JP2006090749A - Temperature regulator - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a temperature regulator capable of measuring a sample stored in a micro plate while heating or heat-retaining the sample efficiently. <P>SOLUTION: This temperature regulator is provided with a container 3 having a sample vessel with at least one portion of a bottom face comprising a translucent material, and for holding the sample containing an aqueous solution in the sample vessel, a temperature control member 2 having a protruded part corresponding to a shape of the sample vessel, and a controller 10 for controlling a temperature of the temperature control member, and a temperature of the sample stored in the sample vessel is controlled by the protruded part of the temperature control member. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a temperature adjusting device for adjusting the temperature of a biological sample in an apparatus for measuring a physical or chemical change of the biological sample.

  Fluorescence correlation spectroscopy is known as a method for measuring physical or chemical changes in biological samples.

  In fluorescence correlation spectroscopy, proteins or colloidal particles labeled with a fluorescent substance are suspended in a medium within the field of view of a confocal optical microscope, and this is irradiated with laser light to excite the fluorescent substance in the sample. To do. The fluorescent material that absorbs light emits fluorescence, but the fluorescent material performs Brownian motion in the medium, and the fluorescence intensity fluctuates with time. The fluctuation of the fluorescence intensity is received as a time-series signal by a photodetector, and this is statistically analyzed to obtain an autocorrelation function. The average number of molecules in the confocal region of the target fine substance and the molecular Measure translational diffusion coefficient.

  Based on these analysis results, it is possible to quantitatively measure a structural change caused by a chemical reaction or a binding reaction of a fine biological sample at a molecular level. For example, in Patent Document 1, based on a confocal optical microscope, a solution containing a fluorescently labeled sample on a sample stage is irradiated with a laser beam collected by a lens to detect fluctuations in fluorescence intensity emitted from the sample. Describes a method and apparatus for performing correlation spectroscopic analysis of detection signals to determine statistical properties such as translational diffusion coefficients of fluorescent molecules and interactions between molecules.

  Furthermore, by using this method to analyze fluctuations in fluorescence intensity emitted from a sample, for example, quantitative analysis of protein behavior inside and outside the cell and tracking of DNA binding reactions can be performed. Can do.

  In this measurement, if a microplate having a plurality of sample vessels is used as a container for holding a sample, a large number of samples are stored in different wells (a plurality of grooves for storing samples on the microplate) at the same time. Independent measurements can be performed on wells. Therefore, many samples can be processed almost simultaneously in a short time. The sample may be a very small amount of about several tens of μl or less.

Since these biological samples usually proceed most effectively at a temperature of about 35 to 40 ° C., if the biological reaction is to be measured alive in the vessel holding the sample, the vessel holding the sample is It is desirable to warm or keep warm. As a technique for warming and maintaining the container that holds the sample, laying a metal plate with good thermal conductivity on the entire bottom surface of the microplate, circulating the heated air and sending it around the microplate, the entire microplate (For example, refer to Patent Document 2), and a cooling means above the microplate and a heating means by a thermal heater below the microplate, respectively, and heating and cooling are performed simultaneously ( For example, see Patent Document 3).
JP-T-11-502608 JP-A-5-157684 JP 2001-74750 A

  However, in any of the methods disclosed in Patent Documents 2 and 3, the entire microplate is first heated, and then the sample is measured again. Therefore, these methods have the following problems to be solved.

  The first problem is that since the heating of the microplate and the measurement of the sample are separate processes, the sample cannot be measured simultaneously while heating the microplate. In other words, after controlling the temperature of the microplate, it must be placed on the sample stage, and the measurement must be started after adjusting the light spot on the sample again. As a result, it takes time and effort for the measurement. Was.

  The second problem is that the heating efficiency and heat retention performance are low. Usually, the microplate used for measurement is made of a material with poor thermal conductivity, such as plastic or glass, and even if it contacts a metal plate with good thermal conductivity, it can be heated efficiently in a short time. I can't. Furthermore, in the conventional method, temperature control is applied to the entire microplate, but the sample is accommodated in each well, and the temperature control is performed through the wall of each well. The temperature was not adjusted properly.

