Nucleic acid analysis device

By employing a combination design of two translation units and one rotation unit in the nucleic acid analysis device, the problem of increased device size when processing multiple flow cells was solved, achieving miniaturization of the stage and device and efficient analysis.

CN115516317BActive Publication Date: 2025-11-14HITACHI HIGH TECH CORP
View PDF 4 Cites 0 Cited by

Patent Information

Application Number
CN202080100589.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2020-05-27
Publication Date
2025-11-14
Estimated Expiration
2040-05-27

AI Technical Summary

Technical Problem

Existing nucleic acid analysis devices require a large amount of movement when processing multiple flow cells, which increases the size of the stage and device, making miniaturization difficult.

Method used

The design employs a platform mechanism, comprising two translation units and at least one rotation unit. One translation unit is located on the top surface of the rotation unit, and the other is located on the bottom surface of the rotation unit. By combining rotation and translation, the amount of movement is reduced to achieve miniaturization.

Benefits of technology

When dealing with multiple flow cells, it can effectively reduce the amount of movement, miniaturize the stage mechanism and device, and improve analysis efficiency.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure CN115516317B_ABST
    Figure CN115516317B_ABST
Patent Text Reader

Abstract

This invention provides a nucleic acid analysis device that does not increase the required amount of movement when processing multiple flow cells, thus miniaturizing the stage mechanism and the device itself. The nucleic acid analysis device of this invention is characterized by comprising a sample container containing a nucleic acid sample as the object of analysis, a camera unit for observing the nucleic acid sample, and a stage mechanism for moving the sample container. The stage mechanism has two translation units and at least one rotation unit, with one translation unit disposed on the top surface of the rotation unit and the other on the bottom surface of the rotation unit.
Need to check novelty before this filing date? Find Prior Art

Description

Technical Field

[0001] This invention relates to a nucleic acid analysis device for recognizing the base sequence of nucleic acids such as DNA (deoxyribonucleic acid) or RNA (ribonucleic acid). In particular, it relates to a nucleic acid analysis device having the function of reacting reagents with a nucleic acid sample as the analyte and the function of optically detecting the nucleic acid sample or its reaction products. Background Technology

[0002] In recent years, a method has been proposed in nucleic acid analysis devices that uses a flow cell as a sample container to carry multiple DNA fragments as the target of analysis on a planar substrate, and identifies the base sequence of the multiple carried DNA fragments in parallel.

[0003] In this method, a matrix containing fluorescent dye corresponding to the bases is introduced into a flow cell carrying multiple DNA fragments. The flow cell is then irradiated with excitation light, and a camera unit is used to detect the fluorescence emitted from each DNA fragment to identify the base sequence.

[0004] Then, in the nucleic acid analysis apparatus, complementary probes (fragments of nucleic acids) that have been fluorescently labeled with nucleic acids are extended using DNA polymerase and DNA ligase. Multiple nucleic acids are identified in parallel by detecting fluorescence at each extension reaction.

[0005] In addition, in order to analyze a large number of DNA fragments, the analysis area is usually divided into multiple detection fields. The detection field is changed each time the excitation light is irradiated to analyze the entire analysis area and identify the base sequence.

[0006] As background technology in this field, there is Japanese Patent No. 6068227 (Patent Document 1). Patent Document 1 describes a nucleic acid analysis apparatus having a dispensing nozzle that attracts and ejects liquid; a nozzle drive unit that moves the dispensing nozzle to a desired position; a liquid level detection unit that detects the liquid level by contacting the liquid level with the front end of the dispensing nozzle; and a reaction unit including 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 (refer to paragraph 0010).

[0007] Furthermore, as background technology in this field, there is Japanese Patent No. 5687514 (Patent Document 2). Patent Document 2 describes a nucleic acid sequence analysis device that uses a coolant circulation type temperature adjustment unit mounted on a horizontal drive stage to adjust the temperature of the set surface of the flow cell to a predetermined temperature (see paragraph 0008).

