JP2009058391A - Reaction container plate and reaction treatment apparatus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To accurately measure the temperature of the liquid in a reaction container without increasing the cost of a disposable reaction container plate. <P>SOLUTION: A temperature measuring container 6 is provided in the vicinity of the reaction containers 5. Each of the temperature measuring containers 6 has the same shape and volume as each of the reaction containers 5 to house a temperature measuring liquid 8 in the temperature measuring containers 6. The upper surfaces of the temperature measuring containers 6 are hermetically closed by a hermetically closing member 16 through which a member having a sharp leading end shape can pierce. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  INDUSTRIAL APPLICABILITY The present invention deals with a disposable reaction vessel plate suitable for performing various analyzes and analyzes in the field of medical analysis and chemistry in the field of biological analysis, biochemical analysis, or chemical analysis in general, and the reaction vessel plate. It is related with the reaction processing apparatus for doing.

A micro multi-chamber apparatus is used as a small reaction apparatus used for biochemical analysis or normal chemical analysis. As such an apparatus, for example, a microwell reaction vessel plate such as a microtiter plate in which a plurality of wells are formed on a flat substrate surface is used (see, for example, Patent Document 1).
Moreover, as a trace liquid weighing structure capable of quantitatively handling a trace amount of liquid, a first channel and a second channel, a third channel opening in the channel wall of the first channel, A structure having a fourth channel having a property of opening the channel wall of the two channels and connecting one end of the third channel and the second channel so that capillary attraction is relatively difficult to work than the third channel. Some are provided (see, for example, Patent Documents 2 and 3). According to the trace liquid weighing structure, after the liquid introduced into the first flow path is drawn into the third flow path, the liquid remaining in the first flow path is removed, and the volume of the third flow path is increased. A corresponding volume of liquid can be weighed into the second flow path.

  When performing a PCR reaction using the reaction container plate as described above, a temperature control mechanism using a temperature control element such as a Peltier element is disposed below the reaction container plate, and a sample to which a reagent is added in the reaction container The reagent and the sample liquid are reacted while controlling the temperature of the liquid to a predetermined temperature.

However, if the product produced by the PCR reaction is released to the outside of the reaction vessel plate, it causes contamination and contamination of the surrounding environment. Therefore, the temperature measurement terminal is inserted directly into the sample solution in the reaction vessel. It is not preferable to perform this. Due to such problems, conventionally, a temperature measurement terminal is provided on the temperature adjustment mechanism side, or a temperature measurement terminal is incorporated in the reaction vessel plate.
JP-A-2005-177749 JP 2004-163104 A JP 2005-114430 A

  If a temperature measurement terminal is provided on the temperature adjustment mechanism side, the temperature measurement terminal is more strongly affected by the temperature adjustment element than the reaction vessel and shows a temperature different from the actual temperature in the reaction vessel. It is necessary to empirically calculate it by experiment, numerical analysis, etc. based on the measured value by the temperature measuring terminal. However, this method is not accurate because the influence from the periphery of the reaction vessel cannot be reflected in the calculation result.

  When the temperature measurement terminal is incorporated into the reaction container plate, the temperature measurement terminal is also disposable, which increases the cost of the reaction container plate. In addition, thin temperature measurement terminals that can be incorporated into reaction vessel plates have large individual differences, so calibration is required for each temperature measurement, and if calibration is performed for each temperature measurement terminal, the efficiency of reaction processing decreases. is there.

  SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to enable accurate measurement of the liquid temperature in a reaction container without increasing the cost of a disposable reaction container plate.

The reaction container plate according to the present invention includes at least one reaction container, and the reaction container is provided with a reaction liquid flow channel to which a liquid involved in the reaction is supplied, and is discarded for every measurement of one sample. It is a possible reaction container plate, characterized in that it is provided with a temperature measurement container that is independent of the reaction container and contains a temperature measurement liquid and is sealed by a member that can be penetrated by the tip of the temperature sensor unit. Is. Thereby, the liquid temperature of the reaction container plate can be measured by inserting the temperature measurement terminal into the temperature measurement container.
Since the temperature measurement container contains the temperature measurement liquid and is sealed with a sealing member that can be penetrated by a member having a sharp tip shape, the temperature measurement liquid is measured by the sealing member until immediately before the temperature measurement is performed. Can be held in a container. Further, since the temperature measurement container is sealed by the sealing member until the temperature measurement, it is possible to prevent the intrusion of the substance that affects the temperature change into the temperature measurement container.

  The temperature measurement container may be provided with a flow path for supplying the temperature measurement liquid independently of the reaction liquid flow path.

  In the reaction processing apparatus of the present invention for performing the reaction with the liquid feeding in the reaction container of the reaction container plate of the present invention described above, the sensor unit is provided on the tip side, and the temperature measurement liquid containing the temperature measurement liquid is accommodated. A temperature measurement terminal that is inserted into the container from the tip to measure the temperature of the temperature measurement liquid, and is driven at least in the vertical direction to hold the temperature measurement terminal and insert and withdraw the sensor part from the temperature measurement container. And a drive mechanism.

  The sensor portion of the temperature measurement terminal is preferably covered with a heat conductive protective cover having a sharp tip. Then, when the container for temperature measurement of the reaction container plate is sealed with a penetrable lid member with a sharp member, the temperature measurement terminal penetrates the sealing member while preventing damage to the sensor part of the temperature measurement terminal. And it can be made to enter the inside of the container for temperature measurement as it is.

It is preferable that the drive mechanism includes an elastic member in a portion that holds the temperature measurement terminal, and the temperature measurement terminal is elastically held so that it can expand and contract in the axial direction.
When the temperature measurement terminal is lowered and the sensor part is inserted into the temperature measurement container, the sensor part at the tip of the temperature measurement terminal comes into contact with the bottom of the temperature measurement container and is pressed further, and the sensor part is compressed and damaged. It is possible to do. Therefore, by providing an elastic member at the portion of the drive mechanism that holds the temperature measurement terminal so that it can extend and contract in the axial direction, the tip of the temperature measurement terminal contacts the bottom of the temperature measurement container, and the drive mechanism further Even if the measurement terminal is driven downward, the elastic member is elastically deformed to absorb the stress applied to the temperature measurement terminal and prevent the temperature measurement terminal from being damaged.

  In the reaction container plate of the present invention, there are a reaction container that is shut off from the outside, and a temperature measurement container that is independent of the reaction container and contains a temperature measurement liquid and is sealed by a member that can be penetrated by the tip of the temperature sensor unit. Since it is provided, the temperature temperature can be measured by inserting the temperature measurement terminal into the temperature measurement container. As a result, the liquid temperature of the reaction vessel plate can be measured in a state in which the reaction vessel is kept sealed without inserting a temperature measurement terminal in the reaction vessel, so that contamination and contamination of the surrounding environment can be prevented. it can. Since the temperature of the liquid actually contained in the container of the reaction container plate can be measured, the temperature can be measured more accurately than before. Further, since the temperature measurement terminal does not directly contact the sample solution in the reaction vessel, the reaction product does not adhere to the temperature measurement terminal, and the temperature measurement terminal can be used repeatedly, thereby suppressing an increase in cost. .

