Reaction vessel and reaction apparatus

Abstract

The present invention provides a reaction vessel that allows for appropriate temperature control and can be smoothly inserted into a reaction apparatus, and a reaction apparatus that allows for appropriate temperature control and smooth insertion of the reaction vessel. [Solution] The reaction vessel is a reaction vessel having at least one microchannel, the microchannel comprising a first heated section corresponding to the denaturation temperature range and a second heated section corresponding to the extension / annealing temperature range, an intermediate section connecting the first heated section and the second heated section, a first connecting section capable of connecting the first heated section and the liquid delivery mechanism, and a second connecting section capable of directly or indirectly connecting the second heated section and the liquid delivery mechanism, the sample solution in the microchannel in the intermediate section can be measured, and a guide surface is formed at the end of the reaction vessel on the advancing side in the insertion direction when it is inserted into the inlet of the reaction apparatus, such that the thickness decreases towards the tip.

Description

Technical Field

[0001] The present disclosure relates to a reaction processing container and a reaction processing apparatus.

Background Art

[0002] Genetic testing is widely used for examinations in various medical fields, identification of agricultural crops and pathogenic microorganisms, food safety assessment, and further testing of pathogenic viruses and various infectious diseases. In order to detect a trace amount of DNA, which is a gene, with high sensitivity, a method of analyzing a product obtained by amplifying a part of the DNA is known. Among them, the PCR method (PCR: Polymerase Chain Reaction) is a notable technique for selectively amplifying a specific portion of a very small amount of DNA collected from a living organism or the like. In the PCR method, a predetermined thermal cycle is applied to a sample solution obtained by mixing a biological sample containing DNA and a PCR reagent including primers, enzymes, and the like, to cause reactions such as denaturation, annealing, and elongation to occur repeatedly, thereby selectively amplifying the specific portion of the DNA.

[0003] In the PCR method, it is common practice to place a predetermined amount of a target sample solution into a reaction processing container such as a PCR tube or a microplate (microwell) having a plurality of holes formed therein. On the other hand, in recent years, the use of a reaction processing container (also referred to as a chip) provided with fine flow channels formed on a substrate has been put into practical use (for example, Patent Documents 1 and 2).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of Invention

Problems to be Solved by the Invention

[0005] When attaching a reaction vessel to a reaction apparatus, a slide-in mechanism is sometimes used for ease of operation, where the reaction vessel is slid into the insertion port. However, in order to properly adjust the temperature of the reaction vessel in each temperature range, it is necessary to ensure that the temperature adjustment section is in close contact with the corresponding part of the reaction vessel. However, when using the aforementioned slide-in mechanism, there is a problem in that when inserting the reaction vessel into the reaction apparatus, the part of the temperature adjustment section that protrudes into the insertion space catches on the reaction vessel, hindering smooth insertion.

[0006] This disclosure was made to solve these problems and aims to provide a reaction vessel that can be smoothly inserted into a reaction apparatus while enabling appropriate temperature control, and a reaction apparatus that allows the reaction vessel to be smoothly inserted while enabling appropriate temperature control. [Means for solving the problem]

[0007] The reaction vessel according to this disclosure is a reaction vessel having at least one microchannel, the microchannel comprising a first heated section corresponding to a denaturation temperature range and a second heated section corresponding to an extension / annealing temperature range, an intermediate section connecting the first heated section and the second heated section, a first connecting section that can directly or indirectly connect the first heated section and a liquid delivery mechanism, and a second connecting section that can directly or indirectly connect the second heated section and a liquid delivery mechanism, the intermediate section being capable of measuring the sample solution in the microchannel, and a guide surface formed at the end of the reaction vessel on the advancing side in the insertion direction when inserted into the inlet of the reaction apparatus, such that the thickness decreases towards the tip.

[0008] The reaction vessel has a microchannel comprising a first heated section, a second heated section, an intermediate section, a first connecting section, and a second connecting section. Therefore, by attaching the reaction vessel to the reaction apparatus, nucleic acid amplification can be performed by moving the sample solution back and forth between the denaturation temperature zone and the extension / annealing temperature zone using a liquid delivery mechanism. Furthermore, it is possible to measure the absorbance and fluorescence intensity of the sample solution in the intermediate section. Here, when the reaction vessel is inserted into the insertion port of the reaction apparatus, a guide surface is formed on the end of the reaction vessel on the advancing side in the insertion direction, such that the thickness decreases towards the tip. In this case, when the reaction vessel is inserted into the insertion port of the reaction apparatus, the reaction vessel moves toward the advancing side in the insertion direction, with the end with the guide surface as the leading edge. For example, in order to improve contact with the reaction vessel, a component of the temperature control section may protrude into the space inside the reaction apparatus. In this case, the reaction vessel can move toward the advancing side in the insertion direction smoothly by contacting the protruding part with the guide surface, thereby suppressing snagging. Therefore, by enabling smooth insertion of the reaction vessel and improving the contact between the reaction vessel and the temperature control unit components, appropriate temperature control can be achieved. Thus, a reaction vessel that allows for appropriate temperature control while being smoothly inserted into the reaction apparatus can be provided.

[0009] The microchannel may include a third heated section between the second heated section and the second connection section. This allows for the formation of other temperature zones in addition to the denaturation temperature zone and the extension / annealing temperature zone. Alternatively, a third heated section may be included between the first heated section and the first connection section.

