Nucleic acid amplifier and nucleic acid inspection device employing the same

A nucleic acid amplifier comprises a holder 3 which is provided with a plurality of temperature control blocks 10 each designed to hold at least one reaction vessel 105 storing a reaction solution. The temperature of the reaction solution in each reaction vessel 105 is controlled individually by using temperature control devices 14 and 15 arranged in each of the temperature control blocks 10. The temperature that is set in each temperature control block 10 and the timing for temperature changes are controlled independently of the temperatures of other temperature control blocks 10. This configuration makes it possible to provide a nucleic acid amplifier and a nucleic acid inspection device (employing the nucleic acid amplifier) capable of processing multiple types of samples differing in the protocol in parallel (parallel processing) and starting a process for a different sample even when there is a process in execution.

TECHNICAL FIELD

The present invention relates to a nucleic acid amplifier targeted for samples deriving from a biological body and a nucleic acid inspection device employing the nucleic acid amplifier.

BACKGROUND ART

Nucleic acid amplification technology used for inspecting nucleic acid contained in a sample deriving from a biological body includes a technique employing the polymerase chain reaction (hereinafter referred to as a “PCR method”), for example. In the PCR method, a desired type of base sequences can be selectively amplified by controlling the temperature of a reaction solution (mixture of the sample and a reagent) according to preset conditions.

A temperature control device described in Patent Literature 1 is known as an example of conventional technology related to the nucleic acid amplification employing the aforementioned PCR method. The temperature control device comprises a disk-shaped microchip having a bath region into which a reaction solution as the object of the experiment is injected. After the microchip is set at a desired position by rotating the microchip in a circumferential direction in parallel with a stage, the microchip is pushed toward the stage by using a cover member so as to bring the microchip's bath region into contact with one of heat transfer parts that are arranged in the circumferential direction of the stage and set at different temperatures, by which the temperature of the bath region is controlled.

PRIOR ART LITERATURE

Patent Literature

SUMMARY OF THE INVENTION

Problem to be Solved by the Invention

In the nucleic acid amplification technology employing the PCR method, the conditions of amplification such as the reagent used for the amplification process, the temperature and the time (protocol) vary depending on the base sequence as the target of amplification. Therefore, when multiple types of samples differing in the base sequence as the target of amplification are processed in parallel, the temperature and the time specified in the protocol for each type of sample have to be set individually.

In the conventional technology described in the above Patent Literature 1, however, only one protocol can be handled at one time and it is impossible to process multiple types of samples differing in the protocol in parallel (parallel processing). Further, even with samples to be processed with the same protocol, processes differing in the starting time cannot be executed in parallel and a new process for a different sample cannot be started until the current process in execution finishes. Therefore, the conventional technology still has room for improvement in terms of processing efficiency, etc.

The object of the present invention, which has been made in consideration of the above problem, is to provide a nucleic acid amplifier capable of processing multiple types of samples differing in the protocol in parallel (parallel processing) and starting a process for a different sample even when there is a process in execution. Another object of the present invention is to provide a nucleic acid inspection device employing such a nucleic acid amplifier.

Means for Solving the Problem

To achieve the above objects, the present invention provides a nucleic acid amplifier for amplifying nucleic acid in a reaction solution as a mixture of a sample and a reagent, comprising: a plurality of temperature control blocks each designed to hold a reaction vessel storing a reaction solution; a temperature control device which is provided to each of the temperature control blocks and controls the temperature of the reaction solution; and a disk-shaped base member, wherein: the base member is arranged to be rotatable, and the temperature control blocks are arranged along the periphery of the base member to be separate from each other.

Effect of the Invention

According to the present invention, multiple types of samples differing in the protocol can be processed in parallel and a process for a different sample can be started even when there is a process in execution.

MODE FOR CARRYING OUT THE INVENTION

Referring now to the drawings, a description will be given in detail of preferred embodiments in accordance with the present invention.