  The third problem is that the heating mechanism hinders observation. In the conventional technology, an optically opaque member for heating or keeping warm is arranged so as to cover the well portion of the microplate. Therefore, measurement cannot be performed by irradiating the sample with light while heating or keeping warm.

  This invention is made | formed in view of the situation which concerns, Comprising: It aims at providing the temperature control apparatus which can perform a measurement, heating or keeping warm the sample accommodated in the microplate efficiently.

  In order to solve the above-mentioned problem, the temperature adjusting device according to claim 1 according to the present invention has a sample tank in which at least a part of the bottom surface is made of a light-transmitting material, and a sample containing an aqueous solution is contained in the sample tank. A temperature control member having a protrusion corresponding to the shape of the sample tank, and a controller for controlling the temperature of the temperature control member, and the sample by the protrusion of the temperature control member. The temperature of the sample stored in the tank is controlled.

  According to a second aspect of the present invention, there is provided the temperature control device according to the second aspect, wherein the temperature control member is configured to be replaceable in accordance with a shape of a container that holds a sample to be used. .

  According to a third aspect of the present invention, there is provided the temperature adjusting device according to the third aspect, wherein a plurality of the temperature control members are arranged in accordance with the shape of the container holding the sample and used for measurement. Selection means for selecting the temperature control member according to the shape of the container.

  According to a fourth aspect of the present invention, there is provided the temperature adjusting device according to the fourth aspect, wherein the temperature control member is capable of changing the height of the protrusion according to the amount of the sample.

  According to a fifth aspect of the present invention, there is provided the temperature adjusting device according to the fifth aspect, wherein the detector detects the shape of the container holding the sample, and the output signal of the detector. And changing means for changing the height of the protrusion of the temperature control member.

  The temperature adjusting device according to claim 6 of the present invention is the temperature adjusting device according to the invention described above, and has a film stacked in multiple layers covering the protrusion of the temperature control member, Each layer can be peeled off.

  According to a seventh aspect of the present invention, there is provided the temperature adjusting device according to the seventh aspect, wherein the protrusion of the temperature control member has a structure for discharging the air in the sample tank.

  The temperature adjusting apparatus according to claim 8 of the present invention is the temperature adjusting apparatus according to the above-described invention, wherein the shape of the protrusion of the temperature control member is substantially the same as the shape of the sample tank of the container holding the sample. The protrusions of the temperature control member are in contact with the sample through a film covering the protrusions.

  The temperature adjusting device according to claim 9 of the present invention is the temperature adjusting device according to the above invention, wherein the container for holding the sample is a microplate.

  According to a tenth aspect of the present invention, there is provided the temperature adjusting device according to the tenth aspect of the present invention, further comprising a temperature setting device for setting a control target temperature for each sample tank.

  The temperature control apparatus according to claim 11 of the present invention includes a sample tank having at least a part of a bottom surface made of a light-transmitting material, and a container for holding a sample containing an aqueous solution in the sample tank; A projection having a shape corresponding to the shape of the sample tank, a member for controlling the temperature of the sample, a controller for controlling the temperature of the temperature control member, means for holding the container, and observing or measuring the sample And a means for generating warm air, and the temperature of the atmosphere in the sealed container is controlled by the means for generating warm air.

  By using the temperature adjusting device of the present invention, it is possible to perform measurement while efficiently heating or keeping the sample accommodated in the microplate.

[First Embodiment]
FIG. 1 is a diagram showing a temperature adjustment device according to an embodiment of the present invention.

  The temperature adjustment device includes an XY stage 1, a heating unit 2, a microplate 3, an objective lens 4, an objective lens Z-axis drive mechanism 5, a temperature adjustment box 6, a hot air generator 8, a tube 9, and a heating unit drive device 10. It has. And the temperature control box 6 is provided with the upper cover part 6a and the plate-shaped receiving part 6b, and forms sealed space.

  The XY stage 1 is configured to be able to move in an XY plane with a microplate 3 mounted thereon. The microplate 3 has a structure in which the well portion is optically transparent, and the heating unit 2 is disposed on the upper opening side of the microplate 3.

