JP5290235B2 - Temperature controller used in nucleic acid sequence analyzer - Google Patents

Description

  The present invention relates to a temperature control device used in a nucleic acid sequence analyzer for decoding the base sequence of a nucleic acid such as DNA or RNA.

  A nucleic acid sequence measurement apparatus is composed of a chemical reaction for sequentially proceeding with a base extension reaction and an optical measurement for measuring the result. In general, chemical reactions require more time than optical measurements.

  Therefore, in order to improve the throughput, it is important to shorten the time required for the chemical reaction. However, it is difficult to dramatically shorten the chemical reaction. As a method of overcoming this, there is a method of mounting two flow cells in an apparatus as described in Patent Document 1.

  In a two-flow cell system equipped with two flow cells, optical measurement is performed in the other flow cell while a chemical reaction is performed in one flow cell. By repeating this alternately, the optical measurement can be continued in parallel during the chemical reaction time.

  If the chemical reaction time can be shortened to the optical measurement time, the CCD camera can be operated 100% during the operation of the apparatus, and the performance of the apparatus can be maximized. That is, in the 1 flow cell system, the chemical reaction and the optical measurement can be processed only in series, whereas in the 2 flow cell system, these can be processed in parallel, so that the throughput can be improved up to 2 times. Therefore, a two-flow cell system is effective for improving the throughput of the apparatus.

  Since the chemical reaction is a reaction using an enzyme such as polymerase or ligase, it is necessary to adjust the temperature of the reaction field. The temperature control range is generally performed at about 4 ° C to 95 ° C. The device of the device for achieving this is called a cell holder.

  The general configuration of the cell holder is a heat block for fixing the flow cell, a Peltier element that is a temperature adjusting element that cools and heats the flow cell, a fin for radiating heat generated by the Peltier element, and for forcibly cooling this I am a fan.

US Patent Publication US2009 / 0139311A1

  In the prior art described above, it has been difficult to adopt a configuration in which two cell holders are arranged on an XY stage in a state where a fan is provided for each of the two cell holders.

  The reason is resonance. When two fans are used, since the natural frequency of each fan is almost the same, the vibration of the fan is extremely increased by the resonance phenomenon. This large vibration makes it difficult to perform stable fluorescence measurement.

  In order to overcome the above problem, a means is adopted in which a fan is installed on the outer wall of the apparatus and blows air to the two cell holders through a duct.

  However, this method has problems in the following points.

  (1) Since the cooling fins directly below the flow cell cannot be cooled by directly blowing air with a fan, the performance of the Peltier element as the temperature adjusting element cannot be maximized.

  (2) Since the duct is coupled to the XY stage via the cell holder, a load is applied to the XY stage, and the driving accuracy of the XY stage is impaired.

  (3) Since the duct is coupled to the two cell holders and blown to the respective flow cells, it is difficult to make the size of the two cell holders compact.

  An object of the present invention is to realize a temperature controller of a nucleic acid sequence analyzer and a nucleic acid sequence analyzer using the same, in which vibration of the cooling fan is suppressed and air can be directly blown from the cooling fan to the flow cell.

  In order to achieve the above object, the present invention is configured as follows.

The temperature controller for a nucleic acid sequence analyzer of the present invention dissipates heat generated by the temperature control element of the flow cell support member for conducting heat with a plurality of flow cells by the heat dissipating means, and forcibly dissipates the heat dissipating means by the forced cooling means. Allow to cool. This forced cooling means can be used as a resonance preventing means as one fan .

  According to the present invention, it is possible to realize a temperature control device of a nucleic acid sequence analyzer and a nucleic acid sequence analyzer using the same, in which vibration of the cooling fan is suppressed and air can be directly blown from the cooling fan to the flow cell.

