JP2016214096A - Analyzer and analysis method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a simplified analyzer of a gene or the like.SOLUTION: An analyzer comprises a main body case 1, an analysis container installing tray 3, a rotary drive part 5, a control part, and tilting means, in which the analysis container installing tray 3 is provided in the main body case 1, and has an analysis container installation surface on which the analysis container is installed, the rotary drive part 5 is provided in the main body case 1, rotates the analysis container installing tray 3 about a rotation axis 4 in a state of being installed on the analysis container installation surface, a control part controls rotation of the rotary drive part 5, the tilting means gives an inclination angle to the analysis container installation surface of the analysis container installing tray 3 with respect to a horizontal direction.SELECTED DRAWING: Figure 1

Description

  The present invention relates to an analysis apparatus and analysis method for genes, for example.

  A conventional analyzer is used for analyzing a liquid specimen injected into an analysis container. A flow path for processing the liquid specimen is provided in the analysis container. The liquid specimen injected into the flow path is subjected to a surface tension due to capillary action or a centrifugal force generated by rotating the analysis container, so that the liquid specimen sequentially passes through the flow path along a predetermined path. It is configured to flow.

For example, Patent Documents 1 and 2 describe analyzers configured to change the direction in which the liquid specimen moves by changing the direction of the centrifugal force applied to the analysis container.
These analysis apparatuses include a rotation mechanism for revolving to rotate the tray with respect to the analysis container installed on the tray, and a rotation mechanism for rotation to rotate the position of the analysis container itself with respect to the tray. ing.

Japanese Patent No. 4901333 Japanese Patent No. 5359965

The problem with the conventional example is that the configuration of the apparatus is complicated.
That is, in the above conventional example, in order to change the direction of the centrifugal force with respect to the analysis container, a rotation mechanism for rotating the tray on which the analysis container is installed, and a rotation mechanism for rotating the analysis container itself with respect to the tray, Is required for each. For this reason, it is necessary to combine a plurality of mechanism parts, and the configuration of the apparatus may be complicated.

  Therefore, the present invention aims to simplify the configuration of the apparatus.

  And in order to achieve this objective, the analysis apparatus of this invention is equipped with the main body case, the analysis container installation tray, the rotation drive part, the control part, and the inclination means. The analysis container installation tray is provided in the main body case and has an analysis container installation surface on which the analysis container is installed. The rotation drive unit is provided in the main body case, and rotates the analysis container installation tray around the rotation axis while being placed on the analysis container installation surface. The control unit controls the rotation of the rotation driving unit. The tilting means tilts the analysis container installation surface of the analysis container installation tray with respect to the horizontal direction.

As described above, according to the configuration of the present invention, the configuration of the apparatus can be simplified.
That is, in the present invention, since the analysis container installation surface is provided with an inclination means that makes an inclination angle with respect to the horizontal direction, the control container controls the rotation of the rotation drive unit, so that the analysis container is installed in the analysis container. The position on the tray can be changed while sliding the analysis container installation surface of the tray below the inclined surface.

As a result, since the rotation center position of the analysis container installation tray with respect to the analysis container changes, the direction of the centrifugal force with respect to the analysis container can be changed.
Thereby, since it becomes possible to change the direction of the centrifugal force with respect to the analysis container without having a plurality of rotation mechanisms as in the prior art, the configuration of the apparatus can be simplified.

The perspective view of the analyzer which shows one Embodiment of this invention. The functional block diagram of the analyzer which shows one Embodiment of this invention. The perspective view of the analysis container which shows one Embodiment of this invention. The perspective view of the principal part of the analyzer which shows one Embodiment of this invention. The perspective view of the analyzer and analysis container which show one Embodiment of this invention. The perspective view of the principal part of the analyzer which shows one Embodiment of this invention. The top view of the principal part of the analyzer which shows one Embodiment of this invention. The side view of the principal part of the analysis container which shows one Embodiment of this invention. Sectional drawing of the principal part of the analyzer which shows one Embodiment of this invention. The bottom view of the principal part of the analyzer which shows one Embodiment of this invention. (A)-(d) is a perspective view of the principal part of the analyzer which shows one Embodiment of this invention. The assembly drawing of the principal part of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. Sectional drawing of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The flowchart of an analysis process. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The top view of the analysis container which shows one Embodiment of this invention. The sectional view of the chamber in one embodiment of the present invention. (A) And (b) is a side view of the principal part of the analyzer which shows one Embodiment of this invention. (A)-(c) is a perspective view of the chamber in one Embodiment of this invention. The flowchart which shows the flow of the analysis process by the analyzer which concerns on one Embodiment of this invention.

An apparatus according to an embodiment of the present invention will be described below with reference to FIGS.
Hereinafter, an example in which an analysis container according to an embodiment of the present invention and an analysis apparatus using the same are applied to a gene analysis apparatus will be described with reference to the accompanying drawings.
(Embodiment 1)
<Device configuration>
FIG. 1 is a perspective view of a perspective view of the gene analyzer. In FIG. 1, the main body case 1 has an opening 2 for inserting an analysis container on the upper surface thereof. Below the opening 2, an analysis container installation tray 3 for installing an analysis container is provided.

In the main body case 1, the analysis container installation tray 3 is connected to the rotation drive unit 5 via the rotation shaft 4.
The rotating shaft 4 is disposed so as to have an inclination angle with respect to the vertical direction. For this reason, the analysis container installation surface of the analysis container installation tray 3 connected to the rotating shaft 4 has an inclination angle with respect to the horizontal direction.

In front of the main body case 1, for example, a display unit 6 for displaying gene analysis results and the state of the device, and an operation unit 7 for operating the device are provided.
<Functional block diagram of the device>
FIG. 2 shows a functional block diagram of the gene analyzer.
In the main body case 1, in addition to the above configuration, the control unit 8 that controls the rotation of the rotation driving unit 5, the optical detection unit 9 that optically detects the analysis result of the analysis container, and the temperature in the apparatus A temperature control unit 10 for controlling is provided.
<Description of analysis container>
FIG. 3 shows a perspective view of the analysis container 11. The analysis container 11 has a substantially cubic shape in outer shape. The analysis container 11 has a substantially rectangular cross section (cross section parallel to the fluid circuit surface 11a).

The fluid circuit surface 11a provided on the upper surface of the analysis container 11 is provided with a plurality of chambers for storing and dispensing a liquid specimen and a liquid reagent, and a flow path for connecting the plurality of chambers.
As shown in FIG. 4, the analysis container 11 is placed on an analysis container installation tray 3 provided inside the apparatus through the opening 2 on the upper surface of the apparatus.
<Configuration of analysis container installation tray 3 and rotation drive unit 5>
FIG. 5 shows the configuration of the analysis container installation tray 3 and the rotation drive unit 5.

The analysis container installation tray 3 is connected to the rotation drive unit 5 through the rotation shaft 4. As described above, the rotation shaft 4 has an inclination angle with respect to the vertical direction. For this reason, the analysis container installation surface 12 of the analysis container installation tray 3 is connected substantially perpendicularly to the rotation shaft 4 and therefore has an inclination angle with respect to the horizontal direction.
Therefore, the analysis container 11 installed on the analysis container installation surface 12 is installed in the direction of the arrow 13 due to the gravity generated on the inclined surface and the swing of the analysis container installation tray 3 by the rotation drive unit 5. Slide on surface 12. And the analysis container 11 is fixed in the state contact | abutted by the inner wall 14 protruded substantially perpendicular | vertical on the outer peripheral side of the analysis container installation surface 12. FIG.

  Here, the static frictional force generated between the analysis container installation surface 12 and the sliding surface 28 provided on the lower surface of the analysis container 11 is caused by gravity that moves the analysis container 11 due to the inclination of the analysis container installation surface 12. It is set to be large. For this reason, the analysis container 11 does not move only by the inclination of the analysis container installation surface 12. On the other hand, when the analysis container installation tray 3 is swung, the influence of the static friction force acting between the analysis container installation surface 12 and the sliding surface 28 of the analysis container 11 is reduced, and the analysis container 11 is inclined by gravity. It moves while sliding in a predetermined direction on the surface.

Therefore, the control unit 8 can move the analysis container 11 in a desired direction by controlling the rotation of the rotation driving unit 5 and controlling the swinging. Moreover, since it is necessary to move the analysis container 11 in an arbitrary direction, the control unit 8 also performs control to stop the analysis container installation tray 3 at an arbitrary rotation angle.
<Relationship between analysis container installation tray 3 and analysis container 11>
FIG. 6 shows the relationship between the analysis container installation tray 3 and the analysis container 11.

The analysis container installation surface 12 has a columnar protrusion 15 that protrudes substantially perpendicularly to the analysis container installation surface 12 at a substantially central portion serving as a rotation center. The shape of the upper surface of the analysis container installation tray 3 is substantially circular. And the inner wall 14 is provided in the upper surface of the analysis container installation tray 3 in the position which opposes every 90 degree intervals on the same periphery.
The length of one side of the upper surface of the cubic analysis container 11 is substantially equal to the radius of the circular upper surface of the analysis container installation tray 3. For this reason, the length between the columnar protrusion 15 and the inner wall 14 is about 1 mm longer than the length of one side of the upper surface of the analysis container 11, but is substantially equal.

