Shaking device and culture system

Abstract

A shaking device (10) is provided with: a shaking table (11) having a placement surface (11a) for placing a culture container accommodating a culture solution containing an object to be cultured; and a shaking mechanism (30) for shaking the shaking table in a plane parallel to the placement surface. The shaking mechanism comprises: a guide member (31) that movably supports the shaking table along a first axis (X axis) and a second axis (Y axis) that intersect each other in the plane parallel to the placement surface; a drive belt (32) that moves the shaking base along the first axis and the second axis; and a drive unit (33) 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.

Description

Vibrator and culture system

[0001] The present invention relates to a vibrator and a culture system. This application claims priority from Japanese Patent Application No. 2024-168459 filed in Japan on September 27, 2024, and Japanese Patent Application No. 2025-039423 filed in Japan on March 12, 2025, and incorporates their contents herein by reference.

[0002] As one method of culturing a culture object such as a microorganism such as bacteria or a cell, a method of culturing while vibrating (shaking) a culture solution containing the culture object is known. Specifically, a vibrator is used that vibrates a culture container such as a flask containing the culture solution under certain culture conditions using a shaking table. By vibrating the culture container, for example, it is possible to effectively take in oxygen, enzymes, etc. into the culture solution and stir the culture solution, so that the growth (cultivation) of the culture object can be promoted.

[0003] As this type of vibrator, for example, in Patent Document 1 below, a vibrator capable of smoothly rotating a shaking table at high speed is known (see Patent Document 1). This vibrator includes a main housing including a fixed shaft body rotationally driven by a motor, an eccentric shaft body arranged eccentrically with respect to the fixed shaft body, an eccentric housing connected to the main housing, a shaking table connected to the eccentric shaft body, and a rotation restricting mechanism for restricting the rotation of the shaking table.

[0004] Japanese Patent Application Laid-Open No. 2004-290084

[0005] According to the conventional shaking device described above, the main housing, including the fixed shaft, is rotationally driven, allowing the shaking platform to revolve (orbit) via the eccentric shaft while restricting its rotation with a rotation-restricting mechanism. Therefore, the culture vessel set on the shaking platform can be shaken while being stably rotated. However, conventional shaking devices can only periodically perform the same action, such as rotating the shaking platform using the eccentric rotation mechanism (main housing and eccentric housing). When culturing a substance, there is a need to appropriately adjust or change the shaking conditions, taking into account various conditions such as the type of substance and culture medium, the purpose of cultivation, the application, and the progress of cultivation. In this respect, the conventional shaking device described above is limited to the specific movement of rotating the shaking platform, and therefore cannot adequately address such needs, leaving room for improvement.

[0006] This invention has been made in consideration of these circumstances, and its purpose is to provide a shaking device that can easily adjust and change shaking conditions, and a culture system equipped with the shaking device.

[0007] (1) The shaking device according to the present invention comprises a shaking platform having a mounting surface on which a culture container containing a culture medium containing a substance to be cultured is placed, and a shaking mechanism for shaking the shaking platform in a plane parallel to the mounting surface. The shaking mechanism comprises guide members that support the shaking platform so as to be movable along a first axis and a second axis that intersect each other in a plane parallel to the mounting surface, a drive belt for moving the shaking platform along the first axis and the second axis, and a drive unit for driving the drive belt. The drive unit is characterized in that it drives the drive belt while independently controlling the movement of the shaking platform along the first axis and the movement of the shaking platform along the second axis.

[0008] According to the shaking device of the present invention, a shaking platform is supported by a guide member so as to be movable along a first axis and a second axis that intersect each other in a plane parallel to the mounting surface (horizontal plane). As a result, by driving a drive belt with a drive unit, the shaking platform can be moved along the first axis and the second axis while being guided by the guide member. Therefore, the shaking platform can be periodically moved and shaken using the drive belt. Consequently, the culture medium 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 shaker platform along the first and second axes, allowing the shaker platform to be shaken in a variety of shaking patterns. For example, it is possible to shake the shaker platform in a pattern where it moves linearly along the first or second axis, or in a pattern where it moves in a circular or elliptical motion by combining movement along the first and second axes. Furthermore, it is also possible to shake the shaker platform in a pattern where it repeats a semicircular motion back and forth, or in a pattern where it traces a figure eight. In particular, by creating continuous motion with a complex trajectory, it is possible to generate motion that deliberately shifts the natural frequency of the culture vessel. This can create a more disturbed liquid surface, which is expected to efficiently incorporate air and other substances into the culture medium. In addition, since adjustment is possible on two axes (X axis and Y axis), it is possible to change the shaking conditions to match the culture vessel being used, even when using different culture vessels.

[0010] Therefore, instead of being limited to specific shaking patterns as in the past, the shaking platform can be shaken with fine and diverse shaking patterns. Consequently, the shaking conditions can be easily adjusted and changed according to the situation, and the culture medium in the culture vessel can be mixed in an optimal state each time. In particular, it is possible to shake the culture medium with a stimulus that changes in intensity rather than a constant stimulus. Consequently, optimal cultivation can be performed according to the culture target and culture medium.

[0011] (2) The guide member may include a fixed base, a movable base positioned above the fixed base and below the shaking base, a first guide member positioned between the fixed base and the movable base and supporting the movable base so as to be movable along the first axis relative to the fixed base, and a second guide member positioned between the movable base and the shaking base and supporting the shaking base so as to be movable along the second axis relative to the movable base. The drive belt may be continuously stretched between the fixed base, the movable base and the shaking base.

[0012] In this case, the drive belt is continuously stretched between the fixed base, the movable base, and the shaking base. Therefore, by driving the drive belt, it is possible to move, for example, the movable base supported by the first guide member relative to the fixed base, and move the entire movable base and shaking base along the first axis. Furthermore, by driving the drive belt, it is possible to move, for example, the shaking base supported by the second guide member relative to the movable base, and move the shaking base along the second axis. Furthermore, by driving the drive belt, it is possible to move the shaking base along both the first and second axes by moving the movable base relative to the fixed base and the shaking base relative to the movable base. In this way, the shaking base can be vibrated with fine and diverse vibration patterns using a single drive belt (endless belt).

[0013] (3) The drive unit may also include 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, and a motor control unit that controls the driving of the first drive motor and the second drive motor, respectively, and rotates the first drive pulley and the second drive pulley in forward and reverse directions, respectively.

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

[0015] (4) The culture system according to the present invention comprises the shaking device, a first measuring device for measuring the turbidity of the culture medium, and a control unit for controlling the drive unit. The control unit is characterized in that it provides feedback control to the drive unit to change the shaking conditions of the shaking platform based on the first measurement result from the first measuring device.

[0016] According to the culture system of the present invention, during the process of culturing the culture medium while shaking the culture vessel using a shaking device, the turbidity of the culture medium can be measured using a first measuring device. As a result, the control unit can understand the culture state of the culture medium containing the target organism based on the first measurement result (turbidity of the culture medium). Therefore, the control unit can determine whether the culture has been properly completed by the shaking device or whether the culture is insufficient. If the control unit determines, for example, that the culture is insufficient, it provides feedback control to the drive unit to change the shaking conditions of the shaking platform. This makes it possible to promote culture while shaking the culture vessel with different shaking patterns, enabling reliable and efficient culturing.

[0017] (5) The system may also include a second measuring device for measuring the culture state of the cultured material contained in the culture medium. The control unit may provide feedback control to the drive unit to change the shaking conditions of the shaker platform based on the second measurement result from the second measuring device.

[0018] In this case, the culture state of the target organism can be measured using the second measuring device. Therefore, the control unit can understand the culture state of, for example, proteins or bacteria, based on the second measurement result, and determine whether the desired number and quantity of the target organism has been obtained. If the control unit determines, for example, that the production of the target organism is insufficient, it provides feedback control to the drive unit to change the shaking conditions of the shaking platform. This allows the culture to be promoted while shaking the culture vessel with different shaking patterns, enabling efficient and appropriate acquisition of the target organism.

[0019] (6) The second measuring device may also measure the fluorescence intensity of the fluorescence emitted by the culture target.

[0020] In this case, the second measuring device measures the fluorescence intensity from the cultured substance, allowing the control unit to determine that a certain amount of the cultured substance has been produced through cultivation and expressed by various expression systems. This is particularly effective when the cultured substance is a protein that emits fluorescence.