It is explanatory drawing about the cell holder which forcibly air-cools two fins and a heat block using one fan in 1st Example of this invention. It is explanatory drawing about the 2nd Example of this invention. It is explanatory drawing about the 3rd Example of this invention. It is explanatory drawing about the 4th Example of this invention. It is explanatory drawing about the 5th Example of this invention. It is explanatory drawing about the 6th Example of this invention. It is a whole schematic block diagram for demonstrating the optical measurement system of the nucleic acid sequence analyzer to which this invention is applied, and a control meter system. It is explanatory drawing about the 7th Example of this invention. It is explanatory drawing about the 8th Example of this invention. It is explanatory drawing about the 8th Example of this invention.

  Embodiments of the present invention will be described below with reference to the accompanying drawings.

  FIG. 1 is an explanatory view of a main part of a temperature control apparatus according to a first embodiment of the present invention. In addition, the example shown below is an example using the cell holder which adjusts the temperature of several flow cells.

  1A is a comparative example for comparison with the embodiment of the present invention, and the examples shown in FIGS. 1B and 1C are the first embodiment of the present invention.

  In FIGS. 1B and 1C, a cell holder having a holding mechanism 102 and the like for holding two flow cells 101 for reacting a specimen is fixed on an XY stage 108. Each of the two heat blocks (flow cell support members) 104 has a mechanism 102 that holds the flow cell 101. In the first embodiment of the present invention, two Peltier elements 105 are attached to one heat block 104 in contact with each other. Further, the Peltier element 105 is in contact with the fin 106 for radiating heat.

  The heat block 104, the Peltier element 105, and the fin 106 are bonded to each other with grease having high thermal conductivity. Further, since the Peltier element 105 serves as a heat source for cooling as well as heating, it is necessary to prevent condensation. Therefore, the space in which the Peltier element 105 is sandwiched between the heat block 104 and the fin 106 is sealed with silicon rubber and a heat insulating material.

  In order to cool the flow cell 101, it is necessary to cool the upper surface of the Peltier element 105. At that time, the lower surface of the Peltier element 105 is in a high temperature state. The heat generated on the lower surface of the Peltier element 105 is transmitted to the fin 106 via the grease. The heat transferred to the fins 106 is forcibly air-cooled by one fan 107 (fan resonance prevention means) arranged corresponding to the fins 106.

  The fan 107 rotates and blows air to the fin 106. For this reason, in order to prevent the vibration generated by the rotation of the fan 107 from being directly transmitted to the fin 106, the fin 106 and the fan 107 are independently held by the support 109. Further, the fin 106 and the fan 107 are not in direct contact. The support 109 also has a function of maintaining a space between the fan 107 and the XY stage 108 so that the fan 107 can efficiently intake and exhaust air.

  The flow cell crimping portion 102 has a function of fixing the flow cell 101 to the heat block 104. The optical sensor 103 is disposed on the flow cell crimping portion 102 to detect whether the flow cell 101 is fixed on the heat block 104. The thermal fuse 110 is an element for preventing an accident such as heating or ignition by turning off the power when the temperature of the flow cell 101 becomes abnormally high.

  When the flow cell 101 is not fixed on the heat block 104, the optical sensor 103 transmits an abnormal signal to the device control unit 726 described later, and thus measurement does not start without the flow cell 101.

  The resistance temperature detector 111 measures the temperature of the heat block 104, and the thermistor 112 measures the temperature of the fin 106. The measured temperature is used for feedback control of the output of the Peltier element 105. The Peltier element 105 is controlled by parameters for PID control.

  The Peltier element 105 has the highest heating / cooling efficiency when the temperature difference (ΔT) between the upper surface and the lower surface is 0 ° C. Therefore, the more efficiently the heat transmitted to the fin 106 is released into the air, the more efficiently the Peltier element 105 can be driven.

  Conversely, when the upper surface of the flow cell 101 is heated, the lower surface of the Peltier element 105 is cooled. In this case, the fin 106 is cooler than room temperature. Since the fan 107 blows room temperature air to the fins 106, as a result, the lower surface of the Peltier element 105 approaches room temperature. As a result, the temperature difference between the upper surface and the lower surface of the Peltier element 105 decreases, and in this case as well, the function of the Peltier element 105 is improved by forced air cooling by the fan 107.