As a result, the inner wall 14 and the columnar protrusion 15 serve as a guide, and the analysis container 11 can be guided. Therefore, the analysis container 11 can accurately move to the position of the opposing inner wall 14 along the inclination of the analysis container installation surface 12.
For example, when the analysis container 11 moves in the direction of the arrow 13 shown in FIG. 6, the analysis container 11 moves from the inner wall 14 a to the inner wall 14 c while being sandwiched between the inner wall 14 b and the protrusion 15. To do. During this movement, the inner wall 14b and the projection 15 guide the analysis container 11, so that the analysis container 11 is accurately moved from the inner wall 14a toward the opposing inner wall 14c and fixed.

FIG. 7 shows the relationship between the arrangement of the analysis container 11 and the centrifugal force.
In FIG. 7, for convenience of explanation, three analysis containers 11 are illustrated as being arranged on the analysis container installation tray 3. One analysis container 11 which moves is shown.
The direction in which the centrifugal force acts on the analysis container 11 changes according to the position on the analysis container installation tray 3.

For example, when the analysis container 11 is disposed at the upper left corner in FIG. 7, the rotation center 16 is located at the lower right of the analysis container 11, so that the direction in which the centrifugal force acts is the direction of the arrow 17a. The direction of the diagonal line from the lower right to the upper left.
When the analysis container 11 is arranged at the lower left corner of the drawing, the rotation center 16 is at the upper right of the analysis container 11. Therefore, the centrifugal force acting on the analysis container 11 is in the direction of the arrow 17b, that is, the diagonal line from the upper right to the lower left of the analysis container 11.

When the analysis container 11 is arranged at the lower right corner on the drawing, the rotation center 16 is at the upper left of the analysis container 11. Therefore, the centrifugal force acting on the analysis container 11 is in the direction of the arrow 17c, that is, the direction of the diagonal line from the upper left to the lower right of the analysis container 11.
<Description of guide rail>
FIG. 8 is a side view of the analysis container 11, and FIG. 9 is a longitudinal sectional view of the analysis container installation tray 3.

The analysis container 11 has a guide mechanism so that the analysis container 11 can accurately move along the inclination of the analysis container installation surface 12. As shown in FIG. 8, a convex guide 20 is provided on the sliding surface 28 side of the lower surface of the analysis container 11. Moreover, as shown in FIG. 9, the concave rail 21 is formed in the analysis container installation surface 12 side.
<Description of analysis container detector>
The configuration of the analysis container detection unit is shown in FIG.

The position of the analysis container 11 on the analysis container installation tray 3 is detected by the analysis container detection unit.
The analysis container detection unit includes an LED (analysis container detection unit) 82 as a light output unit provided so as to sandwich the analysis container installation tray 3 up and down, and a photosensor (analysis container detection unit) 83 as a light receiving unit. Have.

For example, when the analysis container 11 is not moved with respect to the position where the analysis container detection unit is provided, the light from the LED 82 enters the photosensor 83 as it is, as shown in FIG. Thereby, it can detect that the analysis container 11 is not in a predetermined position by detecting light in the photo sensor 83.
On the other hand, when the analysis container 11 moves with respect to the position where the analysis container detection unit is provided, the light from the LED 82 is blocked by the analysis container 11 as shown in FIG. Do not enter directly. Thereby, it is possible to detect that the analysis container 11 is in a predetermined position because no light is detected by the photosensor 83.

That is, in the analysis apparatus of the present embodiment, it is possible to determine whether or not the analysis container 11 has moved by determining the light receiving state of the photosensor 83.
<Description of balance ball>
FIG. 10 shows a view of the analysis container installation tray 3 as viewed from the lower surface.
In the present embodiment, the analysis container 11 installed on the analysis container installation tray 3 is configured to be able to change the position. However, since the analysis container installation tray 3 itself rotates, the analysis container 11 depends on the position of the analysis container 11. It is necessary to balance rotation.

Therefore, in this embodiment, in order to balance the rotation of the analysis container 11 while offsetting the weight of the analysis container 11, the balance ball 22 is moved to a diagonal position of the place where the analysis container 11 is installed. Let
By arranging the balance ball 22 at a position diagonal to the place where the analysis container 11 is installed, the balance of rotation can be balanced even if the position of the analysis container 11 changes. Therefore, it is possible to suppress sound and vibration caused by imbalance that occurs during rotation.

FIG. 11A to FIG. 11C show a process of arranging the balance ball 22.
FIG. 11A shows a state where the analysis container installation tray 3 is rotating at high speed.
In this state, the analysis container 11 is positioned on the upper right side of the analysis container installation tray 3, whereas the balance ball 22 is disposed on the lower left side in order to keep the balance of rotation.
FIG. 11B shows a state where the analysis container installation tray 3 is stopped, and the analysis container installation surface 12 is inclined with the upper side of the drawing being high and the lower side being low.

FIG. 11C shows a state where the analysis container installation tray 3 is rocked.
In this state, by swinging, the analysis container installation tray 3 forms a state of fine vibration in the clockwise and counterclockwise directions, so that the frictional force between the analysis container installation surface 12 and the analysis container 11 is It becomes smaller by changing from static friction to dynamic friction. And the analysis container 11 slides the analysis container installation surface 12 toward the lower side of a figure with the gravity concerning the analysis container 11 arrange | positioned on an inclined surface.

FIG. 11D shows a state in which the analysis container installation tray 3 is rotated and stopped so that the diagonal position is lowered in order to move the balance ball 22 to the diagonal position of the analysis container 11.
In this state, the balance ball 22 moves to the diagonal position of the analysis container 11. On the other hand, since the analysis container 11 is in a state in which the static frictional force is larger than the gravity, the analysis container 11 can be kept stationary on the inclined surface.

The guide rail 23 forms a movement path of the balance ball 22 and has a substantially square shape as shown in FIG. The guide rail 23 has a curved portion 24 that is curved inward at the center of each side of a substantially rectangular shape.
And the hollow 25 which has the shape along the external shape of the balance ball 22 toward the outer side is formed in the four corners of the substantially square guide rail 23. As a result, the balance ball moved to the corners at the four corners is easily held at the position of the recess 25.
<Description of analysis container>
FIG. 12 shows an assembly diagram of the analysis container 11.

The analysis container 11 has a cube-shaped main body 26, an upper cover 27 that sandwiches the main body 26 in the vertical direction, and a sliding surface 28 that serves as a lower cover.
FIG. 13 shows a top view of the analysis container 11.
The analysis container 11 has a substantially square fluid circuit surface 11a surrounded by four points A, B, C, and D arranged along the counterclockwise direction on the upper surface thereof. The four points A, B, C, and D are points A and C, and points B and D are opposite vertices of the substantially square fluid circuit surface 11a.

The fluid circuit surface 11a is provided with a plurality of chambers for storing and dispensing a liquid specimen and a liquid reagent, and a flow path for connecting the plurality of chambers. The flow path and the chamber are roughly divided into four blocks.
The first block is a liquid sample quantification unit 29 that quantifies blood as a liquid sample. The second block is a liquid reagent holding unit 30 that supplies a solution and a cleaning solution in stages. The third block is a BF separation unit that separates nucleic acids and contaminants in the reaction chamber 40. The fourth block is the nucleic acid amplification reaction unit 31, which amplifies the nucleic acid after mixing the nucleic acid amplification reagent.

FIG. 14 shows a ZZ ′ cross-sectional view of the analysis container 11.
The analysis container 11 has a two-layer structure. When viewed from above, the first layer is a reaction channel layer 57 provided with channels and chambers, and the second layer is a waste liquid storage layer for storing waste liquid. 58.
Here, since the conventional analysis container sends liquid using surface tension such as capillary action or siphon phenomenon, a deep channel or chamber cannot be formed in the depth direction. Therefore, in the conventional analysis container, the length in the depth direction is only about one-tenth of the length in the width direction, and has a planar shape.

On the other hand, the analysis container 11 of the present embodiment is configured to perform liquid feeding only by centrifugal force without using a capillary phenomenon. For this reason, the flow path and the chamber are deeply formed so as not to cause capillary action. Therefore, the depth direction and the width direction length of the analysis container 11 are set to be substantially the same, and the main body 26 of the analysis container 11 has a three-dimensional cube shape.
In this way, by changing the analysis container 11 from the conventional thin plate shape to a three-dimensional shape, even in the same installation area, it is long in the depth direction. Can handle seed liquids.
<Description of the configuration of the liquid specimen quantification unit of the analysis container>
FIG. 15 shows a top view of the analysis container 11.