First Embodiment

FIG. 14is a diagram schematically showing the overall configuration of a nucleic acid inspection device100in accordance with a first embodiment of the present invention. Referring toFIG. 14, the nucleic acid inspection device100comprises a plurality of sample vessels101each storing a sample containing nucleic acid as a target of an amplification process, a sample vessel rack102storing the sample vessels101, a plurality of reagent vessels103storing various reagents to be added to the samples, a reagent vessel rack104storing the reagent vessels103, a plurality of reaction vessels105each of which is used for mixing a sample and a reagent, and a reaction vessel rack106storing a plurality of unused reaction vessels105. The nucleic acid inspection device100also comprises a reaction solution adjustment position107at which unused reaction vessels105are set and the samples and the reagents are dispensed from the sample vessels101and the reagent vessels103to the reaction vessels105, a plugging unit108for hermetically sealing the reaction vessels105(each storing a reaction solution as a liquid mixture of a sample and a reagent) with cover members (not shown), and a stirring unit109for stirring the reaction solutions stored in the hermetically sealed reaction vessels105.

The nucleic acid inspection device100further comprises a robot arm device112, a gripper unit113, a dispensing unit114, a plurality of nozzle chips115, a nozzle chip rack116, a nucleic acid amplifier1, a waste box117, and a control device120. The robot arm device112has a robot arm X-rail110provided on the nucleic acid inspection device100to extend in an X-axis direction (horizontal direction inFIG. 14) and a robot arm Y-rail111arranged to extend in a Y-axis direction (vertical direction inFIG. 14) and attached to the robot arm X-rail110to be movable in the X-axis direction. The gripper unit113, which is attached to the robot arm Y-rail111to be movable in the Y-axis direction, grips and conveys a reaction vessel105to various parts of the nucleic acid inspection device100. The dispensing unit114, which is attached to the robot arm Y-rail111to be movable in the Y-axis direction, sucks in a sample stored in a sample vessel101or a reagent stored in a reagent vessel103and discharges (dispenses) the sample or reagent to a reaction vessel105which has been set at the reaction solution adjustment position107. Each nozzle chip115is attached to a part of the dispensing unit114that makes contact with a sample or reagent. The nozzle chip rack116stores a plurality of unused nozzle chips115. The nucleic acid amplifier1performs a nucleic acid amplification process on the reaction solution stored in each reaction vessel105. Used nozzle chips115and used reaction vessels105(after inspection) are discarded to the waste box117. The control device120includes an input device118(keyboard, mouse, etc.) and a display device119(liquid crystal monitor, etc.) and controls the operation of the entire nucleic acid inspection device100including the nucleic acid amplifier1.

Each sample vessel101is managed in terms of the stored sample by using identification information (e.g., bar code) and using positional information (e.g., coordinates) assigned to each position in the sample vessel rack102. Similarly, each reagent vessel103is managed in terms of the stored reagent by using identification information (e.g., bar code) and using positional information (e.g., coordinates) assigned to each position in the reagent vessel rack104. The identification information and positional information are previously registered and managed in the control device120. Each reaction vessel105is also managed similarly by using identification information and positional information.

Next, the details of the nucleic acid amplifier1will be explained below referring toFIGS. 1-4.

FIGS. 1-3are a partial sectional perspective view, a plan view and a side view showing the overall configuration of the nucleic acid amplifier1in accordance with the first embodiment of the present invention.FIG. 4is a perspective view excerpting and magnifying a temperature control block10of a holder3. InFIGS. 2 and 3, a cover7is not shown for convenience of explanation.

Referring toFIGS. 1-3, the nucleic acid amplifier1mainly comprises a base2serving as the base of the nucleic acid amplifier1, a holder3provided with a plurality of temperature control blocks10each having a configuration for holding a reaction vessel105, fluorescence detectors6for detecting fluorescence from the reaction solutions stored in the reaction vessels105, and a cover7covering the holder3and the fluorescence detectors6.