  FIG. 2 is a configuration diagram of the heating unit shown with the surface in contact with the microplate 3 facing upward.

  The heating unit 2 includes a Peltier element 11, a protruding temperature control member 12, a temperature sensor 13, and a film (not shown) 14. As shown in FIG. 2, the protruding temperature control member 12 is provided with a protruding portion 15 corresponding to the upper opening of the microplate 3, that is, the well.

  The microplate 3 is made of commonly used resin, plastic such as polypropylene, and glass, and has 96 wells (circular groove for accommodating a sample). The bottom surface of each well is a window made of a material that transmits visible light such as glass (not shown). The shape of the protrusion of the protrusion 15 shown in FIG. 2 is cylindrical. Since the diameter of these cylindrical protrusions is slightly smaller than the inner diameter of the well, it can be smoothly put in and out of the well.

  An objective lens 4 and an objective lens Z-axis drive mechanism 5 are disposed below the microplate 3. The objective lens Z-axis drive mechanism 5 is position-controlled automatically or manually on the Z-axis so that the focus position of the objective lens is aligned with the sample 20 in the well of the microplate 3.

  The protruding temperature control member 12 is brought into close contact with the upper portion of the microplate 3 containing the sample in the well and is held on the XY stage 1 together with the microplate 3. The XY stage 1 and the objective lens 4 are accommodated in a temperature adjustment box 6.

  As shown in FIG. 1, the temperature adjustment box 6 has a structure manufactured by joining plate members having excellent heat conduction performance such as metal, and is divided into an upper lid portion 6a and a dish-shaped receiving portion 6b. These two parts are connected by screws.

  Before the measurement is performed, one screw of the temperature adjustment box 6 is removed to open the upper lid portion 6a, and the heating unit 2 is installed from above the microplate 3. At this time, the projecting portion 15 is disposed close to the inner wall of the microplate well via the film 14.

  In this manner, the XY stage 1, the heating unit 2, the microplate 3, the objective lens 4, and the objective lens Z-axis moving mechanism 5 are housed in the temperature adjustment box 6. Hot air is introduced into the sealed space by the hot air generator 8 through the tube 9 to keep the ambient temperature constant.

  FIG. 3 is a diagram showing a state in which the heating unit is attached to the microplate. FIG. 4 is an enlarged cross-sectional view of one well. As shown in FIGS. 3 and 4, the tip of the protrusion 15 on the lower surface of the protrusion-like temperature control member 12 is covered with a film 14. The film 14 can be exchanged, and prevents contamination of other samples and entry of foreign matters such as dust during microplate measurement.

  The film 14 is preferably waterproof and breathable and has good thermal conductivity. For example, polytetrafluoroethylene having an open-cell porous structure is used. Since polytetrafluoroethylene has high water repellency, it has a property that liquids with a large surface tension such as water cannot be permeated. On the other hand, since the holes are continuously formed, the gas permeates.

  Further, the material of the protruding temperature control member 12 is desired to have high thermal conductivity. For example, a metal such as copper, iron, stainless steel, brass, aluminum, or a plate member such as ferrite is used.

  As shown in FIG. 3, an electrode 17 and a cord 18 are attached to the heating unit 2. The electrode 17 is made of a metal such as copper or aluminum, and is connected to the heating unit driving device 10 via a cord 18. A current is supplied to the Peltier element 11 from the heating unit driving device 10 via the electrode 17 to heat the protruding temperature control member 12. Then, the sample 20 in each well is heated via the film 14 by the warmed protrusion 15.

  A temperature sensor 13 attached in close contact with the protruding temperature control member 12 measures the temperature of the protruding temperature control member 12. The temperature sensor 13 uses a thermocouple, a resistance temperature detector, or a semiconductor temperature sensor. The output signal of the temperature sensor 13 is guided to a signal processing circuit (not shown), and the heating unit driving device 10 controls the driving current to the Peltier element by the signal sent from the signal processing circuit, and the projection temperature control member 12 Control the temperature.