First, the liquid specimen quantification unit 29 includes a liquid specimen injection chamber 32, a flow path 33, a liquid specimen quantitative chamber 35, a flow path 36, and a waste liquid chamber 34.
Each positional relationship is a waste liquid chamber 34, a quantitative chamber 35, and a liquid specimen injection chamber 32 in order from the point A.
In addition, the liquid specimen injection chamber 32 and the quantitative chamber 35 are connected by a flow path 33, and the quantitative chamber 35 and the waste liquid chamber 34 are connected by a flow path 36. For this reason, when a centrifugal force is applied in the direction from point C to point A, blood flows from the liquid specimen injection chamber 32 through the flow path 33 to the liquid specimen quantification chamber 35.

At this time, the blood that overflows and fills the quantitative chamber 35 flows into the waste liquid chamber 34 through the flow path 36. The waste liquid chamber 34 stores an excess of a blood sample as a liquid sample. It is possible to confirm whether or not a sufficient blood sample has been injected by confirming the presence or absence of the surplus blood sample by detection such as light detection.
As a result, blood is quantified and stored in the quantitative chamber 35 of the flow path 33.
<Description of Configuration of Liquid Reagent Holding Unit of Analysis Container>
Next, the liquid reagent holding unit 30 includes a liquid reagent holding chamber 37, a liquid reagent shift chamber 38, and channels 93a to 93f and channels 94a to 94e that connect them. The positional relationship between the liquid reagent shift chamber 38 and the liquid reagent holding chamber 37 is as follows from the point A.

As a result, when a centrifugal force is applied in the direction from point C to point A, the liquid reagent moves from the liquid reagent holding chamber 37 to the liquid reagent shift chamber 38 through the flow path 93.
In the present embodiment, assuming that the combination of the liquid reagent holding chamber 37 and the liquid reagent shift chamber 38 is one pair, there are a total of six combinations from the first chamber pair to the sixth chamber pair. In the configuration shown in FIG. 15, the first chamber pair is a liquid reagent holding chamber 37a and a liquid reagent shift chamber 38a, and hereinafter, the sixth chamber pair is a liquid reagent holding chamber 37f and a liquid reagent shift chamber 38f.

The chamber pairs are connected by a flow path 94 from the liquid reagent shift chamber 38 of the adjacent chamber pair to the liquid reagent holding chamber 37 closer to the point B than the liquid reagent shift chamber 38.
That is, with respect to the positional relationship between the liquid reagent holding chamber 37 and the liquid reagent shift chamber 38, for example, in the first chamber pair, the liquid reagent shift chamber 38a is disposed closer to the point A than the liquid reagent holding chamber 37a. Has been. The liquid reagent holding chamber 37a is disposed so as to be closer to the point B than the liquid reagent shift chamber 38b of the second chamber pair.

  As a result, when a centrifugal force is applied in the direction from the point C to the point A with respect to the analysis container 11 in which the liquid reagent is placed in the liquid reagent holding chambers 37a to 37f of the first to sixth chamber pairs. The liquid reagent placed in the liquid reagent holding chambers 37a to 37f moves to the liquid reagent shift chambers 38a to 38f. Thereafter, by applying a centrifugal force in the direction from point D to point B, the liquid reagent moved to the liquid reagent shift chambers 38b to 38f moves to the adjacent liquid reagent holding chambers 37a to 37e.

  Then, the six types of liquid reagents move from the liquid reagent shift chamber 38a to the reaction chamber 40 step by step. The reaction chamber 40 is provided at a position closer to the point B than the liquid reagent shift chamber 38a. Therefore, when a centrifugal force is applied in the direction from point D to point B, the liquid reagent that has entered the liquid reagent shift chamber 38a passes through the flow path 90, the flow path 92, and the flow path 91 to the reaction chamber 40. Moving.

Here, when a centrifugal force is applied in the direction from point D to point B, the blood quantified in the liquid sample quantification chamber 35 passes through the flow path 39, the flow path 92, and the flow path 91. Move to reaction chamber 40. Then, the liquid reagent and blood that have moved from the liquid reagent shift chamber 38 a are mixed in the reaction chamber 40.
<Configuration of BF separation unit and nucleic acid amplification reaction unit of analysis container>
The BF separation unit includes a reaction chamber 40 containing magnetic beads that specifically bind to nucleic acids, a via 44 that introduces waste liquid in the reaction chamber 40 into a waste liquid storage layer 58 on the lower surface, a quantification chamber 35, and a reaction chamber 40. A flow path 39 connecting the liquid reagent shift chamber 38a and the reaction chamber 40, a flow path 91 connecting the via 44 and the reaction chamber 40, and a flow path 39 and the flow path 91. A channel 92 that connects the channel 90 and the channel 91 to each other. As for these positional relationships, the reaction chamber 40 is disposed near the point B, and the via 44 is disposed near the point A.

  Thereby, by alternately applying a centrifugal force from the point D to the point B and from the point C to the point A, the liquid reagent is introduced into the reaction chamber 40 or the liquid in the reaction chamber is transferred to the waste liquid storage layer 58 on the lower surface. Can be discharged. Specifically, when a centrifugal force is applied in the direction from point D to point B, the liquid reagent in the liquid reagent shift chamber 38 a is introduced into the reaction chamber 40 via the channel 90, the channel 92, and the channel 91. When a centrifugal force is applied in the direction from point C to point A, the liquid in the reaction chamber 40 is discharged to the waste liquid storage layer 58 on the lower surface via the flow path 91 and the via 44.

With such a configuration, the introduction of the liquid into the reaction chamber 40 and the discharge of the liquid from the reaction chamber 40 can be performed a plurality of times. Therefore, nucleic acid extraction using magnetic beads that is generally performed can be performed in the analysis container 11.
The nucleic acid amplification reaction unit 31 includes a quantification chamber 41 for quantifying the nucleic acid extract, a via 43 for discharging excess liquid overflowing from the quantification chamber 41 to the waste liquid storage layer 58 on the lower surface, a measurement chamber 42, a quantification chamber 41, and And a flow path connecting the measurement chamber 42.

The reaction chamber 40, the quantitative chamber 41, and the measurement chamber 42 are sequentially connected by a flow path.
The measurement chamber 42 is arranged closer to the point C than the quantitative chamber 41, and the quantitative chamber 41 is arranged closer to the point C than the reaction chamber 40. For this reason, when a centrifugal force is applied from point A to point C, the nucleic acid extract moves from the reaction chamber 40 to the quantitative chamber 41. Then, the nucleic acid extract moves from the quantitative chamber 41 to the measurement chamber 42.

  The flow path connecting the quantitative chamber 41 and the measurement chamber 42 is a fine flow path. In addition, the flow path wall surface is hydrophobic, and the nucleic acid extract does not flow from the quantitative chamber 41 toward the measurement chamber 42 unless the rotational speed exceeds a certain value. For this reason, when the rotation speed is such that the nucleic acid extract does not flow into the measurement chamber 42, the nucleic acid extract can be temporarily stored in the quantitative chamber 41.

At this time, a quantitative nucleic acid extract is stored in the quantitative chamber 41, and the excess liquid overflowing from the quantitative chamber 41 flows into the lower waste liquid storage layer 58 via the via 43, whereby the nucleic acid extract can be quantitatively determined. Thereafter, the rotational speed is increased, and the nucleic acid extract quantified in the quantification chamber 41 is moved to the measurement chamber 42.
As a final step, in the measurement chamber 42, temperature control is performed in a state where the nucleic acid amplification reagent and the nucleic acid extract are mixed to perform specific nucleic acid amplification, and optically confirm the presence or absence of the gene. .

In the present embodiment, the analysis apparatus and the analysis container have been described for the purpose of nucleic acid amplification technology, but the present invention can also be applied to an analysis apparatus that requires BF separation, such as an immunoassay technique, and its analysis container.
<Description of features of chamber and flow path configuration>
Although the chamber and the flow path configuration of the fluid circuit surface 11a in the present embodiment have been described, the characteristic portions of this configuration will be described below.
<Description of the flow path configuration of FIG. 17>
FIG. 17 shows a configuration including a first chamber 47, a second chamber 48, and a flow channel 49 connecting the chambers as one of the basic configurations of the chamber and the flow channel of the fluid circuit surface 11a. explain.

The dotted line in the figure is an auxiliary line drawn for easy understanding of the positional relationship between the chamber and the flow path, and is a concentric circle from the rotation center 16.
With respect to the positional relationship between the two chambers, the first chamber 47 has the second chamber 48 with respect to the points A, B, C, and D arranged counterclockwise in the same plane of the fluid circuit surface 11a. It is arranged so as to be closer to the point C and farther from the point A.

The positional relationship between the connection point 60 between the flow path 49 and the first chamber 47 and the connection point 61 between the flow path 49 and the second chamber 48 is such that the connection point 60 is more point C than the connection point 61. It is arranged to be close to.
Further, the connection point 60 is disposed at a position farthest from the point C in the first chamber 47. The inner surface shape of the chamber 47 is formed so as to be connected to the connection point 60 away from the point C.

Points A, B, C, and D are points A and C, and points B and D are the opposite vertices of the quadrangle of the main body 26 of the analysis container 11, respectively.
Thereby, when a centrifugal force is applied in the direction from the point C to the point A, the liquid reagent in the first chamber 47 can move toward the second chamber 48 by the centrifugal force.
<Description of the flow path configuration of FIG. 18>
FIG. 18 shows a configuration of two sets of the first chamber 47, the second chamber 48, and the flow paths 49 and 50.