[0021] (7) The device may also include a container holding section that is placed on the aforementioned surface and holds the culture container, a thermoelectric element provided in the container holding section for heating and cooling the culture container, and a temperature control section for controlling the thermoelectric element. The control section may provide feedback control to change the temperature conditions under which the thermoelectric element heats and cools based on the first measurement result from the first measuring device.

[0022] In this case, the container holder can be used to hold the culture container against the mounting surface of the shaking platform, allowing for stable culture. In particular, since a thermoelectric element is provided in the container holder, the temperature control unit can heat or cool the culture medium by controlling the thermoelectric element. Therefore, for example, it is possible to perform culture under constant temperature conditions, or to rapidly cool the culture medium after reaching a certain turbidity to promote the expression of the target substance (e.g., protein). Furthermore, if the control unit determines that the culture is insufficient based on the first measurement result (turbidity of the culture medium) from the first measuring device, it can provide feedback control to the temperature control unit to perform culture under different temperature conditions. This makes it possible to accelerate the culture.

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

[0024] This is a perspective view showing an embodiment of the culture system according to the present invention. This is a front view of the culture system shown in Figure 1, viewed from the front. This is a perspective view of the shaking device shown in Figure 1. This is a top view of the shaking device shown in Figure 3. This is a perspective view of the shaking device shown in Figure 4. This is a cross-sectional view of the shaking device along the line A-A shown by arrow A in Figure 3. This is a perspective view of the area around the shaking platform and heat sink shown in Figure 1. This is a perspective view showing the state after the heat transfer member has been removed from the state shown in Figure 7. This is a perspective view of the area around the heat sink, container holder, and measurement unit shown in Figure 1. This is a perspective view of the area around the heat sink and container holder shown in Figure 9. This is a perspective view showing the state after the culture container and pressing member have been removed from the state shown in Figure 10. This is a perspective view showing the state after the heat conductive sheet has been removed from the state shown in Figure 11. This is a perspective view of the measurement unit shown in Figure 1. This is a cross-sectional view showing the relationship between the measurement unit and the culture container shown in Figure 13. This is an example of an image (scattered light image, fluorescence image) captured by the combined imaging unit.

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

[0026] As shown in Figures 1 and 2, the culture system 1 of this embodiment comprises a shaking device 10 having a shaking platform 11, a container holding unit 12, a first measuring device 13, a second measuring device 14, and a control unit 15. A culture container 2 containing a culture medium W containing the target substance is placed on the shaking platform 11. The shaking device 10 shakes (vibrates) the culture container 2. The container holding unit 12 holds the culture container 2 relative to the shaking platform 11. The first measuring device 13 measures the turbidity of the culture medium W. The second measuring device 14 measures the culture state of the target substance contained in the culture medium W. The control unit 15 comprehensively controls each of these devices.

[0027] The target product refers to substances produced by microorganisms through processes such as fermentation and metabolism, and includes, for example, proteins, organic compounds produced by lactic acid bacteria through fermentation, peptides, etc. In this embodiment, protein is assumed to be the target product. Therefore, culture system 1 is assumed to be a protein culture system capable of simultaneously measuring the turbidity of the culture medium W in which the protein is expressed and measuring the fluorescence intensity of the protein.

[0028] The culture medium W, which expresses the target substance, is contained in the culture vessel 2. The culture vessel 2 is shaken under predetermined culture conditions by a shaking device 10 that constitutes the culture system 1. As a result, the culture medium W is cultured in the culture vessel 2, and its turbidity increases as the culture progresses. The culture system 1 measures the turbidity of the culture medium W to understand the progress of the culture (culture state), and also measures the fluorescence intensity of the target substance to understand 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 between the bottom 3 and the side wall 4 is an annular curved surface 5 that extends continuously around the entire circumference of the bottom 3. However, the culture vessel 2 is not limited to an Erlenmeyer flask; various flasks such as pear-shaped flasks, round-bottom flasks, and shaking flasks may also be used. Furthermore, test tubes, petri dishes, and cylindrical containers such as beakers may also be used as the culture vessel 2.

[0030] Furthermore, the bounce and agitation of the culture medium W during shaking will differ depending on the shape of the culture vessel used. Therefore, it is possible to configure the system to change the shaking conditions for each type of culture vessel to achieve the optimal shaking conditions for the culture vessel being used. Specifically, this can be achieved by controlling the first drive motor 80 and the second drive motor 82 with the motor control unit 84, described later, to shake the shaking platform 11 with shaking conditions corresponding to the culture vessel being used. In this way, it is possible to perform shaking with shaking conditions corresponding to the culture vessel, rather than simply placing the culture vessel on the shaking platform 11.

[0031] Furthermore, in this embodiment, we will explain using an example in which Escherichia coli is used as the host cell, an expression vector whose expression is induced in a temperature-dependent manner is used, and the target substance is expressed by the E. coli cold shock expression system method. Accordingly, the culture medium W contains E. coli transformed with an expression vector (an expression vector containing a target gene encoding the target substance).

[0032] Furthermore, the expression vector contains a specific promoter that includes the E. coli cold shock gene, whose expression is induced when the culture temperature of E. coli is low (e.g., 15°C). Specifically, the specific promoter is the lactose operon (lac I, Lac operator). The lactose operon controls the expression of the E. coli cold shock gene promoter. It is known that the control of the lactose operon can be released by reagents (expression inducers) such as IPTG (Isopropyl-β-D-thiogalactopyranoside), thereby allowing the expression of the E. coli cold shock gene promoter. However, specific promoters such as the lactose operon are not essential and do not need to be included in the expression vector.

[0033] <Shaking Device> As shown in Figures 1 to 5, the shaking device 10 comprises a shaking platform 11 having a mounting surface 11a on which the culture vessel 2 is placed, and a shaking mechanism 30 for shaking the shaking platform 11. The culture vessel 2 may be placed directly on the mounting surface 11a of the shaking platform 11, but in this embodiment, the case in which it is placed indirectly on the mounting surface 11a via a heat sink 16 and a container holding part 12 is given as an example.

[0034] In this embodiment, as shown in Figure 1, two directions that intersect orthogonally within a plane (horizontal plane) parallel to the mounting surface 11a of the shaking platform 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, the axis line that passes vertically through the center of the shaking platform 11 is defined as the central axis O. Furthermore, in a plan view from the top and bottom, the direction intersecting the central axis O is defined as the radial direction, and the direction that circles around the central axis O is defined as the circumferential direction. Furthermore, of the front-rear direction L1, the direction from the central axis O toward the first drive motor 80 and the second drive motor 82, which will be described later, is defined as the front FW, and the opposite direction is defined as the rear BK.

[0035] (Shaking platform) As shown in Figures 3 to 5, the shaking platform 11 is formed in the shape of a plate with a constant thickness in the vertical direction, and is formed in a rectangular shape in plan view, which is longer in the front-to-back direction L1 than in the left-to-right direction L2. However, the shape of the shaking platform 11 is not limited to this case, and for example, it may be formed in a rectangular shape in plan view, which is longer in the left-to-right direction L2 than in the front-to-back direction L1, or it may be formed in a square shape in plan view.

[0036] A connecting piece 20, to which a drive belt 32 (described later) is linked, is integrally fixed to the shaking platform 11. The connecting piece 20 is formed in an L-shape when viewed from the side, a so-called L-angle. The connecting piece 20 is fixed to the shaking platform 11 so as to contact the mounting surface 11a of the shaking platform 11 from above. Furthermore, the connecting piece 20 is fixed to the shaking platform 11 so as to contact the front side surface of the shaking platform 11 facing forward FW from the forward FW. As shown in Figure 5, a grooved plate 21 with multiple grooves formed therein is fixed to the front surface of the connecting piece 20 facing forward FW. The multiple grooves formed in the grooved plate 21 are formed in a vertically elongated shape along the vertical direction, and multiple grooves are formed at intervals in the left-right direction L2. These multiple grooves are formed to correspond to multiple grooves and protrusions (not shown) formed on the drive belt 32.

[0037] (Shaking Mechanism) As shown in Figures 3 to 5, the shaking mechanism 30 shakes the shaking platform 11 configured as described above in a plane parallel to the mounting surface 11a. The shaking mechanism 30 includes guide members 31 that support the shaking platform 11 so that it can move along the X axis and Y axis, a drive belt 32 that moves the shaking platform 11 along the X axis and Y axis, and a drive unit 33 that drives the drive belt 32. Note that the drive belt 32 is not shown in Figure 5.