The holder3includes a disk-shaped holder base4arranged with its central axis pointing upward (upward inFIG. 3) and a plurality of temperature control blocks10arranged around the central axis of the holder base4and along and inside the periphery of the holder base4. The holder base4, which is arranged to be rotatable in the circumferential direction around a rotating shaft5aat the center, is driven and rotated by a stepping motor5serving as a rotary driving device.

The holder base4is formed with members excelling in heat insulating properties (e.g. plastic) and configured to reduce interference among the temperatures of the temperature control blocks10. It is also possible to further reduce the temperature interference by providing a heat insulating layer made of a heat insulating material (e.g., polyurethane foam) between the holder base4and the temperature control blocks10.

As shown inFIG. 4, the temperature control block10includes a base11serving as the base of the temperature control block10, a setting position12formed like a through hole penetrating the base11in the vertical direction (vertical direction inFIG. 3), a Peltier element14and a radiation fin13provided under the base11to serve as a temperature control device, and a temperature sensor15arranged in the base11for detecting the temperature of the reaction solution in the reaction vessel105by measuring the temperature in the vicinity of the setting position12. A thermistor, a thermocouple, a temperature detecting resistor, etc. can be used for the temperature sensor15.

The base11is formed of a thermal conductor such as copper, aluminum and various types of alloys. The temperature of the reaction vessel105held in the setting position12of the base11is controlled and adjusted by heating and cooling the base11by using the Peltier element14. The radiation fin13is provided on a surface of the Peltier element14opposite to the base11and enhances the heat radiation efficiency of the Peltier element14. The reaction vessel105is inserted into the setting position12of the base11from above, by which the reaction vessel105is held in the temperature control block10with its bottom exposed to the outside of the temperature control block10.

Returning toFIGS. 1-3, one or more fluorescence detectors6(four in this embodiment, for example) are arranged along the periphery of the holder3at even intervals. Each fluorescence detector6is placed below the reaction vessels105(below the path of the movement of the reaction vessels105) and detects fluorescence when a reaction vessel105passes over the fluorescence detector6due to the rotation of the holder3. When there are two or more fluorescence detectors6, the fluorescence detectors6perform the detection or measurement of the reaction solutions in the reaction vessels105independently from each other.

The fluorescence detector6includes an excitation light source (not shown) for applying excitation light to the bottom (exposed part) of the reaction vessel105held in the setting position12of the temperature control block10and a detector element (not shown) for detecting the fluorescence from the reaction solution. In the reaction solution stored in the reaction vessel105, base sequences as the target of amplification by use of the reagent have been fluorescently labeled. The amount of the base sequences as the target of amplification in the reaction solution is measured with the passage of time by detecting the fluorescence from the reaction solution (caused by the irradiation of the reaction vessel105with the excitation light emitted from the excitation light source) with the fluorescence detector6. The results of the detection are sent to the control device120. A light-emitting diode (LED), a semiconductor laser (laser diode), a xenon lamp, a halogen lamp, etc. can be used as the excitation light source. A photodiode, a photomultiplier, a CCD, etc. can be used as the detector element.

The cover7is employed for the purpose of reducing the incidence of external light onto the fluorescence detectors6of the nucleic acid amplifier1(light shielding effect) by covering the holder3and the fluorescence detectors6in cooperation with the base2. The cover7has a gate7awhich can be opened and closed (seeFIG. 14). The reaction vessels105are loaded/unloaded into/from the inside of the cover7(i.e., loaded/unloaded into/from the nucleic acid amplifier1) via the gate7a. Incidentally, the gate7aof the cover7is not shown inFIG. 1for brevity.

The control device120controls the operation of the entire nucleic acid inspection device100. The control device120executes the nucleic acid amplification processes based on protocols (set through the input device118) and using a variety of software, etc. previously stored in a storage unit (not shown), stores analysis results (fluorescence detection results, etc.), operational status of the nucleic acid amplifier1, etc. in the storage unit, displays the analysis results, the operational status, etc. on the display device119, and so forth.