  The positional relationship among the first chambers 47a, 47b, the second chambers 48a, 48b, and the flow paths 49a, 49b is the same as that of the first chamber 47, the second chamber 48, and the flow path 49 described with reference to FIG. This is the same as the positional relationship. Specifically, the first chambers 47a and 47b are arranged closer to the point C and further from the point A than the second chambers 48a and 48b, respectively.

The first chamber 47a and the second chamber 48a are set as a first set of chamber pairs, and the first chamber 47b and the second chamber 48b are set as a second set of chamber pairs.
The first set of first chambers 47 a and the second set of second chambers 48 b are connected by a flow path 50. The first set of first chambers 47a is arranged closer to the point B and further away from the point D than the second set of second chambers 48b.

The positional relationship between the connection point 66 between the flow path 50 and the second chamber 48 b and the connection point 67 between the flow path 50 and the first chamber 47 a is such that the connection point 66 is more point C than the connection point 67. It is arranged to be close to.
Further, the connection point 66 is disposed at a position farthest from the point D in the second chamber 48b. The inner surface shape of the chamber 48b is formed so as to be connected to the connection point 66 away from the point D.

Here, point A and point C, point B and point D are the opposite vertices of the substantially rectangular main body 26 of the analysis container 11.
Thereby, when a centrifugal force is applied from point C to point A, the liquid reagent in the first chamber 47a can move toward the second chamber 48a by this centrifugal force. (2) The liquid reagent in the first chamber 47b can move toward the second chamber 48b (see FIG. 19).

Next, when a centrifugal force is applied from the point D to the point B, (1) the liquid reagent in the second chamber 48a is held in the second chamber 48a as it is by this centrifugal force. (2) The liquid reagent in the second chamber 48b can move toward the first chamber 47a (see FIG. 20).
When a centrifugal force is again applied from point C to point A, (1) the liquid reagent in the second chamber 48a is held in the second chamber 48a as it is by this centrifugal force. (2) The liquid reagent in the first chamber 47a can move toward the second chamber 48a (see FIG. 21).

That is, the liquid reagent put in the first chambers 47a and 47b is sent to the second chamber 48a step by step.
In the present embodiment, the first chamber 47 corresponds to the liquid reagent holding chamber 37 of the liquid reagent holding unit 30, and the second chamber 48 corresponds to the liquid reagent shift chamber 38 of the liquid reagent holding unit 30. The flow path 49 corresponds to the flow path 93, and the flow path 50 corresponds to the flow path 94.

Accordingly, the liquid reagents held in the six liquid reagent holding chambers 37a to 37f can be supplied to the reaction chamber 40 step by step.
As described above, the fluid circuit surface 11a surrounded by the points A, B, C, and D arranged counterclockwise in the same plane, and the first chamber 47 and the second chamber are surrounded by the fluid circuit surface 11a. An analysis container provided with a chamber 48, wherein the first chamber 47 is closer to the point C than the second chamber 48 and is farther from the point A. A pair of chambers 48 and a flow path 49 connecting the chambers. The chamber pair (47, 48) and at least two sets of flow paths 49 connecting the chambers are provided. The second chamber 48b and the first set of first chambers 47a are connected by the flow path 50, and the second set of second chambers 48b is closer to the point D than the first set of first chambers 47a. , Away from point B Since the deployed configuration, it is possible to perform stepwise mixing of the sample and the two or more reagents.

That is, in this embodiment, the centrifugal force is applied from the point C to the point A to the analysis container 11, and then the centrifugal force is applied from the point D to the point B, whereby the reagent in the first chamber 47 is obtained. It is outputted from the second chamber 48 step by step according to the centrifugal force.
Thereby, by connecting the second chamber 48a and the chamber containing the specimen, the specimen and the two or more types of reagents can be mixed stepwise.
<Description of the flow path configuration of FIG. 22>
FIG. 22 shows the configuration of the fluid circuit.

  The configuration of the fluid circuit shown in FIG. 22 is the same as the configuration of the fluid circuit shown in FIG. 18, except that the first chamber 47c, the second chamber 48c, the flow path 49c connecting these two chambers, A chamber 53, a flow path 51 that connects the third chamber 53 and the second chamber 48a, and a flow path 52 that connects the third chamber 53 and the second chamber 48c are added. .

The positional relationship between the first chamber 47c and the second chamber 48c is the same as that of the first chamber 47 and the second chamber 48 described in FIG. Specifically, the first chamber 47c is arranged so as to be closer to the point C and farther from the point A than the second chamber 48c.
The third chamber 53 is disposed closer to the point B and farther from the point D than the two second chambers 48a and 48c.

As shown in FIG. 23, the positional relationship of the connection point 73 between the second chamber 48a and the flow path 51 and the connection point 74 between the third chamber 53 and the flow path 51 are as follows. It arrange | positions so that it may be closer to the point D than.
Further, regarding the positional relationship between the connection point 76 between the second chamber 48 c and the flow path 52 and the connection point 77 between the third chamber 53 and the flow path 52, the connection point 76 is closer to the point D than the connection point 77. It is arranged to be.

The connection point 73 is disposed at a position farthest from the point D in the second chamber 48a. The inner shape of the chamber 48 a is formed so as to be connected to the connection point 73 so as to be away from the point D.
The connection point 76 is disposed at a position farthest from the point D in the second chamber 48c. The inner surface shape of the chamber 48c is formed so as to be connected to the connection point 76 so as to be away from the point D.

The connection points 74 and 77 are disposed in the third chamber 53 at a position closest to the point D.
With this arrangement, when a centrifugal force is applied from point C to point A, (1) the liquid reagent in the first chamber 47a moves toward the second chamber 48a by this centrifugal force. can do. (2) The liquid reagent in the first chamber 47b can move toward the second chamber 48b. Further, (3) the blood in the first chamber 47c can move toward the second chamber 48c. (See FIG. 22).

  Next, when a centrifugal force is applied in the direction from point D to point B, (1) the liquid reagent in the second chamber 48 a can move toward the third chamber 53 by this centrifugal force. . (2) The liquid reagent in the second chamber 48b can move toward the first chamber 47a. Further, (3) the blood in the second chamber 48c can move toward the third chamber 53 (see FIG. 23).

Next, when a centrifugal force is applied in the direction from the point C to the point A, (1) the liquid reagent and the blood in the third chamber 53 are held in the third chamber 53 as they are due to this centrifugal force. (2) The liquid reagent in the first chamber 47a can move toward the second chamber 48a (see FIG. 24).
Next, when a centrifugal force is applied in the direction from the point D to the point B, (1) the liquid reagent and blood in the third chamber 53 are held in the third chamber 53 as they are due to this centrifugal force. (2) The liquid reagent in the second chamber 48a can move toward the third chamber 53 (see FIG. 25).

That is, the liquid reagent previously stored in the first chamber 47 a and the blood previously stored in the first chamber 47 c can be input into the third chamber 53 in synchronization. Thereafter, the liquid reagent previously contained in the first chamber 47b can be introduced into the third chamber 53 stepwise and mixed.
In the present embodiment, the first chambers 47 a and 47 b correspond to the liquid reagent holding chamber 37 of the liquid reagent holding unit 30. The second chambers 48 a and 48 b correspond to the liquid reagent shift chamber 38 of the liquid reagent holding unit 30. The first chamber 47 c corresponds to the liquid sample injection chamber 32 of the liquid sample determination unit 29, the second chamber 48 c corresponds to the liquid sample determination chamber 35, and the third chamber 53 corresponds to the reaction chamber 40.

The flow paths 49 a and 49 b correspond to the flow path 93, the flow path 50 corresponds to the flow path 94, and the flow path 49 c corresponds to the flow path 33. The flow path 51 corresponds to the flow path 90, and the flow path 52 corresponds to the flow path 39.
Therefore, the blood in the liquid specimen injection chamber 32 and the liquid reagent in the liquid reagent holding chamber 37 can be mixed in synchronization with the reaction chamber 40.
In addition, the liquid reagent that has been placed in the liquid reagent holding chambers 37a and 37b is gradually added to the reaction chamber 40 via the liquid reagent shift chamber 38a. Therefore, for example, as a liquid reagent, the liquid reagent holding chamber 37a is set to have a dissolving solution and the liquid reagent holding chamber 37b is set to have a cleaning solution. When added, the lysate enters the liquid reagent shift chamber 38a, and thereafter, when a centrifugal force is applied in the direction from point D to point B, the lysate moves from the liquid reagent shift chamber 38a to the reaction chamber 40.

When a centrifugal force is applied from the point C to the point A for the second time, the cleaning liquid that has entered the liquid reagent holding chamber 37b enters the liquid reagent shift chamber 38a. Thereby, when a centrifugal force is applied in the direction from point D to point B, the cleaning liquid moves from the liquid reagent shift chamber 38a to the reaction chamber 40.
That is, by changing the direction in which the centrifugal force is applied stepwise, the step can be performed stepwise, for example, after the dissolution step is performed, the cleaning step is performed.