[0038] (Guiding Members) The guide member 31 comprises a fixed base 40, a movable base 50, a first guide member 60, and a second guide member 70. The movable base 50 is positioned above the fixed base 40 and below the shaking table 11. The first guide member 60 is positioned between the fixed base 40 and the movable base 50 and supports the movable base 50 so that it can move along the X-axis relative to the fixed base 40. The second guide member 70 is positioned between the movable base 50 and the shaking table 11 and supports the shaking table 11 so that it can move along the Y-axis relative to the movable base 50.

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

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

[0041] Support columns 43 extending downwards 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 Figure 1, the shaking device 10 has an outer cover 17 that surrounds each component, such as the fixing base 40, the support columns 43, and the shaking platform 11, from the outside. As a result, each component, including the fixing base 40, the support columns 43, and the shaking platform 11, is hidden from view by the outer cover 17. Note that the outer cover 17 is not shown in Figure 2.

[0042] As shown in FIGS. 3 to 5, the pair of second fixing plates 42 has a greater thickness than the first fixing plate 41 and is formed in a rectangular shape in 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 in a long shape along the front-rear direction L1 so as to cover the entire length of the first fixing plate 41 from above. 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 arranged to be parallel to each other with a gap therebetween in the left-right direction L2.

[0043] Support plates 44 for supporting a first drive motor 80 and a second drive motor 82, which will be described later, are respectively fixed to the front end portions of the pair of second fixing plates 42. The support plates 44 have the same thickness as the second fixing plates 42 and are arranged so as to overlap the upper surfaces of the second fixing plates 42, respectively. Further, the support plates 44 are formed so as to project forward FW from the second fixing plates 42. A circular insertion hole 45 penetrating the support plate 44 in the up-down direction is formed in the support plate 44. Further, a guide groove 46 that opens rearward BK and upward is formed in the support plate 44.

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

[0045] The movable base 50 comprises a pair of first movable plates 51 and a second movable plate 52. The pair of first movable plates 51 are arranged to overlap the pair of second fixed plates 42 from above. The second movable plate 52 connects 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 the pair of first movable plates 51 and the second movable plate 52 are integrated. However, it is not limited to this case, and the movable base 50 may also be constructed by forming the pair of first movable plates 51 and the second movable plate 52 separately and then combining them integrally.

[0046] Each of the pair of first movable plates 51 has the same thickness as the second fixed plate 42 and is formed in a rectangular shape in plan view, with the length in the front-to-back direction L1 being longer than the left-to-right direction L2. The first movable plates 51 are formed such that the width along the left-to-right direction L2 is smaller than the width of the second fixed plate 42, and the length along the front-to-back direction L1 is smaller than the length of the second fixed plate 42. The pair of first movable plates 51 are positioned above the pair of second fixed plates 42 so that they are parallel to each other with a gap in the left-to-right direction L2. The pair of first movable plates 51 are positioned outside the front connecting plate 47 in the left-to-right direction L2 and are positioned behind the support plate 44 at BK. Furthermore, the pair of first movable plates 51 are positioned so that they can enter the inside of the guide groove 46 formed in the support plate 44 from the rear BK.

[0047] The second movable plate 52 has the same thickness as the pair of first movable plates 51 and is formed in a rectangular shape in 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 such that the length along the front-rear direction L1 is smaller than the length of the first movable plate 51 and is formed so as to shift toward the rear BK side from the front end portion of the first movable plate 51. In addition, a through hole 53 penetrating the second movable plate 52 in the vertical direction is formed in the central portion of the second movable plate 52. The through hole 53 is formed in a rectangular shape in plan view that is longer in the left-right direction L2 than in the front-rear direction L1 corresponding to the shape of the second movable plate 52 and mainly functions as a relief 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 includes a pair of first guide rails 61 respectively fixed to the upper surfaces of the pair of second fixed plates 42 and first movable blocks 62 respectively fixed 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 respectively positioned below the pair of first movable plates 51. The pair of first guide rails 61 are formed to extend along the front-rear direction L1 and are formed longer in the front-rear direction L1 than the first movable plate 51. The pair of first guide rails 61 are arranged at intervals in the left-right direction L2 and are arranged parallel to each other. Further, on the side surfaces of the first guide rails 61 facing the left-right direction L2, guide grooves are formed that are recessed inward and extend along the front-rear direction L1.

[0050] The first movable block 62 is assembled to the first guide rail 61 from above so as to be able to move relative to it 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 manner that prevents it from coming off upward, and also in a manner that provides high sliding properties. Multiple (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] Since a first guide member 60 having a first guide rail 61 and a first movable block 62 is provided between the second fixed plate 42 and the first movable plate 51, 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. Alternatively, a plurality of balls (rolling elements) may be provided in the first movable block 62 so as to be circulating, and the balls may be configured to 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. Therefore, it becomes possible to move the movable base 50 even more smoothly with less resistance relative to the fixed base 40.

[0052] As shown in Figures 3 to 6, a second guide member 70 is provided between the movable base 50 and the shaking base 11. The second guide member 70 comprises 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 base 11.

[0053] The pair of second guide rails 71 are formed to extend along the left-right direction L2 and are longer in the left-right direction L2 than the shaking platform 11. The pair of second guide rails 71 are spaced apart in the front-rear direction L1 with a through hole 53 in between them, and are also arranged parallel to each other. Furthermore, guide grooves are formed on the sides of the second guide rails 71 facing the front-rear direction L1, which are recessed inward and extend along the left-right direction L2.

[0054] The second movable block 72 is assembled to the second guide rail 71 from above so as to be able to move relative to it 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 where it is prevented from coming off upward and is assembled in a state where it has high sliding properties. The second movable block 72 is attached to the lower surface of the front FW side and the lower surface of the rear BK side of the shaking platform 11, and multiple (two) of them are attached at intervals in the left-right direction L2.

[0055] Since 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 platform 11, the shaking platform 11 can be moved smoothly along the left-right direction L2 (Y axis) relative to the movable platform 50. Therefore, the second guide member 70 functions as a linear motion guide mechanism that realizes smooth linear movement of the shaking platform 11 along the left-right direction L2. In addition, the second movable block 72 may also be configured to have a plurality of balls (rolling elements) that can be circulated so that the balls circulate 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. Therefore, it becomes possible to move the shaking platform 11 even more smoothly with less resistance relative to the movable platform 50.

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

[0057] The drive unit 33 includes a first drive motor 80, a second drive motor 82, and a motor control unit 84. The first drive motor 80 has a first drive pulley 81 around which the drive belt 32 is wound, and is mounted on the fixed base 40. The second drive motor 82 has a second drive pulley 83 around which the drive belt 32 is wound, and is mounted on the fixed base 40. The motor control unit 84 controls the driving of the first drive motor 80 and the second drive motor 82, respectively, and also 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 protrude above the support plate 44 by being inserted through insertion holes 45 formed in the support plate 44. The first drive pulley 81 and the second drive pulley 83 are connected to the output shafts of the first drive motor 80 and the second drive motor 82. As a result, the first drive pulley 81 and the second drive pulley 83 are rotatable in conjunction with the driving 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, and rotation direction can be controlled by pulse signals.

[0060] The motor control unit 84 digitally controls the rotation of the output shafts at a predetermined rotation angle, rotation speed, and rotation direction by outputting pulse signals, which are electrical signals, to the first drive motor 80 and the second drive motor 82, respectively. The motor control unit 84 is mounted on a control board 18, for example, as shown in Figure 1. The control board 18 is positioned below the fixed base 40 and is supported by support members (not shown). Furthermore, the control board 18 also has a control unit 15 mounted on it, which comprehensively controls 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. Note that the control board 18 is not shown in Figure 2.

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

[0062] The pulleys other than the first drive pulley 81 and the second drive pulley 83 will now be described. In this embodiment, the 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 mounted on the upper surface of the rear end of a pair of second fixed plates 42 that constitute the fixed base 40. As a result, the first driven pulley 90 is positioned at a distance L1 in the front-rear direction from the first drive pulley 81 and is aligned in a straight line along the front-rear direction L1. Similarly, the second driven pulley 91 is positioned at a distance L1 in the front-rear direction from the second drive pulley 83 and is aligned in a straight line along the front-rear direction L1.