[0008] Existing technical documents

[0009] Patent documents

[0010] Patent Document 1: Japanese Patent No. 6068227

[0011] Patent Document 2: Japanese Patent No. 5687514 Summary of the Invention

[0012] The problem that the invention aims to solve

[0013] Patent Document 1 describes a nucleic acid analysis device with a flow cell mounted on a stage capable of being driven in a two-dimensional direction in a horizontal plane. Patent Document 2 also describes a nucleic acid sequence analysis device (nucleic acid analysis device) with a flow cell mounted on a stage capable of being driven in a two-dimensional direction in a horizontal plane, similar to Patent Document 1.

[0014] However, in the nucleic acid analysis devices described in Patent Documents 1 and 2, since only a single translation unit is used to perform translational movement in one direction, the amount of movement required increases, for example, when processing multiple flow cells, resulting in the problem of increasing the size of the stage and the device.

[0015] Therefore, the present invention provides a nucleic acid analysis device that, for example, does not increase the required amount of movement when processing multiple flow cells, thereby miniaturizing the stage mechanism and the device.

[0016] Technical solutions for solving the problem

[0017] To address the aforementioned issues, the nucleic acid analysis apparatus of the present invention is characterized by comprising a sample container containing a nucleic acid sample as the object of analysis, a camera unit for observing the nucleic acid sample, and a stage mechanism for moving the sample container. The stage mechanism has two translation units and at least one rotation unit, with one of the two translation units disposed on the top surface of the rotation unit and the other disposed on the bottom surface of the rotation unit.

[0018] Invention Effects

[0019] According to the present invention, a nucleic acid analysis device can be provided, for example, without increasing the required amount of movement when processing multiple flow cells, thereby miniaturizing the stage mechanism and the device.

[0020] In addition, issues, structures, and effects other than those described above will be explained through the following embodiments. Attached Figure Description

[0021] Figure 1 This is an explanatory diagram illustrating the schematic structure of the nucleic acid analysis device 1 described in Example 1.

[0022] Figure 2 This is a perspective view illustrating the analysis unit of the nucleic acid analysis device 1 described in Example 1.

[0023] Figure 3 This is a perspective view of the platform mechanism 10 described in Embodiment 1, viewed from above, unfolded with the rotating unit 200 as the center.

[0024] Figure 4 This is a perspective view of the platform mechanism 10 described in Embodiment 1, viewed from below, unfolded with the rotating unit 200 as the center.

[0025] Figure 5 This is a top view illustrating the operation of the analysis unit in the camera described in Embodiment 1.

[0026] Figure 6 This is a perspective view illustrating the operation of the analysis unit in the camera described in Embodiment 1.

[0027] Figure 7 This is an explanatory diagram illustrating the schematic structure of the sample container 60 described in Example 1.

[0028] Figure 8 This is a perspective view illustrating the state in Example 1 where the rotating worktable 205 is rotated 90° when changing nucleic acid samples.

[0029] Figure 9 This is a perspective view illustrating the state of each workbench after it has been moved to the new position of the nucleic acid sample as described in Example 1. Detailed Implementation

[0030] Hereinafter, embodiments of the present invention will be described using the accompanying drawings. Wherein, substantially the same or similar structures are given the same reference numerals, and descriptions may be omitted where they are repeated. Furthermore, these embodiments conform to the principles of the present invention; the invention is specifically described for ease of understanding and is not intended to be limiting.

[0031] In addition, this embodiment uses DNA fragments as the analysis object, but in addition to DNA, RNA or proteins can also be used as the analysis object. This embodiment can be used for various in vivo related substances.

[0032] Example 1

[0033] First, the general structure of the nucleic acid analysis device 1 described in Example 1 will be explained.

[0034] Figure 1 This is an explanatory diagram illustrating the schematic structure of the nucleic acid analysis device 1 described in Example 1.

[0035] Nucleic acid analysis device 1 is a device for identifying (analyzing) the base sequence of nucleic acids. As an analysis unit, it includes an analysis unit that has the function of reacting reagents with nucleic acid samples as the object of analysis and the function of optically detecting nucleic acid samples or their reaction products.

[0036] The nucleic acid analysis device 1 is a device that performs the following actions: it sets up a rectangular sample container (flow cell) containing (sealed) a nucleic acid sample, and starts the operation of the device via a specified user interface with a display device and input device such as a touch panel, and automatically performs nucleic acid analysis and identifies base sequences.