In the analysis container 11 of this embodiment, as described above, the second chamber 48a of the first pair of chamber pairs 47a and 48a and the third chamber 53 connected by the flow path 51 are provided. The third chamber 53 is disposed so as to be closer to the point B and farther from the point D than the second chamber 48a of the first pair of chambers 47a and 48a.
As a result, a centrifugal force is applied to the analysis container 11 in the direction from the point C to the point A, and thereafter, a centrifugal force is applied in the direction from the point D to the point B, whereby the reagent in the first chamber 47 is obtained. It is outputted from the second chamber 48 step by step according to the centrifugal force. Therefore, by connecting the second chamber 48a and the third chamber 53 containing the specimen, the specimen and the two or more types of reagents can be mixed stepwise in the third chamber 53.
<Description of the flow path configuration of FIG. 26>
Next, the configuration of the fluid circuit of FIG. 26 is shown.

The configuration of the fluid circuit shown in FIG. 26 is the same as the configuration of the fluid circuit of FIG. 22, the fourth chamber 55, the flow channel 54 connecting the fourth chamber 55 and the third chamber 53, The flow path 56 provided between the flow paths 51 and 52 is added.
The positional relationship between the connection point 78 between the flow path 54 and the third chamber 53 and the connection point 79 between the flow path 54 and the fourth chamber 55 is as shown in FIG. It is provided at a position farthest from the point C in the chamber 53. Further, the connection point 79 is provided at a position farther from the point C than the connection point 78.

The fourth chamber 55 is connected to the waste liquid storage layer 58 provided in the lower layer of the fluid circuit surface 11 a by the via 44.
Thereby, when a centrifugal force is applied in the direction from the point C to the point A, the liquid reagent in the first chambers 47a and 47b is directed toward the second chambers 48a and 48b by this centrifugal force. Moving. (2) The blood in the first chamber 47c moves toward the second chamber 48c (see FIG. 26).

  Next, when a centrifugal force is applied in the direction from point D to point B, (1) the liquid reagent that has entered the second chamber 48b is moved to the first chamber 47a by this centrifugal force. (2) The liquid reagent that has entered the second chamber 48 a moves toward the third chamber 53. Furthermore, (3) the blood that has entered the second chamber 48c also moves toward the third chamber 53 (see FIG. 27)).

That is, the liquid reagent and blood are mixed in the third chamber 53 in synchronization.
When a centrifugal force is applied again in the direction from point C to point A, (1) the liquid reagent in the first chamber 47a moves to the second chamber 48a by this centrifugal force. (2) The liquid reagent and blood mixed in the third chamber 53 move from the third chamber 53 toward the fourth chamber 55. Further, the liquid reagent and the blood (3) move from the fourth chamber 55 to the waste liquid storage layer 58 (see FIG. 28)).

Next, when a centrifugal force is applied in the direction from point D to point B, (1) the liquid reagent that has entered the second chamber 48a moves toward the third chamber 53 (see FIG. 29). ).
When a centrifugal force is applied again from the point C to the point A, the liquid reagent mixed in the third chamber 53 is directed from the third chamber 53 toward the fourth chamber 55. Moving. Then, the liquid reagent moves from the fourth chamber 55 to the waste liquid storage layer 58 (see FIG. 30).

That is, in the third chamber 53, the liquid reagent previously stored in the first chambers 47a and 47b can be moved to the third chamber 53 step by step.
Further, the liquid reagent that has entered the third chamber 53 is processed as waste liquid through the fourth chamber 55 in the next stage.
In the present embodiment, the first chambers 47 a and 47 b correspond to the liquid reagent holding chamber 37 of the liquid reagent holding unit 30. The second chambers 48 a and 48 b correspond to the liquid reagent shift chamber 38 of the liquid reagent holding unit 30. The first chamber 47c corresponds to the liquid sample injection chamber 32 of the liquid sample determination unit 29, the second chamber 48c corresponds to the liquid sample determination chamber 35, and the third chamber corresponds to the reaction chamber 40. The fourth chamber 55 corresponds to the via 44.

The flow paths 49a and 49b correspond to the flow path 93, the flow path 50 corresponds to the flow path 94, the flow path 49c corresponds to the flow path 33, the flow path 51 corresponds to the flow path 90, and the flow path 52 corresponds to the flow path 39. It corresponds to. The flow path 56 corresponds to the flow path 92, and the flow path 54 corresponds to the flow path 91.
Therefore, the blood in the liquid specimen injection chamber 32 and the liquid reagent in the liquid reagent holding chamber 37 can be mixed in the reaction chamber 40 in synchronization.

  The liquid reagent stored in the liquid reagent holding chambers 37a and 37b moves to the reaction chamber 40 stepwise via the liquid reagent shift chamber 38a. For this reason, for example, as a liquid reagent, a centrifugal force is applied from the point C to the point A for the first time by putting a solution in the liquid reagent holding chamber 37a and a cleaning liquid in the liquid reagent holding chamber 37b. In some cases, the lysate moves into the liquid reagent shift chamber 38a. Then, when centrifugal force is applied in the direction from point D to point B, the lysate moves from the liquid reagent shift chamber 38 a to the reaction chamber 40.

When a centrifugal force is applied from the point C to the point A for the second time, the cleaning liquid that has entered the liquid reagent holding chamber 37b moves to the liquid reagent shift chamber 38a. Then, the solution in the reaction chamber 40 moves to the via 44.
Thereafter, when a centrifugal force is applied in the direction from point D to point B, the cleaning liquid moves from the liquid reagent shift chamber 38 a to the reaction chamber 40.

When a centrifugal force is applied in the direction from point C to point A, the cleaning liquid in the reaction chamber 40 moves to the via 44.
In other words, by changing the direction in which the centrifugal force is applied, for example, after the dissolution process is performed, the solution is treated as waste liquid, and after the washing process is performed, the washing liquid is treated as waste liquid. It becomes possible to perform a process.

Furthermore, by providing the flow path 56, the liquid in the third chamber 53 can be moved to the fourth chamber 55 more reliably.
As shown in FIG. 28, the connection point 80 is arranged so as to be closer to the point C than the liquid level 95 formed when the centrifugal force is applied from the point C to the point A.
Further, as shown in FIG. 27, the connection point 80 between the flow path 56 and the flow paths 51 and 52 and the connection point 81 between the flow path 56 and the flow path 54 are as follows. Are arranged so as to be close to the point B. Then, as shown in FIG. 26, the connection point 81 is arranged so as to be closer to the point A than the connection point 80.

  Thereby, (1) when a centrifugal force is applied from point C to point A, the liquid in the chamber 53 flows into the flow paths 51 and 52 via the flow paths 54 and 56 without causing the siphon effect. Can be prevented. (2) Whether the centrifugal force is applied from the point C to the point A or from the point B to the point D, the flow path 56 is always centrifuged only from the connection point 80 to the connection point 81. A one-way flow path can be formed without any force acting. Therefore, when a centrifugal force is applied from point C to point A, waste liquid from the chamber 53 can be prevented from flowing into the flow paths 51 and 52 via the flow path 56 due to the centrifugal force.

In the present embodiment, as described above, the fourth chamber 55 connected to the third chamber 53 by the flow path 54 is further provided, and the fourth chamber 55 is located at the point A more than the third chamber 53. It is arranged so as to be near and far from the point C.
Thereby, a centrifugal force is applied to the analysis container 11 from the point C to the point A, and thereafter, the centrifugal force is applied from the point D to the point B, so that the reagent in the first chamber 47 responds to the centrifugal force. The output is output from the second chamber 48 step by step. Therefore, by connecting the second chamber 48a and the third chamber 53 containing the specimen, the specimen and the two or more types of reagents can be mixed stepwise in the third chamber 53. Further, after that, when a centrifugal force is applied from the point C to the point A, the reagent moves from the first chamber 47 to the second chamber 48, and the mixed liquid in the third chamber 53 is transferred to the fourth chamber. 55.

That is, the liquid mixture in the third chamber 53 can be discarded in synchronization with the preparation of the next reagent.
Furthermore, by placing a substance that binds to a specific component in the liquid mixture in the third chamber 53, it is possible to leave only the specific component in the liquid mixture and discard only the remaining liquid mixture. .

In particular, in this embodiment, magnetic beads that specifically bind to nucleic acids are placed in the third chamber 53 in advance. By holding the magnetic beads with the magnetic force of the magnet, the nucleic acid component can be taken out from the mixed solution and the remaining mixed solution can be discarded.
Note that the fourth chamber 55 may be composed of only a via, not a chamber.
<Measures against residual liquid and backflow>
As in the present embodiment, the remaining liquid and the back flow often become a problem in a flow path in which a liquid to be sent later follows a path through which another liquid reagent has passed. This is because if a large amount of liquids of different components are mixed into the liquid to be sent later due to residual liquid or backflow, the subsequent reaction system may be adversely affected and measurement may fail.