[0010] The reaction vessel may have a notch formed in it for fixing it in the reaction apparatus when inserted into the apparatus. In this case, the reaction vessel can be securely fixed to the reaction apparatus. This allows for accurate positioning of the intermediate part of the detection unit and the reaction vessel, thereby improving measurement accuracy.

[0011] The reaction apparatus according to this disclosure is a reaction apparatus having an insertion port for inserting the above-mentioned reaction vessel, and includes a temperature adjustment unit that adjusts the temperature by contacting positions corresponding to the first heated portion and the second heated portion of the inserted reaction vessel, the temperature adjustment unit being able to contact the reaction vessel while being pressed by an elastic mechanism.

[0012] In this reaction apparatus, the temperature control unit is made contact with the reaction vessel while being pressed against it by an elastic mechanism. This improves the contact between the reaction vessel and the temperature control unit, enabling appropriate temperature control. Furthermore, although the presence of such an elastic mechanism may cause a component of the temperature control unit to protrude into the space inside the reaction apparatus, the reaction vessel has the aforementioned guide surface, allowing it to be smoothly inserted into the reaction apparatus. Thus, a reaction apparatus is provided that allows for smooth insertion of the reaction vessel while maintaining appropriate temperature control.

[0013] The reaction apparatus may have a protrusion that fits into a notch formed in the reaction vessel. In this case, the reaction vessel can be securely fixed to the reaction apparatus. This allows for accurate positioning of the detection unit and the intermediate part of the reaction vessel, thereby improving measurement accuracy.

[0014] The reaction apparatus according to this disclosure is a reaction apparatus having an insertion port for inserting the above-mentioned reaction vessel, and includes a temperature adjustment unit that adjusts the temperature by contacting positions corresponding to the first heated portion, second heated portion and third heated portion of the inserted reaction vessel, wherein the temperature adjustment unit can contact the reaction vessel while being pressed by an elastic mechanism. [Effects of the Invention]

[0015] According to this disclosure, it is possible to provide a reaction vessel that can be smoothly inserted into a reaction apparatus while enabling appropriate temperature control, and a reaction apparatus that can smoothly insert the reaction vessel while enabling appropriate temperature control. [Brief explanation of the drawing]

[0016] [Figure 1] This is a perspective view of a reaction processing apparatus into which a reaction processing container according to an embodiment of the present disclosure is inserted. [Figure 2] This is a schematic configuration diagram of the reaction processing apparatus. [Figure 3] This is a plan view showing the reaction processing container (note that the microchannel 60 shown in the figure is formed on the lower surface 50f). [Figure 4] This is a plan view showing a state where the reaction processing container is mounted on the reaction processing container mounting portion. [Figure 5] This is a schematic cross-sectional view showing a state where the reaction processing container is mounted on the reaction processing container mounting portion. [Figure 6] This is a schematic cross-sectional view showing a state when the reaction processing container is inserted into the reaction processing container mounting portion. [Figure 7] This is a schematic diagram showing the structure of a pressing mechanism. [Figure 8] This is a schematic configuration diagram showing a reaction processing container according to a modified example. [Figure 9] This is a schematic configuration diagram showing a reaction processing container according to a modified example. [Figure 10] This is a schematic configuration diagram showing a reaction processing container according to a modified example. [Figure 11] This is a schematic cross-sectional view of another aspect showing a state where the reaction processing container is mounted on the reaction processing container mounting portion. [Mode for Carrying Out the Invention]

[0017] Hereinafter, the reaction processing container and the reaction processing apparatus according to an embodiment of the present disclosure will be described with reference to the accompanying drawings. In the description of the drawings, the same elements are denoted by the same reference numerals, and overlapping descriptions are omitted.

[0018] Figure 1 is a perspective view of a reaction apparatus 1 into which a reaction vessel 50 according to an embodiment of this disclosure is inserted. Figure 2 is a schematic configuration diagram of the reaction apparatus 1. Figure 3 is a plan view showing the reaction vessel 50. The microchannels 60 shown in the figures are formed on the lower surface 50f, but are shown with solid lines to clearly show the structure of the microchannels 60. The reaction apparatus 1 can accommodate the reaction vessel 50 by inserting it through an insertion port 30. In this embodiment, the insertion port 30 is formed on the side of the reaction apparatus 1 and is equipped with a slide-in mechanism for inserting the reaction vessel 50 by sliding it horizontally. The reaction vessel 50 has a rectangular plate shape. When inserted, the reaction vessel 50 is inserted into the reaction apparatus 1 with its main surface horizontal and its longitudinal direction parallel to the insertion direction. Here, in this specification, an XY coordinate system may be set for the reaction apparatus 1 for explanation. The insertion direction of the reaction vessel 50 is the Y-axis direction. In this case, the forward insertion direction Y is considered the positive side, and the backward insertion direction Y is considered the negative side. The width direction perpendicular to the insertion direction Y is considered the X-axis direction. One side of the width direction X is considered the positive side, and the other side of the width direction X is considered the negative side. The reaction processing vessel 50 can freely change its orientation relative to the reaction processing apparatus 1. However, when describing the configuration of the reaction processing vessel 50, the orientation in the state when inserted into the reaction processing apparatus 1, or immediately before insertion, is used as the reference. Therefore, when describing the configuration of the reaction processing vessel 50, XY coordinates may also be used.