[0037] The nucleic acid analysis device 1 includes an analysis unit having an imaging unit 20 for observing (analyzing) fluorescently labeled nucleic acid samples for identifying base sequences, and an analysis stage mechanism 10 for moving a sample container 60 containing the nucleic acid sample as the object of analysis.

[0038] In addition, the stage mechanism 10 carries at least two sample containers (two sample containers in Embodiment 1) for photographing (observing) the entire analysis area of ​​the sample container 60 or for moving the sample container 60 to replace it.

[0039] In addition, the nucleic acid analysis device 1 has a reagent storage section 80 for storing reagents (reagents for fluorescent labeling) required for analysis.

[0040] Then, the nucleic acid analysis device 1 has a delivery unit 70 for conveying reagents from the reagent storage section 80 to the sample container 60. The delivery unit 70 has a dispensing nozzle 701 for attracting and dispensing (distributing) reagents for fluorescent labeling on nucleic acids and an arm 702 for moving the dispensing nozzle 701 to a required position.

[0041] The nucleic acid analysis apparatus 1 uses polymerase chain reaction (PCR) to extend the base sequence of nucleic acids. PCR is a method that selectively amplifies the desired nucleic acid base sequence by controlling the temperature of the reaction solution according to predetermined conditions. To implement this method, the nucleic acid analysis apparatus 1 has a temperature adjustment mechanism (not shown) for controlling the temperature of the reaction solution.

[0042] Next, the analysis unit of the nucleic acid analysis device 1 described in Example 1, namely the stage mechanism 10 and the camera unit 20, will be explained.

[0043] Figure 2 This is a perspective view illustrating the analysis unit of the nucleic acid analysis device 1 described in Example 1.

[0044] The analysis unit includes an imaging unit 20 for optically observing fluorescently labeled nucleic acid samples, an optical base (optical support component) 30 for holding (supporting) the imaging unit 20, two sample containers 60A and 60B, a stage mechanism 10 for transporting (moving) the two sample containers 60A and 60B, a stage base 40 for holding the stage mechanism 10, and a vibration damping base 50 for maintaining the weight of these components and blocking vibrations from the outside.

[0045] In the nucleic acid analysis device 1, because the imaging range of the camera unit 20 is small, the analysis area of ​​the sample container (flow cell) 60 is divided into multiple detection fields, and the entire analysis area is observed by changing the detection field. Therefore, this process is repeated to keep the stage mechanism 10 in a specific position. Figure 2 The movement is measured in minute increments along the X and Y directions, and the image is captured locally. This allows observation of the entire analysis area.

[0046] The platform mechanism 10 has a first translation unit 100 disposed on the top surface of the rotating unit 200 and a second translation unit 300 disposed on the bottom surface of the rotating unit 200.

[0047] The second translation unit 300 includes a translation worktable that moves relative to the base part (platform base 40) which is fixed as a whole, a translation slider that smoothly supports the translation worktable, a drive unit such as an electric motor that generates power for translation, and a linear motion mechanism such as a ball screw that transmits the power of the drive unit.

[0048] The rotating unit 200 includes a base portion (the translation worktable of the second translation unit 300), a rotating worktable that is displaced in the rotational direction relative to the base portion, a rotating slider such as a crossed roller bearing that smoothly supports the rotating worktable, a drive unit such as an electric motor that generates power for rotational movement, and a gear mechanism that transmits the power of the drive unit. Furthermore, in Embodiment 1, one rotating unit 200 is provided.

[0049] The first translation unit 100 includes a base (the rotary table of the rotation unit 200), a translation table that moves the loaded object (sample container 60, etc.) by displacement relative to the base, a translation slider that smoothly supports the translation table, a drive unit such as an electric motor that generates power for translation, and a linear motion mechanism such as a ball screw that transmits the power of the drive unit.

[0050] The camera unit 20 includes camera elements such as CCD and CMOS image sensors (not shown), a light source such as a xenon lamp (not shown) connected to the camera elements, and an optical lens (not shown) that focuses the excitation light emitted from the light source.

[0051] Then, the camera unit 20 detects the fluorescence produced by the nucleic acid sample (DNA fragment) held in the reaction flow path of the sample container 60 by irradiating the sample container 60 with excitation light from the light source.