1A and 1B are diagrams showing an embodiment of a reaction vessel plate. FIG. 1A is a schematic plan view, and FIG. 1B is a sectional view taken along a line AA in FIG. The schematic cross-sectional view which added the cross section of the sample container air vent flow path 19 and 21, the liquid drain space 29, the air drain space 31, and the bellows 53, (C) is the outline which expands and shows the syringe 51 and the bellows 53 vicinity. FIG. FIG. 2 is an exploded sectional view showing this embodiment and a schematic exploded perspective view of the switching valve. FIG. 3 is a schematic view showing the vicinity of one reaction vessel of this embodiment, where (A) is a plan view, (B) is a perspective view, and (C) is a cross-sectional view. 4A and 4B are enlarged views of the sample container. FIG. 4A is a plan view, and FIG. 4B is a cross-sectional view taken along the line BB in FIG. 5A and 5B are enlarged views of the reagent container. FIG. 5A is a plan view, and FIG. 5B is a cross-sectional view taken along the line CC in FIG. 6A and 6B are enlarged views of the air suction container. FIG. 6A is a plan view, and FIG. 6B is a cross-sectional view taken along the DD line in FIG.
An embodiment of the reaction vessel plate will be described with reference to FIGS.

The reaction vessel plate 1 includes a plurality of reaction vessels 5 having openings on one surface of the vessel base 3. In this embodiment, 6 × 5 rows + 5 reaction vessels 5 and one temperature measurement vessel 6 are arranged in a staggered manner. A reagent 7 and wax 9 are accommodated in the reaction vessel 5. The temperature measuring container 6 has the same shape and volume as the reaction container 5, and a temperature measuring liquid 8 is accommodated therein. The temperature measuring liquid 8 is a liquid having a specific heat close to that of a reagent such as pure water.
In this embodiment, only one temperature measuring container 6 is provided, but two or more temperature measuring containers 6 may be provided.

  The material of the container base 3 including the reaction container 5 and the temperature measuring container 6 is not particularly limited. However, when the reaction container plate 1 is used as disposable, it is preferably a material that can be obtained at low cost. . Examples of such materials include resin materials such as polypropylene and polycarbonate. When the substance in the reaction vessel 5 is detected by absorbance, fluorescence, chemiluminescence, bioluminescence or the like, it must be formed of a light transmissive resin so that optical detection can be performed from the bottom side. Is preferred. In particular, when fluorescence detection is performed, the container base 3 is made of a material such as a resin having a low autofluorescence property (a property of generating less fluorescence from itself) and a light transmitting resin, such as polycarbonate. Is preferred. The thickness of the container base 3 is 0.2 to 4.0 mm (millimeters), preferably 1.0 to 2.0 mm. From the viewpoint of low autofluorescence for fluorescence detection, the container base 3 is preferably thinner.

  Referring to FIGS. 1 and 3, the flow path base 11 is disposed on the container base 3 so as to cover the arrangement region of the reaction container 5 and the temperature measurement container 6. The channel base 11 is made of, for example, PDMS (polydimethylsiloxane) or silicone rubber. The thickness of the channel base 11 is, for example, 1.0 to 5.0 mm. The flow path base 11 has a groove on the joint surface with the container base 3. The groove and the surface of the container base 3 form a main channel 13, a metering channel 15, an injection channel 17, reaction vessel air vent channels 19 and 21, and drain space air vent channels 23 and 25. The main channel 13, the metering channel 15 and the injection channel 17 constitute a reaction vessel channel. A concave portion 27 disposed on the reaction vessel 5 is also formed on the joint surface of the flow path base 11 with the vessel base 3. In FIG. 1A and FIGS. 3A and 3B, only the groove and the concave portion of the flow path base 11 are illustrated.

  An opening 18 is provided at a position corresponding to the temperature measurement container 6 of the flow path base 11. A sealing member 16 that can be penetrated by a member having a sharp tip shape is attached to the upper surface of the temperature measuring container 6, and the temperature measuring container 6 is sealed until the sealing member 16 is penetrated. The sealing member 16 is made of an aluminum seal or an aluminum seal bonded with a silicone rubber sheet or a PDMS sheet. In particular, if a silicon rubber sheet or a PDMS sheet bonded to an aluminum seal is used, the temperature of the container 6 for temperature measurement is closed by using the elastic force of the silicone rubber sheet or PDMS sheet to close the through hole of the aluminum seal after temperature measurement. It is possible to prevent leakage of the liquid in the inside or to prevent evaporation of the liquid by closing the gap between the through holes of the aluminum seal during temperature measurement.

  The main flow path 13 is composed of a single flow path and is formed to be bent so as to pass through the vicinity of all the reaction vessels 5. One end of the main flow path 13 is connected to a flow path 13 a formed of a through hole provided in the container base 3. The flow path 13a is connected to a port of a switching valve 63 described later. The other end of the main channel 13 is connected to a liquid drain space 29 formed in the container base 3. The dimensions of the grooves constituting the main flow path 13 are, for example, a depth of 400 μm (micrometer) and a width of 500 μm. In addition, the main flow path 13 has a predetermined length downstream of the position where the measurement flow path 15 is connected, for example, a 250 μm portion is formed to be narrower than other portions, for example, the width is 250 μm. It is.

  The measuring channel 15 is branched from the main channel 13 and provided for each reaction vessel 5. The end of the measuring channel 15 opposite to the main channel 13 is disposed in the vicinity of the reaction vessel 5. The depth of the groove constituting the measuring channel 15 is 400 μm, for example. The measuring channel 15 has an internal capacity of a predetermined capacity, for example, 2.5 μL (microliter). The width dimension of the part connected to the main flow path 13 of the measurement flow path 15 is larger than the narrow part of the main flow path 13 described above, for example, 500 μm. Thereby, the flow resistance of the main flow path 13 is larger than that of the measurement flow path 15 in the portion where the measurement flow path 15 is branched with respect to the liquid flowing from one end of the main flow path 13. The liquid flowing from one end of the main channel 13 first flows into the metering channel 15, and after the metering channel 15 is filled with the liquid, it flows downstream through the narrowed portion of the main channel 13. It has become.

An injection channel 17 is also provided for each reaction vessel 5. One end of the injection channel 17 is connected to the metering channel 15. The other end of the injection channel 17 is connected to a recess 27 disposed on the reaction vessel 5 and led to the reaction vessel 5. The injection channel 17 is formed with a dimension that maintains liquid tightness in the reaction vessel 5 in a state where there is no pressure difference between the reaction vessel 5 and the injection channel 17. In this embodiment, the injection channel 17 is composed of a plurality of grooves, and the dimensions of the grooves are, for example, a depth of 10 μm, a width of 20 μm, a pitch of 20 μm, and 13 grooves in a width region of 500 μm. Is formed. Here, the area of the boundary between the groove constituting the injection channel 17 and the metering channel 15, that is, the cross-sectional area of the groove constituting the injection channel 17 is 200 μm ² . The recess 27 has a depth of, for example, 400 μm, and the planar shape is a circle smaller than the reaction vessel 5.

  The reaction vessel 5 is connected to the main channel 13 via the metering channel 15 and the injection channel 17, but the temperature measuring vessel 6 is provided independently from the reaction vessel 5 and the main channel 13. In this embodiment, there is no flow path connected to the temperature measurement container 6, but the temperature measurement container flow path 6a independent of the main flow path 13 is used for temperature measurement as shown in FIG. The container 6 may be connected. In that case, the flow path 6 a is connected to one port of the syringe 51 and is a flow path for feeding the temperature measurement liquid 8 injected from the outside to the temperature measurement container 6. In this embodiment, the temperature measuring liquid 8 is initially stored in the temperature measuring container 6 and discarded together with the reaction container plate 1 after the reaction in the reaction container 5 is completed. ing.