The operation in this embodiment configured as above will be described below.

First, as the preparation for the nucleic acid amplification processes, sample vessels101each storing a sample containing nucleic acid as the target of the amplification process are stored in the sample vessel rack102of the nucleic acid inspection device100, and reagent vessels103storing various reagents (previously determined by the protocols) to be added to the samples are stored in the reagent vessel rack104. Further, unused reaction vessels105are stored in the reaction vessel rack106, and unused nozzle chips115are stored in the nozzle chip rack116. In this state, the nucleic acid amplification processes are started by operating the control device120.

In response to the instruction for starting the nucleic acid amplification processes, a necessary number of unused reaction vessels105are conveyed by the gripper unit113to the reaction solution adjustment position107. Subsequently, an unused nozzle chip115is attached to the dispensing unit114, and each sample is dispensed from a prescribed sample vessel101to reaction vessels105. Thereafter, the nozzle chip115which has been used is discarded to the waste box117in order to prevent contamination. Subsequently, also for each reagent, the dispensing to prescribed reaction vessels105is carried out in a similar manner, by which each reaction solution is generated through the mixture of a reagent with a sample.

When a necessary number of dispensing operations are finished, the reaction vessels105storing the reaction solutions are conveyed by the gripper unit113to the plugging unit108and hermetically sealed with the cover members. The hermetically sealed reaction vessels105are further conveyed to the stirring unit109and undergo a stirring process. Each reaction vessel105after undergoing the stirring process is conveyed by the gripper unit113through the gate7aof the cover7of the nucleic acid amplifier1, inserted into one of the setting positions12of the holder3at a prescribed position, and held in the setting position12. In this step, the holder3is driven, rotated and controlled so that a prescribed one of the setting positions12is placed at the position of the gate7a. When there are two or more reaction vessels105to be processed, the hermetic sealing with the cover member and the stirring process are conducted to each of the reaction vessels105, and the hermetically sealed and stirred reaction vessels105are successively conveyed to prescribed setting positions12.

Then, the nucleic acid amplification process is executed by controlling the temperature of a reaction vessel105held in the holder3in a periodical and stepwise manner by controlling the Peltier element14of the temperature control device based on the protocol corresponding to the sample stored in the reaction vessel105. As above, the PCR method as a type of the nucleic acid amplification technology selectively amplifies a desired type of base sequences by changing the temperature of the reaction solution (mixture of a sample and a reagent) in a periodical and stepwise manner based on the protocol corresponding to each sample. Also when two or more reaction vessels105are processed in parallel, each nucleic acid amplification process is started successively when each reaction vessel105is held in a setting position12, and the temperature of each reaction vessel105is changed in a periodical and stepwise manner based on the protocol corresponding to each sample. During the nucleic acid amplification process, the amount of the base sequences as the target of amplification in the reaction solution is measured with the passage of time by driving and rotating the holder3and detecting the fluorescence from the reaction solution with the fluorescence detector6. The results of the detection are successively sent to the control device120.

After a prescribed nucleic acid amplification process is finished, the reaction vessel105is conveyed by the gripper unit113to the waste box117through the gate7aand discarded to the waste box117.

Effects achieved in this embodiment configured as above will be described below.

In the nucleic acid amplification technology employing the PCR method, the conditions of amplification such as the reagent used for the amplification process, the temperature and the time (protocol) vary depending on the base sequence as the target of amplification. Therefore, when multiple types of samples differing in the base sequence as the target of amplification are processed in parallel, the temperature and the time specified in the protocol for each type of sample have to be set individually. In the conventional technology, however, only one protocol can be handled at one time and it is impossible to process multiple types of samples differing in the protocol in parallel (parallel processing). Further, even with samples to be processed with the same protocol, processes differing in the starting time cannot be executed in parallel and a new process for a different sample cannot be started until the current process in execution finishes.