[0064] Furthermore, the first driven pulley 90 and the second driven pulley 91 are mounted on a pair of second fixed plates 42, and are therefore immovable in the front-rear direction L1 and the left-right direction L2. In addition, the first drive pulley 81, the second drive pulley 83, the first driven pulley 90, and the second driven pulley 91 are 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 mounted on the upper surface of the movable base 50. The first intermediate pulley 92 and the second intermediate pulley 93 are mounted on the upper surface of the front end of a pair of first movable plates 51 that constitute the movable base 50. In this case, the first intermediate pulley 92 and the second intermediate pulley 93 are arranged in a straight line along the left-right direction L2. The first intermediate pulley 92 is positioned closer to the first drive pulley 81, and the second intermediate pulley 93 is positioned closer to the second drive 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 in a straight line along the left-right direction L2 and are positioned rearward BK than the first intermediate pulley 92 and the second intermediate pulley 93. Furthermore, the third intermediate pulley 94 and the fourth intermediate pulley 95 are positioned such that their circumferential surfaces are at the same position in the front-rear direction L1 relative to the front surface of the grooved plate 21 fixed to the shaking platform 11.

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

[0068] The first drive pulley 81, second drive pulley 83, first driven pulley 90, second driven pulley 91, first intermediate pulley 92, second intermediate pulley 93, third intermediate pulley 94, and fourth intermediate pulley 95, configured as described above, are each positioned 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, second intermediate pulley 93, second drive pulley 83, second driven pulley 91, third intermediate pulley 94, fourth intermediate pulley 95, and first driven pulley 90, and back to the first drive pulley 81. In particular, the drive belt 32 is stretched across multiple pulleys while maintaining a constant tension and suppressing slack. Furthermore, the drive belt 32 is stretched across multiple pulleys while restricting vertical displacement and slippage.

[0069] Furthermore, multiple elongated grooves corresponding to the grooves and protrusions of the drive belt 32 are formed around the entire circumference 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 across the multiple pulleys in a state where slippage is suppressed by its engagement with the grooves.

[0070] Furthermore, the drive belt 32 is linked to the shaker table 11 in a manner in which slippage is suppressed by its engagement with grooves formed on the front surface of the grooved plate 21 fixed to the shaker table 11. This makes it possible to move the shaker table 11 in conjunction with the drive of the drive belt 32.

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

[0072] Furthermore, the shaking mechanism 30 of this embodiment includes a first position detection switch 100 and a second position detection switch 101 for detecting excessive movement of the shaking platform 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 positioned with the switch portion 100a facing the rear BK. The first position detection switch 100 switches from the OFF state to the 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 which constitutes the movable base 50. The second position detection switch 101 is positioned with the switch portion 101a facing inward in the left-right direction L2 (facing the shaking base 11). The second position detection switch 101 switches from the OFF state to the ON state when the shaking base 11 comes into contact with the switch portion 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 is capable of detecting, based on the first and second detection signals, when the shaking platform 11 moves excessively in the forward / backward direction L1 and the left / right direction L2 while the shaking platform 11 is being shaken. This allows the motor control unit 84 to stop the pulse signals output to the first drive motor 80 and the second drive motor 82. As a result, it is possible to perform appropriate shaking.

[0075] As shown in Figures 1 and 2, the culture system 1 includes a heat sink 16 and a container holder 12, which are combined with the shaking platform 11 of the shaking device 10 configured as described above. The heat sink 16 is combined with the shaking platform 11, which is mounted on the mounting surface 11a via a relay member 110. The container holder 12 is combined with the heat sink 16, which is positioned above the heat sink 16. As a result, the culture container 2 is held by the container holder 12 indirectly on the mounting surface 11a of the shaking platform 11 via the container holder 12 and the heat sink 16.

[0076] As shown in Figure 7, the intermediate member 110 is formed in a cylindrical shape having an upper flange portion 111 and a lower flange portion 112, and is arranged coaxially with the central axis O. The lower flange portion 112 is fixed to the shaking table 11 while resting on the mounting surface 11a of the shaking table 11. In this way, the intermediate member 110 is integrally assembled 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, an upper connecting portion 121, and a plurality of heat dissipation fins 122. The lower connecting portion 120 is placed on the lower flange portion 112 by being superimposed on the lower flange portion 112 from above. The upper connecting portion 121 is positioned above the lower connecting portion 120, with a certain distance between them. The plurality of heat dissipation fins 122 are positioned between the lower connecting portion 120 and the upper connecting portion 121. The heat sink 16 is positioned coaxially with the central axis O.

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

[0079] As shown in Figures 7 and 8, a heat transfer member 130 is assembled to the upper connecting portion 121 from above. The heat transfer member 130 comprises a cylindrical first heat transfer member 131 positioned inside the through hole, and a second heat transfer member 132 that is square in plan view and superimposed on the bulging portion 126 from above. The first heat transfer member 131 is fitted, for example, inside the through hole, and its lower surface protrudes below 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 above 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 disc shape with an outer diameter larger than the outer dimensions of the shaking platform 11. Multiple heat dissipation fins 122 are arranged coaxially with the central axis O, spaced vertically between the lower connecting portion 120 and the upper connecting portion 121. Specifically, a vertically elongated heat transfer rod (not shown) extending in the vertical direction is arranged between the lower connecting portion 120 and the heat transfer member 130 combined with the upper connecting portion 121. Multiple heat transfer rods are arranged circumferentially with the central axis O as the center, and are also arranged to penetrate multiple heat dissipation fins 122 in the vertical direction. The upper ends of the heat transfer rods are in contact with the lower surface of the second heat transfer member 132. As a result, the heat transfer member 130 and the heat transfer rods are thermally connected. Furthermore, spacers 135 (see Figure 2), inserted into the heat transfer rods, are placed between vertically adjacent heat dissipation fins 122. As a result, the multiple heat dissipation fins 122 are arranged to overlap each other via spacers 135, maintaining a constant distance between them in the vertical direction, and are supported by heat transfer rods.

[0081] The heat transfer member 130, heat dissipation fins 122, heat transfer rod, and spacer 135 are made of a material with excellent thermal conductivity (heat dissipation), and may be made of metal or non-metal.

[0082] (Container holding section) As shown in Figures 9 to 11, the container holding section 12 comprises a container support section 140 and a ring-shaped pressing member 150. The container support section 140 is assembled to the upper connecting section 121 from above and supports the culture container 2 from below. The pressing member 150 surrounds the culture container 2 from the radial outside and locks to the container support section 140 from above.

[0083] As shown in Figure 12, the container support portion 140 comprises a first support portion 141 and a second support portion 145. The first support portion 141 has a circular support body 142 in plan view, with a flat support surface 142a on its upper surface. The second support portion 145 is formed in a ring shape that surrounds the support body 142 from the radial outside. The first support portion 141 is assembled to the upper connecting portion 121 in a state where it overlaps the upper connecting plate 125 from above. A fitting hole 143 is formed in the center of the support body 142, penetrating the support body 142 in the vertical direction. The fitting hole 143 is formed in a rectangular shape in 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 assembled to the upper connecting portion 121 with the second heat transfer member 132 fitted inside the fitting hole 143.

[0084] As shown in Figure 12, the second support portion 145 is assembled to the first support portion 141 from above, surrounding the support body 142 from the radial outside. The second support portion 145 has a locking piece 146 that protrudes upward and extends along the circumferential direction, and is arc-shaped in plan view. Two locking pieces 146 are provided spaced apart in the circumferential direction. In the illustrated example, the two locking pieces 146 are arranged to face each other radially across the central axis O. However, this is not the only example; for example, three or more locking pieces 146 may be provided spaced apart in the circumferential direction.

[0085] As shown in Figures 10 and 12, the locking piece 146 is positioned radially outward from the curved surface 5 and side wall 4 of the culture container 2 when the culture container 2 is set. Furthermore, the locking piece 146 is formed to decrease in diameter from bottom to top, corresponding to the slope of the side wall 4 of the culture container 2.

[0086] As shown in Figures 9 and 10, the retaining member 150 is formed in a ring shape that surrounds the curved surface 5 and side wall 4 of the culture container 2 from the radial outside, and is assembled to the second support portion 145 from above. The retaining member 150 is formed so that its diameter decreases from bottom to top, corresponding to the inclination of the side wall 4 of the culture container 2. A pair of locking pieces 146 can be inserted from below into the lower surface of the retaining member 150, and a pair of locking holes (not shown) are formed into which the locking pieces 146 are locked. Therefore, after setting the culture container 2 on the support surface 142a, the retaining member 150 can be set from above and the locking pieces 146 can be locked into the locking holes, thereby integrally assembling the retaining member 150 with the container support portion 140.