  A reaction vessel air vent channel 19 is provided for each reaction vessel 5. One end of the reaction container air vent channel 19 is connected to a recess 27 disposed on the reaction container 5 at a position different from the injection channel 17 and disposed on the reaction container 5. The reaction container air vent channel 19 is formed with a dimension that maintains liquid tightness in the reaction container 5 in a state where there is no pressure difference between the reaction container 5 and the reaction container air vent channel 19. The other end of the reaction vessel air vent channel 19 is connected to the reaction vessel air vent channel 21. In this embodiment, the reaction vessel air vent channel 19 is composed of a plurality of grooves, and the dimensions of the grooves are, for example, a depth of 10 μm, a width of 20 μm, a pitch of 20 μm, and 13 in a 500 μm width region. Grooves are formed.

  In this embodiment, a plurality of reaction vessel air vent channels 21 are provided. A plurality of reaction vessel air vent channels 19 are connected to each reaction vessel air vent channel 21. The reaction container air vent channel 21 is for connecting the reaction container air vent channel 19 to an air drain space 31 formed in the container base 3. The dimensions of the grooves constituting the reaction vessel air vent channel 21 are, for example, a depth of 400 μm and a width of 500 μm.

  The drain space air vent channel 23 is for connecting the liquid drain space 29 to a port of a switching valve 63 described later. One end of the drain space air vent channel 23 is disposed on the liquid drain space 29. The other end of the drain space air vent channel 23 is connected to a channel 23 a formed of a through hole provided in the container base 3. The flow path 23a is connected to a port of a switching valve 63 described later. The dimensions of the grooves constituting the drain space air vent channel 23 are, for example, a depth of 400 μm and a width of 500 μm.

  The drain space air vent channel 25 is for connecting the air drain space 31 to a port of a switching valve 63 described later. One end of the drain space air vent channel 25 is disposed on the air drain space 31. The other end of the drain space air vent channel 25 is connected to a channel 25 a formed of a through hole provided in the container base 3. The flow path 25a is connected to a port of a switching valve 63 described later. The dimensions of the grooves constituting the drain space air vent channel 25 are, for example, a depth of 400 μm and a width of 500 μm.

  A flow path cover 33 (not shown in FIG. 1A) is disposed on the flow path base 11. The flow path cover 33 is for fixing the flow path base 11 to the container base 3. A through hole is formed in the flow path cover 33 at a position on the reaction vessel 5.

  Referring to FIGS. 1 and 4, a sample container 35, a reagent container 37, and an air suction container 39 are formed on the container base 3 at positions different from the arrangement region of the reaction container 5 and the drain spaces 29 and 31. Yes.

  In the container base 3 in the vicinity of the sample container 35, a sample channel 35a penetrating from the bottom of the sample container 35 to the back surface and a sample container air vent channel 35b penetrating from the surface to the back surface are formed. A protrusion 35 c is disposed on the container base 3 around the opening of the sample container 35. A sample container air vent channel 35d made of a through hole is formed in the protrusion 35c on the sample container air vent channel 35b. A sample container air vent channel 35e that connects the sample container 35 and the sample container air vent channel 35d is formed on the surface of the protrusion 35c.

  The sample container air vent channel 35e is formed by, for example, one or a plurality of pores having a width of 5 to 200 μm and a depth of 5 to 200 μm. In the sample container 35 and the sample container air vent channel 35d, This is for maintaining the liquid tightness of the sample container 35 in a state where there is no pressure difference. A septum 41, which is an elastic member, is formed on the projection 35c so as to cover the sample container 35 and the air vent channel 35d. The septum 41 is made of, for example, an elastic material such as silicone rubber or PDMS. The septum 41 can be penetrated by a dispensing device having a sharp tip, and the through-hole can be closed by elasticity when the dispensing device is pulled out after penetration. A septum stopper 43 for fixing the septum 41 is disposed on the septum 41. The septum stopper 43 has an opening on the sample container 35. In this embodiment, the reagent 45 is accommodated in the sample container 35 in advance.

  As shown in FIG. 5, the reagent base 37 in the vicinity of the reagent container 37 has a reagent channel 37 a that penetrates from the bottom to the back of the reagent container 37 and a reagent container air vent channel 37 b that penetrates from the front to the back. Is formed. A protrusion 37 c is arranged on the container base 3 around the opening of the reagent container 37. A reagent container air vent channel 37d made of a through hole is formed in the protrusion 37c on the reagent container air vent channel 37b. A reagent container air vent channel 37e that connects the reagent container 37 and the reagent container air vent channel 37d is formed on the surface of the protrusion 37c.

  The reagent container air vent channel 37e is formed of, for example, one or a plurality of pores having a width of 5 to 200 μm and a depth of 5 to 200 μm. In the reagent container 37 and the reagent container air vent channel 37d, This is for maintaining the liquid tightness of the reagent container 37 in a state where there is no pressure difference. A film 47 made of, for example, aluminum is formed on the protrusion 37c so as to cover the reagent container 37 and the air vent channel 37d. Dilution water 49 is accommodated in the reagent container 37.

  As shown in FIG. 6, the air suction container 39 has the same configuration as the reagent container 37. That is, the air suction flow path 39a penetrating from the bottom to the back surface of the air suction container 39 and the air suction container air venting flow penetrating from the front surface to the back surface are disposed on the container base 3 near the air suction container 39. A path 39b is formed. On the container base 3 around the opening of the air suction container 39, a protrusion 39c having air suction container air vent channels 39d and 39e is disposed. A film 47 made of, for example, aluminum is formed on the protrusion 39c. The air suction container 39 contains no liquid or solid, and is filled with air.

  1 and 2, the syringe 51 is provided on the surface of the container base 3 at a position different from the arrangement region of the reaction container 5, the drain spaces 29 and 31, and the containers 35, 37, and 39. Yes. The syringe 51 is formed by a cylinder 51a formed in the container base 3, a plunger 51b disposed in the cylinder 51a, and a cover body 51d. A syringe channel 51c penetrating from the discharge port provided at the bottom of the cylinder 51a to the back surface is formed in the container base 3.

  The cover body 51d has flexibility in the sliding direction of the plunger 51b, and is connected to the cylinder 51a and the plunger 51b. The cover body 51d is for blocking the portion of the inner wall of the cylinder 51a where the plunger 51b comes into contact with the atmosphere outside the cylinder 51a while maintaining airtightness, and is surrounded by the cylinder 51a, the plunger 51b, and the cover body 51d. A sealing space 51e is formed. The end of the cover body 51d on the side connected to the cylinder 51a is fixed to the upper end of the cylinder 51a with a cylinder cap 51f while ensuring airtightness. The end of the cover body 51d on the side connected to the plunger 51b is connected to the upper surface of the plunger 51b with an adhesive while ensuring airtightness. However, the method and position of connecting the cover body 51d to the cylinder 51a and the plunger 51b are not limited to this.

  Thus, the cover body 51d is connected to the cylinder 51a and the plunger 51b to form a sealed space 51e surrounded by the cylinder 51a, the plunger 51b, and the cover body 51d, so that the space between the cylinder 51a and the plunger 51b is formed. Therefore, it is possible to prevent foreign substances from entering and environmental contamination of the liquid to the outside. Since the cover body 51d is flexible in the sliding direction of the plunger 51b, the sliding operation of the plunger 51b is possible.

  In this embodiment, the plunger 51b and the cover body 51d are formed by separate members, but the plunger and the cover body may be integrally formed. An example of the integrally formed plunger and cover material is silicone rubber.