In contrast, the nucleic acid amplifier1in this embodiment is configured to comprise the holder3, which is provided with a plurality of temperature control blocks10each designed to hold a reaction vessel105storing a reaction solution, and to adjust the temperature of each reaction solution with the temperature control device mounted on each temperature control block10. Therefore, multiple types of samples differing in the protocol can be processed in parallel (parallel processing) and a new process for a different sample can be started even when there is a process in execution. As a result, the processing efficiency can be increased significantly.

Each temperature control block10is detachable from the holder base4, and thus inspection/replacement of temperature control blocks10can be conducted with ease when a temperature control block10has failed. By changing the shape of the setting position12formed in the base of each temperature control block10, reaction vessels having different shapes can be set on the holder base4at the same time. The base11, the temperature control device14and the temperature sensor15of any temperature control block10can be optimized to deal with a particular analysis item, and the optimized temperature control block10can be mounted on the holder base4. With this configuration, various analysis items can be carried out using the same holder base4, in a device status optimized for the specified temperatures. Incidentally, a fan may be installed to promote the heat exchange by the radiation fin13(forced air cooling). The heat radiation efficiency may be increased further by using a duct for guiding the wind from the fan to a desired position.

In order to suppress the rise in the atmospheric temperature inside the nucleic acid amplifier1covered by the cover7, it is possible to install an intake fan for supplying the outside air to the inside of the cover7and an exhaust fan for discharging the air. With this configuration, the atmospheric temperature inside the nucleic acid amplifier1can be kept constant and the temperature change (temperature control) of the holder base4and the temperature control blocks10can be conducted continuously.

Further, to promote the radiation of heat such as the Joule heat caused by the energization of the Peltier elements and the sensors, it is possible to form the holder base4and the rotating shaft5awith materials excelling in heat conductivity (e.g., aluminum), while also increasing the surface areas of the holder base4and the rotating shaft5a, using heat conductive grease for contact interfaces between the members, or increasing the adhesion between the members by reducing the surface roughness at the contact interfaces between the members.

It is also possible to actively promote the heat transmission from the holder base4and the rotating shaft5ato other members by installing heat pipes in/on the holder base4, the rotating shaft5a, etc. The heat radiation efficiency can be increased further by properly installing a fin, a fan, a duct, a water-cooling mechanism, etc.

The relative speed between the reaction vessels105and the fluorescence detectors6during the fluorescence measurement can be controlled by controlling the revolution speed (relative revolution speed) of the holder base4with respect to the fluorescence detectors6. The fluorescence detection may be conducted either by keeping the relative speed at a constant speed or by temporarily stopping a reaction vessel105at a position facing a fluorescence detector6.

Modification

A modification of the first embodiment of the present invention will be described below with reference toFIG. 5.

FIG. 5is a plan view showing a holder3A in accordance with this embodiment (modification). InFIG. 5, components identical with those explained in the first embodiment are assigned the same reference characters as in the first embodiment and repeated explanation thereof is omitted for brevity. In this embodiment, each temperature control block10of the holder3in the first embodiment is provided with two or more setting positions12.

Referring toFIG. 5, the holder3A in this embodiment includes a disk-shaped holder base4A arranged with its planar part facing upward and a plurality of temperature control blocks10A arranged along the periphery of the holder base4A. Each temperature control block10A is provided with two or more setting positions12(two in this embodiment).

The other configuration is equivalent to that in the first embodiment.

Also in this embodiment configured as above, effects similar to those of the first embodiment can be achieved.

Further, since each temperature control block10A is configured to be able to hold two or more reaction vessels105, the nucleic acid amplification processes of two or more reaction solutions according to the same protocol can be conducted at the same time, by which the processing efficiency can be increased further.