  If the temperature of the protruding temperature control member 12 falls below a set temperature (for example, 37 ° C.), a signal flows from the temperature sensor 13 to the heating unit driving device 10 and the current flowing to the Peltier element 11 is adjusted to adjust the protrusion. The temperature of the temperature control member 12 is controlled. The current flowing from the heating unit driving device 10 to the protruding temperature control member 12 is automatically adjusted so as to become a set temperature (for example, 37 ° C.) or higher.

  The film 14 may be replaced one by one for each measurement, or a plurality of films 14 having a stacked structure may be peeled one by one for each measurement. Alternatively, after the measurement, the film 14 may be washed and reused. As described above, the film may be laminated in multiple layers and molded according to the protrusions 15 or may be pasted so as to cover the plurality of protrusions 15 as a whole.

  The heating unit 2 may have a heating function or a cooling function, or both heating and cooling functions by combining a plurality of Peltier elements. Further, in order to improve the heat exchange efficiency between the Peltier element 11 and the protruding temperature control member 12, it is also possible to sandwich a soft heat conductive material such as silicon between the Peltier element 11 and the protruding temperature control member 12. . When silicon is used, the contact area between the Peltier element 11 and the protruding temperature control member 12 is increased, so that the heat conduction efficiency can be increased.

  When the Peltier element 11 is used, when one surface becomes the heat generation side, the other surface becomes the heat absorption side. Accordingly, the warm air can be compensated by blowing warm air into the sealed space by the warm air generating device 8, and the temperature adjustment effect can be enhanced by making the ambient temperature uniform.

  The current supplied to the Peltier element 11 may be a direct current or an alternating current, but an alternating current is more effective in consideration of restrictions on the capacity of the power source.

[Modification 1 of the first embodiment]
FIG. 5 is a diagram illustrating another configuration of the heating unit 2.

  The heating unit 2 having this configuration is provided with a protruding temperature control member 12 divided into a plurality of rows, a Peltier element 11 and a temperature sensor (not shown) attached to each divided protruding temperature control member 12. ing. If the heating unit 2 of this configuration is used, current control according to each set temperature can be individually supplied to perform temperature control, so that temperature control with higher accuracy can be performed.

  Instead of dividing the protruding temperature control member 12 in units of rows, it may be divided in groups of 3 to 5 wells, and the Peltier element 11 and temperature sensor may be attached to each group to perform temperature control. In addition, temperature control may be performed for each well.

[Modification 2 of the first embodiment]
FIG. 6 is a diagram showing a state in which the heating unit is attached to the microplate. FIG. 7 is an enlarged cross-sectional view of one well.

  As shown in FIGS. 6 and 7, the protruding temperature control member 12 and the Peltier element 11 are provided with circular ventilation holes 21 in the vertical direction. The diameter of the vent hole 21 is about 10 to 30% of the well diameter. When the heating unit 2 is installed in the microplate 3 from above the microplate 3, the air in the well is discharged to the outside through the vent hole 21 provided in the Peltier element 11 and the protruding temperature control member 12. Therefore, the sample 20 does not overflow from the well.

  In the present embodiment, a Peltier element is used for the heating unit 2, but the present invention is not limited to this, and a heating heater such as an electric heater or nichrome wire may be used when only heating is required.

[Second Embodiment]
The second embodiment is different from the first embodiment in that a plunger type Peltier element is used for the heating unit 2. Accordingly, the same parts as those in the first embodiment are denoted by the same reference numerals, and detailed description thereof is omitted.

  FIG. 8 is a perspective view in which a part of the protrusion 15 incorporating the plunger type Peltier element 25 is cut away.

  The protruding portion 15 of the protruding temperature control member 12 has a hollow cylindrical structure as illustrated. A cylindrical plunger type Peltier element 25 having a vent hole 21 is installed in the projection 15. A spring 26 is provided on the other end face of the plunger type Peltier element 25, and the plunger type Peltier element 25 is applied with a force toward the tip of the protruding portion 15 of the protruding temperature control member 12.