  The container base 3 is also provided with a bellows 53 at a position different from the arrangement region of the reaction container 5, the drain spaces 29 and 31, the containers 35, 37, and 39 and the syringe 51. The bellows 53 has an internal space sealed, and the internal capacity is passively variable by expanding and contracting. For example, the bellows 53 is disposed in a through hole 53 a provided in the container base 3.

  A container bottom 55 is attached to the back surface of the container base 3 at a position different from the arrangement region of the reaction containers 5. An air vent channel 53 b is provided in the container bottom 55 at a position communicating with the bellows 53. The bellows 53 is in close contact with the surface of the container bottom 55. The container bottom 55 is for guiding the flow paths 13a, 23a, 25a, 35a, 35b, 37a, 37b, 39a, 39b, 51c, 53b to a predetermined port position.

The container base 3 container and the bottom 55 are provided with a syringe air vent channel 53 c having one end connected to the sealed space 51 e and the other end made a bellows 53. Illustration of the syringe air vent channel 53c in FIG. 1 (A) is omitted.
Thus, since the syringe air vent channel 53c having one end connected to the sealed space 51e and the other end bellows 53 is provided, the sealed space 51e is blocked from the atmosphere outside the reaction vessel plate 1. When the plunger 51b slides, the pressure change in the sealed space 51e accompanying the change in the internal capacity of the sealed space 51e can be alleviated, and the plunger 51b can be slid smoothly.

  A rotary switching valve 63 including a disc-shaped seal plate 57, a rotor upper 59, and a rotor base 61 is provided on the surface of the container bottom 55 opposite to the container base 3. The switching valve 63 is attached to the container bottom 55 by a lock 65.

The seal plate 57 is provided in the vicinity of the peripheral edge thereof, and is connected to any of the flow paths 13a, 35a, 37a, 39a, and the flow paths 23a, 25a, 35b, A through groove 57b connected to at least two of 37b, 39b, and 53b and a through hole 57c provided in the center and connected to the syringe flow path 51c are provided.
The rotor upper 59 includes a through hole 59a provided at the same position as the through hole 57a of the seal plate 57, a groove 59b provided on the surface corresponding to the through groove 57b of the seal plate 57, and a through hole provided in the center. A hole 59c is provided.
The rotor base 61 is provided with a groove 61a on its surface for connecting two peripheral holes 59a and 59c disposed at the center and the peripheral portion of the rotor upper 59.

The syringe channel 51c is connected to one of the channels 13a, 35a, 37a, 39a by the rotation of the switching valve 63, and at the same time, the air vent channel 53b is connected to the channels 23a, 25a, 35b, 37b, 39b. Connected to at least one of them.
In the position of the switching valve 63 shown in FIG. 1A, the syringe flow path 51c is not connected to any of the flow paths 13a, 35a, 37a, 39a, and the air vent flow path 53b is also connected to the flow paths 23a, 25a. , 35b, 37b, 39b are not connected to the initial position.

  In the reaction vessel plate 1, the injection channel 17 is formed so as to maintain the liquid tightness of the reaction vessel 5 with no pressure difference between the reaction vessel 5 and the injection channel 17. The reaction vessel air vent channel 19 is also formed so as to maintain the liquid tightness of the reaction vessel 5 in the state where there is no pressure difference between the reaction vessel 5 and the reaction vessel air vent channel 19. The main flow path 13 of the reaction container flow path, the liquid drain space 29 to which the main flow path 13 is connected, and the drain space air vent flow path 23 can be sealed by switching the switching valve 63. The containers 35, 37, and 39 are sealed with a septum 41 or a film 47. The flow paths 35a, 35b, 37a, 37b, 39a, 39b connected to the containers 35, 37, 39 can be sealed by switching the switching valve 63. One end of the air vent channel 53b is connected to the bellows 53 and sealed. Thus, the container and flow path inside the reaction container plate 1 are formed in a closed system. Even when the air vent channel 53b is connected to the atmosphere outside the reaction vessel plate 1 without the bellows 53, the air vent channel 53b is switched to the reaction vessel by switching the switching valve 63. Since it can block | block with the flow paths other than the container inside the plate 1 and the air vent flow path 53b, the container and flow path in which a liquid is accommodated or a liquid flows can be made into a closed system.

FIG. 7 is a view showing a reaction processing apparatus for processing the reaction container plate 1 shown in FIG. (C) is the sectional drawing which shows the structure of a temperature measurement terminal. In addition, since the structure of the reaction container plate 1 is the same as FIG. 1, the description is abbreviate | omitted.
The reaction processing apparatus drives a temperature adjustment mechanism 67 for adjusting the temperature of the reaction vessel 5, a temperature measurement terminal 68 for measuring the temperature of the temperature measurement liquid 8 in the temperature measurement vessel 6, and the syringe 51. The switching valve driving unit 71 for switching the syringe driving unit 69 and the switching valve 63 is provided.
When other temperature measurement containers are provided on the reaction container plate 1 in addition to one temperature measurement container 6, in addition to the temperature measurement terminals 68, there are temperature measurement terminals for the respective temperature measurement containers. It may be provided. Note that the temperature of the temperature measurement liquid in the temperature measurement container other than the temperature measurement container 6 may be measured using the temperature measurement terminal 68.

  The temperature adjustment mechanism 67 is composed of, for example, a Peltier element and is disposed below the reaction vessel 5 of the reaction vessel plate 1 to uniformly heat or cool each reaction vessel 5. The temperature adjustment mechanism 67 is connected to the temperature measurement terminal 68 and performs temperature control based on the measurement value of the temperature measurement terminal 68.

  The temperature measurement terminal 68 is disposed above the temperature measurement container 6 and is moved up and down by a drive mechanism (not shown). At the time of temperature measurement, as shown in FIG. 7B, the tip portion penetrates into the temperature measurement liquid 8 through the sealing member 16 attached to the upper surface of the temperature measurement container 6. As shown in (C), the temperature measurement terminal 68 has a sensor portion 68a at the tip. The sensor unit 68a is a temperature measuring element such as a thermocouple or a thermistor. Reference numeral 68b denotes a lead wire of the sensor unit 68a. The sensor unit 68a is housed in a protective cover 68c together with thermally conductive grease such as G-765 and KS-613 (both products of Shin-Etsu Chemical Co., Ltd.). The protective cover 68c is made of a heat conductive material such as aluminum or stainless steel. The tip shape of the protective cover 68c is sharp so that the sealing member 16 can be penetrated. The lead wire 68b is supported by an insulating support member 68d.

FIG. 19 shows a specific example of the structure of the portion that holds the temperature measurement terminal 68. (A) of the figure shows a state before the temperature measurement terminal 68 is inserted into the temperature measurement container 6 (normal time), and (B) shows the tip of the temperature measurement terminal 68 at the bottom of the temperature measurement container 6. The state inserted up to is shown.
In this example, the temperature measurement terminal 68 is slidably held at the tip of the holding member 90 in the vertical direction. The holding member 90 has a structure capable of moving the tip end portion holding the temperature measurement terminal 68 in the vertical direction. As an example of a structure that allows the tip of the holding member 90 to move in the vertical direction, a structure in which the holding member 90 is screwed onto a ball screw that is supported in the vertical direction and whose rotation is controlled by a stepping motor or the like can be given. In this method, the holding member 90 can be accurately moved in the vertical direction by controlling the number of rotations of the stepping motor. As another structural example, there is a structure in which the distal end portion is driven in the vertical direction by rotating the holding member 90 around a base end portion (not shown).