[0052] The two sample containers 60A and 60B are generally referred to as flow cells, in which nucleic acid samples (DNA fragments) are fixed and form a flow path for reagents.

[0053] In addition, the nucleic acid analysis device 1 has a liquid delivery unit 70 for introducing a matrix with fluorescent dye corresponding to the nucleic acid into the interior of two sample containers 60A and sample containers 60B for fluorescent labeling and for flowing reagents to extend the base reaction.

[0054] In addition, in Embodiment 1, the liquid delivery unit 70 is a so-called dispensing mechanism having a dispensing nozzle 701 and an arm 702 that moves the dispensing nozzle 701 to the required position. However, piping can also be provided inside the liquid delivery unit 70 to directly deliver reagents to the two sample containers 60A and 60B using a pump.

[0055] Thus, the nucleic acid analysis device 1 has a sample container 60 containing a nucleic acid sample as the object of analysis, an imaging unit 20 for observing the nucleic acid sample, and a stage mechanism 10 for moving the sample container 60. The stage mechanism 10 has two translation units (100 and 300) and at least one rotation unit 200. One of the two translation units (100 and 300) is disposed on the top surface of the rotation unit 200, and the other is disposed on the bottom surface of the rotation unit 200.

[0056] Therefore, even when handling multiple sample containers 60, the required amount of movement will not increase, enabling the miniaturization of the stage mechanism 10 and the device.

[0057] In addition, the following four types of movement are required for the platform mechanism 10.

[0058] (1) Movement used to change the detection field of view in order to observe the entire analysis area of ​​the sample container 60;

[0059] (2) Used to switch the movement of the observed object in two sample containers 60A and 60B;

[0060] (3) The sample container 60 moves within the range of motion of the dispensing mechanism when the reagent for fluorescent labeling is injected;

[0061] (4) Used to move the sample container 60 after the observation is completed.

[0062] According to Embodiment 1, the required amount of movement will not increase during such movement, which enables miniaturization of the platform mechanism 10 and the device.

[0063] In addition, the nucleic acid analysis device 1 uses a sample container 60 to hold a nucleic acid sample as the object of analysis on a planar substrate and identifies the base sequence of the nucleic acid in the nucleic acid sample in parallel.

[0064] Then, in sample container 60, nucleic acids are introduced into a matrix containing fluorescent dye (to perform a fluorescent labeling reaction), sample container 60 is irradiated with excitation light, and the fluorescence generated from each nucleic acid sample (DNA fragment) is detected by imaging unit 20 (to perform fluorescence observation).

[0065] At this point, nucleic acids are introduced into a matrix containing fluorescent dye. For complementary probes (fragments of nucleic acids) that have been fluorescently labeled with nucleic acids, DNA polymerase and DNA ligase are used to elongate (amplify) the DNA bases (perform an elongation reaction).

[0066] Therefore, by detecting fluorescence at each extension reaction, the base sequence of multiple nucleic acids can be identified in parallel.

[0067] In addition, the analysis area is divided into multiple detection fields, and the detection field is changed every time the excitation light is irradiated, so as to analyze the entire analysis area and identify the base sequence.

[0068] Then, using a new extension reaction, a new matrix containing fluorescent dye is introduced, and the entire analytical region is analyzed using the same procedure as described above to identify the base sequence. By repeating this process, the base sequence can be identified efficiently.

[0069] Next, the structure of the platform mechanism 10 described in Embodiment 1, which unfolds around the rotating worktable 205 of the rotating unit 200, will be explained.

[0070] Figure 3 This is a perspective view of the platform mechanism 10 described in Embodiment 1, viewed from above, unfolded with the rotating unit 200 as the center.

[0071] Figure 4 This is a perspective view of the platform mechanism 10 described in Embodiment 1, viewed from below, unfolded with the rotating unit 200 as the center.

[0072] The stage mechanism 10 has a base (rotary worktable 205), a first translation worktable 103 that moves sample containers 60A and 60B relative to the base and moves sample containers 60A and 60B, a first translation slider 105 that smoothly supports the first translation worktable 103, a drive unit such as an electric motor that generates power for translation, namely a first drive motor 101, and a first linear motion mechanism 102 such as a ball screw that transmits power to the first drive motor 101, as a first translation unit 100.

