Patent Publication Number: US-2023136020-A1

Title: Nucleic acid analysis device

Description:
TECHNICAL FIELD 
     The present invention relates to a nucleic acid analysis device used in order to identify the base sequence of a nucleic acid such as deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). In particular, the present invention relates to a nucleic acid analysis device having a function of causing a reaction between a nucleic acid sample to be analyzed and a reagent and a function of optically detecting the nucleic acid sample or a reaction product thereof. 
     BACKGROUND ART 
     In recent years, in the field of nucleic acid analysis devices, a method has been proposed for using a flow cell, which is a sample container, carrying multiple DNA fragments to be analyzed on a flat substrate, and identifying in parallel the base sequences of the carried multiple DNA fragments. 
     In this method, a fluorescent dye-attached substrate corresponding to a base is introduced into the flow cell carrying the multiple DNA fragments, the flow cell is irradiated with excitation light, fluorescence generated from each DNA fragment is detected by an imaging means, and the base sequence is identified. 
     Further, in the nucleic acid analysis device, a complementary probe (nucleic acid fragment) obtained by fluorescently labeling a nucleic acid is extended by DNA polymerase or DNA ligase. The base sequences of multiple nucleic acids are identified in parallel by detecting fluorescence for each extension reaction. 
     In addition, in order to analyze a large amount of DNA fragments, an analysis region is usually divided into a plurality of detection fields, and the entire analysis region is analyzed while changing the detection field for each excitation light irradiation to identify the base sequence. 
     As a background art in this technical field, there is disclosed in JP-B-6068227 (PTL 1). Described in PTL 1 is a nucleic acid analysis device that has a dispensing nozzle suctioning and discharging a liquid, a nozzle drive unit moving the dispensing nozzle to a desired position, a liquid surface detection unit detecting a liquid surface by contact between a tip of the dispensing nozzle and the liquid surface, and a reaction unit having a flow path system having an injection port, a reaction flow path connected to the injection port, and a waste liquid flow path connected to the reaction flow path (see paragraph 0010). 
     In addition, as a background art in this technical field, there is disclosed in JP-B-5687514 (PTL 2). Described in PTL 2 is a nucleic acid sequence analysis device in which a refrigerant circulation-type temperature adjustment unit is mounted on a horizontal drive stage and the temperature adjustment unit adjusts a temperature of an installation surface of a flow cell to a predetermined temperature (see paragraph 0008). 
     CITATION LIST 
     Patent Literature 
     PTL 1: JP-B-6068227 
     PTL 2: JP-B-5687514 
     SUMMARY OF INVENTION 
     Technical Problem 
     PTL 1 describes a nucleic acid analysis device in which a flow cell is mounted on a stage that can be driven in two-dimensional directions in a horizontal plane. Likewise, PTL 2 describes a nucleic acid sequence analysis device (nucleic acid analysis device) in which a flow cell is mounted on a stage that can be driven in two-dimensional directions in a horizontal plane. 
     However, in the nucleic acid analysis devices described in PTL 1 and PTL 2, single translation means alone performs a unidirectional translational operation. Accordingly, in a case where, for example, a plurality of flow cells are handled, problems arise as a required movement amount increases, the stage becomes large, and the device becomes large. 
     In this regard, the present invention provides a nucleic acid analysis device with which a stage mechanism and the device can be reduced in size without an increase in the required movement amount even in a case where, for example, a plurality of flow cells are handled. 
     Solution to Problem 
     In order to solve the above problems, a nucleic acid analysis device of the present invention includes: a sample container containing a nucleic acid sample to be analyzed; an imaging means for observing the nucleic acid sample; and a stage mechanism moving the sample container, in which the stage mechanism has two translation means and at least one rotation means, one of the two translation means is installed on an upper surface of the rotation means, and the other is installed on a lower surface of the rotation means. 
     Advantageous Effects of Invention 
     According to the present invention, it is possible to provide a nucleic acid analysis device with which the stage mechanism and the device can be reduced in size without an increase in a required movement amount even in a case where, for example, a plurality of flow cells are handled. 
     It should be noted that problems, configurations, and effects other than those described above will be clarified by the description of the following example. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG.  1    is an explanatory diagram illustrating a schematic configuration of a nucleic acid analysis device  1  described in Example 1. 