  Stoppers 92 a and 92 b are provided on the upper side and the lower side of the portion where the temperature measurement terminal 68 is held by the holding member 90. A spring 94 as an elastic member is inserted between the lower stopper 92 b and the holding member 90. One end of the spring 94 is in contact with the lower portion of the holding member 90, and the other end is in contact with the stopper 92b. According to this structure, as shown in FIG. 19B, even if the holding member 90 is further pushed downward from the state in which the temperature measuring terminal 68 is inserted to the bottom of the temperature measuring container 6, the spring Since the force applied to the tip end portion of the temperature measurement terminal 68 is absorbed by the spring 94 when the 94 is contracted, the tip end of the temperature measurement terminal 68 can be prevented from being damaged.

  8 to 14 are plan views for explaining the operation of introducing the sample liquid from the sample container 35 into the reaction container 5. This operation will be described with reference to FIGS. 1 and 8 to 14.

  For example, 5 μL of sample liquid is dispensed into the sample container 35 through the septum 41 on the sample container 35 using a dispensing device (not shown) having a sharp point. After dispensing the sample solution, pull out the dispensing device. The through hole of the septum 41 when the dispensing instrument is pulled out is closed by the elasticity of the septum 41.

The syringe drive unit 69 is connected to the plunger 51 b of the syringe 51, and the switching valve drive unit 71 is connected to the switching valve 63.
As shown in FIG. 8, the switching valve 63 is rotated from the state of the switching valve 63 shown in FIG. 1A to connect the sample flow path 35a and the syringe flow path 51c, and the sample container air vent flow path 35b is aired. It connects with the extraction flow path 53b. At this time, the air vent channels 37b and 39b are also connected to the air vent channel 53b. For example, 45 μL of the reagent 45 is accommodated in the sample container 35.

  The plunger 51b of the syringe 51 is slid to mix the sample liquid and the reagent 45 in the sample container 35. Thereafter, the mixed solution in the sample container 35 is sucked into the flow path in the switching valve 63, the syringe flow path 51c, and the syringe 51 by, for example, 10 μL. At this time, since the sample container 35 is connected to the bellows 53 via the air vent channels 35e, 35d, 35b, the switching valve 63 and the air vent channel 53b, the gas capacity in the sample container 35 is changed. The bellows 53 expands and contracts. Further, the sliding of the plunger 51b deforms the cover body 51d, and the internal capacity of the sealed space 51e (see FIG. 1C) changes. Since the sealed space 51e is connected to the bellows 53 via the syringe air vent channel 53c, the bellows 53 expands and contracts even when the internal capacity of the sealed space 51e changes. Even in the operation process described below, the bellows 53 expands and contracts with the change in the internal capacity of the sealed space 51e due to the sliding of the plunger 51b.

  As shown in FIG. 9, the switching valve 63 is rotated to connect the reagent channel 37a and the syringe channel 51c, and the reagent container air vent channel 37b is connected to the air vent channel 53b. For example, 190 μL of dilution water 49 is accommodated in the reagent container 37. The mixed solution sucked into the flow path in the switching valve 63, the syringe flow path 51 c and the syringe 51 is injected into the reagent container 37, and the syringe 51 is slid to mix the mixed liquid and the dilution water 49. For example, all of the diluted mixed solution is sucked into the flow path in the switching valve 63, the syringe flow path 51c, and the syringe 51, that is, 200 μL. At this time, since the reagent container 37 is connected to the bellows 53 via the air vent channels 37e, 37d, 37b, the switching valve 63 and the air vent channel 53b, the gas capacity in the reagent container 37 is changed. The bellows 53 expands and contracts.

  As illustrated in FIG. 10, the switching valve 63 is rotated to connect the flow path 13 a connected to one end of the main flow path 13 and the syringe flow path 51 c, and the flow connected to the liquid drain space 29 and the air drain space 31. The paths 23a and 25a are connected to the air vent channel 53b. The syringe 51 is driven in the pushing direction to send the diluted mixed solution sucked into the flow path in the switching valve 63, the syringe flow path 51 c, and the syringe 51 to the main flow path 13. The diluted mixed liquid injected from the flow path 13a side into the main flow path 13 fills the metering flow path 15 in order from the flow path 13a side and reaches the liquid drain space 29 as indicated by the embossments and arrows. In the introduction pressure state when the diluted mixture is introduced into the main channel 13 and the metering channel 15, the injection channel 17 allows gas to pass but does not allow the diluted mixture to pass. The gas in the metering channel 15 moves into the reaction vessel 5 through the injection channel 17 as the metering channel 15 is filled with the diluted mixed solution. As this gas moves, a part of the gas in the reaction vessel 5 moves to the reaction vessel air vent channels 19 and 21. Furthermore, the gas in the flow path from the reaction container air vent flow path 19 to the bellows 53 sequentially moves to the bellows 53 side (see white arrow). Further, when the diluted mixed liquid is injected into the liquid drain space 29, the gas in the flow path from the liquid drain space 29 to the bellows 53 sequentially moves toward the bellows 53 (see the white arrow). As a result, the bellows 53 expands.

  As shown in FIG. 11, the switching valve 63 is rotated to connect the air suction channel 39a and the syringe channel 51c, and the air suction container air vent channel 39b is connected to the air vent channel 53b. The syringe 51 is driven to the suction side, and the gas in the air suction container 39 is sucked into the flow path in the switching valve 63, the syringe flow path 51 c, and the syringe 51. At this time, since the air suction container 39 is connected to the bellows 53 via the air vent channels 39e, 39d, 39b, the switching valve 63 and the air vent channel 53b, the pressure inside the air suction container 39 is reduced. As a result, the bellows 53 contracts (see the white arrow).

  As shown in FIG. 12, the switching valve 63 is rotated to connect the flow path 13a and the syringe flow path 51c, and connect the flow paths 23a and 25a to the air vent flow path 53b as in the connection state of FIG. The syringe 51 is driven in the pushing direction, and the flow path in the switching valve 63, the syringe flow path 51c, and the gas in the syringe 51 are sent to the main flow path 13 to purge the diluted mixed liquid in the main flow path 13 (open arrow) reference). In the purge pressure state at this time, the dilute mixed liquid does not pass through the injection flow path 17, and therefore the dilute mixed liquid remains in the measuring flow path 15 (see embossing). The purged diluted liquid mixture is accommodated in the liquid drain space 29. Further, when the diluted mixed liquid is injected into the liquid drain space 29, the gas in the flow path from the liquid drain space 29 to the bellows 53 sequentially moves toward the bellows 53 (see the white arrow). As a result, the bellows 53 expands.

  As shown in FIG. 13, the switching valve 63 is rotated to connect the air suction flow path 39a and the syringe flow path 51c as in the connection state of FIG. 11, and the air suction container air vent flow path 39b is vented. Connect to the flow path 53b. The syringe 51 is driven to the suction side, and the gas in the air suction container 39 is sucked into the flow path in the switching valve 63, the syringe flow path 51 c, and the syringe 51. At this time, the bellows 53 contracts as described with reference to FIG. 11 (see the white arrow).