[0073] The first translational worktable 103 is translated by the first linear movement mechanism 102 and the first drive motor 101.

[0074] The first translation unit 100 has the ability to... Figure 3 The translation area of ​​the analysis region is moved along the X-axis to observe at least 60A of the sample container.

[0075] In addition, the platform mechanism 10 has a base (second translational worktable 303), a rotary worktable 205 that is displaced in the rotational direction relative to the base (rotary worktable 205 that rotates around the rotation center), a rotary slider 204 such as a cross roller bearing that smoothly supports the rotary worktable 205, a drive unit such as a rotary motor 201 that generates power for rotational movement, and a gear mechanism such as a first gear 202 and a second gear 203 that transmits the power of the drive unit, as a rotation unit 200.

[0076] The rotary table 205 rotates and moves via the first gear 202, the second gear 203, and the rotary motor 201.

[0077] The rotating unit 200 has a rotational movement area that can rotate at least 180° to switch the positions of sample container 60A and sample container 60B.

[0078] Here, in the stage mechanism 10, in order to suppress the dimension in the thickness direction and reduce the number of parts, the rotary table 205 serves as the base part of the first translation unit 100, and the rotary table 205 is the same as the base part of the first translation unit 100.

[0079] That is, the first translational worktable 103 is directly connected to the rotary worktable 205 via the first translational slider 105. Thus, the direction of movement of the first translational unit 100 can be changed by the rotary unit 200.

[0080] The stage mechanism 10 has a second translation worktable 303 that moves sample containers 60A and 60B by displacement relative to the base (stage base 40), a second translation slider 304 that smoothly supports the second translation worktable 303, a drive unit such as a motor that generates power for translation, namely a second drive motor 301, and a second linear motion mechanism such as a ball screw that transmits power to the second drive motor 301, as a second translation unit 300.

[0081] The second translation worktable 303 is translated by the second linear movement mechanism 302 and the second drive motor 301.

[0082] The second translation unit 300 has the ability to... Figure 3 The translational area of ​​the analysis region that moves along the Y-axis, at least 60A of the sample container.

[0083] Here, in the stage mechanism 10, in order to suppress the dimension in the thickness direction and reduce the number of parts, the second translation stage 303 functions as the base part of the rotation unit 200. The second translation stage 300 is the same as the base part of the rotation unit 200.

[0084] That is, the rotary table 205 is directly connected to the second translational table 303 via the rotary slider 204. Thus, the direction of movement of the second translational unit 300 can be changed by the rotary unit 200.

[0085] In addition, the stage mechanism 10 has a temperature adjustment unit (temperature adjustment mechanism) 400 for heating and cooling sample containers 60A and 60B into which nucleic acids are injected for observation. The temperature adjustment unit 400 is provided for sample containers 60A and 60B respectively.

[0086] The temperature adjustment unit 400 is used as a stage for the sample containers 60A and 60B into which the reaction solution is injected, and is used to adjust the temperature of the sample containers 60A and 60B to the appropriate reaction temperature and observation temperature.

[0087] Furthermore, the temperature adjustment unit 400 internally includes a Peltier element, capable of adjusting the temperatures of sample containers 60A and 60B to appropriate reaction and observation temperatures. Additionally, the temperature adjustment unit 400 includes a heat sink 401 for cooling the Peltier element. The heat sink 401 is constructed of a highly conductive metal block. A flow path for circulating coolant liquid (pure water or antifreeze, etc.) is formed inside the heat sink 401.

[0088] Therefore, the nucleic acid analysis device 1 can perform fluorescence observation in one sample container 60 and extension reaction and fluorescence labeling reaction in another sample container 60, thereby improving the throughput of the device. In addition, by setting up two sample containers 60A and 60B, the nucleic acid analysis device 1 can also increase the amount of nucleic acid sample to be analyzed.

[0089] According to Embodiment 1, the nucleic acid analysis device 1 can use the rotation unit 200 to make the two translation units (100 and 300) disposed on its top and bottom surfaces move in the same direction, so that the two translation units (100 and 300) move in the same direction.