         FIG.  2    is a perspective view illustrating an analysis means of the nucleic acid analysis device  1  described in Example 1. 
         FIG.  3    is a perspective view in which a stage mechanism  10  described in Example 1 developed around a rotation means  200  is viewed from above. 
         FIG.  4    is a perspective view in which the stage mechanism  10  described in Example 1 developed around the rotation means  200  is viewed from below. 
         FIG.  5    is a top view illustrating an operation of the analysis means during imaging described in Example 1. 
         FIG.  6    is a perspective view illustrating the operation of the analysis means during imaging described in Example 1. 
         FIG.  7    is an explanatory diagram illustrating a schematic configuration of a sample container  60  described in Example 1. 
         FIG.  8    is a perspective view illustrating a state where a rotating table  205  is rotated by 90° during replacement of a nucleic acid sample described in Example 1. 
         FIG.  9    is a perspective view illustrating a state of each table after movement to a replacement position of the nucleic acid sample described in Example 1. 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     An example of the present invention will be described below with reference to the drawings. It should be noted that substantially identical or similar configurations are denoted by the same reference numerals and redundant description may be omitted. In addition, the present example is to specifically describe the present invention so that the present invention is described in an easy-to-understand manner in accordance with the principle of the present invention and does not limit the interpretation of the present invention. 
     In addition, although a DNA fragment is analyzed in the present example, RNA, protein, and so on as well as DNA may be analyzed and the present example can be used for bio-related substances in general. 
     Example 1 
     First, a schematic configuration of a nucleic acid analysis device  1  described in Example 1 will be described. 
       FIG.  1    is an explanatory diagram illustrating the schematic configuration of the nucleic acid analysis device  1  described in Example 1. 
     The nucleic acid analysis device  1  is a device for identifying (analyzing) the base sequence of a nucleic acid and has, as an analysis means, the analysis means having a function of causing a reaction between a nucleic acid sample to be analyzed and a reagent and a function of optically detecting the nucleic acid sample or a reaction product thereof. 
     Further, as for the nucleic acid analysis device  1 , a rectangular sample container (flow cell) containing (enclosing) the nucleic acid sample is set, an operation of the device is started via a predetermined user interface having a display device or an input device such as a touch panel, nucleic acid analysis is automatically performed, and the base sequence is identified. 
     The nucleic acid analysis device  1  has, for base sequence identification, the analysis means having an imaging means  20  for observing (analyzing) the fluorescently labeled nucleic acid sample and a stage mechanism  10  moving a sample container  60  containing the nucleic acid sample to be analyzed. 
     It should be noted that at least two sample containers  60  (two sample containers in Example 1) are mounted on the stage mechanism  10  and the sample containers  60  are moved so that the entire analysis regions of the sample containers  60  are imaged (observed) or the sample containers  60  are replaced. 
     The nucleic acid analysis device  1  also has a reagent storage portion  80  where the reagent required for analysis (reagent for fluorescent labeling) is stored. 
     Further, the nucleic acid analysis device  1  has a liquid sending means  70  for sending the reagent from the reagent storage portion  80  to the sample container  60 . The liquid sending means  70  has a dispensing nozzle  701  suctioning and discharging (dispensing) the reagent for fluorescently labeling the nucleic acid and an arm portion  702  moving the dispensing nozzle  701  to a desired position. 
     The nucleic acid analysis device  1  uses polymerase chain reaction (PCR) method to extend the base sequence of the nucleic acid. The PCR method is a technique with which the base sequence of a desired nucleic acid can be selectively amplified by controlling the temperature of a reaction solution in accordance with predetermined conditions. In order to carry out this technique, the nucleic acid analysis device  1  has a temperature adjustment mechanism (not illustrated) for reaction solution temperature control. 
     Next, the stage mechanism  10  and the imaging means  20  as the analysis means of the nucleic acid analysis device  1  described in Example  1  will be described. 
       FIG.  2    is a perspective view illustrating the analysis means of the nucleic acid analysis device  1  described in Example 1. 
