A fixed stand and A movable table is disposed above the fixed table and below the shaking table; a first guide member disposed between the fixed base and the movable base and supporting the movable base movably along the first axis relative to the fixed base; A second guide member is disposed between the movable table and the shaking table and supports the shaking table movably along the second axis relative to the movable table. The shaking device, wherein the drive belt is continuously stretched across each of the fixed table, the movable table, and the shaking table. <3> <2> In the shaking device according to the present invention, The drive unit is a first drive motor provided on the fixed base and having a first drive pulley around which the drive belt is wound; a second drive motor provided on the fixed base and having a second drive pulley around which the drive belt is wound; the shaking device further comprising: a motor control unit that controls the driving of the first drive motor and the second drive motor, and rotates the first drive pulley and the second drive pulley in forward and reverse directions, respectively. <4> <1> from <3> A shaking device according to any one of the above items, A first measurement device for measuring the turbidity of the culture solution; A control unit that controls the drive unit, A culture system, characterized in that the control unit feedback-controls the drive unit so as to change the shaking conditions of the shaking table based on the first measurement result from the first measurement device. <5> <4> In the culture system according to the present invention, A second measurement device is provided for measuring the culture state of the culture object contained in the culture solution, The control unit feedback-controls the drive unit so as to change the shaking conditions of the shaking table based on the second measurement result from the second measurement device. <6> <5> In the culture system according to the present invention, A culture system, wherein the second measurement device measures the fluorescence intensity of the fluorescence emitted by the culture object. <7> <4> from <6> In the culture system according to any one of the above, a container holder that is placed on the placement surface and holds the culture container; a thermoelectric element provided in the container holder and configured to heat and cool the culture container; A temperature control unit that controls the thermoelectric element, A culture system, wherein the control unit feedback controls the temperature control unit so as to change the temperature conditions for heating and cooling by the thermoelectric element based on a first measurement result from the first measurement device. [Explanation of symbols]

[0157] W…Culture solution 1. Culture system 2…Culture container 10...Shaking device 11...Shaking table 11a...Shaking table mounting surface 12...Container holding part 13…First measuring device 14…Second measuring device 15...Control section 30...Shaking mechanism 31...Guide member 32...Drive belt 33...Drive unit 50…Movable base 60...First guide member 70…Second guide member 80...First drive motor 81…First drive pulley 82...Second drive motor 83…Second driving pulley 84...Motor control unit 160...Peltier element (thermoelectric element) 170...Temperature control unit

Claims

1. A shaking table having a mounting surface on which a culture vessel containing a culture solution containing a culture object is mounted; A shaking mechanism for shaking the shaking table in a plane parallel to the mounting surface, The shaking mechanism includes: A guide member that supports the shaking table movably along a first axis and a second axis that intersect with each other in a plane parallel to the placement surface; A drive belt that moves the shaking table along the first axis and the second axis; A drive unit that drives the drive belt, The drive unit drives the drive belt while independently controlling the movement of the shaking table along the first axis and the movement of the shaking table along the second axis, The guide member is A fixed stand and A movable table is disposed above the fixed table and below the shaking table; a first guide member disposed between the fixed base and the movable base and configured to support the movable base movably along the first axis relative to the fixed base; A second guide member is disposed between the movable table and the shaking table and supports the shaking table movably along the second axis relative to the movable table. The shaking device is characterized in that the drive belt is continuously stretched across the fixed table, the movable table and the shaking table.

2. The shaking device according to claim 1, The drive unit is a first drive motor provided on the fixed base and having a first drive pulley around which the drive belt is wound; a second drive motor provided on the fixed base and having a second drive pulley around which the drive belt is wound; a motor control unit that controls the driving of the first drive motor and the second drive motor, and rotates the first drive pulley and the second drive pulley in forward and reverse directions, respectively.

3. A shaking device according to claim 1 or 2, A first measurement device for measuring the turbidity of the culture solution; A control unit that controls the drive unit, The culture system, wherein the control unit feedback-controls the drive unit so as to change shaking conditions of the shaking table based on a first measurement result from the first measurement device.

4. In the culture system according to claim 3, A second measurement device is provided for measuring a culture state of a culture object contained in the culture solution, The control unit feedback-controls the drive unit so as to change the shaking conditions of the shaking table based on the second measurement result from the second measurement device.

5. The culture system according to claim 4, A culture system, wherein the second measurement device measures the fluorescence intensity of the fluorescence emitted by the culture object.

6. In the culture system according to claim 3, a container holder that is placed on the placement surface and holds the culture container; a thermoelectric element provided in the container holder and configured to heat and cool the culture container; A temperature control unit that controls the thermoelectric element, A culture system, wherein the control unit feedback controls the temperature control unit so as to change the temperature conditions for heating and cooling by the thermoelectric element based on a first measurement result from the first measurement device.

Images