[0090] Therefore, the nucleic acid analysis device 1 can achieve the action of moving the sample container 60 in a specified direction using two translation units (100 and 300). Thus, the necessary movement amount of each translation unit (100 and 300) in the nucleic acid analysis device 1 is reduced. Furthermore, the nucleic acid analysis device 1 allows for the miniaturization of each translation unit (100 and 300), thereby enabling device miniaturization.

[0091] Furthermore, the nucleic acid analysis device 1 can switch between the two sample containers 60A and 60B using a rotational motion. This eliminates the need to ensure a clear area for non-observation sample containers, allowing for miniaturization of the analysis unit.

[0092] Next, the operation of the analysis unit during imaging (sample analysis or observation) as described in Example 1 will be explained.

[0093] Figure 5 This is a top view illustrating the operation of the analysis unit in the camera described in Embodiment 1.

[0094] Figure 6 This is a perspective view illustrating the operation of the analysis unit in the camera described in Embodiment 1.

[0095] The nucleic acid analysis device 1 performs imaging (fluorescence observation of nucleic acid (bases)) on one of the two sample containers 60 (mounted on the translation unit 100 mounted on the top surface of the rotating unit 200) in sample container 60A, and performs nucleic acid (base) extension reaction and fluorescence labeling reaction in the other sample container 60B.

[0096] In nucleic acid analysis device 1, for sample container 60A, in order to... Figure 5 The entire analysis area, represented by fx and fy, is observed (in order to photograph the entire area), while the stage mechanism 10 is moved in the X and Y directions as shown by the dashed arrows.

[0097] Here, the rotary table 205 stops at the first translational table 103, making it capable of... Figure 5 The position of the state that has moved in the X direction.

[0098] Then, in this state, for sample container 60A, the first translation unit 100 is used to move it in the X direction, and the second translation unit 300 is used to move it in the Y direction.

[0099] The nucleic acid analysis device 1 performs N repeated imaging processes for each detection field of view in the imaging unit 20. Here, N is the number of detection fields. A detection field is equivalent to dividing the analysis area (the whole) into N regions. The size of the detection field is the size that can be observed (detected) by a two-dimensional sensor using a single fluorescence observation, and is set according to the design of the optical system.

[0100] In order to detect N fields of view, the nucleic acid analysis device 1 uses the first translation unit 100 and the second translation unit 300 to position the sample container 60A at the position where it is illuminated by the excitation light from the imaging unit 20 (light source), and performs imaging with the imaging unit 20 within a specified exposure time, and repeatedly moves and stops.

[0101] The nucleic acid analysis device 1 takes a picture of one of the two sample containers 60, 60A, and performs an extension reaction and a fluorescent labeling reaction in the other sample container 60B.

[0102] Regarding the reagents used in the extension reaction and the fluorescent labeling reaction, as described above, the sample container 60 can be injected using a dispensing mechanism, but tubing and a pump can also be used to deliver the solution to the sample container 60. Alternatively, here, the reaction solution (reagent) is injected into the sample container 60 using a dispensing mechanism.

[0103] The sample container 60 has an injection port 61 on its top surface for injecting reagents using a dispensing mechanism (dispensing nozzle 701).

[0104] Furthermore, the width 30Y of the optical base 30 and the rotation center C of the rotary stage 205 in the nucleic acid analysis device 1 are set in such a way that the dispensing mechanism can reach the sample container 60B from above. That is, the sample container 60B (the sample container 60B for performing the extension reaction and the fluorescent labeling reaction) is located at a position exposed from the optical base 30, and is located outside the width 30Y of the optical base 30.

[0105] That is, the optical base 30 is configured such that the upper part of one of the two sample containers 60A and sample containers 60B mounted on the stage mechanism 10 is open.

[0106] Therefore, the reagent can be injected directly into the injection port 61 of the sample container 60B using the dispensing mechanism.

[0107] Next, the general structure of the sample container 60 described in Example 1 will be explained.

[0108] Figure 7 This is an explanatory diagram illustrating the schematic structure of the sample container 60 described in Example 1.

[0109] The sample container 60 has an injection port 61 on its top surface for injecting reagents using a dispensing mechanism. The injection port 61 has an inclined surface to guide the dispensing mechanism (dispensing nozzle 701) when it is inserted.