[0019] Furthermore, the reaction apparatus 1 is a device that uses the PCR (polymerase chain reaction) method, which performs thermal cycling by moving the sample solution back and forth between two temperature zones within the microchannel of the attached reaction vessel 50. The reaction apparatus 1 amplifies nucleic acids by utilizing denaturation, annealing of the primer pair to the target strand, and primer elongation that leads to an exponential increase in the copy number of the target nucleic acid sequence. The nucleic acid amplification method using the reaction apparatus 1 according to this embodiment may use DNA as a template or RNA as a template. When using RNA as a template, it is preferable to use reverse transcriptase in combination.

[0020] As shown in Figure 2, the reaction apparatus 1 comprises a reaction vessel mounting section 2, temperature adjustment sections 3A, 3B, 3C, liquid supply mechanisms 4A, 4B, a detection section 5, and a control section 10.

[0021] The reaction vessel mounting section 2 is the part where the reaction vessel 50 is mounted. The reaction vessel 50 mounted in the reaction vessel mounting section 2 is positioned relative to the various components of the reaction apparatus 1. The detailed structure of the reaction vessel mounting section 2 will be described later.

[0022] Now, with reference to Figure 3, the configuration of the reaction vessel 50 will be described. As shown in Figure 3, the reaction vessel 50 is constructed by forming microchannels 60 in a plate-shaped container body 51.

[0023] The container body 51 for forming the microchannel 60 is preferably made of a material that satisfies some or all of the following requirements: (i) low autofluorescence, (ii) stability within the temperature range required for PCR, (iii) resistance to corrosion by electrolyte solutions and organic solvents, and (iv) low adsorption of nucleic acids and proteins. Specifically, the material of the container body 51 is exemplified by, but is not limited to, various plastics such as glass, quartz, silicon, and cycloolefin polymer (COP).

[0024] The microchannels 60 are constructed by forming grooves on the surface of the container body 51 and sealing the grooves with a seal (preferably a transparent seal made of polyolefin, for example). The grooves are formed by methods such as machining by NC machining, injection molding, nanoimprinting, or soft lithography. Alternatively, the microchannels 60 can be formed inside the container body 51 by three-dimensional printing. The cross-sectional shape of the microchannels 60 is not particularly limited and can be semicircular, circular, rectangular, trapezoidal, etc. The cross-sectional shape of the microchannels 60 can be, for example, about 10 to 1000 μm in width and about 10 to 1000 μm in depth. The width and depth of the microchannels 60 can be constant, or partially varied.

[0025] In the example shown in Figure 3, the microchannel 60 has heated sections 61A, 61B, 61C, intermediate sections 62A, 62B, and connecting sections 63A, 63B.

[0026] The heated sections 61A, 61B, and 61C are heated by the temperature control sections 3A, 3B, and 3C (see Figure 2), thereby adjusting the temperature of the sample solution passing through them. The heated section 61A is formed in the container body 51 at a position corresponding to the temperature zone 66A heated by the temperature control section 3A. The heated section 61B is formed in the container body 51 at a position corresponding to the temperature zone 66B heated by the temperature control section 3B. The heated section 61C is formed in the container body 51 at a position corresponding to the temperature zone 66C heated by the temperature control section 3C. The shape of the heated sections 61A, 61B, and 61C can be a curved flow path such as a loop-shaped meandering shape or a spiral shape in order to secure the flow path length, i.e., the area where the sample solution resides in each temperature zone 66A, 66B, and 66C.

[0027] An inlet 54 for the sample solution is formed in the heated section 61C. The inlet 54 can be sealed with a seal or valve as needed. In this embodiment, the inlet 54 is sealed with a seal 64 after the sample solution is injected. The position of the inlet 54 can be changed as appropriate and is not limited to the shape shown in Figure 3. For example, it is possible to provide a branching point in the heated section 61C, form a branched flow path with one end connected to the branching point, and provide an inlet at the other end of the branched flow path. When introducing the sample solution from the inlet 54, it is preferable that the communication port 52A is open and the communication port 52B is sealed.

[0028] The intermediate section 62A is the part that connects the heated section 61A and the heated section 61B. That is, the heated section 61A and the heated section 61B are arranged to be spaced apart from each other in a direction parallel to the surface of the container body 51. Therefore, the intermediate section 62A is positioned between the heated section 61A and the heated section 61B. The intermediate section 62B is the part that connects the heated section 61B and the heated section 61C. That is, the heated section 61B and the heated section 61C are arranged to be spaced apart from each other in a direction parallel to the surface of the container body 51. Therefore, the intermediate section 62B is positioned between the heated section 61B and the heated section 61C. In the example shown in Figure 3, the intermediate sections 62A and 62B have a linear or substantially linear shape, but they may also have a curved shape. Furthermore, the connection points between the heated sections 61A and 61B and the intermediate section 62A are configured as inlets and outlets for each temperature zone 66A and 66B. Also, the connection points between the heated sections 61B and 61C and the intermediate section 62B are configured as inlets and outlets for each temperature zone 66B and 66C.