Furthermore, since the temperature control range in each temperature control block10A becomes wider compared to the case with only one setting position12, it is possible to install a fan integrally in each temperature control block10A and control the operating status of the fan at times of temperature rise and temperature drop for each temperature control range. Consequently, the speeds of the temperature rise and the temperature drop can be increased.

Second Embodiment

A second embodiment in accordance with the present invention will be described below with reference toFIGS. 6 and 7.

FIGS. 6 and 7are a plan view and a side view showing a nucleic acid amplifier1in accordance with this embodiment. InFIGS. 6 and 7, components identical with those explained in the first embodiment are assigned the same reference characters as in the first embodiment and repeated explanation thereof is omitted for brevity. This embodiment is configured to carry out the fluorescence detection for the reaction solutions stored in the reaction vessels105by fixing the holder3employed in the first embodiment while driving the fluorescence detectors6in the circumferential direction of the holder3. Incidentally, the cover is not shown inFIGS. 6 and 7for convenience of explanation.

Referring toFIGS. 6 and 7, the nucleic acid amplifier1mainly comprises a base2serving as the base of the nucleic acid amplifier1, a holder3provided with a plurality of temperature control blocks10each having a configuration for holding a reaction vessel105, fluorescence detectors6for detecting the fluorescence from the reaction solutions stored in the reaction vessels105, and a cover (not shown) covering the holder3and the fluorescence detectors6.

The holder3includes a holder base4and a plurality of temperature control blocks10. The holder base4is fixed to a base2by using a support member55provided at the center of the holder base4.

One or more fluorescence detectors6(four in this embodiment, for example) are fixed on a detector base51so that the fluorescence detectors6are arranged below the reaction vessels105and along the periphery of the holder3at even intervals. The detector base51is coupled to the support member55via a detector base rotating shaft54arranged coaxially with the support member55. The detector base51is arranged to be drivable and rotatable in the circumferential direction by use of a configuration such as a roller bearing between the support member55and the detector base rotating shaft54. The detector base rotating shaft54is linked with a motor52(for driving and rotating the detector base rotating shaft54) via a belt53. The fluorescence detection is carried out when a fluorescence detector6passes under a reaction vessel105due to the rotation of the detector base rotating shaft54and the detector base51driven by the motor52. When there are two or more fluorescence detectors6, the fluorescence detectors6perform the detection or measurement of the reaction solutions in the reaction vessels105independently from each other. The relative speed between the reaction vessels105and the fluorescence detectors6during the fluorescence measurement can be controlled by controlling the revolution speed (relative revolution speed) of the holder base4with respect to the fluorescence detectors6. The fluorescence detection may be conducted either by keeping the relative speed at a constant speed or by temporarily stopping a fluorescence detector6at a position facing a reaction vessel105.

A cover7is used for the purpose of reducing the incidence of external light onto the fluorescence detectors6of the nucleic acid amplifier1(light shielding effect) by covering the holder3and the fluorescence detectors6in cooperation with the base2. The cover7has a gate7awhich can be opened and closed (seeFIG. 14). The reaction vessels105are loaded/unloaded into/from the inside of the cover7(i.e., loaded/unloaded into/from the nucleic acid amplifier1) via the gate7a. The gate7ain this embodiment is configured so that the reaction vessels can be set in the setting positions12from the outside of the cover7. The gate7amay be placed at a position corresponding to a desired setting position12(as the target of setting a reaction vessel105) by expanding the gate7aor by moving part or all of the cover7, for example.

Incidentally, while the nucleic acid amplifier1in this embodiment is configured to conduct the fluorescence detection of the reaction solutions stored in the reaction vessels105by fixing the holder3and moving the fluorescence detectors6in the circumferential direction of the holder3, the fluorescence detection of the reaction solutions may also be implemented by configuring both the holder3and the fluorescence detectors6to be rotatable and controlling the relative rotation of the holder3and the fluorescence detectors6.

The other configuration is equivalent to that in the first embodiment.

Also in this embodiment configured as above, effects similar to those of the first embodiment can be achieved.