Therefore, hereinafter, countermeasures against residual liquid and backflow in the present embodiment will be described.
<Measures for residual liquid>
First, the corner in the chamber is chamfered so that capillary action does not occur.
Specifically, the shape in which the angle formed between the surfaces in the chamber is 90 degrees or less is avoided as much as possible. Preferably, the chamfering process is performed so that the angle of the portion where the surfaces intersect each other is 120 degrees or more.

As a result, it becomes difficult for the capillary phenomenon to occur in the chamber, and it is possible to prevent the liquid from entering the capillary and being difficult to be discharged. Therefore, the liquid can be smoothly fed to the next chamber.
Next, the inner surface shape of the chamber is formed so as to be away from the center of rotation and connected to the chamber outlet, which is a connection point with the flow path, when liquid is fed from one chamber to the next. . For example, in FIG. 26, the chamber outlets corresponding to the first chambers 47a to 47c are connection points 60a to 60c, and liquid is supplied from the chambers 47a to 47c to the next chambers 48a to 48c. When liquid is fed, a centrifugal force is applied from point C to point A.

At this time, in each of the first chambers 47a to 47c, the distance from the point C gradually increases from the point closest to the point C in each chamber toward the chamber outlet (that is, from the point closest to the rotation center 16). A chamber is formed.
Further, as shown in FIG. 31, a taper structure is adopted also on the side wall of the chamber, and when the centrifugal force is applied, the chamber is formed so that the distance from the rotating shaft 62 gradually increases toward the chamber outlet 63. Has been.

Thereby, in the chamber, the centrifugal force gradually increases toward the chamber outlet, and the centrifugal force is maximized at the chamber outlet. Therefore, the liquid in the chamber can be smoothly collected at the chamber outlet and sent to the next chamber.
<Countermeasures for backflow>
First, a description will be given using the second chamber 48b as an example of counterflow countermeasures.

FIG. 33A to FIG. 33C are perspective views that three-dimensionally show the second chamber 48b in the present embodiment.
In this embodiment, depending on the situation, the direction in which centrifugal force is applied is properly used, the analysis container installation tray is rotated, centrifugal force is applied to the analysis container, or rotation of the analysis container installation tray is stopped and centrifugal force is applied to the analysis container. May not give. Thus, in each case, care must be taken that the liquid in the chamber does not flow back to the previous chamber.

  That is, even if the centrifugal force is applied in the direction shown in FIG. 33A (point C to point A) or the centrifugal force is applied in the direction shown in FIG. 33B (point D to point B), FIG. Even when centrifugal force is not applied as shown in (c), in addition to the arrangement of the chamber inlet 61b, the liquid volume and the chamber volume so that the formed liquid levels 68, 69, 70 do not contact the chamber inlet 61b. It is necessary to design the shape in advance.

As a result, the liquid level does not cover the chamber inlet both when the centrifugal force is applied and when the centrifugal force is not applied, so that the liquid flows back to the previous chamber even when the direction of the centrifugal force is switched. Can be prevented.
Next, as another counterflow countermeasure, it is preferable that a one-way flow path is provided in a part of the flow path connecting the chambers.

26 and 27 will be described as an example.
The flow paths 49a to 49c, the flow path 50, and the flow path 56 are liquid when the centrifugal force is applied in the direction from the point C to the point A or when the centrifugal force is applied in the direction from the point D to the point B. Is a one-way flow path that flows only in one direction. For example, the flow path 49a has a connection point both when the centrifugal force is applied in the direction from the point C to the point A (see FIG. 26) and when the centrifugal force is applied in the direction from the point D to the point B (see FIG. 27). The liquid flows in a direction from 60a toward the connection point 61a.

In order to make such a one-way flow path, taking the flow path 49 as an example, as shown in FIG. 26, the connection point 60a of the flow path 49a is disposed closer to the point C than the connection point 61a, and As shown in FIG. 27, it is necessary to simultaneously satisfy the two conditions of disposing the connection point 60a of the flow path 49a closer to the point D than the connection point 61a.
Thus, by providing a one-way flow path in a part of the flow path connecting the chambers, when a centrifugal force is applied in the direction from point C to point A, it is applied in the direction from point D to point B. The liquid can be prevented from flowing only in the direction from the connection point 60a to the connection point 61a. Therefore, even when the liquid is applied to the chamber inlet when the analysis container setting tray is swung, it is possible to prevent the liquid from flowing back to the previous chamber due to the centrifugal force.

  Further, similarly, in the waste liquid storage layer 58, when the centrifugal force is applied in some directions or when no centrifugal force is applied, the inlet of the waste liquid storage layer 58 (connection between the via 44 and the waste liquid storage layer 58). In addition to the arrangement of the inlet of the waste liquid storage layer 58, the volume of the total waste liquid, the capacity of the waste liquid storage layer 58, and the height are designed so that the liquid level formed by the waste liquid is not applied to the point. It is necessary to keep it.

Thereby, it is possible to prevent the liquid level of the waste liquid from covering the inlet of the waste liquid storage layer 58 even when the centrifugal force is applied or when the centrifugal force is not applied. Therefore, it is possible to prevent the waste liquid that has fallen from the fluid circuit surface 11a to the waste liquid storage layer 58 from flowing back toward the fluid circuit surface 11a.
The concept of countermeasures against residual liquid / backflow described above is applied to all chambers, flow paths, vias, and waste liquid storage layer 58 in the present embodiment.
<Description of analysis process>
Now that the basic configuration of the analysis container 11 has been described, the analysis process will be described.

FIG. 16 shows a flowchart of the analysis process.
Step 1 (S1) is a blood quantification process. When a centrifugal force is applied to the analysis container 11 from the point C to the point A, the blood passes through the flow path 33 from the liquid specimen injection chamber 32. And flows into the liquid specimen quantification chamber 35. At this time, the blood overflowing the reaction chamber 40 flows into the waste liquid chamber 34 through the flow path 36.

In the waste liquid chamber 34, an excess of a blood sample as a liquid sample is stored, and whether or not a sufficient blood sample has been injected by checking the presence or absence of this excess by detection such as light detection. Can be confirmed.
As a result, blood is quantified and stored in the quantitative chamber 35 of the flow path 33.
When centrifugal force is applied in the direction from point C to point A, the blood is quantified as described above, and the liquid reagent placed in the liquid reagent holding chambers 37a to 37f of the first to sixth chamber pairs. Move to the liquid reagent shift chambers 38a-38f.

  Step 2 (S2) is a dissolution process, and by applying centrifugal force to the analysis container 11 in the direction from point D to point B, the blood quantified in the liquid sample quantification chamber 35 flows. It moves to the reaction chamber 40 via the path 39. The lysate contained in the liquid reagent shift chamber 38a also moves to the reaction chamber 40 via the flow path and is mixed with blood. At the same time, the liquid reagent put in the liquid reagent shift chambers 38b to 38f moves to the liquid reagent holding chambers 37a to 37e.

Thereafter, the rotation is stopped and the analysis container installation tray 3 is swung to agitate and mix the blood, the lysate, and the magnetic beads in the reaction chamber 40. As a result, the lysing solution has a function of dissolving the cell walls of the cells in the blood to expose the nucleic acid, so that the blood in the reaction chamber 40 is in a state where the cell walls are dissolved and the nucleic acid inside is released into the lysing solution. It becomes.
Here, the magnetic beads previously contained in the reaction chamber 40 specifically bind to the nucleic acid. Therefore, in the reaction chamber 40, the magnetic beads bonded to the nucleic acid and other components are mixed.

Step 3 (S3) is a waste liquid process, in which a centrifugal force is applied to the analysis container 11 in the direction from the point C to the point A, so that the magnetic beads bound to the nucleic acid in the reaction chamber 40 and the others A force is applied to the component in the direction of the via 44.
Here, the state in which the centrifugal force is applied to the analysis container 11 in the direction from the point C to the point A is a state in which the analysis container 11 is disposed at the upper left corner in the drawing in FIG. In this state, a magnet 45 is provided on the inner wall 14a side. Therefore, since the magnetic beads in the reaction chamber 40 are attracted by the magnetic force of the magnet 45, even if a centrifugal force is applied from the point C to the point A, the magnetic beads do not move in the via 44 direction. As a result, the liquid containing components other than the magnetic beads moves in the direction of the via 44 and flows into the waste liquid storage layer 58 on the lower surface.

At the same time, the liquid reagents in the liquid reagent holding chambers 37a to 37e move to the liquid reagent shift chambers 38a to 38e.
Step 4 (S4) is a washing process, and the washing liquid moves from the liquid reagent shift chamber 38a into the reaction chamber 40 by applying a centrifugal force to the analysis container 11 from the point D to the point B. . At the same time, the liquid reagent in the liquid reagent shift chambers 38b to 38e moves to the liquid reagent holding chambers 37a to 37e.