[0029] The connection sections 63A and 63B connect the communication ports 52A and 52B to the liquid supply mechanisms 4A and 4B (see Figure 2) with the heated sections 61A and 61C. The connection section 63B can also be described as indirectly connecting the heated section 61B to the liquid supply mechanism 4B via the heated section 61C and the intermediate section 62B. A configuration in which the heated section 61C is omitted is also possible. In this case, the connection section 63B connects the heated section 61B to the liquid supply mechanism 4B (without going through the heated section 61C and the intermediate section 62B). In this connection relationship, the connection section 63B can be described as directly connecting the heated section 61B to the liquid supply mechanism 4B. Filters 53A and 53B are provided at the connection sections 63A and 63B. Filters 53A and 53B are components that prevent the evaporated sample solution (aerosol) from contaminating the liquid delivery mechanisms 4A and 4B. The connection points between the heated sections 61A and 61C and the connecting sections 63A and 63B are configured as inlets and outlets for each temperature zone 66A and 66C.

[0030] As described above, the reaction vessel 50 has a rectangular plate shape. The reaction vessel 50 has an end face 50a on the positive side (advancing side) of the insertion direction Y, an end face 50b on the negative side (retracting side) of the insertion direction Y, a side surface 50c on the positive side of the width direction X, a side surface 50d on the negative side of the width direction X, an upper surface 50e constituting the upper main surface, and a lower surface 50f constituting the lower main surface. The heated section 61A, intermediate section 62A, heated section 61B, intermediate section 62B, and heated section 61C are arranged in this order from the positive side to the negative side of the insertion direction Y, near the side surface 50c. The communication ports 52A and 52B are located near the side surface 50d.

[0031] Returning to Figure 2, the temperature control units 3A, 3B, and 3C form temperature zones 66A, 66B, and 66C, respectively. It is preferable that the temperature control units 3A, 3B, and 3C maintain each of the temperature zones 66A, 66B, and 66C at a constant temperature. To achieve this temperature maintenance, it is preferable that the temperature control units 3A, 3B, and 3C are composed of heat sources such as cartridge heaters and plate heaters. However, the temperature control units 3A, 3B, and 3C are not particularly limited as long as they are temperature-adjustable devices.

[0032] The temperature control units 3A, 3B, and 3C maintain the temperatures of temperature zones 66A, 66B, and 66C at a constant level, thereby maintaining the heated portions 61A, 61B, and 61C of the microchannels 60 formed in each temperature zone 66A, 66B, and 66C at the corresponding temperatures. Therefore, the temperature control units 3A, 3B, and 3C can change the temperature of the sample solution that has moved to each temperature zone 66A, 66B, and 66C to the desired temperature in each temperature zone 66A, 66B, and 66C.

[0033] For example, the temperature control unit 3A may maintain temperature zone 66A as the denaturation temperature zone, at the temperature required for the DNA denaturation reaction in PCR. The temperature of the denaturation temperature zone is preferably around 90 to 100°C, and more preferably around 95°C. The temperature control unit 3B may maintain temperature zone 66B as the extension / annealing temperature zone, at the temperature required for the DNA annealing and extension reactions in PCR. The temperature of the extension / annealing temperature zone is preferably around 40 to 75°C, and more preferably around 55 to 65°C. The temperature control unit 3C may maintain temperature zone 66C as the reverse transcription reaction temperature zone, at the temperature required for the reverse transcription reaction. The temperature of the reverse transcription reaction temperature zone is preferably around 37 to 60°C, and more preferably around 42 to 55°C.

[0034] The temperature control units 3A, 3B, and 3C are connected to drivers 21A, 21B, and 21C, and temperature monitoring units 22A, 22B, and 22C. Drivers 21A, 21B, and 21C are devices that control the temperature control units 3A, 3B, and 3C based on control signals from the control unit 10, so that the temperature control units 3A, 3B, and 3C generate heat to maintain each temperature zone 66A, 66B, and 66C at the desired temperature. Temperature monitoring units 22A, 22B, and 22C are devices that monitor the temperature of the temperature control units 3A, 3B, and 3C and transmit the monitoring results to the control unit 10.

[0035] The liquid delivery mechanisms 4A and 4B are mechanisms that move the sample solution within the microchannel 60 so as to move back and forth between temperature zone 66A and temperature zone 66B. This allows the sample solution to move back and forth between the denaturation temperature zone and the extension / annealing temperature zone. As liquid delivery mechanisms 4A and 4B, a mechanism is used in which the air pressure at the air intake and air discharge sections becomes equal when liquid delivery stops. Examples of liquid delivery mechanisms 4A and 4B in which the air pressure at the air intake and air discharge sections becomes equal when liquid delivery stops include microblowers and fans.

[0036] The liquid delivery mechanisms 4A and 4B are connected to the communication ports 52A and 52B (see Figure 3) of the reaction processing vessel 50, respectively, via the air supply channels 23A and 23B. The liquid delivery mechanisms 4A and 4B are connected to the drivers 24A and 24B. The drivers 24A and 24B are devices that control the liquid delivery mechanisms 4A and 4B based on control signals from the control unit 10, so that the liquid delivery mechanisms 4A and 4B supply air at the desired timing. When liquid delivery mechanism 4A supplies air, the sample solution in the microchannel 60 (see Figure 3) is delivered from the temperature zone 66A side to the temperature zone 66B side. When liquid delivery mechanism 4B supplies air, the sample solution in the microchannel 60 (see Figure 3) is delivered from the temperature zone 66B side to the temperature zone 66A side.