     The analysis means has the imaging means  20  for optically observing the fluorescently labeled nucleic acid sample, an optical base (optical support member)  30  holding (supporting) the imaging means  20 , two sample containers  60 A and  60 B, the stage mechanism  10  transporting (moving) the two sample containers  60 A and  60 B, a stage base  40  holding the stage mechanism  10 , and an anti-vibration mount  50  holding the weight of these components and blocking vibration from the outside. 
     An imaging range of the imaging means  20  is minute, and thus the nucleic acid analysis device  1  divides the analysis region of the sample container (flow cell)  60  into a plurality of detection fields and observes the entire analysis region while changing the detection field. Accordingly, the stage mechanism  10  is moved by a minute amount in an XY direction in  FIG.  2    and local imaging is repeated. As a result, the entire analysis region can be observed. 
     The stage mechanism  10  has a first translation means  100  installed on an upper surface of a rotation means  200  and a second translation means  300  installed on a lower surface of the rotation means  200 . 
     The second translation means  300  has a translation table displaced relative to a base portion (stage base  40 ) fixing the whole, a translation slider smoothly supporting the translation table, a drive means, such as a motor, for generating power for translational movement, and a linear motion mechanism, such as a ball screw, transmitting the power of the drive means. 
     The rotation means  200  has a base portion (translation table of the second translation means  300 ), a rotating table displaced in a rotational direction relative to the base portion, a rotating slider, such as a cross roller bearing, smoothly supporting the rotating table, a drive means, such as a motor, for generating power for rotational movement, and a gear mechanism transmitting the power of the drive means. It should be noted that one rotation means  200  is installed in Example 1. 
     The first translation means  100  has a base portion (rotating table of the rotation means  200 ), a translation table displaced relative to the base portion and moving an object to be loaded (such as the sample container  60 ), a translation slider smoothly supporting the translation table, a drive means, such as a motor, for generating power for translational movement, and a linear motion mechanism, such as a ball screw, transmitting the power of the drive means. 
     The imaging means  20  has an imaging element such as a CCD or CMOS image sensor (not illustrated), a light source, such as a xenon lamp (not illustrated), connected to the imaging element, and an optical lens (not illustrated) collecting excitation light emitted from the light source. 
     Further, the imaging means  20  detects fluorescence generated from the nucleic acid sample (DNA fragment) held in a reaction flow path of the sample container  60  by irradiating the sample container  60  with excitation light from the light source. 
     The two sample containers  60 A and  60 B are generally referred to as flow cells, in which the nucleic acid sample (DNA fragment) is fixed and a reagent flow path is formed. 
     In addition, the nucleic acid analysis device  1  has the liquid sending means  70  for introducing a fluorescent dye-attached substrate corresponding to the nucleic acid into the two sample containers  60 A and  60 B for fluorescent labeling and causing a reagent for a base extension reaction to flow. 
     It should be noted that although the liquid sending means  70  in Example 1 is a so-called dispensing mechanism having the dispensing nozzle  701  and the arm portion  702  moving the dispensing nozzle  701  to a desired position, the reagent may be directly sent by a pump to the two sample containers  60 A and  60 B with a pipe installed in the liquid sending means  70 . 
     In this manner, the nucleic acid analysis device  1  has the sample container  60  containing the nucleic acid sample to be analyzed, the imaging means  20  for observing the nucleic acid sample, and the stage mechanism  10  moving the sample container  60 , in which the stage mechanism  10  has two translation means ( 100  and  300 ) and at least one rotation means  200 , one of the two translation means ( 100  and  300 ) is installed on the upper surface of the rotation means  200 , and the other is installed on the lower surface of the rotation means  200 . 
     As a result, even in a case where a plurality of the sample containers  60  are handled, the stage mechanism  10  and the device can be reduced in size without an increase in a required movement amount. 
     It should be noted that the following four movements are required for the stage mechanism  10 .
         (1) Movement for changing the detection field in order to observe the entire analysis region of the sample container  60 ,   (2) Movement for switching an observation target between the two sample containers  60 A and  60 B,   (3) Movement of the sample container  60  into an operation range of the dispensing mechanism in injecting the reagent for fluorescent labeling, and   (4) Movement for replacing the sample container  60  after observation completion.       