  As shown in FIG. 14, the switching valve 63 is rotated to connect the flow path 13a and the syringe flow path 51c, and connect the flow path 25a to the air vent flow path 53b. This connection state differs from the connection states shown in FIGS. 10 and 12 in that the liquid drain space 29 to which the downstream end of the main flow path 13 is connected is not connected to the flow path in the switching valve 63. The syringe 51 is driven in the pushing direction. Since the downstream end of the main flow path 13 is not connected to the bellows 53, the inside of the main flow path 13 is pressurized larger than the liquid introduction pressure and the purge introduction pressure. As a result, the diluted mixed solution in the metering channel 15 is injected into the reaction vessel 5 through the injection channel 17. After the diluted mixed solution is injected into the reaction vessel 5, a part of the gas in the main channel 13 flows into the reaction vessel 5 through the metering channel 15 and the injection channel 17. At this time, the reaction vessel 5 is connected to the bellows 53 via the reaction vessel air vent channels 19 and 21, the air drain space 31, the drain space air vent channel 25a, and the air vent channel 53b. The gas between the bellows 53 sequentially moves toward the bellows 53 (see the white arrow). As a result, the bellows 53 expands.

After the switching valve 63 is connected as shown in FIG. 1 and the container, flow path and drain space inside the reaction container plate 1 are sealed, the reaction container 5 is heated by the temperature control mechanism 67 to melt the wax 9. Thereby, the diluted mixed solution injected into the reaction vessel 5 enters under the wax 9, and the diluted mixed solution and the reagent 7 are mixed and reacted. At this time, the temperature measurement terminal 68 penetrates the sealing member 16 and enters the temperature measurement container 6 to measure the temperature of the temperature measurement liquid 8. Since the temperature measurement liquid 8 has a temperature close to the liquid temperature in each reaction vessel 5, the measurement value by the temperature measurement terminal 68 can be handled as the measurement value of the liquid temperature in the reaction vessel 5. Therefore, the temperature of the liquid in the reaction vessel 5 can be accurately controlled based on the measurement value of the temperature measurement terminal 68.
Before injecting the diluted mixed solution into the reaction vessel 5, the reaction vessel 5 is heated by the temperature control mechanism 67 to melt the wax 9, and the wax 9 is injected when the diluted mixed solution is injected into the reaction vessel 5. May be melted. In this case, the diluted mixed solution injected into the reaction vessel 5 immediately enters under the wax 9, and the diluted mixed solution and the reagent 7 are mixed and reacted. Even if the connection state of the switching valve 63 is the state shown in FIG. 14, the sealed system is secured by the bellows 53. If the switching valve 63 is brought into the connection state shown in FIG. 1 after the diluted mixed solution is injected, the container, flow path and drain space inside the reaction container plate 1 can be sealed. Here, the timing for switching the switching valve 63 to the connected state in FIG. 1 may be any timing from immediately after the injection of the diluted mixed solution to the end of the reaction of the diluted mixed solution and the reagent 7, or the diluted mixed solution and the reagent 7. It may be after the completion of the reaction.

  In this embodiment, the grooves for forming the flow paths 13, 15, 17, 19, 21, and 23 are formed in the flow path base 11, but the present invention is not limited to this, and the flow of these is not limited. A groove for forming all or part of the path may be formed on the surface of the container base 3.

  FIG. 15 is an enlarged schematic cross-sectional view showing the vicinity of a reaction vessel in another embodiment of the reaction vessel plate. This embodiment is the same as the above-described embodiment described with reference to FIGS. 1 to 14 except that a flow path spacer is disposed between the reaction vessel base and the flow path base.

  A flow path spacer 73 is disposed on the container base 3 so as to cover the arrangement region of the reaction containers 5, and a flow path base 11 and a flow path cover 33 are further disposed in that order. The channel spacer 73 is made of, for example, PDMS or silicone rubber. The thickness of the channel spacer 73 is, for example, 0.5 to 5.0 mm. The flow path spacer 73 includes a convex portion 75 protruding into the reaction container 5 for each reaction container 5. The convex portion 75 has a substantially trapezoidal cross section. For example, the base end has a width of 1.0 to 2.8 mm, the tip has a width of 0.2 to 0.5 mm, and the tip has a base end. It is thinner than Further, the surface of the convex portion 75 is subjected to super water repellent treatment. However, the surface of the convex portion 75 may not necessarily be subjected to the water repellent treatment.

Further, the flow path spacer 73 is provided with an injection flow path 77 formed of a through hole penetrating from the tip end portion of the convex portion 75 to the opposite surface for each position where the convex portion 75 is formed. The inner diameter of the injection channel 77 is, for example, 500 μm. The opening on the flow channel base 11 side of the injection flow channel 77 is connected to the injection flow channel 17 of the flow channel base 11. In this embodiment, the channel base 11 is not provided with the recess 27 as compared with the above-described embodiment described with reference to FIGS.
Further, the flow path spacer 73 is also provided with a reaction container air vent flow path 79 including a through hole for communicating the reaction container air vent flow path 19 of the flow path base 11 and the reaction container 5.

  Although not shown, the channel spacer 73 includes both end portions of the main channel 13, end portions of the reaction vessel air vent channel 21 on the air drain space 31 side, and both ends of the drain space air vent channels 23 and 25. The part is provided with a through hole, and the flow paths 13, 21, 23, 25 are connected to the containers 29, 31 or the flow paths 23 a, 25 b provided in the container base 3.

  In this embodiment, the end of the injection flow channel 77 opposite to the injection flow channel 15 (the other end of the injection flow channel) is disposed at the tip of a convex portion 75 formed to protrude from the inner upper surface of the reaction vessel 5. Therefore, the liquid injected into the reaction vessel 5 through the injection flow channels 15 and 77 can be easily dropped into the reaction vessel 5.

  Further, when the liquid is discharged from the tip of the convex portion 75 through the injection channel 77, the tip of the convex portion 75 is adjusted so that the liquid droplet formed at the tip of the convex portion 75 contacts the side wall of the reaction vessel 5. If it arrange | positions in the side wall vicinity of the reaction container 5, a liquid can be inject | poured in the reaction container 5 along the side wall of the reaction container 5, and a liquid can be inject | poured in the reaction container 5 more reliably. However, the formation position of the convex portion 75 may be a position where a droplet formed at the tip of the convex portion 75 does not contact the side wall of the reaction vessel 5.

FIG. 16 is a schematic cross-sectional view showing, in an enlarged manner, the vicinity of the reaction vessel of another embodiment of the reaction vessel plate.
This embodiment further includes a protrusion 81 inside the reaction vessel 5 as compared to the embodiment described with reference to FIG. The tip of the protrusion 81 is disposed below the tip of the protrusion 75. Thereby, it becomes easy to guide the droplet formed at the tip of the convex portion 75 into the reaction vessel 5. In particular, it is particularly effective if a hydrophilic treatment is applied to at least the tip surface of the protrusion 81.

FIG. 17 is an enlarged schematic cross-sectional view showing the vicinity of a reaction vessel of still another embodiment of the reaction vessel plate.
In this embodiment, compared to the embodiment described with reference to FIG. 16, the step portion 83 formed on the side wall of the reaction vessel 5 and the upper surface of the reaction vessel 5 are formed on the upper surface of the step portion 83 with a gap. Further provided is a convex ridge 85. The step part 83 and the protruding line part 85 are formed in an annular shape when viewed from above. The tip of the ridge 85 is disposed at a distance from the side wall of the reaction vessel 5.
Since the tip of the ridge 85 is spaced from the upper surface and side surface of the reaction vessel 5, the liquid contained in the reaction vessel 5 reaches the upper surface of the reaction vessel 5 along the side wall of the reaction vessel 5. Can be prevented. This effect is particularly effective when a water-repellent treatment is performed on at least the tip of the ridge 85.