Thereafter, the rotation is stopped, and the analysis container installation tray 3 is swung to agitate and mix the cleaning liquid in the reaction chamber 40 and the magnetic beads.
Here, it demonstrates using FIG. The state in which the centrifugal force is applied to the analysis container 11 in the direction from the point D to the point B is a state in which the analysis container 11 is disposed in the lower left corner on the drawing in FIG. In this state, the magnet 45 is provided on the inner wall 14 a side, but no magnetic force acts on the reaction chamber 40. Therefore, the magnetic beads can be efficiently cleaned by agitation of the analysis container setting tray 3 and stirring the magnetic beads and the cleaning liquid in the reaction chamber 40 without aggregating the magnetic beads due to magnetic force.

Thereby, components other than the magnetic beads bound to the nucleic acid in the reaction chamber 40 can be washed.
Step 5 (S5) is a waste liquid process.
The cleaning process in step 4 and the waste liquid process in step 5 are repeatedly executed by the amount of the cleaning liquid previously held in the liquid reagent holding chambers 37a to 37f.

Step 6 (S6) is an elution process, in which the eluate is moved from the liquid reagent shift chamber 38a into the reaction chamber 40 by applying a centrifugal force to the analysis container 11 from the point D to the point B. To do. The eluate liberates nucleic acids from the magnetic beads by its action.
Thereafter, the rotation is stopped, and the analysis container installation tray 3 is swung to agitate and mix the eluate in the reaction chamber 40 and the magnetic beads.

Step 7 (S7) is a nucleic acid extract quantification step, in which the eluate containing the nucleic acid is quantified in the quantification chamber 41 by applying centrifugal force to the analysis container 11 in the direction from point A to point C. And the reaction solution moves from the quantitative chamber 41 to the measurement chamber 42.
Here, the state in which the centrifugal force is applied to the analysis container 11 in the direction from the point A to the point C is a state in which the analysis container 11 is disposed in the lower right corner of the drawing in FIG.

In this state, a magnet 46 is provided on the inner wall 14b side. Since the magnetic beads in the reaction chamber 40 are attracted by the magnetic force of the magnet 46, even if a centrifugal force is applied in the direction from the point A to the point C, the magnetic beads do not move in the direction of the quantitative chamber 41.
As a result, the liquid containing the nucleic acid moves toward the quantitative chamber 41 and flows into the measurement chamber 42.

Step 8 (S8) is a nucleic acid amplification step, in which the nucleic acid amplification reagent in the measurement chamber 42 and the nucleic acid extract are mixed, and the rotation of the analysis container 11 is stopped. Proper temperature control and nucleic acid amplification.
Step 9 (S9) is a gene detection step, and for example, the presence or absence of amplification by the nucleic acid amplification step is confirmed by an amplification curve. For the detection, a commonly used technique can be used. For example, an optical technique or an electrochemical technique can be used.
<Explanation of analysis container position and movement>
Again, referring back to FIG.

The analysis container installation surface 12 on the analysis container installation tray 3 has a quadrangular shape surrounded by an inner wall 14 on all sides. In FIG. 7, in order to specify the quadrangular shape, four corners of the quadrangular shape are defined as one corner, two corners, three corners, and four corners counterclockwise from the upper left.
Further, the analysis container 11 has a quadrangular upper surface and is surrounded by points A, B, C, and D counterclockwise from the upper left.

In the present embodiment, the analysis container 11 changes the direction in which the centrifugal force works according to the position on the analysis container installation tray 3.
When the analysis container 11 is arranged at one upper left corner in the drawing, the rotation center 16 is at the lower right of the analysis container 11. Therefore, the direction in which the centrifugal force acts is the direction of the arrow 17a, and the centrifugal force is applied from the lower right to the upper left diagonal of the analysis container 11, that is, from the point C to the point A of the analysis container 11.

That is, in the analysis process, the analysis container 11 is positioned at one corner in the blood quantification process in step 1 (S1) and the waste liquid process in step 3 (S3).
Next, when the analysis container 11 is arranged at the two lower left corners in the drawing, the rotation center 16 is located at the upper right of the analysis container 11, so that the direction in which the centrifugal force acts is the direction of the arrow 17b. The centrifugal force is applied in the direction of the diagonal line from the upper right to the lower left of 11, that is, from the point D to the point B of the analysis container 11.

That is, in the analysis process, the analysis container 11 is positioned at two corners in the dissolution process in Step 2 (S2), the washing process in Step 4 (S4), and the elution process in Step 6 (S6).
When the analysis container 11 is arranged at the lower right corner on the drawing, the rotation center 16 is at the upper left of the analysis container 11. Therefore, the direction in which the centrifugal force works is the direction of the arrow 17c, and the centrifugal force is applied in the direction of the diagonal line from the upper left to the lower right of the analysis container 11, that is, the direction from the point A to the point C of the analysis container 11.

That is, in the analysis process, in the nucleic acid extract quantification process of Step 7 (S7), the analysis container 11 is positioned at three corners.
Next, a state in which the analysis container 11 moves on the analysis container installation surface 12 on the analysis container installation tray 3 will be described.
First, in the analysis process, the analysis container 11 is positioned at one corner in the blood quantification process in step 1 (S1) and the waste liquid process in step 3 (S3).

  At the time of this positioning, the analysis container 11 moves from the position of the corner 2 to the position of the corner 1. When moving, the analysis container installation surface 12 is inclined with the corner 2 on the upper side and the corner 1 on the lower side. Then, by periodically swinging the analysis container installation surface 12, the friction between the lower surface of the analysis container 11 and the analysis container installation surface 12 changes from static friction to dynamic friction. Thereby, the gravity applied to the analysis container 11 arranged on the inclined surface becomes larger than the dynamic friction force, so that the analysis container 11 moves from the corner 2 to the corner 1 while sliding on the analysis container installation surface 12.

Next, in the analysis process, the analysis container 11 is positioned at two corners in the elution process of step 2 (S2), the cleaning process of step 4 (S4), and the elution process of step 6 (S6).
During this positioning, the analysis container 11 moves from the corner 1 position to the corner 2 position. During the movement, the analysis container installation surface 12 is inclined with the corner 1 on the upper side and the corner 2 on the lower side. Then, by periodically swinging the analysis container installation surface 12, the friction between the lower surface of the analysis container 11 and the analysis container installation surface 12 changes from static friction to dynamic friction. Thereby, the gravity applied to the analysis container 11 arranged on the inclined surface becomes larger than the dynamic friction force, and the analysis container 11 moves from the corner 1 to the corner 2 while sliding on the analysis container installation surface 12.

Next, in the nucleic acid extract quantification step of Step 7 (S7) in the analysis step, the analysis container 11 is positioned at three corners.
At the time of this positioning, the analysis container 11 moves from the position of the corner 2 to the position of the corner 3. During the movement, the analysis container installation surface 12 is inclined with the corner 2 on the upper side and the corner 3 on the lower side. Then, by periodically swinging the analysis container installation surface 12, the friction between the lower surface of the analysis container 11 and the analysis container installation surface 12 changes from static friction to dynamic friction. Thereby, the gravity applied to the analysis container 11 arranged on the inclined surface becomes larger than the dynamic friction force, and the analysis container 11 moves from the corner 2 to the corner 3 while sliding on the analysis container installation surface 12.

Next, the control for adjusting the positional relationship for balancing the analysis container 11 moving on the analysis container installation tray 3 and the balance ball 22 in each of the above steps will be described with reference to FIG. It is.
That is, in step 11 (S11), the analysis container installation tray 3 is positioned in the rotation direction. Specifically, the rotation control is performed so that the position to move the analysis container 11 is below the inclined surface on the analysis container installation tray 3 (see FIG. 11B).

Next, in step 12 (S12), the analysis container setting tray 3 is swung (see FIG. 11C). Specifically, the state where the analysis container installation tray 3 is swung is formed by inverting the analysis container installation tray 3 clockwise and counterclockwise with a fine cycle.
Thereby, the frictional force between the analysis container installation surface 12 and the analysis container 11 can be reduced by changing from static friction to dynamic friction.

Next, in step 13 (S13), the analysis container 11 slides with the analysis container installation surface 12 facing the lower side of the figure due to the gravity applied to the analysis container 11 arranged on the inclined surface of the analysis container installation tray 3. (See FIG. 11C).
Next, in step 14 (S14), the analysis container installation tray 3 is positioned. Specifically, in order to move the balance ball 22 to the diagonal position (downwardly inclined) of the analysis container 11, the analysis container installation tray 3 is rotated and stopped so that the diagonal position is lowered (FIG. 11 ( d)).

Next, in step 15 (S15), the balance ball 22 is moved to the diagonal position of the analysis container 11 by weight (see FIG. 11D).
At this time, the analysis container 11 is in a state in which the static frictional force is larger than the gravity, so that the analysis container 11 can be kept stationary on the inclined surface.
Next, in step 16 (S16), the analysis container installation tray 3 starts to rotate at high speed.

As described above, in the analysis apparatus of this embodiment, the balance ball 22 is diagonally separated from the analysis container 11 when each process is performed while moving the analysis container 11 to a desired position on the analysis container installation tray 3. Control to move up.
As a result, the analysis container installation tray 3 can always be rotated at high speed while the analysis container 11 and the balance ball 22 are balanced regardless of the position of the analysis container 11 on the analysis container installation tray 3. .