Third Embodiment

A third embodiment in accordance with the present invention will be described below with reference toFIGS. 8 and 9.

FIGS. 8 and 9are a plan view and a perspective view showing a nucleic acid amplifier1in accordance with this embodiment. InFIGS. 8 and 9, components identical with those explained in the first embodiment are assigned the same reference characters as in the first embodiment and repeated explanation thereof is omitted for brevity. In this embodiment, the temperature control blocks10of the holder3employed in the first embodiment are arranged on the periphery of the holder base4and notch parts16are formed between the temperature control blocks10as spaces for heat insulation.

Referring toFIGS. 8 and 9, a holder3B in this embodiment includes a disk-shaped holder base4B arranged with its planar part facing upward and a plurality of temperature control blocks10B arranged in the circumferential direction on the outer surface of the periphery of the holder base4B. The holder base4B and the temperature control blocks10B are formed of a thermal conductor such as aluminum, copper and various types of alloys. The temperature control blocks10B are formed integrally with the holder3B. Between adjacent temperature control blocks10B arranged in the circumferential direction of the holder base4B, a notch part16extending from the periphery toward the center of the holder base4B is formed. By such spaces provided between the temperature control blocks10B arranged in the circumferential direction of the holder base4B, heat isolation properties between the temperature control blocks10B are enhanced. Each temperature control block10B is equipped with a Peltier element17as a temperature control device and a temperature sensor15for detecting the temperature of the reaction solution in the reaction vessel105by measuring the temperature in the vicinity of the setting position12. The Peltier element17is installed so that one of its two heat exchanging surfaces closely adheres to the temperature control block10B and the other heat exchanging surface closely adheres to the holder base4B. Incidentally, the temperature of the holder base4B is lower than the temperature control blocks10B performing the temperature control of the reaction vessels since the temperatures used for the nucleic acid amplification are generally higher than room temperature. This promotes the transmission of heat from each temperature control block10B to the holder base4B when the temperature of the temperature control block10B is lowered, by which the temperature drop can be achieved more quickly. Further, it is possible in this embodiment to set the volume of the holder base4B larger than that of the temperature control blocks10B. Since the heat capacity of the holder base4B can be set sufficiently high just by forming both the holder base4B and the temperature control blocks10B with the same material (e.g., aluminum), high heat radiation efficiency of each temperature control block10B can be achieved. Furthermore, when the holder base4B performs the heat exchange with two or more temperature control blocks10B at the same time, the effect of the heat exchange between the holder base4B and a temperature control block10B on the heat exchange between the holder base4B and another temperature control block10B can be minimized.

Arranged at the center of the holder base4B are a Peltier element18as a temperature control device, a temperature sensor15afor detecting the temperature in the vicinity of the Peltier element18, a radiation fin41connected with the Peltier element18, and a fan40for sending air to the radiation fin41. Therefore, heat radiation/absorption efficiency of the Peltier element17of each temperature control block10B can be increased further by keeping the temperature of the holder base4B at a constant level (e.g., 40° C.) with the temperature control device18. When the PCR method as a type of the nucleic acid amplification technology is conducted, a prescribed temperature cycle including a temperature rise and a temperature drop is repeatedly applied to the reaction vessel by the temperature control block10B. By properly setting the temperature of the holder base4B in this temperature control, the speed of the temperature change can be increased and the balance between the temperature rise speed and the temperature drop speed can be controlled. For example, the temperature drop speed can be increased by controlling the holder base4B at temperatures lower than the temperature range implemented by the temperature control block10B. The maximum temperature and the temperature rise speed can be increased by controlling the temperature of the holder base4B within (between the upper limit and the lower limit of) the temperature range implemented by the temperature control block10B. Meanwhile, in the NASBA method as a type of the nucleic acid amplification technology, the reaction vessel is kept at a constant temperature (41° C.) with the temperature control block10. This temperature control can be performed precisely by properly setting the temperature of the holder base4B. Further, by providing the base2and the cover7with fans, an air flow is forcefully caused inside the nucleic acid amplifier1and the heat insulation effect can be enhanced by the passage of the air flow through the notch parts16.