The structure provided with the step part 83 and the protruding line part 85 shown in FIG. 17 can also be applied to the embodiment shown in FIG.
Moreover, in each Example demonstrated with reference to FIG.15, FIG16 or FIG.17, the groove | channel for forming the flow path 13,15,17,19,21,23 is formed in the flow path base 11. FIG. However, the present invention is not limited to this, and the grooves for forming all or part of the flow paths are the surface of the flow path spacer 73 on the flow path base 11 side, the container base 11 of the flow path spacer 73. It may be formed on either the side surface or the surface of the container base 3.

In addition, regarding the syringe 51, a part of the cylinder 51 a may be formed by a part of the switching valve 63.
18A and 18B are views showing still another embodiment of the reaction vessel plate. FIG. 18A is a schematic plan view, and FIG. 18B is a cross-sectional view taken along the line AA in FIG. Schematic cross-sectional view including the cross section of the channel 17, the sample container air vent channels 19, 21, the liquid drain space 29, the air drain space 31, and the bellows 53, (C) is an enlarged view of the vicinity of the syringe 51 and the bellows 53. It is a schematic sectional drawing shown. FIG. 19 is a schematic exploded view of the switching valve, in which (A) is a plan view and a cross-sectional view of the seal plate, (B) is a plan view and a cross-sectional view of the rotor upper, and (C) is a plan view of the rotor base and A cross-sectional view is shown.

In this embodiment, the cylinder 87 a of the syringe 87 is formed of a resin material such as polypropylene or polycarbonate, and is integrally formed with the rotor upper 91 of the switching valve 95.
The syringe 87 is formed by a cylinder 87a disposed in a through hole formed in the container base 3 and the container bottom 55, a plunger 87b disposed in the cylinder 87a, and a cover body 87d.

  The cover body 87d has flexibility in the sliding direction of the plunger 87b, and is connected to the cylinder 87a and the plunger 87b. The cover body 87d is for shutting off the portion of the inner wall of the cylinder 87a that contacts the plunger 87b while maintaining airtightness from the atmosphere outside the cylinder 87a. The cover body 87d is surrounded by the cylinder 87a, the plunger 87b, and the cover body 87d. A sealing space 87e is formed.

  The end of the cover body 87d on the side connected to the cylinder 87a is fixed to the upper end of the cylinder 87a with a cylinder cap 87f while ensuring airtightness. Further, the end of the cover body 87d on the side connected to the plunger 87b is connected to the upper surface of the plunger 87b with an adhesive while ensuring airtightness. However, the method and position for connecting the cover body 87d to the cylinder 87a and the plunger 87b are not limited thereto. The plunger and the cover body may be integrally formed. An example of the integrally formed plunger and cover material is silicone rubber.

  As described above, the cover body 87d is connected to the cylinder 87a and the plunger 87b to form a sealed space 87e surrounded by the cylinder 87a, the plunger 87b, and the cover body 87d, so that the space between the cylinder 87a and the plunger 87b is formed. Therefore, it is possible to prevent foreign substances from entering and environmental contamination of the liquid to the outside. Since the cover body 87d has flexibility in the sliding direction of the plunger 87b, the sliding operation of the plunger 87b is possible.

The syringe air vent channel 53c and the switching valve 95 will be described with reference to FIG.
The switching valve 95 is formed by a disc-shaped seal plate 89, a rotor upper 91 and a rotor base 93. The switching valve 95 is attached to the container bottom 55 by a lock 65.

  The seal plate 89 is provided in the vicinity of the peripheral edge portion thereof, and is connected to any of the flow paths 13a, 35a, 37a, 39a, and the flow paths 23a, 25a, 35b, A through groove 89b connected to at least two of 37b, 39b, and 53b and a through hole 89c provided at the center and into which the cylinder 87a is inserted are provided. A fluororesin layer (not shown) is formed on the surface of the seal plate 89 facing the container bottom 55.

  The rotor upper 91 corresponds to a cylindrical cylinder 87 a provided at the center of one surface thereof, a through hole 91 a provided at the same position as the through hole 89 a of the seal plate 89, and a through groove 89 b of the seal plate 89. Then, a groove 91b provided on the surface, a through hole 91c provided in the groove 91b, and a through hole 91d provided in the center are provided. The through hole 91d is provided at the bottom of the cylinder 87a and constitutes a discharge port of the cylinder 87a.

  The rotor upper 91 is also formed with a syringe air vent channel 53c formed of a through hole penetrating from the upper end surface of the cylinder 87a to the back surface of the rotor upper 91. A cutout is formed in the upper end surface of the cylinder 87a from the inner wall of the cylinder 87a to the syringe air vent channel 53c. By this notch, as shown in FIG. 18C, the sealing space 87e and the syringe air vent channel 53c communicate with each other with the upper end surface of the cylinder 87a covered with the cover body 87d.

  The rotor base 93 has a groove 93a for connecting the through hole 91a and the through hole 91d formed in the rotor upper 91 on the surface bonded to the back surface of the rotor upper 91, and a syringe air vent formed in the rotor upper 91. A groove 93b for connecting the flow paths 53c and 91c is provided.

As shown in FIG. 18, the seal plate 89, the rotor upper 91, and the rotor base 93 are arranged such that a cylinder 87 a is inserted into a through hole 89 c of the seal plate 89 and overlapped to form a switching valve 95.
The through hole 91d of the rotor upper 91 that constitutes the discharge port of the cylinder 87a is connected to the through hole 89a of the seal plate 89 through the groove 93a of the rotor base 93 and the through hole 91a of the rotor upper 91.
The sealing space 87e (see FIG. 18) is connected to the through groove 89b of the seal plate 89 through the syringe air vent channel 53c, the groove 93b of the rotor base 93, the through hole 91c and the through groove 91b of the rotor upper 91. The

  The embodiments of the present invention have been described above, but the present invention is not limited to these, and the shape, material, arrangement, number, dimensions, flow path configuration, etc. are examples, and are described in the claims. Various modifications are possible within the scope of the present invention.

For example, the bellows 53 connected to the air vent channel 53b may have another structure as long as the capacity is a variable capacity member whose internal capacity is passively variable. Examples of such a structure include a bag-like material made of a flexible material and a syringe-like material.
Further, the capacity variable member such as the bellows 53 may not necessarily be provided.
In addition, if the containers 35, 37, and 39 do not contain a liquid such as a reagent in advance, it is not always necessary to provide the flow paths 35e, 37e, and 39e made of pores in a part of the air vent flow path.

Further, in the above embodiment, the air vent channels 35b, 37b, 39b provided in communication with the containers 35, 37, 39 as sealing containers are connected to the air vent channel 53b via the switching valve 63. However, the air vent channel provided in communication with the sealing container may be directly connected to the outside of the reaction container plate or a capacity variable part such as the bellows 53.
Moreover, you may use the cap which can be opened and closed as a sealing method of the containers 35, 37, and 39.

Moreover, in the said Example, although the container base 3 is formed with one component, the container base may be formed with several components.
The reagent in the reaction vessel 5 may be a dry reagent.
In addition, the reagent may not be stored in advance in the sample container 35 or the reaction container 5.
In the above embodiment, the dilution water 49 is stored in the reagent container 37, but the reagent may be stored instead of the dilution water 49.

  Further, the container base 3 may be provided with a gene amplification container for performing a gene amplification reaction. For example, if the reagent container 37 is emptied, it can be used as a gene amplification container.

In addition, if a reagent for performing a gene amplification reaction is accommodated in the reaction container 5, the gene amplification reaction can be performed in the reaction container 5.
Further, when a gene is contained in the liquid introduced into the main flow path 13, a probe that reacts with the gene may be provided in the reaction vessel 5.