[0037] The detection unit 5 is a device for detecting the sample solution in the reaction processing vessel 50. The detection unit 5 detects the sample solution and transmits the detection result to the control unit 10. The detection unit 5 detects the sample solution in the reaction processing vessel 50 between temperature zone 66A and temperature zone 66B. Specifically, the detection unit 5 detects the sample solution in a detection region 67 near the center of the intermediate part 62A of the microchannel 60 (see Figure 3). The channel width of the microchannel 60 in the detection region 67 may be larger than the channel width of the microchannel 60 in other parts. Increasing the channel width improves the detection accuracy of the detection unit 5. The detection unit 5 is composed of, for example, a fluorescence detector.

[0038] The control unit 10 comprises a heating control unit 11, a signal detection unit 12, and a liquid delivery mechanism control unit 13. The heating control unit 11 controls the temperature adjustment units 3A, 3B, and 3C so that the temperatures in temperature zones 66A, 66B, and 66C remain constant at a desired temperature. The signal detection unit 12 receives detection results from the detection unit 5. The liquid delivery mechanism control unit 13 may control the liquid delivery mechanisms 4A and 4B based on the signals received by the signal detection unit 12 so that the sample solution in the microchannel 60 moves as desired.

[0039] Next, the characteristic parts of the reaction processing vessel 50 and the reaction processing apparatus 1 according to this embodiment will be described in detail with reference to Figures 4 to 7. Figure 4 is a plan view showing the reaction processing vessel 50 mounted on the reaction processing vessel mounting section 2. In Figure 4, the upper wall of the reaction processing vessel mounting section 2 is omitted. Also, in Figure 4, some structures such as the microchannel 60 are omitted in order to clarify the characteristics. Figure 5 is a schematic cross-sectional view showing the reaction processing vessel 50 mounted on the reaction processing vessel mounting section 2. Figure 6 is a schematic cross-sectional view showing the reaction processing vessel 50 being inserted into the reaction processing vessel mounting section 2. Figure 7 is a schematic diagram showing the structure of the pressing mechanism 71.

[0040] As shown in Figures 4 and 5, a guide surface 31 is formed on the end 55 of the reaction treatment container 50 on the positive side (advancing side) in the insertion direction Y when it is inserted into the insertion port 30 of the reaction treatment apparatus 1. The guide surface 31 is formed by an inclined surface formed between the lower surface 50f and the end surface 50a. The guide surface 31 is inclined upward as it extends from the lower surface 50f toward the positive side in the insertion direction Y. As a result, the vertical dimension of the end surface 50a is smaller than the thickness dimension of the reaction treatment container 50 in other parts.

[0041] As shown in Figure 4, a notch 32 is formed on the negative side surface 50d in the width direction X of the reaction apparatus 1, at a position closer to the negative side in the insertion direction Y. This notch 32 is a structure for fixing the reaction apparatus 1 when the reaction apparatus 50 is inserted into the reaction apparatus 1. When viewed from above, the notch 32 is formed by a groove shape that recesses from the side surface 50d toward the positive side in the width direction X. The notch 32 has a tapered surface 32a (see Figure 3) that widens toward the negative side in the width direction X to facilitate the fitting and unfitting of the protruding part described later. When inserted, the inlet 54 is closed with a seal 64.

[0042] Furthermore, as shown in Figure 4, a tapered surface 33 is formed at the corner between the end face 50a and the side surface 50c of the reaction apparatus 1 by chamfering. In addition, anti-slip portions 34 are formed on the side surfaces 50c and 50d of the end 56 on the negative side in the insertion direction Y. The anti-slip portions 34 have multiple uneven shapes, making them less likely to slip when the user pinches them with their fingers.

[0043] The reaction processing vessel mounting section 2 has a structure that guides the reaction processing vessel 50, as described above, to slide toward the positive side in the insertion direction Y when it is inserted through the insertion port 30, and also suppresses rattling after insertion. Specifically, the reaction processing vessel mounting section 2 comprises side wall sections 41 and 42, a lower wall section 44, and an upper wall section 46 (see Figure 5). The side wall section 41 is positioned to face the side surface 50d of the reaction processing vessel 50 from the negative side in the width direction X and extends toward the insertion direction Y. As a result, the side wall section 41 guides the side surface 50d toward the insertion direction Y during insertion and restricts the movement of the side surface 50d toward the negative side in the width direction X. The side wall section 42 is positioned to face the side surface 50c of the reaction processing vessel 50 from the positive side in the width direction X and extends toward the insertion direction Y. As a result, the side wall section 42 guides the side surface 50c toward the insertion direction Y during insertion and restricts the movement of the side surface 50c toward the positive side in the width direction X. As shown in Figure 5, the lower wall portion 44 is positioned to face the lower surface 50f of the reaction processing vessel 50 from below and extends in the insertion direction Y. As a result, the lower wall portion 44 guides the lower surface 50f in the insertion direction Y during insertion and restricts the downward movement of the lower surface 50f. The upper wall portion 46 is positioned to face the upper surface 50e of the reaction processing vessel 50 from above and extends in the insertion direction Y. As a result, the upper wall portion 46 guides the upper surface 50e in the insertion direction Y during insertion and restricts the upward movement of the upper surface 50e. The side walls 41, 42 and the lower wall portion 44 and upper wall portion 46 may have one or more openings or recesses, as long as they can perform the above functions.