The other configuration is equivalent to that in the first embodiment.

Also in this embodiment configured as above, effects similar to those of the first embodiment can be achieved.

Fourth Embodiment

A fourth embodiment in accordance with the present invention will be described below with reference toFIGS. 10 and 11.

FIGS. 10 and 11are a plan view and a side view showing a holder3C in accordance with this embodiment. InFIGS. 10 and 11, components identical with those explained in the first embodiment are assigned the same reference characters as in the first embodiment and repeated explanation thereof is omitted for brevity. In this embodiment, a holder3C not in a disk shape is employed instead of the holder3in the first embodiment.

Referring toFIGS. 10 and 11, the holder3C in this embodiment includes a rectangular plate-like holder base4C arranged with its planar part facing upward and a plurality of temperature control blocks10C arranged in a line on the holder base4C. Each temperature control block10C is provided with a plurality of (four in this embodiment) setting positions12. Although not shown in the figures, similarly to the configuration shown inFIG. 4in the first embodiment, each temperature control block10C is equipped with a Peltier element and a radiation fin for serving as a temperature control device and a temperature sensor for detecting the temperature of the reaction solutions in the reaction vessels105by measuring the temperature in the vicinity of the setting positions12. A fluorescence detector6is placed below the reaction vessels105(below the path of the movement of the reaction vessels105) and detects fluorescence when a reaction vessel105passes over the fluorescence detector6due to the driving of the holder3C. The holder base4C is arranged to be movable in the X-axis direction (horizontal direction inFIGS. 10 and 11) and in the Y-axis direction (vertical direction inFIG. 10) and to be driven linearly by not shown driving devices.

The other configuration is equivalent to that in the first embodiment.

Also in this embodiment configured as above, effects similar to those of the first embodiment can be achieved.

Other Embodiments

While several embodiments in accordance with the present invention have been described above, a variety of design changes and combinations are possible within the spirit and scope of the present invention.

For example, while the temperature control blocks are provided on the holder base of the holder in the first and second embodiments, the configuration with the notch parts formed between the temperature control blocks may also be employed similarly to the third embodiment. In the first and second embodiments, the heat radiation/absorption efficiency of the Peltier element of each temperature control block may be increased by forming the holder base with a thermal conductor, providing the temperature control device, and keeping the holder base at a constant temperature (e.g., 40° C.) similarly to the third embodiment.

While a radiation fin is provided for enhancing the heat radiation efficiency of the Peltier element of the temperature control device in the above embodiments of the present invention, the configuration for enhancing the heat radiation efficiency of the Peltier element is not restricted to this example. For example, the heat radiation efficiency of the Peltier element may be enhanced by water cooling, by providing a pipe line for circulating a coolant instead of the radiation fin.

While the fluorescence detection is performed in the above embodiments by irradiating each reaction vessel105held in a setting position12with the excitation light from below, the configuration for irradiating the reaction vessels105with the excitation light is not restricted to this example. For example, a configuration shown inFIGS. 12 and 13may be employed, wherein reaction vessels105arranged on a holder base4D are fixed by fixed holders10b, while detectors6are arranged on a detector base51athat can be rotated by a motor52aaround a detector base rotating shaft54a. The irradiation with the excitation light and the detection of the fluorescence are performed from the inside of the holder base4D via detection windows10a.

It is also possible to irradiate each reaction vessel105with the excitation light from below, from above, or from the side of the reaction vessel105and perform the fluorescence detection in a direction differing from the irradiating direction of the excitation light.

It goes without saying that the various methods described in the above embodiments of the present invention can be employed selectively so that the method for setting the reaction vessels105and the timing are optimized for each purpose of use of the device.

DESCRIPTION OF REFERENCE CHARACTERS