  In contrast to FIGS. 1B and 1C, in the comparative example shown in FIG. 1A, two cell holders exist independently on the XY stage 108. As in the example shown in FIGS. 1B and 1C, the support 109 and the fan 107 are required for each cell holder, so that the number of parts required for configuring the flow cell system is increased.

  In the example shown in FIG. 1A, since the two fans 107 having the same frequency are arranged at a very close distance, resonance occurs due to the rotational operation of the two fans 107. This causes vibration of each cell holder and makes it difficult to measure the reaction field on the micron order level fixed on the flow cell 101.

  Therefore, the example shown in FIG. 1A is difficult to realize.

  In contrast, in the two-flow cell system employed in the embodiment of the present invention shown in FIGS. 1B and 1C, a system in which two fins 106 are cooled or heated by one fan 107 is employed. .

  As a result, the resonance problem that occurs in the example shown in FIG. 1A can be solved.

  Further, according to the embodiment of the present invention, since resonance does not occur, the fan 107 can be directly installed in the cell holder directly under the flow cell 101, so that the performance of the Peltier element 105 can be maximized. In addition, compared with the example shown in FIG. 1A, in the example shown in FIG. 1B, since the two fins 106 can be cooled by one fan 107, the cell holder can be made compact. can do. This brings about an effect that the size of the XY stage 108 and the whole nucleic acid sequence analyzer can be made compact. As a result, the apparatus cost can be reduced. The above-described effect can be achieved by adopting a configuration in which heat is discharged from two cell holders using one fan.

  In the example shown in FIG. 1B, the fan 107 is configured to exhaust air downward. In this method, air is sucked from both sides of the fin 106 and exhausted toward the XY stage 108. The advantage of this method is that, for example, even when an optical bench holding an objective lens and a CCD camera is present in the vicinity of the cell holder, measurement can be performed without heating or cooling the optical bench. Have

  On the other hand, in the example shown in FIG. 1C, a configuration is employed in which exhaust is performed upward, so that exhaust of the XY stage 108 can prevent the XY stage 108 from being heated.

  Next, a second embodiment of the present invention will be described.

  FIG. 2 is an explanatory view of a main part of a temperature adjusting device according to a second embodiment of the present invention. The example shown in FIG. 2 is an example in which the vibration absorbing member 121 is disposed between the fan 107 and the XY stage 108. The vibration absorbing member 121 (fan resonance preventing means) is an elastic body such as rubber or plastic. Other configurations are the same as the example shown in FIG.

  The example shown in FIG. 2A is an example in which each of the two flow cells is cooled by a separate fan 107, and vibrations of the two fans 107 are transmitted to each other via the XY stage 108. The vibration absorbing member 121 prevents the resonance of the two fans 107.

  The examples shown in FIGS. 2B and 2C correspond to the examples shown in FIGS. 1B and 1C, and the vibration of the fan 107 is transmitted through the XY stage 108 by the vibration absorbing member 121. Transmission to the cell holder is prevented.

  The second embodiment of the present invention has the effects of the first embodiment. In addition, there is an effect of further suppressing transmission of vibration by the fan 107 to the cell holder.

  Next, as a third embodiment of the present invention, a cell holder for adjusting the temperature of a plurality of flow cells by one fan 211 will be described with reference to FIG. Other configurations are the same as the example of FIG.

  The upper limit of the maximum throughput in a certain nucleic acid sequence analyzer is determined by the transfer speed of a CCD that is an element for imaging a flow cell. Therefore, the key to improving the throughput is to keep the CCD in a constantly driven state.

  A chemical reaction in which a base extension reaction is performed on a flow cell generally requires several times longer than optical measurement.