[0087] Therefore, the retaining member 150 can be assembled with a single touch without using fastening members such as bolts. In particular, since the retaining member 150 is tapered in diameter from bottom to top to correspond to the shape of the culture container 2, it can hold the culture container 2 while restricting its upward movement.

[0088] In this embodiment, the case in which the retaining member 150 is combined with the container support portion 140 using the locking piece 146 has been described as an example, but the invention is not limited to this case. For example, instead of providing the locking piece 146, magnets or the like can be provided on the container support portion 140 and the retaining member 150, and the retaining member 150 can be combined using magnetic force.

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

[0090] (Thermoelectric element) As shown in Figure 12, the container holding section 12 configured as described above is provided with a Peltier element 160 as a thermoelectric element for heating and cooling the culture container 2 that is set in place. As shown in Figures 7 and 8, the Peltier element 160 is formed in a square shape in 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 Peltier element 160 has its first main surface 161 facing upward and its second main surface 162 in surface contact with the heat transfer surface 132a. Based on the principle of the inverse of the Seebeck effect, 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.

[0091] As shown in Figure 12, the Peltier element 160 is positioned inside the fitting hole 143 formed in the support 142 of the container support 140, with its first main surface 161 flush with the support surface 142a. This allows the Peltier element 160 to heat and cool the culture container 2 from the bottom 3. As shown in Figure 11, a heat conductive sheet 165 is provided inside the second support 145, covering the entire first main surface 161 and the support surface 142a from above. Therefore, the entire bottom 3 of the culture container 2 can be heated and cooled efficiently and evenly via the heat conductive sheet 165.

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

[0093] Furthermore, as shown in Figure 1, the multiple heat dissipation fins 122 are covered from the radial outside by the upper cover 19, thus concealing them from the outside. The upper cover 19 is, for example, combined with the outer cover 17. In addition, a fan or the like (not shown) may be provided on the upper cover 19. By providing a fan, for example, outside air can be supplied to the inside of the upper cover 19, or outside air can be discharged from the inside of the upper cover 19. Therefore, it is possible to increase the heat exchange efficiency of the heat dissipation fins 122.

[0094] As shown in Figure 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 a control board 18, for example, as shown in Figure 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 energizing time, the direction of the current, etc., based on signals from the control unit 15. This makes it possible to control the heating and cooling of the culture container 2 using the Peltier element 160. The container holder 12 incorporating the Peltier element 160, the heat dissipation fins 122, the temperature control unit 170, etc., function as a temperature control device that heats and cools the culture container 2.

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

[0096] <First measuring device, second measuring device> As shown in Figures 1 and 2, the culture system 1 is equipped with a measuring unit 180. The measuring unit 180 includes a first measuring device 13 for measuring the turbidity of the culture medium W, and a second measuring device 14 for measuring the culture state of the target substance contained in the culture medium W. The measuring unit 180 is positioned above the shaking device 10 and is located outside the culture container 2, which is held by the container holding part 12. Specifically, the measuring unit 180 is positioned outside in the left-right direction L2, with a gap between it and the culture container 2 and the pressing member 150. The measuring 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 it may be provided separately from the shaking device 10. The measurement unit 180 may also be positioned in front of the culture vessel 2 FW or behind it BK.

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

[0099] (Light Irradiation Unit) As shown in Figure 14, the light irradiation unit 181 irradiates excitation light EL towards the interface between the inner surface of the culture container 2 and the culture medium W through the measurement hole 151 (see Figure 9) of the retaining member 150. The light irradiation unit 181 is positioned to irradiate the excitation light EL diagonally downward. For example, an LED light source can be used as the light irradiation unit 181. However, the light irradiation unit 181 is not limited to an LED light source; other light sources can be used as long as they can irradiate light that includes the wavelength range of the excitation light EL.

[0100] Furthermore, the light irradiation unit 181 is combined with a heat dissipation member 187 that includes multiple heat dissipation fins 186. This makes it possible to dissipate the heat generated by the light irradiation unit 181 through the heat dissipation member 187.

[0101] (Excitation Filter) As shown in Figures 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 vessel 2. The excitation filter 182 allows transmission of light in a specific wavelength range used as excitation light EL from the light irradiation 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 employed. In particular, the excitation filter 182 allows transmission of light in a wavelength range different from the wavelength range that the fluorescence filter 184 allows to pass through.

[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 excitation filter body 182a around its entire circumference. The excitation filter body 182a is formed to have a diameter at least larger than that of the light irradiation portion 181. The excitation filter 182 is held in a retaining case 185 in a replaceable manner.

[0103] (Combined Imaging Unit) The combined imaging unit 183 has the function of capturing an image of scattered light reflected at the interface between the inner surface of the culture vessel 2 and the culture medium W from the excitation light EL irradiated from the light irradiation unit 181, and acquiring it as a scattered light image 191 (see Figure 15). Furthermore, the combined imaging unit 183 has the function of capturing an image of 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 combined imaging unit 183 serves as both a first imaging unit for acquiring the scattered light image 191 and a second imaging unit for acquiring the fluorescence image 192, and is capable of acquiring both the scattered light image 191 and the fluorescence image 192, respectively.

[0104] The dual-purpose imaging unit 183 includes, for example, a flexible or rigid tubular imaging guide 200 and an imaging unit 201 provided at the tip of the imaging guide 200. Inside the imaging unit 201 are at least an objective lens (not shown) and an image sensor (not shown) that performs imaging through the objective lens. As the image sensor, for example, a CMOS sensor or a CCD sensor can be used.

[0105] The dual-purpose imaging unit 183 is held in the holding case 185 by being inserted into a holding hole 185a formed in the holding case 185. The dual-purpose imaging unit 183 is positioned with the imaging unit 201 facing the culture vessel 2. The base end of the imaging guide 200 is pulled out to the outside of the holding case 185. Inside the imaging guide 200, there are wiring cables (power lines, signal lines) (not shown) electrically connected to the image sensor, and the two captured images (scattered light image 191, fluorescence image 192) are output to the control unit 15.

[0106] (Fluorescence Filter) The fluorescence filter 184 is held in a holding case 185 so as to be located between the dual-purpose imaging unit 183 and the culture vessel 2. The fluorescence filter 184 transmits light in a wavelength range that includes the wavelength of 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 fluorescence filter 184 is a framed filter having a fluorescence filter body 184a having a dielectric multilayer film or the like, and a ring-shaped frame portion 184b that surrounds the fluorescence filter body 184a around its entire circumference.

[0107] The retaining case 185 is provided with a filter plate 210 positioned closer to the culture vessel 2 than the fluorescent filter 184. The filter plate 210 has a first imaging hole 211 and a second imaging hole 212 that penetrate through the filter plate 210 in the thickness direction. The dual-purpose imaging unit 183 is positioned so that its imaging axis IA penetrates 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 culture vessel 2 side, the imaging units 201 of the dual-purpose imaging unit 183 are positioned inside the first imaging hole 211 and the second imaging hole 212, respectively. The imaging axis IA is positioned to intersect the interface to which the excitation light EL is irradiated. In particular, the dual-purpose imaging unit 183 is positioned so that its imaging axis IA is non-coaxial with respect to the optical axis of the excitation light EL reflected from its inner surface.

[0108] Therefore, as shown in Figure 15, the dual-purpose imaging unit 183 can acquire a fluorescence image 192 through the fluorescence filter 184 and the first imaging aperture 211, and can also acquire a scattered light image 191 through the second imaging aperture 212. Thus, it is possible to acquire both the scattered light image 191 and the fluorescence image 192 using a single dual-purpose imaging unit 183. Furthermore, the fluorescence image 192 and the scattered light image 191 can be included in a single image 190 captured by the dual-purpose imaging unit 183.

[0109] As shown in Figure 13, the dual-purpose imaging unit 183 is positioned such that the imaging axis IA intersects the interface to which the excitation light EL is irradiated. Therefore, as shown in Figure 15, the optical center LO of the excitation light EL irradiated to the interface can be positioned at the center of the captured image 190. Furthermore, as shown in Figure 15, a portion of the frame 184b is intentionally included in the captured image 190. In this way, the fluorescence filter 184 uses the frame 184b to block strong reflected light from the optical center LO from entering the captured image 190.