     According to Example 1, the stage mechanism  10  and the device can be reduced in size without an increase in the required movement amount even in these movements. 
     In addition, the nucleic acid analysis device  1  uses the sample container  60 , carries the nucleic acid sample to be analyzed on a flat substrate, and identifies the nucleic acid base sequence of the nucleic acid sample in parallel. 
     Further, the fluorescent dye-attached substrate is introduced into the nucleic acid in the sample container  60  (for fluorescent labeling reaction), the sample container  60  is irradiated with excitation light, and the fluorescence generated from each nucleic acid sample (DNA fragment) is detected by the imaging means  20  (fluorescence observation). 
     At this time, the fluorescent dye-attached substrate is introduced into the nucleic acid and a complementary probe (nucleic acid fragment) obtained by fluorescently labeling the nucleic acid is subjected to DNA base extension (amplification) by DNA polymerase or DNA ligase (extension reaction). 
     As a result, fluorescence is detected for each extension reaction and the base sequences of multiple nucleic acids are identified in parallel. 
     In addition, the analysis region is divided into a plurality of detection fields, and the entire analysis region is analyzed while changing the detection field for each excitation light irradiation to identify the base sequence. 
     Then, a new fluorescent dye-attached substrate is introduced using a new extension reaction, and the entire analysis region is analyzed and base sequence identification is performed by the same procedure as above. Base sequence identification can be efficiently performed by repeating this. 
     Next, the rotation means  200  of the stage mechanism  10  described in Example 1 developed around a rotating table  205  will be described. 
       FIG.  3    is a perspective view in which the stage mechanism  10  described in Example 1 developed around the rotation means  200  is viewed from above. 
       FIG.  4    is a perspective view in which the stage mechanism  10  described in Example 1 developed around the rotation means  200  is viewed from below. 
     The stage mechanism  10  has, as the first translation means  100 , a base portion (rotating table  205 ), a first translation table  103  displaced relative to the base portion, allowing the sample containers  60 A and  60 B to be installed, and moving the sample containers  60 A and  60 B, a first translation slider  105  smoothly supporting the first translation table  103 , a first drive motor  101  as a drive means, such as a motor, for generating power for translational movement, and a first linear motion mechanism  102 , such as a ball screw, transmitting the power of the first drive motor  101 . 
     The first translation table  103  is translated by the first linear motion mechanism  102  and the first drive motor  101 . 
     Further, the first translation means  100  moves in an X-axis direction in  FIG.  3    and has a translational region where at least the analysis region of the sample container  60 A is observed. 
     In addition, the stage mechanism  10  has, as the rotation means  200 , a base portion (second translation table  303 ), the rotating table  205  displaced in a rotational direction relative to the base portion (rotating table  205  rotationally displaced around a rotation center), a rotating slider  204 , such as a cross roller bearing, smoothly supporting the rotating table  205 , a rotary motor  201  as a drive means, such as a motor, for generating power for rotational movement, and a first gear  202  and a second gear  203  as gear mechanisms transmitting the power of the drive means. 
     The rotating table  205  is rotationally moved by the first gear  202 , the second gear  203 , and the rotary motor  201 . 
     Further, the rotation means  200  has a rotational movement region rotating by at least 180° in order to switch the positions of the sample container  60 A and the sample container  60 B. 
     Here, as for the stage mechanism  10 , the rotating table  205  serves as the base portion of the first translation means  100 , and the rotating table  205  and the base portion of the first translation means  100  are identical for thickness-direction dimension suppression and component count reduction. 
     In other words, the first translation table  103  is directly connected to the rotating table  205  via the first translation slider  105 . As a result, a direction of movement of the first translation means  100  can be changed by the rotation means  200 . 
     The stage mechanism  10  has, as the second translation means  300 , the second translation table  303  displaced relative to the base portion (stage base  40 ) and moving the sample container  60 A and the sample container  60 B, a second translation slider  304  smoothly supporting the second translation table  303 , a second drive motor  301  as a drive means, such as a motor, for generating power for translational movement, and a second linear motion mechanism  302 , such as a ball screw, transmitting the power of the second drive motor  301 . 
     The second translation table  303  is translated by the second linear motion mechanism  302  and the second drive motor  301 . 