[0044] The side wall portion 41 has a projection 43 positioned towards the negative side in the insertion direction Y, which fits into a notch 32 formed in the reaction processing vessel 50. The projection 43 can be made of an elastic member such as a leaf spring or kick spring having a mountain-shaped form that is inserted into the notch 32. The projection 43 may also have a structure in which a latch portion is connected to the elastic member, and the latch portion fits into the notch 32. The side wall portion 41 has an opening 41a for allowing the projection 43 to protrude toward the notch 32. The side wall portion 41 also has a support wall portion 41b for supporting the projection 43 from the negative side in the width direction X. As a result, during the insertion of the reaction processing vessel 50, the projection 43 is pressed against the side surface 50d and pushed toward the negative side in the width direction X relative to the support wall portion 41b. Once the insertion of the reaction vessel 50 is complete (as shown in Figure 4), the elastic force of the protrusion 43 is released, and it fits into the notch 32. As a result, the reaction vessel 50 is fixed to the reaction vessel mounting section 2 by the notch 32 and the protrusion 43.

[0045] A slide member 70 is provided at the positive end of the reaction processing container mounting section 2 in the insertion direction Y. When the reaction processing container 50 is inserted all the way in, the slide member 70 is pushed by the end face 50a and slides toward the positive side of the insertion direction Y (see Figure 6). Once the insertion of the reaction processing container 50 is complete, the slide member 70 protrudes out of the reaction processing container mounting section 2. Therefore, the user can push the reaction processing container 50 out of the insertion opening 30 by pushing the slide member 70 toward the negative side of the insertion direction Y.

[0046] When the reaction vessel 50 is mounted on the reaction vessel mounting section 2, nozzles 47A and 47B, which communicate with the liquid supply mechanisms 4A and 4B (see Figure 2), are joined to the communication ports 52A and 52B. The nozzles 47A and 47B are made of a material that can ensure airtightness between them and the upper surface 50e. In addition, the detection unit 5 is positioned above the detection area 67.

[0047] As shown in Figure 5, when the reaction vessel 50 is mounted on the reaction vessel mounting section 2, the temperature adjustment sections 3A, 3B, and 3C can adjust the temperature by contacting the lower surface 50f at positions corresponding to the heated sections 61A, 61B, and 61C. Here, the temperature adjustment sections 3A, 3B, and 3C each include a contact member 3a and an elastic mechanism 3b. These contact member 3a and elastic mechanism 3b are provided to be housed in recesses formed in the lower wall section 44. The contact member 3a is a block-shaped member that directly contacts the lower surface 50f. The contact member 3a is made of a material with high thermal conductivity, such as aluminum, aluminum alloy, or copper alloy. The elastic mechanism 3b is a member or mechanism that generates elastic force, and any material with heat resistance can be used, such as a spring member, elastomer, or rubber material. The elastic mechanism 3b supports the contact member 3a so that, in the state before insertion, the contact member 3a protrudes above the upper surface of the lower wall portion 44 (see Figure 6(a)). The elastic mechanism 3b generates an elastic force as the contact member 3a moves downward (see Figure 6(c)). As a result, the contact member 3a can contact the lower surface 50f while being pressed against the reaction processing vessel 50. The heater may be integrated with the contact member 3a or placed between the contact member 3a and the elastic mechanism 3b.

[0048] Referring to Figure 6, the operation of the temperature control units 3A, 3B, 3C and nozzles 47A, 47B when the reaction processing vessel 50 is inserted will be explained. As shown in Figure 6(a), immediately after the end 55 of the reaction processing vessel 50 is inserted into the insertion port 30, the contact members 3a of the temperature control units 3A, 3B, 3C protrude slightly above the upper surface of the lower wall 44. As shown in Figure 6(b), when the reaction processing vessel 50 is inserted further, the contact members 3a of the temperature control units 3B, 3C come into contact with the lower surface 50f. At this time, the upper surface of the contact member 3a is pushed downward by the lower surface 50f and becomes the same height as the upper surface of the lower wall 44. Therefore, the contact member 3a is pressed against the lower surface 50f by the elastic force of the elastic mechanism 3b. As a result, the contact member 3a can be tightly pressed against the lower surface f.

[0049] Here, the protruding portion of the contact member 3a comes into contact with the guide surface 31 when it comes into contact with the end 55 on the positive side in the insertion direction Y of the reaction processing container 50. As a result, the contact member 3a is guided by the guide surface 31 and can sink smoothly downwards. Therefore, the end 55 of the reaction processing container 50 can move smoothly toward the positive side in the insertion direction Y without getting caught on the protruding portion of the contact member 3a.

[0050] As shown in Figure 6(c), once the insertion of the reaction vessel 50 is complete, all the contact members 3a of the temperature control sections 3A, 3B, and 3C sink in and come into close contact with the lower surface 50f. At this time, the end 55 of the reaction vessel 50 pushes the slide member 70 toward the positive side of the insertion direction Y. Also, the nozzles 47A and 47B move downward and come into close contact with the upper surface 50e of the reaction vessel 50 at the positions of the communication ports 52A and 52B (see Figure 4). As a result, the nozzles 47A and 47B communicate with the communication ports 52A and 52B while ensuring airtightness, and the reaction vessel 50 can be pressed against the lower wall 44 and fixed in place.