[0110] (Control Unit) The control unit 15, mounted on the control board 18 shown in Figure 1, is connected to the light irradiation unit 181 and the combined imaging unit 183, as shown in Figure 14, and controls their operation. For example, the control unit 15 controls the irradiation timing and irradiation time of the light irradiation unit 181, as well as the imaging timing of the combined imaging unit 183. Furthermore, the control unit 15 includes at least a memory unit 220 and a measurement unit 221. The memory unit 220 stores the scattered light image 191 and the fluorescence image 192 captured by the combined imaging unit 183, respectively. The measurement unit 221 measures the turbidity of the culture medium W and the fluorescence intensity of the target substance based on the scattered light image 191 and the fluorescence image 192.

[0111] In this embodiment, since a single captured image 190 contains both a scattered light image 191 and a fluorescence image 192, the memory unit 220 stores the scattered light image 191 and the fluorescence image 192 in association. As shown in Figure 15, the measurement unit 221 defines the region of the scattered light image 191 and fluorescence image 192 contained in the captured image 190 that is at the same distance from the optical center LO as the data acquisition region R, and extracts partial images of the scattered light image 191 and the fluorescence image 192 within the data acquisition region R. The measurement unit 221 measures the turbidity of the culture medium W and the fluorescence intensity of the target substance from these partial images.

[0112] The light irradiation unit 181, excitation filter 182, combined imaging unit 183, and measurement unit 221 function as a first measuring device 13 for measuring the turbidity of the culture medium W. Furthermore, the light irradiation unit 181, excitation filter 182, fluorescence filter 184, combined imaging unit 183, and measurement unit 221 function as a second measuring device 14 for measuring the culture state of the target substance contained in the culture medium W. Therefore, the scattered light image 191 functions as the first measurement result, and the fluorescence image 192 functions as the second measurement result.

[0113] Furthermore, the control unit 15 comprehensively controls the various components constituting the culture system 1 by having the CPU execute various programs as appropriate, thereby enabling the culture system 1 to perform the culture operation. The various programs are recorded on a computer-readable recording medium (not shown).

[0114] "Computer-readable recording media" refers to portable media such as flexible disks, magneto-optical disks, CD-ROMs, and semiconductor memory, which are read via a drive device (e.g., a CD-ROM drive) or interface (e.g., a USB interface). Furthermore, "computer-readable recording media" are not limited to the above-mentioned portable media, but may also include storage units such as hard disks built into computer systems (which include hardware such as operating systems and peripheral devices). Moreover, "computer-readable recording media" may also include those that dynamically hold programs for a short period of time, such as communication lines used when transmitting programs over networks such as the Internet or communication lines such as telephone lines, and those that hold programs for a fixed period of time, such as volatile memory inside computer systems that act as servers or clients in such cases.

[0115] Furthermore, the control unit 15 provides feedback control to the motor control unit 84, which constitutes the drive unit 33, to change the shaking conditions of the shaking platform 11 based on the turbidity results measured by the measurement unit 221 (measurement results from the first measurement device 13). Furthermore, the control unit 15 provides feedback control to the motor control unit 84 to change the shaking conditions of the shaking platform 11 based on the fluorescence intensity results of the target substance measured by the measurement unit 221 (measurement results from the second measurement device 14). Furthermore, the control unit 15 provides feedback control to the temperature control unit 170 to change the temperature conditions for heating and cooling the Peltier element 160 based on the turbidity results.

[0116] (Operation of the Culture System) Next, we will explain the sequence of steps involved in culturing the culture medium W, measuring the turbidity of the culture medium W, and measuring the fluorescence intensity of the expressed target substance using the culture system 1 configured as described above. This explanation will also include the cultivation of E. coli and the expression of the target substance.

[0117] First, E. coli containing the expression vector is added to the culture medium W contained in the culture vessel 2. Next, the culture vessel 2 is held using the container holder 12, which is combined with the shaking platform 11 shown in Figures 1 and 2. Then, the culture vessel 2 is shaken using the shaking device 10 while maintaining a predetermined culture temperature (for example, 37°C). This allows the E. coli to be cultured. The turbidity of the culture medium W tends to increase as the E. coli culture progresses.

[0118] After holding the culture container 2 using the container holding section 12, the temperature control unit 170, instructed by the control unit 15, controls the Peltier element 160 to heat the culture container 2 via the first main surface 161. This allows the bottom 3 of the culture container 2 to be heated efficiently and evenly using the heat conductive sheet 165. Consequently, the culture medium W can be heated and maintained at a predetermined culture temperature.

[0119] In this configuration, 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 multiple heat dissipation fins 122, the heat absorption efficiency can be increased. Consequently, a temperature difference can be easily created between the first main surface 161 and the second main surface 162, thereby improving the heat dissipation performance (heating performance) of the first main surface 161. Therefore, the culture medium W can be heated efficiently.

[0120] Furthermore, simultaneously with or before / after the heating of the culture vessel 2 described above, the motor control unit 84, receiving instructions from the control unit 15, controls the first drive motor 80 and the second drive motor 82 shown in Figure 3 to drive the drive belt 32. This allows the shaker platform 11 to be moved in the forward / backward 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 shaker platform 11 to be periodically moved using the drive belt 32, thereby causing the shaker platform 11 to shake. As a result, the culture medium W contained in the culture vessel 2 can be stirred, promoting cultivation.

[0121] In particular, the drive unit 33 drives the drive belt 32 while independently controlling the movement of the shaker table 11 along the X and Y axes, so that the shaker table 11 can be shaken in various shaking patterns. Specifically, by using the motor control unit 84 to control 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 adjusted via the first drive pulley 81 and the second drive pulley 83. More specifically, by using the motor control unit 84 to adjust the rotation direction, rotation speed, rotation timing, etc., of the first drive motor 80 and the second drive motor 82, the drive pattern of the drive belt 32 can be freely adjusted. As a result, for example, it is possible to shake the shaker table 11 in a shaking pattern that moves the shaker table 11 linearly in the forward / backward direction L1 along the X axis or in the left / right direction L2 along the Y axis, or in a shaking pattern that causes the shaker table 11 to move in a circular motion or an elliptical motion by combining movement along the X and Y axes. Furthermore, by combining movements along the X and Y axes, it is possible to shake the shaking platform 11 in shaking patterns that repeat semicircular motions or shaking patterns that trace a figure eight.

[0122] For example, as shown in Figures 3 and 4, the culture vessel 2 can be shaken along the front-rear direction L1 by rotating the first drive motor 80 and the second drive motor 82 in opposite directions at the same rotational speed. Specifically, the first drive motor 80 is rotated in the direction indicated by arrow M1, and the second drive motor 82 is rotated in the direction indicated by arrow M2. This allows the entire assembly of the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 to move forward FW via the drive belt 32. Furthermore, the first drive motor 80 is rotated in the direction indicated by arrow M3, and the second drive motor 82 is rotated in the direction indicated by arrow M4. This allows the entire assembly of the first intermediate pulley 92, the second intermediate pulley 93, the third intermediate pulley 94, and the fourth intermediate pulley 95 to move backward BK via the drive belt 32. Therefore, by performing the above-described operations alternately, the entire movable platform 50 and the shaking platform 11 can be moved linearly back and forth along the X-axis (front-to-back direction L1) along the first guide rail 61 of the first guide member 60. This allows the culture container 2 to be shaken along the front-to-back direction L1.

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

[0124] Furthermore, the above-described operations can be combined by, for example, rotating the first drive motor 80 and the second drive motor 82 at different rotational speeds and in the same or opposite directions. Therefore, the culture vessel 2 can be shaken in various patterns, such as a reciprocating motion at an angle, circular motion, elliptical motion, semicircular motion, or figure-eight motion.

[0125] Therefore, the shaking device 10 of this embodiment allows for the shaking of the shaking platform 11 and the culture vessel 2 with fine and diverse shaking patterns, rather than being limited to specific movements as in conventional devices. Consequently, the shaking conditions can be easily adjusted and changed according to the situation, and the culture medium W in the culture vessel 2 can be stirred in an optimal state each time. In particular, it is possible to perform shaking that provides a stimulus of varying intensity to the culture medium W, rather than a constant stimulus. Consequently, optimal cultivation can be performed according to the target substance and the culture medium W.

[0126] When the culture is performed using the shaking device 10 until certain conditions (e.g., the time spent shaking the culture vessel 2, the number of shakes, etc.) are met, the shaking of the shaking platform 11 and the culture vessel 2 is temporarily stopped. Furthermore, as shown in Figure 9, the culture vessel 2 is moved to the vicinity of the measuring unit 180 so that the measuring unit 180 can perform measurements through the observation hole. This allows the relative positional relationship between the culture vessel 2 and the light irradiation unit 181 and the combined imaging unit 183 to be set to an appropriate positional relationship, as shown in Figure 13.