[0110] The reagent injected through injection port 61 flows through flow path 62, which immobilizes the nucleic acid sample, and is filled (injected) inside. Then, when changing reagents, the filled reagent is pushed out through the discharge port 63 by injecting the next reagent through injection port 61.

[0111] Here, the movement of the sample container 60B towards the dispensing area is achieved by positioning it in the XY plane of the stage mechanism 10. When reagent dispensing is complete, the temperature adjustment unit 400 of the sample container 60B controls the amount of current supplied to the Peltier element inside, thereby controlling the temperature of the sample container 60B to a suitable temperature for extending the reaction with the reagent.

[0112] Then, an image was taken of one sample container 60A, and an extension reaction and a fluorescent labeling reaction were carried out in another sample container 60B.

[0113] After these processes are completed, the rotary motor 201 is rotated to perform imaging in another sample container 60B, causing the rotary stage 205 to rotate 180°. Through this rotation, the sample container 60B is moved to a position where it can be imaged by the imaging unit 20, and the sample container 60A is moved to a position where it can be dispensed by the dispensing mechanism.

[0114] At this time, the sample container 60A is positioned at a location exposed from the optical base 30 so that the dispensing mechanism can be accessed from above, and is located on the outside of the width 30Y of the optical base 30.

[0115] Thus, for the two sample containers 60A and 60B, their positions are switched, and imaging, extension reaction, and fluorescent labeling reaction are performed respectively. This treatment is carried out the necessary number of times to observe the nucleic acid samples and identify the base sequences.

[0116] In this way, the nucleic acid analysis device 1 can switch the observation target between the two sample containers 60A and 60B through rotation. As a result, it is not necessary to ensure the area for avoiding non-observation sample containers required in translation operations using only a combination of translation units, thus enabling the miniaturization of the analysis unit.

[0117] Finally, the state of each workbench after rotating the rotary workbench 205 90° and moving it to the position for replacing the nucleic acid sample, as described in Example 1, will be explained.

[0118] Figure 8 This is a perspective view illustrating the state in Example 1 where the rotating worktable 205 is rotated 90° when changing nucleic acid samples.

[0119] Figure 9 This is a perspective view illustrating the state of each workbench after it has been moved to the new position of the nucleic acid sample as described in Example 1.

[0120] After the observation of two sample containers 60A and 60B is completed, in order to remove sample container 60 and replace it with a new sample container 60 for the next analysis, the operator moves sample container 60 to a position where sample container 60 can be picked up and put down.

[0121] Here, the place where you can pick up or put down items is... Figure 8 and Figure 9 The two sample containers 60A and 60B in the W direction are both exposed from the optical base 30.

[0122] During observation, the directions of the first translation slider 105 and the second translation slider 304 are orthogonal (e.g., reference). Figure 3 In response, during replacement, for the first translation unit 100 and the second translation unit 300, the rotary table 205 is rotated as follows. Figure 8 As shown, the first translation stage 103 and the second translation stage 303 can work together in Figure 8 The way the slider moves in the W direction is such that the first translation slider 105 and the second translation slider 304 are aligned.

[0123] That is, in the nucleic acid analysis device 1, the two translation units (100 and 300) are orthogonal to each other during observation, and the two translation units (100 and 300) move in the same direction when changing.

[0124] After that, as Figure 9 As shown, the second translation unit 300 is used to make the rotary table 205 and the first translation unit 100 move together. Figure 9 The first translation worktable 103 moves in the W direction, and then the first translation unit 100 makes the first translation worktable 103 move in the W direction. Figure 9 It moves in the W direction.

[0125] That is, during replacement, the two sample containers 60A and 60B mounted on the first translation stage 103 of the translation unit 100, which is located on the top surface of the rotation unit 200, are fully exposed from the optical base 30.

[0126] As a result, sample containers 60A and 60B are fully exposed to the outside of the optical base 30, allowing the operator to replace sample container 60.

[0127] In this way, the nucleic acid analysis device 1 uses two translation units (100 and 300) to move the sample container 60. As a result, the nucleic acid analysis device 1 can reduce the amount of movement required for each translation unit (100 and 300).

[0128] Then, the nucleic acid analysis device 1 can use the rotation unit 200 to make the two translation units (100 and 300) arranged on its top and bottom surfaces move in the same direction, so that the two translation units (100 and 300) move in the same direction.