     Further, the second translation means  300  moves in a Y-axis direction in  FIG.  3    and has a translational region where at least the analysis region of the sample container  60 A is observed. 
     Here, as for the stage mechanism  10 , the second translation table  303  serves as the base portion of the rotation means  200 , and the second translation table  303  and the base portion of the rotation means  200  are identical for thickness-direction dimension suppression and component count reduction. 
     In other words, the rotating table  205  is directly connected to the second translation table  303  via the rotating slider  204 . As a result, a direction of movement of the second translation means  300  can be changed by the rotation means  200 . 
     The stage mechanism  10  also has a temperature control unit (temperature adjustment mechanism)  400  heating and cooling the sample container  60 A and the sample container  60 B where nucleic acid injection occurs for observation. It should be noted that the temperature control unit  400  is installed in each of the sample container  60 A and the sample container  60 B. 
     The temperature control unit  400  is also used as an installation table for the sample container  60 A and the sample container  60 B where a reaction solution is injected and is used to adjust the temperatures of the sample container  60 A and the sample container  60 B to appropriate reaction or observation temperatures. 
     In addition, the temperature control unit  400  has a Peltier element inside and is capable of adjusting the temperatures of the sample container  60 A and the sample container  60 B to appropriate reaction or observation temperatures. In addition, the temperature control unit  400  has a heat sink  401  for cooling the Peltier element. The heat sink  401  is configured by a highly conductive metal block. A flow path used for refrigerant liquid (such as pure water and antifreeze) circulation is formed in the heat sink  401 . 
     As a result, the nucleic acid analysis device  1  is capable of performing fluorescence observation in one sample container  60  and performing extension and fluorescent labeling reactions in the other sample container  60 , and is capable of improving the throughput of the device. In addition, the nucleic acid analysis device  1  is capable of increasing an amount of nucleic acid samples to be analyzed by the two sample containers  60 A and  60 B being installed. 
     According to Example 1, in the nucleic acid analysis device  1  with the rotation means  200 , directions of movement of the two translation means ( 100  and  300 ) installed on the upper and lower surfaces of the rotation means  200  can be the same and the two translation means ( 100  and  300 ) can be moved in the same direction. 
     As a result, in the nucleic acid analysis device  1 , an operation of moving the sample container  60  in a predetermined direction can be realized by two translation means ( 100  and  300 ). Accordingly, in the nucleic acid analysis device  1 , a required movement amount of each translation means ( 100  and  300 ) decreases. Further, each translation means ( 100  and  300 ) can be reduced in size and the nucleic acid analysis device  1  can be reduced in size. 
     In addition, in the nucleic acid analysis device  1 , the observation target can be switched between the two sample containers  60 A and  60 B by rotation. As a result, there is no need to ensure a region for retracting a non-observation target sample container and the analysis means can be reduced in size. 
     Next, an operation of the analysis means during imaging (at the time of sample analysis or observation) described in Example 1 will be described. 
       FIG.  5    is a top view illustrating the operation of the analysis means during imaging described in Example 1. 
       FIG.  6    is a perspective view illustrating the operation of the analysis means during imaging described in Example 1. 
     The nucleic acid analysis device  1  performs imaging of the sample container  60 A (nucleic acid (base) fluorescence observation) in the sample container  60 A, which is one of the two installed sample containers  60  (mounted on the translation means  100  installed on the upper surface of the rotation means  200 ), and performs nucleic acid (base) extension and fluorescent labeling reactions in the other sample container  60 B. 
     In the nucleic acid analysis device  1 , with regard to the sample container  60 A, the stage mechanism  10  is moved in the X and Y directions as indicated by a dotted arrow so that the analysis region indicated by fx and fy in  FIG.  5    is observed in whole (whole-region imaging). 
     Here, the rotating table  205  is stopped at a position where the first translation table  103  can be moved in the X direction in  FIG.  5   . 
     Further, in this state, the sample container  60 A is moved in the X direction by the first translation means  100  and in the Y direction by the second translation means  300 . 
     The nucleic acid analysis device  1  repeats the imaging processing N times for each detection field of the imaging means  20 . Here, N is the number of detection fields. The detection field corresponds to each region when the analysis region (whole) is divided into N. A two-dimensional sensor is capable of observing (detecting) the size of the detection field by single fluorescence observation, and the size is set by the design of an optical system. 