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

[0128] Therefore, by using the dual-purpose imaging unit 183, an image of the scattered light reflected at the interface can be captured and obtained as the scattered light image 191 shown in Figure 15. At this time, the dual-purpose imaging unit 183 also captures a fluorescence image 192, but since the target substance has not yet been expressed at this stage, it is different from the fluorescence image 192 that was originally intended to be obtained. The captured image 190 obtained by the dual-purpose imaging unit 183 is output to the control unit 15 and stored in the memory unit 220. Furthermore, the measurement unit 221 measures the turbidity of the culture medium W based on the acquired scattered light image 191. Specifically, the measurement unit 221 measures the turbidity based on the light intensity including brightness and luminance of the scattered light image 191, or the change in the RGB color information of the scattered light image 191.

[0129] As a result, the culture status of E. coli can be determined based on the measured turbidity, and it is possible to determine (estimate) whether a certain amount of E. coli has been cultured. If it is confirmed that the E. coli culture has been carried out properly, the expression of the target substance can be induced by cold shock or other means.

[0130] On the other hand, if the turbidity measurement results indicate 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 provides feedback control to the motor control unit 84 to change the shaking conditions of the shaking platform 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 than those previously used, and to restart the shaking of the culture container 2. In particular, by using different shaking conditions, it is possible to promote culture while providing a different stimulus to the culture medium W.

[0131] Furthermore, in addition to changing the shaking conditions, the control unit 15 provides feedback control to the temperature control unit 170 to change the temperature conditions under which the Peltier element 160 heats and cools the culture vessel 2. This allows, for example, the shaking of the culture vessel 2 to be restarted while the temperature of the culture medium W is maintained at a temperature higher than 37°C. Therefore, this can lead to accelerated culture.

[0132] After shaking the mixture again, the turbidity of the culture medium W is measured again using the measurement unit 180. In this way, the culture and turbidity measurement are repeated until the E. coli culture is properly performed. Therefore, the culture can be carried out efficiently.

[0133] If, as a result of these tests, the culture of E. coli is deemed sufficient, a step is performed to express the target substance by inducing cold shock. In this case, the culture vessel 2 is first cooled and maintained at a constant low temperature (approximately 15°C). Specifically, based on instructions from the control unit 15, the temperature control unit 170 controls the Peltier element 160 to cool the culture vessel 2 via the first main surface 161. This allows the bottom 3 of the culture vessel 2 to be cooled efficiently and uniformly using the heat conductive sheet 165. Therefore, the culture medium W can be cooled rapidly and maintained at a low temperature of approximately 15°C. At this time, since the second main surface 162 is thermally connected to a plurality of heat dissipation fins 122, the heat dissipation efficiency can be increased. Therefore, the heat absorption performance (cooling performance) of the first main surface 161 can be increased.

[0134] Next, reagents such as IPTG are added to culture vessel 2. Adding these reagents releases the control of the lactose operon contained in the expression vector, allowing the expression of a specific promoter that is induced under low temperature conditions. On the other hand, the expression of proteins present in 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 has been 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 medium W. As a result, the expressed target substance emits fluorescence due to the irradiation of 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 imaging unit 183 can be used to capture an image of the fluorescence emitted by the target substance and obtain it as the fluorescence image 192 shown in Figure 15. The fluorescence image 192 obtained by the dual-purpose imaging unit 183 is output to the control unit 15 and stored in the memory unit 220. Furthermore, the measurement unit 221 measures the fluorescence intensity of the target substance based on the acquired fluorescence image 192. Specifically, the measurement unit 221 measures the fluorescence intensity based on the light intensity including brightness and luminance of the fluorescence image 192, or changes in the RGB color information of the fluorescence image 192.

[0137] In particular, since the fluorescent filter 184 is placed between the dual-purpose imaging unit 183 and the culture vessel 2, it is possible to block at least the wavelength range of the excitation light EL reflected by the culture vessel 2. Therefore, it is possible to prevent the excitation light EL from reaching the dual-purpose imaging unit 183. As a result, noise caused by the excitation light EL can be removed from the acquired fluorescence image 192, and a high-precision fluorescence image 192 can be obtained. Consequently, the fluorescence intensity of the target substance can be measured by the measurement unit 221 based on the fluorescence image 192, and it is possible to determine whether a certain amount of the target substance has been obtained.

[0138] Furthermore, when capturing the fluorescence image 192 using the dual-purpose imaging unit 183, the scattered light image 191 can also be captured, as shown in Figure 15. Therefore, a single captured image 190 can include both the scattered light image 191 and the fluorescence image 192. Consequently, the memory unit 220 can store the scattered light image 191 and the fluorescence image 192 in association.

[0139] Furthermore, if the fluorescence intensity measurement results indicate that the expression of the target substance is insufficient, the control unit 15 provides feedback control to the motor control unit 84 to restart the shaking of the culture vessel 2 in order to further promote expression. In this case, the control unit 15 provides feedback control to the motor control unit 84 to change the shaking conditions of the shaking platform 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 than those previously used, and to restart the shaking of the culture vessel 2. In particular, since different shaking conditions are used, a different stimulus can be applied to the culture medium W. This can promote the expression of the target substance.

[0140] After shaking the culture medium W again, the fluorescence intensity of the target substance is measured again using the measurement unit 180. In this way, the shaking of the culture medium W and the measurement of fluorescence intensity are repeated until the expressed target substance is obtained in appropriate quantities. Therefore, a certain amount of the target substance can be obtained efficiently.

[0141] As described above, the culture system 1 of this embodiment allows for the measurement of the turbidity of the culture medium W at the necessary timing, while simultaneously measuring the fluorescence intensity of the target substance continuously within a series of steps. In particular, the control unit 15 provides feedback control to the motor control unit 84 and the temperature control unit 170 based on the measurement results of the turbidity of the culture medium W and the measurement results of the fluorescence intensity of the expressed target substance. Therefore, E. coli can be cultured efficiently, and a certain amount of the expressed target substance can be obtained.

[0142] Furthermore, since the turbidity of the culture medium W can be measured based on scattered light reflected at the interface between the inner surface of the culture vessel 2 and the culture medium W, it is less susceptible to influences such as the concentration of the culture medium W or foaming of the culture medium W's surface. Therefore, the turbidity of the culture medium W can be measured stably and accurately, making it easy to accurately grasp the culture state of the culture medium W containing the target substance. Moreover, the fluorescence intensity of the target substance can be measured without removing the culture medium W from the culture vessel 2. Therefore, contamination of the culture medium W can be prevented, and fluorescence intensity can be measured with high accuracy.

[0143] Furthermore, according to the culture system 1 of this embodiment, since scattered light images 191 and fluorescence images 192 are captured using a single multi-purpose imaging unit 183, there is no need to use two imaging units. Therefore, the configuration can be simplified and component costs can be reduced. Moreover, a single image 190 captured by the multi-purpose imaging unit 183 can simultaneously include both the scattered light image 191 and the fluorescence image 192. Therefore, it is possible to understand, for example, the relationship (correlation) between turbidity and fluorescence intensity.

[0144] Furthermore, as shown in Figure 15, the optical center LO of the excitation light EL is located at the center of the captured image 190. Therefore, the scattered light image 191 and the fluorescence image 192 can be included evenly and in a balanced manner within a single captured image 190 captured by the combined imaging unit 183. Moreover, by utilizing the frame portion 184b of the fluorescence filter 184, it is possible to block the reflected light (excitation light EL) from the optical center LO from directly entering the captured image 190. Therefore, it is possible to suppress strong light from entering the captured image 190, and to suppress problems such as overexposure in the scattered light image 191 and fluorescence image 192. As a result, it is possible to obtain scattered light image 191 and fluorescence image 192 in which changes in RGB color information, changes in brightness such as gradients, and changes in luminance are clearly displayed. Therefore, turbidity measurement and fluorescence intensity measurement can be performed with high accuracy.

[0145] Furthermore, the measurement unit 221 extracts a partial image within the data acquisition region R located at the same distance from the optical center LO, thereby acquiring it as a scattered light image 191 and a fluorescence image 192. Therefore, the scattered light image 191 and the fluorescence image 192 can be acquired under conditions of equivalent light intensity. Accordingly, turbidity measurement and fluorescence intensity measurement can be performed based on the scattered light image 191 and fluorescence image 192 acquired under equivalent conditions.