  On the other hand, the tip of the protrusion 15 has a hollow planar structure, and is a mechanism (stopper mechanism) that holds the plunger-type Peltier element 25 in this plane so that it does not protrude outside. With this structure, the plunger-type Peltier element 25 is abutted against the tip of the protruding portion of the protruding temperature control member 12 and is fixed by the spring 26. The spring 26 may be a coil spring. Further, a temperature sensor (not shown) is incorporated in the plunger type Peltier element 25.

  FIG. 9 is a diagram showing a state in which the heating unit is attached to the microplate.

  When the protruding temperature control member 12 is placed on the microplate 3, the air sealed above the sample 20 is discharged from the film 14 to the outside through the vent hole 21 of the plunger type Peltier element 25. The diameter of the vent hole 21 is about 10 to 20% of the well diameter of the microplate 3. The diameter of the protruding portion 15 of the protruding temperature control member 12 is substantially the same as the diameter of the well inner wall of the microplate 3.

  With this configuration, the sample 20 does not overflow from the well portion due to air pressure. Further, the protrusion 15 of the protrusion-like temperature control member 12 can be in close contact with the sample 20 in the well, and the sample 20 in the well can be effectively heated.

  For the purpose of assisting the discharge of air from the vent hole 21 of the protruding temperature control member 12, a suction device (not shown) is provided on the upper portion of the protruding temperature control member, and a plunger tube is interposed via a vinyl tube or the like. Air may be sucked and discharged from the vent hole 21 of the Peltier element 25.

  FIG. 10 is a diagram showing another configuration of the plunger type Peltier element 25.

  As shown in FIG. 10, a groove structure notch may be provided in the longitudinal direction of the outer surface of the plunger-type Peltier element 25 to form a vent hole. The vent hole is not limited to a circular shape, and may have any shape as long as it has a structure capable of discharging air.

  Further, the protruding portion 15 of the protruding temperature control member 12 is not limited to the cylindrical shape, and the shape thereof can be changed according to the shape of the inner wall of the well of the microplate 3. For example, when the shape of the inner wall of the well of the microplate 3 is a square, the shape of the protrusion 15 of the protrusion-like temperature control member 12 is also a rectangle.

  When the well shape is different, the shape of the protrusion 15 of the protrusion temperature control member 12 is deformed or exchanged according to the well shape, but this may be automatically performed. As shown in FIG. 11, when the microplate 3 is placed on the XY stage 3 (not shown), the shape of the well of the microplate 3 is photographed by the CCD camera 30. An image of the photographing result may be taken into a computer (not shown), the shape of the well may be recognized, and the heating unit 2 including the protrusions 15 matching the shape of the well may be disposed.

  On the other hand, the projecting portion 15 of the projecting temperature control member 12 can be structured to be extendable and contractable in the vertical direction as shown in FIG. FIG. 13 is a cross-sectional view showing a protruding portion of the protruding temperature control member. The protruding portion 15 is housed in the holder portion 28 of the protruding temperature control member 12. The protruding portion 15 and the holder portion 28 have a structure of fitting or rubbing. The height of the protrusion 15 can be changed by moving the protrusion 15 up and down in the holder portion 28. In addition, the change of the height of the projection part 15 can also be performed using a piezoelectric motor, for example.

  The height of the protrusion 15 may be automatically adjusted. As shown in FIG. 11, when the microplate 3 is set on the XY stage 3 (not shown), a plurality of wells of the microplate 3 are photographed by the CCD camera 30 with different focal lengths. The image of the photographing result is taken into a computer (not shown), the height of the sample 20 in the well is recognized from the image focused on the sample 20 in the well, and the height of the projection 15 is adjusted according to the height of the sample 20. You may change the height.

  In this embodiment, even if the liquid amount of the sample 20 is different, the sample 20 can be heated by being in close contact with the sample 20 and changing the height of the protruding portion 15 of the protruding temperature control member 12. Further, instead of controlling the temperature of the microplate 3, the temperature may be individually controlled corresponding to each well.