  As shown in case 1 in FIG. 3A, when the ratio of the time required for the chemical reaction and the imaging scan by the CCD is 1: 1, two flow cells can be processed in parallel. That is, even when two flow cells are used, since there is only one objective lens and CCD camera, imaging scanning cannot be performed in parallel. However, since only chemical solutions are filled in the flow cell, the two flow cells are parallel. Can be

  For this reason, after the reaction of one flow cell is completed, the scan is started by the CCD, and at the same time, the reaction of the other flow cell is started. At the end of the scan of one flow cell, the reaction of the other flow cell is completed. The scan of the flow cell can be started, and the CCD can continuously perform an imaging operation.

  As shown in case 2 in FIG. 3A, when the ratio of the time required for the reaction and scanning is 2: 1, the CCD continuously performs the imaging operation, and parallel processing of three flow cells is possible. is there.

  Similarly, if the ratio of the time required for reaction and scanning is 3: 1, parallel processing of four flow cells is possible. If this is generalized and the ratio of the time required for reaction and scanning is n: 1, parallel processing of n + 1 flow cells is possible.

  FIG. 3B shows an example in which four flow cells 201, 202, 203, and 204 can be processed in parallel. In this case, a configuration is adopted in which a single fan 211 is used to forcibly air-cool four of the flow cells 201, 202, 203, and 204 simultaneously. This is to prevent resonance by the two fans as described in the first embodiment.

  Further, the fins 221, 222, 223, and 224 are held by the support body 209 so as not to directly contact the fan 211. Thus, the vibration of the fan 211 is prevented from being directly conducted to the flow cells 201, 202, 203, 204.

  As shown in FIG. 3C, the flow cells 201, 202, and 203 are sequentially scanned and completed while the extension reaction is proceeding in the flow 204. Subsequently, the extension reaction of the flow cell 203 is started. During this extension reaction, scanning of the flow cells 204, 201, 202 is successively performed.

  By repeating the above procedure, a plurality of flow cells can be processed in parallel, and the throughput can be improved four times in this case.

  Reference numeral 205 denotes an objective lens, 206 denotes a lens support member, and 207 denotes an objective lens moving motor.

  In the present embodiment, the maximum n = 3 has been described, but the present invention is not limited thereto.

  FIG. 4 is an explanatory diagram of the fourth embodiment of the present invention. As shown in FIG. 4B, the fourth embodiment is an example in which a plurality of flow cells are cooled by a plurality of fans 211 to 211-n, and the rotational speed of each of the fans 211 to 211-n. This is an example of controlling the rotational speed so that the fans 211 to 211-n do not have the same rotational speed.

  The rotational speed control (fan resonance prevention means) of the fans 211 to 211-n is executed by a personal computer (control unit) 726 described later.

  Case 1 in FIG. 4A is an example in which a fan is disposed in each of two flow cells. In this case, the rotation speed of the fan is switched between high and low. While one flow cell is reacting, the fan of the flow cell is rotated at a high speed, and after the reaction of the flow cell is completed, the fan is rotated at a low speed during an imaging scan.

  During an imaging scan of one flow cell, the other flow cell is reacting, and the fan of this flow cell is rotated at a high rotational speed. During this time, since the fan of one flow cell is rotating at a low speed, the rotational speeds of the two fans are different from each other, and resonance is prevented.

  In other words, the rotation speeds of the two fans are controlled so that when one is at a high rotation speed, the other is at a low rotation speed, and the rotation is different from each other.

  Case 2 in FIG. 4A is an example in which a fan is arranged in each of three flow cells. In this case, three types of high, medium and low rotation speeds of the fan are switched and controlled.

  In other words, the reaction period of one flow cell is twice as long as the imaging period, and from the start of the reaction of one flow cell until half the reaction period, the fan of that flow cell is rotated at a high rotational speed, From the half point of the reaction period to the end point, it is rotated at medium speed. Then, after the reaction of the flow cell is completed, the fan of the flow cell is rotated at a low speed during the imaging scan.

  And the start time of the reaction period of the other flow cell is started with a delay of half of the reaction period.

  As a result, the respective fans (first fan, second fan, and third fan) of the three flow cells are controlled to rotate at different rotational speeds by sequentially repeating high, medium, and low rotational speeds.