[0051] Here, the nozzles 47A and 47B may move downward using the force generated when the slide member 70 slides. The reaction apparatus 1 has a pressing mechanism 71 as shown in Figure 7(a). The pressing mechanism 71 comprises an arm portion 72 fixed to the slide member 70, a base portion 73 that supports the nozzles 47A and 47B from above, and a fixed guide portion 74 that guides the base portion 73. The arm portion 72 is positioned above the slide member 70 and extends in the positive direction of the insertion direction Y. A groove portion 76 extending in the vertical direction is formed on the positive side of the arm portion 72 in the width direction X. The base portion 73 is positioned adjacent to the arm portion 72 in the positive direction of the width direction X. A projection portion 77 is formed on the negative side of the base portion 73 in the width direction X so as to be inserted into the groove portion 76. The projection portion 77 can move relative to the base portion 73 in the vertical direction. Furthermore, the base portion 73 has a guide surface 73a at the end on the positive side in the insertion direction Y. The guide surface 73a is inclined downward as it extends toward the positive side in the insertion direction Y. The fixed guide portion 74 has a guide surface 74a that contacts the guide surface 73a of the base portion 73 in a sliding manner while being fixed so as not to change position.

[0052] As shown in Figure 7(b), when the slide member 70 moves toward the positive side of the insertion direction Y, the arm portion 72 also moves. At this time, the projection 77 is pulled by the groove portion 76, causing the base portion 73 to move toward the positive side of the insertion direction Y. At this time, the base portion 73 moves diagonally downward as the guide surface 73a slides against the guide surface 74a of the fixed guide portion 74. At this time, relative downward movement of the projection 77 is permitted within the groove portion 76. Through this operation, the nozzles 47A and 47B move diagonally downward together with the base portion 73 and come into contact with the reaction processing container 50.

[0053] Next, the operation and effects of the reaction vessel 50 and the reaction apparatus 1 according to this embodiment will be described.

[0054] The reaction vessel 50 has a microchannel 60 comprising a first heated section 61A, a second heated section 61B, (in this embodiment) a third heated section 61C, an intermediate section 62A, a first connecting section 63A, and a second connecting section 63B. Therefore, by attaching the reaction vessel 50 to the reaction apparatus 1, nucleic acid amplification can be performed by moving the sample solution back and forth between the denaturation temperature zone and the extension / annealing temperature zone using the liquid delivery mechanisms 4A and 4B. In addition, it is possible to measure the absorbance and fluorescence intensity of the sample solution in the intermediate section 62A. Here, when the reaction vessel 50 is inserted into the insertion port 30 of the reaction apparatus 1, a guide surface 31 is formed on the end 55 of the reaction vessel 50 on the forward side (positive side) in the insertion direction Y, such that the thickness decreases towards the tip. In this case, when the reaction processing container 50 is inserted into the insertion port 30 of the reaction processing apparatus 1, the reaction processing container 50 moves toward the forward direction of insertion Y, with the end portion 55 having the guide surface 31 as the leading edge (see Figure 6). For example, in order to improve contact with the reaction processing container 50, the contact members 3a of the temperature adjustment units 3A, 3B, and 3C may protrude into the space inside the reaction processing apparatus 1 (protruding from the upper surface of the lower wall portion 44). In this case, the reaction processing container 50 can move smoothly toward the forward direction of insertion Y by contacting the protruding portion of the contact member 3a with the guide surface 31, thereby suppressing snagging. Therefore, by enabling smooth insertion of the reaction processing container 50 and improving the contact between the reaction processing container 50 and the contact members 3a of the temperature adjustment units 3A, 3B, and 3C, appropriate temperature adjustment can be achieved. Thus, a reaction processing container 50 can be provided that can be smoothly inserted into the reaction processing apparatus 1 while enabling appropriate temperature adjustment.

[0055] The microchannel 60 may include a heated section 61C between the heated section 61B and the second connecting section 63B. This allows for the formation of another temperature range (in this embodiment, the reverse transcription reaction temperature range) in addition to the denaturation temperature range and the extension / annealing temperature range.

[0056] The reaction processing container 50 may have a notch 32 formed in it for fixing it in the reaction processing device 1 when inserted into the device. In this case, the reaction processing container 50 can be securely fixed to the reaction processing device 1. This allows for accurate positioning of the detection unit 5 and the intermediate portion 62A of the reaction processing container 50, thereby improving measurement accuracy.

[0057] The reaction apparatus 1 according to this embodiment is a reaction apparatus 1 having an insertion port 30 for inserting the above-described reaction vessel 50, and includes temperature adjustment units 3A, 3B, and 3C that adjust the temperature by contacting positions corresponding to the first heated portion 61A, the second heated portion 61B, and the third heated portion 61C of the inserted reaction vessel 50, and the temperature adjustment units 3A, 3B, and 3C can contact the reaction vessel 50 while being pressed by an elastic mechanism 3b.