Therefore, each process can be implemented in a stable state.
Next, the specification of each part used for the analysis apparatus and analysis container 11 of this embodiment is demonstrated.
In this embodiment, the material of the analysis container installation surface 12 is, for example, polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS), polypropylene (PP), polyethylene (PE), Organic materials such as styrene resin (ABS) and cycloolefin polymer (COP), and inorganic materials such as aluminum, titanium, silicon, glass, and quartz can be used.

  Moreover, the material of the sliding surface 28 provided on the lower surface of the analysis container 11 is not particularly limited. For example, polyethylene terephthalate (PET), polymethyl methacrylate (PMMA), polycarbonate (PC), polystyrene (PS), polypropylene ( Organic materials such as PP), polyethylene (PE), styrene resin (ABS), and cycloolefin polymer (COP), and inorganic materials such as aluminum, titanium, silicon, glass, and quartz can be used.

Since the weight of the analysis container is about 10 g and the current static friction coefficient is about 0.5, the sliding inclination angle obtained from this static friction coefficient is calculated to be about 27 degrees.
Under such conditions, the inclination angle of the analysis container installation surface 12 is set to about 15 degrees.
The inclination angle is set to be smaller than the sliding angle obtained from the static friction coefficient and larger than the sliding angle obtained from the dynamic friction coefficient. By making such an inclination angle, the analysis container 11 slides on the analysis container installation surface 12 when it swings, but it can form a state where it does not slide unless it swings. For this reason, the larger the difference between static friction and dynamic friction, the better.

As for the oscillation cycle and amplitude angle, the oscillation angle is 3.6 degrees and the oscillation frequency is 30 Hz.
As described above, the analysis device according to the present embodiment includes the main body case 1, the rotation drive unit 5 provided in the main body case 1, and the rotation shaft 4 having an inclination angle with respect to the vertical direction, and the rotation of the rotation drive unit 5. An analysis container installation tray 3 connected to the shaft 4 and having an analysis container installation surface 12 and a control unit for controlling the rotation of the rotation drive unit 5 are provided.

Thereby, the structure of an apparatus can be simplified.
That is, in the analysis apparatus of the present embodiment, the rotation shaft 4 has an inclination angle with respect to the vertical direction.
Thereby, the analysis container installation tray 3 connected to the rotating shaft 4 is also inclined with respect to the horizontal direction. Therefore, when the control unit 8 controls the rotation of the rotation driving unit 5, the analysis container 11 can change the position on the analysis container installation tray 3 while sliding on the analysis container installation surface 12 of the analysis container installation tray 3. .

As a result, since the rotation center position of the analysis container installation tray 3 with respect to the analysis container 11 changes, the direction of the centrifugal force with respect to the analysis container 11 can be changed.
Thereby, since the direction of the centrifugal force with respect to the analysis container 11 can be changed without providing a mechanism for moving the analysis container 11 relative to the analysis container installation tray 3, the configuration of the apparatus can be simplified. it can.

  As described above, the present invention provides a main body case, an analysis container installation tray provided in the main body case and having an analysis container installation surface, a rotation drive unit that rotates the analysis container installation tray, and the rotation drive unit. A control unit for controlling rotation, and the analysis container installation surface of the analysis container installation tray is provided with an inclination means for inclining an angle with respect to the horizontal direction, thereby simplifying the configuration of the apparatus Can do.

That is, in the present invention, since the analysis container installation surface is provided with an inclination means that makes an inclination angle with respect to the horizontal direction, the control container controls the rotation of the rotation drive unit, so that the analysis container is installed in the analysis container. The position on the tray can be changed while sliding the analysis container installation surface of the tray below the inclined surface.
As a result, since the rotation center position of the analysis container installation tray with respect to the analysis container changes, the direction of the centrifugal force with respect to the analysis container can be changed.

By adopting such a configuration, it becomes possible to change the direction of the centrifugal force with respect to the analysis container without having a plurality of rotation mechanisms as in the prior art, so the configuration of the apparatus can be simplified. is there.
Therefore, application as an analysis apparatus for genes and the like is highly expected.

DESCRIPTION OF SYMBOLS 1 Main body case 2 Opening part 3 Analysis container installation tray 4 Rotating shaft 5 Rotation drive part 6 Display part 7 Operation part 8 Control part 9 Optical detection part 10 Temperature control part 11 Analysis container 11a Fluid circuit surface 12 Analysis container installation surface 13 Arrow 14 , 14a, 14b, 14c, 14d Inner wall 15 Protrusion 16 Rotation center 17a, 17b, 17c Arrow 20 Guide 21 Rail 22 Balance ball 23 Guide rail 24 Curved portion 25 Depression 26 Main body 27 Upper cover 28 Sliding surface (lower cover)
29 Liquid specimen quantification part 30 Liquid reagent holding part 31 Nucleic acid amplification reaction part 32 Liquid specimen injection chamber 33 Channel 34 Waste liquid chamber 35 Determination chamber 36 Channels 37, 37a, 37b, 37c, 37d, 37f Liquid reagent holding chambers 38, 38a , 38b, 38c, 38d, 38f Liquid reagent shift chamber 39 Flow path 40 Reaction chamber 41 Determination chamber 42 Measurement chamber 43 Via 44 Via 45 Magnet 46 Magnets 47, 47a, 47b, 47c First chamber 48, 48a, 48b, 48c Second chamber 49, 49a, 49b, 49c Channel 50 Channel 51 Channel 52 Channel 53 Third chamber 54 Channel 55 Fourth chamber 56 Channel 57 Reaction channel layer 58 Waste liquid storage layer 60 Connection point (Chamber outlet)
61 Connection point (chamber inlet)
62 Rotating shaft 63 Chamber outlet 64 Taper 65 Liquid level 66 Connection point 67 Connection point 68 Liquid level 69 Liquid level 70 Liquid level 73 Connection point 74 Connection point 76 Connection point 77 Connection point 78 Connection point 79 Connection point 80 Connection point 81 Connection point 82 LED (analysis container detector)
83 Photosensor (analysis container detector)
84 In-circle 85 Four corners 86 Via 90 Channel 91 Channel 92 Channel 93 Channel 94 Channel

Claims (15)

A body case,
An analysis container installation tray provided in the main body case and having an analysis container installation surface on which the analysis container is installed;
A rotation drive unit that is provided in the main body case and is placed on the analysis container installation surface, and rotates the analysis container installation tray around a rotation axis;
A control unit for controlling the rotation of the rotation drive unit;
Inclining means for inclining the analysis container installation surface of the analysis container installation tray with respect to a horizontal direction,
Analysis device with The tilting means is arranged so that the rotation axis has a predetermined tilt angle with respect to the vertical direction.
The analysis device according to claim 1. The analysis container installation surface is slidable with the analysis container.
The analysis device according to claim 1 or 2. The control unit performs control to swing the rotation driving unit.
The analysis device according to any one of claims 1 to 3. The control unit controls the rotation driving unit to stop at an arbitrary rotation angle;
The analysis device according to any one of claims 1 to 4. Provided on the analysis container installation surface of the analysis container installation tray, further comprising a guide for guiding the analysis container;
The analysis device according to any one of claims 1 to 4. The guide has a rail laid on the analysis container installation surface,
The analysis device according to claim 6. The guide has a wall surrounding the analysis container installation surface,
The analysis device according to claim 6. The guide has a columnar protrusion provided at a central portion of the analysis container installation surface.
The analysis device according to claim 6. Further comprising a balance mechanism for balancing the rotation of the analysis container installation tray,
The analysis device according to any one of claims 1 to 9. The balance mechanism includes a balance ball and a rail mechanism that moves the balance ball in a desired direction.
The analysis device according to claim 10. The magnet further provided on the analysis container installation surface,
The analysis device according to any one of claims 1 to 11. The magnet further provided in a part of the guide,
The analysis device according to claim 6. A body case,
An analysis container installation tray provided in the main body case and having a sliding surface on which the analysis container can slide;
Provided in the main body case, and a rotation drive unit for rotating the analysis container installation tray;
A control unit for controlling the rotation of the rotation drive unit;
A plurality of positioning portions that are provided in the analysis container installation tray and are capable of positioning the analysis container in the sliding surface;
Analyzing device equipped with. An analysis method using the analysis apparatus according to claim 1,
A first positioning step of rotating the analysis container installation tray about the rotation axis so that the analysis container placed on the installation surface of the analysis container installation tray moves upward in the inclination;
Moving the analysis container installation tray to move the analysis container to a desired location disposed below the inclination; and
The rotating shaft is arranged so that the analysis container placed on the installation surface of the analysis container installation tray moves upward in the inclination, and the balance ball moves downward in the inclination diagonally to the analysis container by gravity. A second positioning step of rotating the analysis container installation tray around the center,
A moving step of continuously rotating the analysis container setting tray to apply a centrifugal force to the liquid specimen stored in the analysis container;
An analysis method comprising:

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