  Case 3 in FIG. 4A is an example in which a fan is arranged in each of four flow cells. In this case, the rotation speed of the fan is controlled to be switched among four types: high, medium high, medium low, and low.

  In other words, the reaction period of one flow cell is three times as long as the imaging period. From the start of the reaction of one flow cell to one third of the reaction period, the fan of the flow cell is at a high rotation speed. Rotated, rotated at medium to high speed from 1/3 to 2/3 of the reaction period, and rotated at medium to low speed from 2/3 to the end of the reaction period Is done. Then, after the reaction of the flow cell is completed, the fan of the flow cell is rotated at a low speed during the imaging scan.

  And the start time of the reaction period of the other flow cell is started with a delay of one third of the reaction period.

  Thereby, each fan (first fan, second fan, third fan, fourth fan) of the four flow cells repeats high, medium high, medium low, and low rotational speeds sequentially and is different from each other. It is controlled to rotate at the rotational speed.

  FIG. 4B shows an example in which there are four flow cells (201 to 204).

  According to the embodiment shown in FIG. 4, even when a dedicated fan is arranged in each of the plurality of flow cells arranged in parallel, the rotation speed is simultaneously maintained while maintaining the air blowing capacity of the plurality of fans uniformly. Since it is avoided that they are the same, it is possible to avoid a resonance phenomenon due to the rotation of a plurality of fans.

  FIG. 5 is an explanatory diagram of the fifth embodiment of the present invention. As shown in FIG. 5B, the fifth embodiment is an example in which a plurality of flow cells are cooled by a plurality of fans 211 to 211-n, and the rotational speed of each of the fans 211 to 211-n. This is an example in which the frequencies are different from each other so that they do not have the same rotational speed.

  However, the driving frequencies of the fans are different from each other within a range in which the function of the temperature adjusting element such as the Peltier element is improved.

  Reactions and imaging scans of a plurality of flow cells are performed at the same timing as in the fourth embodiment, but one fan is rotated at the same frequency. By controlling the rotation frequency of multiple fans to be different from each other (fan resonance prevention means), it is avoided that the rotation speeds of multiple fans are the same at the same time. Is possible.

  Next, as a sixth embodiment of the present invention, a method for controlling the exhaust direction in temperature adjustment of a plurality of flow cells by one fan will be described with reference to FIG.

  In the sixth embodiment of the present invention, a heat insulating material 315 is attached to one side of the fin 106 in the first embodiment already described in FIG. Thereby, the direction of exhaust can be controlled in one direction.

  Other configurations are the same as those in the first to fifth embodiments.

  According to the sixth embodiment, since there is no fear of heating the vicinity of a part that is not to be heated by exhaust, a cell holder can be arbitrarily arranged in the nucleic acid sequence analyzer. Further, since the fan 107 exhausts upward, the air that has passed through the fins 106 is exhausted in a state of being unidirectionally aligned. This makes it possible to efficiently exhaust in the apparatus in the designed direction. Furthermore, since the exhaust does not directly hit the XY stage, thermal expansion of the XY stage can be prevented.

  FIG. 7 is an overall schematic configuration diagram for explaining a nucleic acid sequence analyzing apparatus to which the present invention is applied.

  In FIG. 7, white light emitted from a xenon lamp light source 742 is introduced into a condenser lens 722 via a cold mirror 743. Here, since the cold mirror 743 transmits only infrared light, only the visible light region necessary for measurement can be reflected and introduced into the condenser lens 722.

  The light condensed by the condenser lens 722 is introduced into the liquid light guide 721. The liquid light guide 721 is highly flexible and has a feature that enables a flexible optical arrangement in a narrow apparatus cabinet. Light emitted from the liquid light guide 721 is converted into parallel light by the condenser lens 723, and a wavelength band necessary for measurement is selected by passing through the band pass filter 741.