     The nucleic acid analysis device  1  sequentially repeats moving and stopping the N detection fields by the first translation means  100  and the second translation means  300  so that the sample container  60 A is aligned with the position where excitation light is emitted from the imaging means  20  (light source) and imaging is performed by the imaging means  20  for a predetermined exposure time. 
     The nucleic acid analysis device  1  performs imaging in the sample container  60 A, which is one of the two installed sample containers  60 , and performs extension and fluorescent labeling reactions in the other sample container  60 B. 
     The reagents used for the extension and fluorescent labeling reactions may be injected into the sample container  60  using the dispensing mechanism as described above or may be sent to the sample solution  60  using a pipe and a pump. It should be noted that here, the reaction solution (reagent) is injected into the sample container  60  by the dispensing mechanism. 
     An upper surface of the sample container  60  is provided with an injection port  61  for reagent injection by the dispensing mechanism (dispensing nozzle  701 ). 
     In addition, a width  30 Y of an optical base  30  and a rotation center C of the rotating table  205  in the nucleic acid analysis device  1  are set such that the dispensing mechanism is capable of accessing the sample container  60 B from above. In other words, the sample container  60 B (sample container  60 B where extension and fluorescent labeling reactions are performed) is installed at a position exposed from the optical base  30  and outside the width  30 Y of the optical base  30 . 
     In other words, the optical base  30  is installed such that an upper portion of one sample container  60  of the two sample containers  60 A and  60 B mounted on the stage mechanism  10  is opened. 
     As a result, the reagent can be directly injected into the injection port  61  of the sample container  60 B by the dispensing mechanism. 
     Next, a schematic configuration of the sample container  60  described in Example 1 will be described. 
       FIG.  7    is an explanatory diagram illustrating the schematic configuration of the sample container  60  described in Example 1. 
     The upper surface of the sample container  60  is provided with the injection port  61  for reagent injection by the dispensing mechanism. The injection port  61  has an inclined surface and guides the dispensing mechanism (dispensing nozzle  701 ) when the dispensing mechanism is inserted. 
     A reagent injected from the injection port  61  flows through a nucleic acid sample-fixed flow path  62  and filling (injection) occurs inside. Then, when the reagent is replaced, by injecting a next reagent from the injection port  61 , the already filled reagent is pushed out and discharged to the outside from a discharge port  63 . 
     Here, the movement of the sample container  60 B to a dispensing region is performed by positioning the stage mechanism  10  in an XY plane. When the dispensing of the reagent is completed, the temperature control unit  400  of the sample container  60 B controls an amount of current supplied to the Peltier element therein and controls the temperature of the sample container  60 B to a temperature suitable for an extension reaction by the reagent. 
     Then, imaging is performed in one sample container  60 A and extension and fluorescent labeling reactions are performed in the other sample container  60 B. 
     After these are completed, the rotary motor  201  is rotated and the rotating stage  205  is rotated by 180° for imaging in the other sample container  60 B. As a result of this rotation, the sample container  60 B moves to a position where the sample container  60 B can be imaged by the imaging means  20  and the sample container  60 A moves to a position where the reagent can be dispensed by the dispensing mechanism. 
     At this time, the sample container  60 A is installed at a position exposed from the optical base  30  and outside the width  30 Y of the optical base  30  such that the dispensing mechanism is capable of accessing the sample container  60 A from above. 
     In this manner, the positions of the two sample containers  60 A and  60 B are switched mutually, and imaging and extension and fluorescent labeling reactions are respectively performed. This is performed a required number of times, the nucleic acid sample is observed, and the base sequence is identified. 
     In this manner, the nucleic acid analysis device  1  is capable of switching the observation target between the two sample containers  60 A and  60 B by rotation. As a result, there is no need to ensure a region for retracting the non-observation target sample container, which is required in a translational operation by a simple combination of translation means, and the analysis means can be reduced in size. 
     Finally, a state of each table after the rotating table  205  is rotated by 90° and moved to a replacement position of the nucleic acid sample during replacement of the nucleic acid sample described in Example 1 will be described. 