[0129] Therefore, the nucleic acid analysis device 1 can achieve the action of moving the sample container 60 in a specified direction using two translation units (100 and 300). Thus, the nucleic acid analysis device 1 can reduce the necessary movement of each translation unit (100 and 300). Furthermore, the nucleic acid analysis device 1 can miniaturize each translation unit (100 and 300), thereby miniaturizing the device itself.

[0130] Furthermore, the present invention is not limited to Embodiment 1 described above, and includes various modifications. For example, Embodiment 1 described above is specifically illustrated for ease of understanding of the present invention and is not limited to having all the structures described.

[0131] Furthermore, while Embodiment 1 was described for the purpose of enabling practitioners of the art to implement the invention, other embodiments are also possible, allowing for structural changes and substitutions of various elements without departing from the scope and spirit of the invention. Therefore, the scope of the claims should not be limited to the description in Embodiment 1.

[0132] Explanation of reference numerals in the attached figures

[0133] 1… Nucleic acid analysis device, 10… Stage mechanism, 20… Camera unit, 30… Optical base, 40… Stage base, 50… Vibration damping base, 60… Sample container, 70… Liquid delivery unit, 100… First translation unit, 101… First drive motor, 102… First linear motion mechanism, 103… First translation stage, 105… First translation slider, 200… Rotation unit, 201… Rotary motor, 202… First gear, 203… Second gear, 204… Rotary slider, 205… Rotary stage, 300… Second translation unit, 301… Second drive motor, 302… Second linear motion mechanism, 303… Second translation stage, 304… Second translation slider, 400… Temperature adjustment unit, 401… Radiator, 701… Dispensing nozzle, 702… Arm.

Claims

1. A nucleic acid analysis device, characterized in that: It includes a sample container containing a nucleic acid sample as the object of analysis, a camera unit for observing the nucleic acid sample, and a stage mechanism for moving the sample container. The platform mechanism has two translation units and at least one rotation unit. One of the two translation units is located on the top surface of the rotation unit, and the other is located on the bottom surface of the rotation unit. The translation unit disposed on the top surface of the rotating unit has a top surface translation unit base and a top surface translation worktable capable of displacement relative to the top surface translation unit base. The rotating unit has a rotary table capable of rotating around a rotation center. The base of the top surface translation unit is the rotary worktable. The translation unit, located on the bottom surface of the rotating unit, has a bottom translation worktable capable of displacement relative to the mounting base. The rotating unit also has a base portion, and the rotating worktable is capable of displacement relative to the base portion in the rotational direction. The bottom translation worktable is the base of the rotating unit.

2. The nucleic acid analysis device as described in claim 1, characterized in that: During observation, the two translation units are orthogonal to each other.

3. The nucleic acid analysis device as described in claim 1, characterized in that: When replacing the two translation units, they move in the same direction.

4. The nucleic acid analysis device as described in claim 1, characterized in that: The translation unit located on the top surface of the rotating unit can carry two sample containers.

5. The nucleic acid analysis device as described in claim 3, characterized in that: During replacement, the two sample containers mounted on the top translation worktable are exposed from the optical base.

6. The nucleic acid analysis device as described in claim 4, characterized in that: An image is captured of one of the two sample containers mounted on the translation unit on the top surface of the rotating unit, and an extension reaction and a fluorescent labeling reaction are performed in the other sample container.

7. The nucleic acid analysis device as described in claim 6, characterized in that: The sample container for performing the extended reaction and fluorescent labeling reaction is exposed from the optical base.

8. The nucleic acid analysis device as described in claim 6, characterized in that: It has a dispensing nozzle for dispensing reagents and an arm for moving the dispensing nozzle to a desired position.

9. The nucleic acid analysis device as described in claim 8, characterized in that: A reagent storage department is provided for storing and analyzing the reagents required.

10. The nucleic acid analysis device as described in claim 1, characterized in that: The sample container has a flow path for reagents to pass through.

Citation Information

Patent Citations

  • Promotor for growth of hair

    JP1981087514A

  • accumulator

    JP1985068227A

  • Rotating sample positioning apparatus

    US20160116495A1

  • Automated priming and library loading device

    WO2019133756A1