  Further, the light is reflected downward by the dichroic mirror 714. The light reflected by the dichroic mirror 714 is condensed on the reaction field on the flow cell 101 by the objective lens 712 to excite the fluorescent substance. The emitted fluorescence is condensed again by the objective lens 712, passes through the dichroic mirror 714, removes the stray light and scattered light of the excitation light by the emission filter 717, passes only the fluorescence to be measured, and passes through the condenser lens 715 to the CCD. An image is formed by being condensed on the light receiving surface of the camera 718. Then, an image picked up by the CCD camera 718 is supplied to a personal computer (control unit) 726, and the personal computer 726 analyzes the nucleic acid sequence of the subject.

  The Z motor 727 that holds the objective lens 712 has a function of focusing on the reaction field on the flow cell. Image capturing timing of the CCD camera 718 and focusing by the Z motor 727 are controlled by a personal computer (control unit) 726.

  The plurality of fans 211 to 211-n on the XY stage 702 are controlled in operation by a command signal from the control unit 726, and the number of rotations is controlled. Reference numeral 703 denotes an outer wall of the apparatus.

  Next, as a seventh embodiment of the present invention, a method for adjusting the temperature of a plurality of flow cells using one sirocco fan (fan resonance prevention means) will be described with reference to FIG. FIG. 8A is a schematic perspective view of the cell holder, and FIG. 8B is a schematic cross-sectional view of the cell holder.

  The difference between the first embodiment and the seventh embodiment described above is that a sirocco fan (multi-blade fan) 403 is employed. Other configurations are the same as those of the first embodiment. The fan shown in the first embodiment is an axial fan, and has a larger air volume but lower static pressure than the sirocco fan 403.

  In FIG. 8, the heat block 402 is heated or cooled by the Peltier element described above. The heat generated by the Peltier element is transmitted to the fin 401, and the heat is forcedly cooled by the sirocco fan 403. The sirocco fan 403 sucks air from above and exhausts it to the right in FIG. Since the sirocco fan 403 has a high static pressure, an air flow can be efficiently formed far away, preferably outside the apparatus, without exhaust ducts and the like, and exhaust can be performed.

  In addition, in the axial fan, the intake and exhaust directions coincide with each other, whereas in the sirocco fan 403, the intake and exhaust directions are orthogonal. As shown in FIG. 1A, the heat generated by the Peltier element is directly moved to the XY stage 108 by blowing air, thereby preventing the drive accuracy of the XY stage 108 from being deteriorated.

  Next, as an eighth embodiment of the present invention, a method of adjusting the temperature of a plurality of flow cells by one sirocco fan and exhausting hot air out of the apparatus through a duct will be described with reference to FIGS. I will explain.

  When the temperature of the flow cell is controlled using a Peltier element in the nucleic acid sequence analyzer, there is a possibility that the intended measurement cannot be performed normally by exhausting heat in the apparatus cabinet.

  One example is fluorescence measurement with a microscope. In optical measurement using a 20 × objective lens, the depth of focus is about ± 1.65 μm. However, the height of the support for holding the fan and fins is about 40 mm at a minimum.

In general, the material used for the support is aluminum, and its thermal expansion coefficient is 2.3 · 10 ⁻⁶ [1 / ° C]. Therefore, in order to maintain the focus within the depth of focus, the inside of the apparatus cabinet is used. Must be kept within +1.8 to −1.8 [° C.].

  For this purpose, it is desirable to employ a method of positively exhausting hot air generated directly under the objective lens to the outside of the apparatus cabinet.

  9A is a schematic perspective view of the cell holder, and FIG. 9B is a schematic cross-sectional view of the cell holder.

  In FIG. 9, the exhaust port of the sirocco fan 403 is connected to a duct 405 that can be expanded and contracted. The duct 405 is connected to a fan 406 installed on the apparatus outer wall 404. Here, the air volume of the fan 406 is larger than the air volume of the sirocco fan 403.

  Therefore, exhaust is smoothly performed without stagnation in the duct 405. The duct 405 can be flexibly expanded and contracted as the XY stage 108 is driven, and is covered with a heat insulating material so as not to transmit heat in the duct 405 pipe to the outside of the pipe.