[0146] Furthermore, the scattered light image 191 and the fluorescence image 192 can be associated and stored in the memory unit 220. Therefore, information such as the correlation between the turbidity state and the expression state of the target substance can be grasped. Consequently, by accumulating this information, it is possible to make predictions, for example, about what level of turbidity will cause the target substance to be expressed. As a result, the process from culturing to the expression of the target substance can be carried out efficiently.

[0147] Furthermore, since it has an excitation filter 182, excitation light EL in a wavelength range suitable for fluorescence emission 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, overlap between the excitation spectrum and the fluorescence spectrum can be prevented. Therefore, a decrease in the contrast of the fluorescence image 192 can be suppressed.

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

[0149] Although embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. Embodiments can be implemented in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. Embodiments and their modifications include, for example, those that can be easily imagined by those skilled in the art, those that are substantially the same, and those that are equivalent.

[0150] For example, in the above embodiment, the expression vector does not need to include a specific promoter such as a lactose operon. In this case, the target substance can be expressed without adding reagents when the culture temperature of E. coli is set to a low temperature (approximately 15°C). Furthermore, although the above embodiment described the case in which an expression vector whose expression is induced in a temperature-dependent manner is used and the target substance is expressed by the E. coli cold shock expression system method, it is not limited to this case. Any other expression vector can be used as long as the target substance can be expressed.

[0151] Furthermore, the target substance can be anything that has the function of emitting fluorescence and is subject to fluorescent staining; it is not limited to any specific substance. For example, a typical protein that is subject to fluorescent staining can be used as the target substance. In addition, other biomolecules that are subject to fluorescent staining, such as nucleic acids, cations, chitin, cellulose, and A-T regions, may also be used as target substances.

[0152] Furthermore, although the above embodiment was described using the example of a triangular flask as the culture vessel 2, as mentioned earlier, 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 imaging unit 183 (first imaging unit, second imaging 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 imaging unit 183 may be arranged so that they are horizontal with respect to the peripheral wall surface of the beaker. In this way, the relative position of the light irradiation unit and the combined imaging unit 183 (first imaging unit, second imaging unit) may be appropriately changed depending on the type, shape, and use of the culture vessel 2.

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

[0154] Furthermore, when the culture medium W is cultured by shaking the culture vessel 2 with the shaking device 10, the target organism for culture is not limited to E. coli as in the above embodiment, but a wide range of other target organisms can be selected. For example, the target organism may be microorganisms such as yeast or bacteria. In particular, when bacteremia (an infectious disease) occurs, which is a condition in which bacteria enter the bloodstream, it is known that blood cultures are performed to identify the causative bacteria. 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 (for example, 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, the culture state of the target substance (protein) was described as being 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, combined imaging unit 183, and measuring unit 221), but the invention is not limited to this case. The second measuring device only needs to be able to measure the culture state of the target substance contained in the culture medium W, and can be configured as appropriate depending on the target substance, etc. For example, when performing the blood culture described above, it is known that the amount of carbon dioxide emitted by the bacteria through respiration increases as the bacterial culture progresses. In this case, the acidity of the culture medium W increases due to the increase in carbon dioxide, so the color of the indicator provided in the culture vessel 2 changes, for example. Therefore, it is possible to measure the culture state of the bacteria by measuring the change in absorbance of the indicator. Accordingly, the second measuring device can be configured to measure the change in absorbance of the indicator. Thus, the second measuring device can be configured as appropriate depending on the target substance, the application of the culture, etc.

[0156] Furthermore, the present invention includes the following embodiments: <1> A shaking device comprising: a shaking platform having a mounting surface on which a culture container containing a culture medium containing a substance to be cultured is placed; a shaking mechanism for shaking the shaking platform in a plane parallel to the mounting surface, wherein the shaking mechanism comprises: guide members that support the shaking platform so as to be movable along a first axis and a second axis that intersect each other in a plane parallel to the mounting surface; a drive belt for moving the shaking platform along the first axis and the second axis; and a drive unit for driving the drive belt, wherein the drive unit drives the drive belt while independently controlling the movement of the shaking platform along the first axis and the movement of the shaking platform along the second axis. <2> The shaking device described in <1>, wherein the guide member comprises: 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 so as to be movable 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 so as to be movable along the second axis relative to the movable base, wherein the drive belt is continuously stretched between the fixed base, the movable base and the shaking base. <3> The shaking device according to <2>, wherein the drive unit comprises: 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; and a motor control unit that controls the driving of the first drive motor and the second drive motor, respectively, and rotates the first drive pulley and the second drive pulley in forward and reverse directions, respectively. <4> The culture system comprising: the shaking device according to any one of <1> to <3>; a first measuring device for measuring the turbidity of the culture medium; and a control unit for controlling the drive unit, wherein the control unit provides feedback control to the drive unit to change the shaking conditions of the shaking base based on a first measurement result from the first measuring device.<5> A culture system according to <4>, further comprising a second measuring device for measuring the culture state of a culture target contained in the culture medium, wherein the control unit provides feedback control to change the shaking conditions of the shaking platform based on the second measurement result from the second measuring device. <6> A culture system according to <5>, wherein the second measuring device measures the fluorescence intensity of the fluorescence emitted by the culture target. <7> A culture system according to any one of <4> to <6>, further comprising a container holding unit that is placed on the mounting surface and holds the culture container, a thermoelectric element provided in the container holding unit for heating and cooling the culture container, and a temperature control unit that controls the thermoelectric element, wherein the control unit provides feedback control to change the temperature conditions for heating and cooling the thermoelectric element based on the first measurement result from the first measuring device.

[0157] According to the present invention, the shaking conditions can be easily adjusted and changed.

[0158] W...Culture medium 1...Culture system 2...Culture container 10...Shaking device 11...Shaking platform 11a...Mounting surface of the shaking platform 12...Container holder 13...First measuring device 14...Second measuring device 15...Control unit 30...Shaking mechanism 31...Guide member 32...Drive belt 33...Drive unit 50...Movable platform 60...First guide member 70...Second guide member 80...First drive motor 81...First drive pulley 82...Second drive motor 83...Second drive pulley 84...Motor control unit 160...Peltier element (thermoelectric element) 170...Temperature control unit

Claims

1. A shaking device comprising: a shaking platform having a mounting surface on which a culture vessel containing a culture medium containing a substance to be cultured is placed; and a shaking mechanism for shaking the shaking platform in a plane parallel to the mounting surface, wherein the shaking mechanism comprises guide members that support the shaking platform so as to be movable along a first axis and a second axis intersecting each other in a plane parallel to the mounting surface; a drive belt for moving the shaking platform along the first axis and the second axis; and a drive unit for driving the drive belt, wherein the drive unit drives the drive belt while independently controlling the movement of the shaking platform along the first axis and the movement of the shaking platform along the second axis.

2. The shaking device according to claim 1, wherein the guide member comprises: 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 so as to be movable 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 so as to be movable along the second axis relative to the movable base, wherein the drive belt is continuously stretched between the fixed base, the movable base and the shaking base.

3. The shaking device according to claim 2, wherein the drive unit comprises: 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; and a motor control unit that controls the driving of the first drive motor and the second drive motor, respectively, and rotates the first drive pulley and the second drive pulley in forward and reverse directions, respectively.

4. A culture system comprising: a shaking device according to any one of claims 1 to 3; a first measuring device for measuring the turbidity of the culture medium; and a control unit for controlling the drive unit, wherein the control unit provides feedback control to the drive unit to change the shaking conditions of the shaking platform based on a first measurement result from the first measuring device.

5. A culture system according to claim 4, comprising a second measuring device for measuring the culture state of a culture target contained in the culture medium, wherein the control unit provides feedback control to the drive unit to change the shaking conditions of the shaker platform based on the second measurement result from the second measuring device.

6. A culture system according to claim 5, wherein the second measuring device measures the fluorescence intensity of the fluorescence emitted by the culture target.

7. A culture system according to any one of claims 4 to 6, comprising: a container holding unit that is placed on the mounting surface and holds the culture container; a thermoelectric element provided in the container holding unit for heating and cooling the culture container; and a temperature control unit for controlling the thermoelectric element, wherein the control unit provides feedback control to the temperature control unit to change the temperature conditions for heating and cooling the thermoelectric element based on a first measurement result from the first measuring device.

Images