Moreover, in the said Example, although the syringe 51 is arrange | positioned on the switching valve 63, the position which arrange | positions the syringe 51 is not limited on the switching valve 63, and may be anywhere.
In the above embodiment, the rotary switching valve 63 is used as the switching valve. However, the switching valve is not limited to this, and various flow path switching valves can be used. A plurality of switching valves may be provided.

  In the above embodiment, when the liquid filled in the metering channel 15 is injected into the reaction vessel 5 through the injection channel 17, the inside of the main channel 13 after air purge is pressurized to supply the liquid to the reaction vessel 5. However, the reaction treatment method of the present invention is not limited to this. For example, by changing the flow path configuration so that the inside of the reaction vessel air vent channel 21 can be made negative pressure using the syringe 51, and by making the inside of the reaction vessel air vent channel 21 and thus the reaction vessel 5 inside negative pressure. You may make it inject | pour into the reaction container 5 through the injection flow path 17 the liquid with which the measurement flow path 15 was filled. Alternatively, a separate syringe may be prepared so that the liquid is injected into the reaction vessel 5 with a positive pressure in the main channel 13 and a negative pressure in the reaction vessel 5.

  Moreover, in the said Example, although the one main flow path 13 was provided and all the measurement flow paths 15 were connected to the main flow path 13, a flow path structure is not limited to this. For example, a plurality of main channels may be provided, and one or a plurality of metering channels may be connected to each main channel.

In the reaction vessel plate of the present invention, the main channel can be sealed, but an example can be given in which the main channel can be sealed by opening and closing both ends of the main channel. Here, “the both ends of the main channel can be opened and closed” means that other space is connected to the end of the main channel, and the end of the other space opposite to the main channel can be opened and closed This includes cases where For example, in the above embodiment, the flow path 13a, the liquid drain space 29, the drain space air vent flow path 23, and the flow path 23a correspond to the other spaces.
In the reaction vessel plate of the present invention, the reaction vessel air vent channel can be sealed, but the end of the reaction vessel air vent channel opposite to the reaction vessel can be opened and closed. An example in which the reaction vessel air vent channel can be hermetically sealed can be given. Here, “the end of the reaction vessel air vent channel opposite to the reaction vessel can be opened and closed” means that the other end of the reaction vessel air vent channel opposite to the reaction vessel This includes a case where a space is connected and the end of the other space opposite to the reaction vessel air vent channel can be opened and closed. For example, in the above embodiment, the air drain space 31, the drain space air vent channel 25, and the channel 25a correspond to the other space.
In such an aspect, after the liquid is introduced into the main channel and the metering channel, the liquid in the main channel is then purged, and the liquid remaining in the metering channel is injected into the reaction vessel, Both ends of the main channel and the end of the reaction vessel air vent channel opposite to the reaction vessel are closed to seal the main channel and the reaction vessel air vent channel.

  The present invention can be used for measurement of various chemical reactions and biochemical reactions.

It is a figure which shows one Example of reaction container plate, (A) is a schematic top view, (B) is a cross section in the AA position of (A), a bellows, drain space, a measurement flow path, an injection flow path FIG. 4C is a schematic cross-sectional view to which a cross section of the sample container air vent channel is added, and FIG. It is sectional drawing which decomposes | disassembles and shows the Example, and a schematic exploded perspective view of a switching valve. It is the schematic which shows the one reaction container vicinity of the Example, (A) is a top view, (B) is a perspective view, (C) is sectional drawing. It is the figure which expanded and showed the sample container of the Example, (A) is a top view, (B) is sectional drawing in the BB position of (A). It is the figure which expanded and showed the reagent container of the Example, (A) is a top view, (B) is sectional drawing in CC position of (A). It is the figure which expanded and showed the container for air suction of the Example, (A) is a top view, (B) is sectional drawing in the DD position of (A). It is a figure which shows the reaction processing apparatus for processing a reaction container plate, (A) is schematic sectional drawing shown with the reaction container plate, (B) is the time of temperature measurement of the liquid for temperature measurement by a temperature measurement terminal. Sectional drawing shown, (C) is a sectional view showing the structure of the temperature measurement terminal. It is a top view for demonstrating the operation | movement which introduce | transduces a sample liquid into a reaction container from a sample container. It is a top view for demonstrating the operation | movement following FIG. FIG. 10 is a plan view for explaining the operation following FIG. 9. It is a top view for demonstrating the operation | movement following FIG. It is a top view for demonstrating the operation | movement following FIG. It is a top view for demonstrating the operation | movement following FIG. It is a top view for demonstrating the operation | movement following FIG. It is a schematic sectional drawing which expands and shows the reaction container vicinity of the other Example of the reaction container plate. It is a schematic sectional drawing which expands and shows the reaction container vicinity of the further another Example of the reaction container plate. It is a schematic sectional drawing which expands and shows the reaction container vicinity of the further another Example of the reaction container plate. It is a top view which shows the further another Example of the reaction container plate. It is a figure which shows the structure of the part holding the temperature measurement terminal of the drive mechanism of a temperature measurement terminal, (A) is a normal state, (B) is when a temperature measurement terminal is inserted to the bottom of a temperature measurement container. State.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Reaction container plate 3 Container base 5 Reaction container 6 Temperature measurement container 6a Temperature measurement container flow path 11 Flow path base 13 Main flow path 15 Measurement flow path 16 Temperature measurement container sealing member 17 Injection flow path 19, 21 Reaction container Air vent channel 35 Sample container 35b, 35d, 35e Sample container air vent channel 37 Reagent container 37b, 37d, 37e Reagent container air vent channel 39 Air suction container 39b, 39d, 39e Air suction container Air vent channel 51,87 Syringe 51a, 87a Cylinder 51b, 87b Plunger 51d, 87d Cover body 51e, 87e Sealing space 53 Bellows (capacity variable part)
53c Syringe air vent channel 63, 95 Switching valve 68 Temperature measurement terminal 73 Channel spacer 75 Protrusion 77 Injection channel 79 Reaction vessel air vent channel

Claims (5)

A reaction vessel plate provided with at least one reaction vessel, wherein the reaction vessel is provided with a reaction liquid channel to which a liquid involved in the reaction is supplied;
A reaction container plate comprising a temperature measurement container which is independent of the reaction container and contains a temperature measurement liquid and is sealed with a member which can be penetrated by a tip of a temperature sensor portion.   The reaction container plate according to claim 1, wherein the temperature measurement container is provided with a flow path to which a temperature measurement liquid is supplied independently of the reaction liquid flow path. A reaction processing apparatus that accommodates the reaction container plate according to claim 1 or 2 and performs a reaction with liquid feeding in the reaction container,
A temperature measuring terminal that is provided on the tip side and is inserted from the tip portion into the temperature measuring container in which the temperature measuring liquid is stored, and measures the temperature of the temperature measuring liquid;
A reaction processing apparatus, comprising: a drive mechanism that holds the temperature measurement terminal and that drives at least a vertical direction in order to insert and withdraw the sensor unit from the temperature measurement container.   The reaction processing apparatus according to claim 3, wherein the sensor portion of the temperature measurement terminal is covered with a heat conductive protective cover having a sharp tip.   The reaction processing apparatus according to claim 3 or 4, wherein the drive mechanism includes an elastic member in a portion that holds the temperature measurement terminal, and the temperature measurement terminal is elastically held so as to be expandable and contractable in an axial direction thereof.

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