[Modification 1 of the second embodiment]
In addition, the temperature control box 6 can also be made into a slide opening / closing structure, as shown in FIG. The slide type upper lid 6 c is slid on the temperature control box 6, and the microplate 3 and the heating unit 2 are put into and out of the temperature control box 6. The sliding opening / closing structure is effective when there is little effective space above the temperature control box 6 in terms of the device configuration.

[Modification 2 of the second embodiment]
Further, as shown in FIG. 15, the shape of the temperature control box 6 may be such that the upper lid 6 d is opened and closed using a hinge 29. With the opening / closing structure using the hinge 29, when there is no space around the apparatus and there is a space above, the opening / closing operation of the upper lid can be easily performed.

  As described above, in the temperature adjustment method according to the present invention, the well bottom made of a material having high light transmittance is provided on the bottom surface of the container holding the sample, and the top surface of each well is sealed on the top surface of the container holding the sample. A plate-like member having excellent transmissibility is placed, a temperature control element is disposed in close contact with the upper surface of the plate-like member, and the temperature of the container holding the sample from the upper surface of each well is controlled by the temperature control element. On the other hand, the temperature adjustment box 6 is disposed so as to surround the microplate, the sample stage holding the microplate, and the objective lens, and warm air is circulated in the temperature adjustment box 6 to heat the entire microplate.

  In order to efficiently heat the sample from the sample opening, a protruding temperature control member corresponding to the well shape is used, and a replaceable film is laid on the protruding temperature control member so that other samples and dust This prevents foreign substances such as from entering the sample tank. This film has a porous structure (having fine pores), and has a property of allowing air to permeate but not allowing a liquid sample containing water as a main component to permeate. Therefore, the sample can be heated by bringing the protruding temperature control member as close as possible to the sample.

  In addition, a height adjusting function may be added to the protruding temperature control member for each well so as to cope with the case where the amount of the sample accommodated in each well varies from well to well. For example, the protruding portion of the protruding temperature control member can be configured to be extendable and contractible. Since the position of the heating part can be changed according to the volume of the sample in each well, the temperature of the sample is controlled efficiently according to the sample because the well is kept in close contact with the sample for warming or warming. Can be done.

  In addition, since the sample can be heated or kept warm from above the microplate, when measurement is performed by irradiating light from the bottom of the well, the measurement can be performed while keeping the sample warm. In particular, in the case of a microplate whose bottom surface is made of a light-transmitting material such as glass or plastic, it is difficult to heat and keep warm from the bottom. If this invention is used, this problem can be solved.

  Further, according to this method, since the lid is provided for each well of the microplate, it is possible to prevent dust and the like from being mixed into the sample from above the well before and during measurement as much as possible.

  Further, the protruding temperature control member 12 constituting the heating unit 2 can be configured to be detachable according to the shape of the microplate 3 holding the sample.

  FIG. 16 shows a configuration example of the heating unit 2. 16A is a cross-sectional view showing the configuration of the heating unit 2, and FIG. 16B is a perspective view showing the configuration of the heating unit 2. As shown in FIG.

  At both ends of the heating unit 2, detachable clips 35 are provided to sandwich the Peltier element 11 and the protruding temperature control member 12. An appropriate number of the attachment / detachment clips 35 can be provided according to the size of the heating unit 2. In order to reduce heat dissipation to the atmosphere, the detachable clip 35 is preferably made of, for example, plastic having a low thermal conductivity.

  FIG. 17 shows another configuration example of the heating unit 2. In this configuration example, holding members 37 are provided at both ends of the Peltier element 11. As shown in FIG. 17 (1), the holder 37 is rotatably attached to the Peltier element 11 by a shaft 38. One end of a spring 39 is fixed to the upper end of the holder 37, and the other end of the spring 39 is fixed to the Peltier element 11. Further, the lower end portion of the holder 37 is provided with a claw-like protrusion 37a.

  With this configuration, as shown in FIG. 17B, the Peltier element 11 and the protruding temperature control member 12 are sandwiched via the holder 37. And as shown to (3) of FIG. 17, the protrusion-like temperature control member 12 can be removed by applying force to the arrow direction.