  Further, since the intake to the heat block 402 is performed from both sides of the fin 401, the temperature uniformity on the heat block 402 is kept extremely high.

  FIG. 10 is an overall schematic configuration diagram of a nucleic acid sequence analyzer to which the eighth embodiment is applied. In the example shown in FIG. 10, the same members as those in the example shown in FIG. 7 are denoted by the same reference numerals, and detailed description thereof is omitted.

  In FIG. 10, the hot air exhausted by the fan 403 is sent to the fan 406 installed on the outer wall 404 of the apparatus via the duct 405 and becomes exhaust 407. Since the fan 403 has a larger air volume than the fans 211 to 211-n and the duct 405 has high heat insulation performance, the heat generated by the Peltier element is efficiently exhausted, which affects the defocus of optical measurement due to temperature. Don't give.

  Therefore, by adopting the configuration of the present embodiment, stable optical measurement can be performed while adjusting the temperature.

  101, 201-204 ... flow cell, 102 ... flow cell holding mechanism (crimping part), 103 ... optical sensor, 104, 402 ... heat block, 105 ... Peltier element, 106, 221-224 , 401 ... fins, 107, 211 to 211-n, 406 ... fan, 108, 702 ... XY stage, 109, 209 ... support, 110 ... thermal fuse, 111 ... RTD, 112 ... Thermistor, 121 ... Damper, 205,712 ... Objective lens, 207,727 ... Z motor, 315 ... Heat insulation, 403 ... Sirocco fan, 404 , 703 ... Outer wall of the apparatus, 405 ... Duct, 714 ... Dichroic mirror, 717 ... Emission filter, 718 ... CCD camera 721 ... Liquid light guide, 722,715 ... condenser lens, 726 ... PC, 741 ... bandpass filter, 742 ... xenon lamp, 743 ... cold mirror

Claims (9)

A plurality of flow cells for reacting the analyte;
A plurality of flow cell support members for supporting the plurality of flow cells and conducting heat to the flow cell;
A plurality of temperature adjusting elements for adjusting the temperature of each of the plurality of flow cell support members;
A plurality of heat dissipating means for dissipating heat generated by the plurality of temperature control elements;
A forced cooling means that is arranged opposite to the plurality of heat radiating means, and includes a single fan that forcibly cools each heat radiated by the plurality of heat radiating means;
A temperature control device for a nucleic acid sequence analyzer.   The nucleic acid sequence analysis according to claim 1, further comprising an outer wall surrounding the plurality of flow cells, the flow cell support member, the temperature adjusting element, the heat radiating means, and the forced cooling means. Temperature control device for equipment.   3. The temperature control device for a nucleic acid sequence analyzer according to claim 2, wherein a duct for allowing exhaust air from the fan to pass through is formed between the fan and the outer wall. .   2. The temperature control apparatus for a nucleic acid sequence analyzer according to claim 1, wherein the temperature control element is a Peltier element.   5. The temperature control device according to claim 4, wherein two or more Peltier elements are arranged for one flow cell.   The temperature control apparatus for a nucleic acid sequence analyzer according to claim 1, further comprising a heat insulating material disposed on a side surface of the heat radiating means.   2. The temperature control device for a nucleic acid sequence analyzer according to claim 1, wherein the fan is a sirocco fan. A temperature control device according to claim 1;
An XY stage that holds the temperature control device and can drive the temperature control device in the XY directions;
An objective lens for observing the flow cell fixed to the temperature control device;
Driving means for driving the objective lens in the vertical direction;
A light source for irradiating the flow cell with light;
Detecting means for detecting fluorescence obtained by irradiating the flow cell with light;
An optical filter for selecting the fluorescence;
Based on the fluorescence selected by the optical filter, an analysis unit that analyzes the nucleic acid sequence of the subject;
A nucleic acid sequence analyzing apparatus comprising:   9. The nucleic acid sequence analyzer according to claim 8, wherein the light source is a xenon lamp and the detection means is a CCD camera.

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