       FIG.  8    is a perspective view illustrating the state where the rotating table  205  is rotated by 90° during the replacement of the nucleic acid sample described in Example 1. 
       FIG.  9    is a perspective view illustrating the state of each table after the movement to the replacement position of the nucleic acid sample described in Example 1. 
     After the observation of the two sample containers  60 A and  60 B is completed, a worker moves the sample container  60  to a position where the sample container  60  can be accessed in order to remove the sample container  60  and replace the sample container  60  with a new sample container  60  to be analyzed next. 
     Here, an accessible position is a position in a W direction in  FIGS.  8  and  9    where both the sample container  60 A and the sample container  60 B are exposed from the optical base  30 . 
     During the observation, directions of the first translation slider  105  and the second translation slider  304  are orthogonal to each other (see, for example,  FIG.  3   ). During the replacement, the rotating table  205  is rotated and, as a result, as illustrated in  FIG.  8   , the directions of the first translation slider  105  of the first translation means  100  and the second translation slider  304  of the second translation means  300  are matched such that both the first translation table  103  and the second translation table  303  are movable in the W direction in  FIG.  8   . 
     In other words, in the nucleic acid analysis device  1 , the two translation means ( 100  and  300 ) are orthogonal to each other during the observation and the directions of movement of the two translation means ( 100  and  300 ) are the same during the replacement. 
     After that, as illustrated in  FIG.  9   , the rotating table  205  and the first translation means  100  are moved in the W direction in  FIG.  9    by the second translation means  300  and, further, the first translation table  103  is moved in the W direction in  FIG.  9    by the first translation means  100 . 
     In other words, during the replacement, the two sample containers  60 A and  60 B mounted on the first translation table  103  of the translation means  100  installed on the upper surface of the rotation means  200  are completely exposed from the optical base  30 . 
     As a result, the sample container  60 A and the sample container  60 B are completely exposed to the outside of the optical base  30 , and the worker can replace the sample container  60 . 
     In this manner, the nucleic acid analysis device  1  moves the sample container  60  with two translation means ( 100  and  300 ). As a result, the nucleic acid analysis device  1  is capable of reducing the required movement amount of each translation means ( 100  and  300 ). 
     Further, in the nucleic acid analysis device  1  with the rotation means  200 , the directions of movement of the two translation means ( 100  and  300 ) installed on the upper and lower surfaces of the rotation means  200  can be the same and the two translation means ( 100  and  300 ) can be moved in the same direction. 
     As a result, in the nucleic acid analysis device  1 , the operation of moving the sample container  60  in a predetermined direction can be realized by two translation means ( 100  and  300 ). Accordingly, in the nucleic acid analysis device  1 , the required movement amount of each translation means ( 100  and  300 ) can be reduced. Further, each translation means ( 100  and  300 ) can be reduced in size and the nucleic acid analysis device  1  can be reduced in size. 
     It should be noted that the present invention includes various modification examples without being limited to Example 1 described above. For example, the above Example 1 has been specifically described so that the present invention is described in an easy-to-understand manner and is not necessarily limited to having every described configuration. 
     In addition, although Example 1 has been described so that those skilled in the art can implement the present invention, other embodiments are also possible and changes in configuration and various element replacements are possible without departing from the scope and spirit of the technical concept of the present invention. Accordingly, the description of the claims should not be construed as being limited to the description of Example 1. 
     REFERENCE SIGNS LIST 
     
         
           1 : nucleic acid analysis device 
           10 : stage mechanism 
           20 : imaging means 
           30 : optical base 
           40 : stage base 
           50 : anti-vibration mount 
           60 : sample container 
           70 : liquid sending means 
           100 : first translation means 
           101 : first drive motor 
           102 : first linear motion mechanism 
           103 : first translation table 
           105 : first translation slider 
           200 : rotation means 
           201 : rotary motor 
           202 : first gear 
           203 : second gear 
           204 : rotating slider 
           205 : rotating table 
           300 : second translation means 
           301 : second drive motor 
           302 : second linear motion mechanism 
           303 : second translation table 
           304 : second translation slider 
           400 : temperature control unit 
           401 : heat sink 
           701 : dispensing nozzle 
           702 : arm portion