  Note that the present invention is not limited to the above-described embodiment as it is, and can be embodied by modifying the constituent elements without departing from the scope of the invention in the implementation stage. Further, various inventions can be formed by appropriately combining a plurality of constituent elements disclosed in the embodiment. For example, some components may be deleted from all the components shown in the embodiment. Furthermore, you may combine suitably the component covering different embodiment.

The figure which shows the temperature control apparatus which concerns on embodiment of this invention. The figure which shows the structure of a heating unit. The figure which shows the state which attached the heating unit to the microplate. Sectional drawing which expands and shows about one well. The figure which shows the other structure of a heating unit. The figure which shows the state which attached the heating unit to the microplate. Sectional drawing which expands and shows about one well. The perspective view which notches and shows a part of protrusion part. The figure which shows the state which attached the heating unit to the microplate. The figure which shows the other structure of a plunger type | mold Peltier element. The figure explaining the method of changing or changing the shape of a projection part according to a well shape. The figure explaining the method of changing or changing the shape of a projection part according to a well shape. Sectional drawing which shows the part of the projection part of a protrusion-shaped temperature control member. The figure which shows the opening / closing structure of a temperature control box. The figure which shows the opening / closing structure of a temperature control box. The figure which shows the structural example of a heating unit. The figure which shows the structural example of a heating unit.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... XY stage, 2 ... Heating unit, 3 ... Microplate, 4 ... Objective lens, 6 ... Temperature control box, 8 ... Warm air generator, 10 ... Heating unit drive device, 11 ... Peltier element, 12 ... Protrusion Temperature control member, 13 ... temperature sensor, 14 ... film, 15 ... projection, 20 ... sample, 21 ... vent, 25 ... plunger type Peltier element, 30 ... CCD camera.

Claims (11)

A container having at least a part of the bottom surface made of a light transmissive material, and holding a sample containing an aqueous solution in the sample tank;
A temperature control member having a protrusion corresponding to the shape of the sample vessel;
A controller for controlling the temperature of the temperature control member;
With
The temperature control apparatus characterized by controlling the temperature of the sample accommodated in the said sample tank by the said projection part of the said temperature control member.   The temperature control device according to claim 1, wherein the temperature control member is configured to be replaceable according to a shape of a container that holds a sample to be used. A plurality of the temperature control members are arranged according to the shape of the container holding the sample,
The temperature adjusting device according to claim 1, further comprising a selection unit that selects the temperature control member according to a shape of the container to be used for measurement.   The temperature control device according to any one of claims 1 to 3, wherein the temperature control member is configured to be able to change a height of the protrusion according to a sample amount. A detector for detecting the shape of the container holding the sample;
The temperature adjusting device according to claim 4, further comprising changing means for changing a height of the protruding portion of the temperature control member based on an output signal of the detector. Having a film stacked in multiple layers covering the protrusion of the temperature control member,
The temperature adjusting device according to claim 4, wherein the film is peelable for each layer.   The temperature adjusting device according to any one of claims 1 to 3, wherein the protrusion of the temperature control member has a structure for discharging air in the sample tank.   The shape of the protrusion of the temperature control member substantially matches the shape of the sample tank of the container holding the sample, and the protrusion of the temperature control member is in contact with the sample through a film covering the protrusion. The temperature adjusting device according to any one of claims 1 to 3.   The temperature control apparatus according to any one of claims 1 to 3, wherein the container for holding the sample is a microplate.   The temperature adjusting device according to any one of claims 1 to 3, further comprising a temperature setting device that sets a control target temperature for each sample tank. A container having at least a part of the bottom surface made of a light transmissive material, and holding a sample containing an aqueous solution in the sample tank;
A member having a protrusion corresponding to the shape of the sample tank and controlling the temperature of the sample;
A controller for controlling the temperature of the temperature control member;
Means for holding the container;
A sealed container containing a means for observing or measuring the sample;
Means for generating warm air,
The temperature adjusting device, wherein the temperature of the atmosphere in the sealed container is controlled by means for generating the warm air.

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