[0058] In this reaction apparatus 1, the temperature control units 3A, 3B, and 3C can contact the reaction vessel 50 while being pressed against it by an elastic mechanism 3b. This improves the contact between the reaction vessel 50 and the temperature control units 3A, 3B, and 3C, enabling appropriate temperature control. Furthermore, although the contact members 3a of the temperature control units 3A, 3B, and 3C may protrude into the space inside the reaction apparatus 1 due to the presence of such an elastic mechanism 3b, the reaction vessel 50 has the guide surface 31 described above, allowing it to be smoothly inserted into the reaction apparatus 1. Thus, a reaction apparatus 1 is provided that allows for smooth insertion of the reaction vessel 50 while maintaining appropriate temperature control.

[0059] The reaction apparatus 1 may have a protrusion 43 that fits into a notch 32 formed in the reaction vessel 50. In this case, the reaction vessel 50 can be securely fixed to the reaction apparatus 1. This allows for accurate positioning of the detection unit 5 and the intermediate portion 62A of the reaction vessel 50, thereby improving measurement accuracy.

[0060] This disclosure is not limited to the embodiments described above.

[0061] For example, the configuration of the reaction vessel mounting section 2 of the reaction apparatus 1 described above is merely an example, and may be modified as appropriate without departing from the spirit of this disclosure.

[0062] Furthermore, the structure of the reaction vessel 50 described above is merely an example and may be modified as appropriate without departing from the spirit of this disclosure. For example, the flow path configuration of the microchannel 60 may be modified as appropriate. Also, the third heated section 61C may be omitted. Alternatively, a heated section 61C may be provided between the heated section 61A and the first connecting section 63A.

[0063] Furthermore, the reaction processing vessel 50 may be flat and plate-shaped, and its thickness may be varied depending on the location. For example, a reaction processing vessel 50 as shown in Figures 8 to 10 may be used. For example, the container body 51 of the reaction processing vessel 50 shown in Figure 8 has a main body portion 51A. The container body 51 also has a thickened portion 51B on the edge of the long side where the communication ports 52A, 52B and filters 53A, 53B are formed. Figure 8(a) is a plan view, Figure 8(b) is a left side view, Figure 8(c) is a right side view, and Figure 8(d) is a front view. The same applies to Figures 9 and 10.

[0064] The container body 51 of the reaction processing vessel 50 shown in Figure 9 has a thick-walled portion 51C on the short side edge where the inlet 54 is formed, in addition to the thick-walled portion 51B shown in Figure 8. A shallow groove 51a is formed in the thick-walled portion 51C at the location of the inlet 54. This groove 51a can accommodate the seal 64 that closes the inlet 54. This prevents the seal 64 from peeling off by pressing down on the thickness of the seal 64 when the reaction processing vessel 50 is inserted into the insertion port 30. In order to prevent the seal 64 from peeling off, the space around the insertion port 30 may be partially wider than the rest of the space in the reaction processing vessel mounting portion 2.

[0065] The container body 51 of the reaction processing vessel 50 shown in Figure 10 has a partially thickened section 51D in addition to the thickened section 51B shown in Figure 8, where the inlet 54 is formed. A shallow groove 51a is formed in the thickened section 51D at the location of the inlet 54.

[0066] In the example shown in Figure 5, each temperature control unit 3A, 3B, and 3C had its own elastic mechanism 3b. Alternatively, the temperature control units 3A, 3B, and 3C shown in Figure 11 may be used. In the example shown in Figure 11, an elastic mechanism 103b extending in the insertion direction Y is provided so as to reach the respective contact members 3a of the temperature control units 3A, 3B, and 3C. In this case, the temperature control units 3A, 3B, and 3C can share the long elastic mechanism 103b. [Explanation of symbols]

[0067] 1...Reaction apparatus, 3A, 3B, 3C...Temperature control unit, 3a...Contact member, 3b, 103b...Elastic mechanism, 50...Reaction vessel, 30...Inlet, 31...Guide surface, 32...Notch, 43...Protruding part, 50...Reaction vessel, 55...End, 60...Microchannel, 61A...First heated part, 61B...Second heated part, 61C...Third heated part, 62A...Intermediate part, 63A...First connection part, 63B...Second connection part.

Claims

1. A reaction vessel having at least one microchannel, The aforementioned microchannel includes a heated portion, When inserting into the insertion port of the reaction processing apparatus, a guide surface is formed on the end of the reaction processing vessel on the side of the insertion direction, such that the thickness decreases towards the tip. When inserted into the aforementioned reaction apparatus, a notch is formed for fixing it in the reaction apparatus. Reaction processing vessel.

2. The reaction processing vessel according to claim 1, wherein the heated section includes a first heated section and a second heated section.

3. The first heated part corresponds to the denaturation temperature range, The second heated part corresponds to the extension and annealing temperature range. The reaction processing vessel according to claim 2.

4. The reaction processing vessel according to claim 2 or claim 3, comprising the first heated section and the intermediate section connecting the second heated section.

5. A reaction apparatus having an insertion port for inserting a reaction processing vessel according to any one of claims 1 to 4, The temperature adjustment unit is provided to adjust the temperature by contacting the position of the heated part of the inserted reaction processing vessel, The reaction apparatus is such that the temperature control unit can be in contact with the reaction vessel while being pressed against it by an elastic mechanism.

6. The reaction apparatus according to claim 5, having a protrusion that fits into a notch formed in the reaction vessel.

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